An evidence summary of Paediatric COVID-19 literature

Cite this article as:
Boast A, Munro A, Goldstein H. An evidence summary of Paediatric COVID-19 literature, Don't Forget the Bubbles, 2020. Available at:
http://doi.org/10.31440/DFTB.24063

This post is a rapid literature review of pertinent paediatric literature regarding COVID-19 disease. We are proud to have joined forces with the UK Royal College of Paediatrics and Child Health to provide systematic search, and selected reviews of all the COVID-19 literature relevant to children and young people.

Our search and review methods have changed as the pace and utility of the published literature has evolved over time. Our process involved a formal literature search (methods can be found here), followed by identification of all papers relevant to children/young people, then reading of every article by one of our team of doctors. Initially we produced a written review of all publications, however on April 17th 2020 we moved to a more selective review process. All articles were read in full, then if high enough quality, determined by consensus and involvement of a clinical academic, a written review was also produced.

As of June 30th 2020, we have again revised our process as the urgent need for rapid evidence synthesis has lessened, and the volume of research published remains extremely high, with much of it adding little to the current body of knowledge. Our search criteria has therefore narrowed, and of the articles identified as relevant, only those felt to be of exceptional quality or impact (as determined by consensus with involvement of a clinical academic) are selected for written review.

Our team of reviewers includes Alasdair Munro, Alison Boast, Henry Goldstein, Grace Leo, Dani Hall, Daniel Yeoh, Tessa Davis, Melody Redman, Sarah Sloan, Tricia Barlow, Anne Bean, Maeve Kelleher, Victoria Dachtler, Irnthu Premadeva, Lilian Nyirongo, Esther Alderson, Sunil Bhopal, Aimee Donald and Rachel Harwood.

Here we present the top 10 papers from each category (Paediatric clinical cases, Epidemiology and transmission, and Neonates). At the top is an Executive summary followed by all New and noteworthy studies.

If you have feedback please email us at hello@dontforgetthebubbles.com

Executive Summary (Updated 10th July)

Epidemiology

Around the world, children make up a minority of confirmed cases of COVID-19, usually contributing to between 1 – 5% of total case numbers. This almost certainly represents some undercounting of children in total case numbers as many countries have focussed on testing the most unwell, but in some populations which undertook widespread population testing, children still account for very low case numbers. Countries which have produced representative population seroprevalence studies (including Switzerland, Spain and Italy) have found proportionately far fewer children have been infected than adults (young children <10 years in particular).

More detailed information has emerged into childhood severity of COVID-19. A large number of children may be asymptomatic, but the true proportion is unknown. Critical illness is very rare (~1%). In data from China, the USA and Europe, infants and older adolescents appear most likely to be hospitalised and to suffer from more severe disease. Deaths in children remain extremely rare from COVID-19.

Transmission

Precise details regarding paediatric transmission are still being ascertained, however important trends are emerging. Low case numbers in children suggest a more limited role than was initially feared. Contact tracing data from Asia, the USA, Europe and Israel have all demonstrated a significantly lower attack rate in children than adults, including testing of asymptomatic household contacts on both PCR and serology. Coupled with low case numbers would suggest that children are less likely to acquire the disease. The role of children in passing the disease to others is unknown, in particular given unknown numbers of asymptomatic cases. Notably, the China/WHO joint commission could not recall episodes during contact tracing where transmission occurred from a child to an adult. Studies of multiple family clusters have revealed children were unlikely to be the index case, in Guangzhou, China, Israel, the USA, Switzerland and internationally. Limited data on positive cases in schools have not demonstrated significant transmission, except within adolescent populations. Studies of younger children in schools have found low rates of transmission, but with very low case numbers.

Several studies have now shown that SARS-CoV-2 can be detected by PCR in the stool of affected children for several weeks after symptoms have resolved. Studies have confirmed there can also be live virus found in the stool of infected individuals. How much virus is present, and the extent to which faecal-oral transmission may be possible is yet to be confirmed.

Clinical features

A significant proportion of children with COVID-19 do not appear to develop any symptoms, or have subclinical symptoms. In the absence of widespread community or serological testing, it is uncertain what this proportion is. The most detailed paediatric population data from China showed 13% of confirmed cases had no symptoms (cases detected by contact tracing). Considering both confirmed and suspected cases, 32% of children aged 6-10yrs were asymptomatic. Data from Italian emergency departments found 21% of SARS-CoV-2 positive children to be asymptomatic. Importantly, these studies did not follow up children to determine if they later developed symptoms, so the true proportion of asymptomatic children is unknown.

Clinical features in symptomatic children are somewhat different to adults. Children tend to have more mild illness. The most common presenting features are cough and fever, occurring in over half of symptomatic patients. Upper respiratory tract symptoms such as rhinorrhoea and sore throat are also relatively common, occurring in 30-40% of patients. It is not uncommon for children to have diarrhoea and/or vomiting (around 10% of cases), even in some cases as their sole presenting features. Several case series of rashes resembling chill blains (often occurring on feet/toes) have been reported from Europe, contemporaneously associated with the COVID-19 outbreak but with few cases simultaneously confirmed to be infected

Blood tests also show slightly different features to adults. Lymphocytopaenia is relatively rare in children, with the majority having normal or sometimes raised lymphocyte counts. Inflammatory markers such as CRP and Procalcitonin are often raised but only very mildly. Slight elevations in liver transaminases appear to be common.

Radiographic features in children are also somewhat different to their adult counterparts. Chest X-rays are often normal, and many CT chest scans are also normal. When present abnormalities are often less severe, however a reasonable number of children have bilateral pneumonia. Changes may be found on CT even in asymptomatic children. Common features in abnormal CT scans include mild, bilateral ground glass opacities, but with less peripheral predominance than is reportedly found in adults.

There appears to be little in the way of clinical signs in children to differentiate COVID-19 from other childhood respiratory virus infections.

PIMS-TS/MIS-C

A new hyperinflammatory syndrome resembling Kawasaki shock, which appears to be a delayed immune response to COVID-19 has been described. It is known as PIMS-TS in Europe and MIS-C in the USA. Published reports from London, Italy, France and the USA in a cohort of children with evidence of past COVID-19 infection have presented with early symptom of abdominal pain, vomiting and diarrhoea, with persistent high-grade fever and commonly progression on to shock with cardiac involvement. High inflammatory markers, myocarditis, macularpapular rashes and non-suppurative conjunctivitis are common. Respiratory involvement is notably absent. Investigations are underway to ascertain a link and mechanism of disease. Most cases recover quickly, but there have been deaths reported.

Consistent with adult literature, children from a Black, Asian and Minority Ethnic (BAME) background seem to be at higher risk of severe disease from acute COVID-19 infection, and are significantly overrepresented in case reports of PIMS-TS

Newborns

A large number of cases of infants born to mothers with COVID-19 have now been reported, including several hundreds from the UK. Mothers and their babies in general appear to do well. There is a small but notable increase in the rates of preterm birth, and signals of increase in rates of foetal loss/stillborn delivery. As yet, cord blood, amniotic fluid and placental swabs persistently testing negative for SARS-CoV-2. There have been a few cases of infants delivered to mothers with COVID-19, who had elevated SARS- CoV-2 IgM. This may indicate intrauterine transmission, however swab PCR from these children has been negative and false positives with IgM tests are not uncommon. When tested, breast milk has usually been negative for SARS-CoV-2, but there have been a small number of instances where it has tested positive. It is unclear if this positive result reflects live, infectious virus, and whether the source was the mother or infants who subsequently also test positive for the virus. The vast majority of newborns have not acquired COVID-19 themselves. There have been case reports of newborns and very young infants testing positive including several within 12 hours of age, however they have mostly not suffered any complications of the disease and required minimal respiratory support.

Children with co-morbidities

There is a growing body of evidence reflecting a small increased risk of children with comorbidities to be hospitalised or need intensive care from COVID-19. Studies from PICU admissions in the US and Italy found the majority have some comorbidities, most commonly respiratory, cardiac or complex neurodisability – groups for whom there is a background increased risk of complications from all respiratory viruses. The rates of complications from SARS-CoV-2 infection do not appear disproportionate to those from other respiratory viruses from this early data. Children with malignancy or immunosuppression are slightly overrepresented in admission and PICU data, however reports indicate that the majority of children with these conditions still largely suffer mild illness. A study from London did not find children with comorbidities to be at significantly increased risk of severe disease.

Conclusion

COVID-19 appears to affect children less often, and with less severity, including frequent asymptomatic or subclinical infection. There is evidence of critical illness, but it is rare. The role of children in transmission is unclear, but consistent evidence is demonstrating a lower likelihood of acquiring infection, and lower rates of children bringing infections into households. Changes in laboratory or radiographic parameters are slightly different to adults, and changes usually mild. There is some evidence of vertical transmission to neonates, however it is unclear is this is perinatal or intrauterine. Evidence suggests both infected mothers and infants are no more severely affected than other groups. There does not appear to be significant increased risk for children with immunosuppression, but further data is needed. Children with respiratory, cardiac and complex neurodisability appear more likely to suffer complications, however not obviously more than would be expected from infection with other respiratory viruses.

New and Noteworthy (Updated 10th July)

Götzinger, F., B. Santiago-García, A. Noguera-Julián, et al. “COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study.” Lancet Child Adolesc Health. https://doi.org/10.1016/S2352-4642(20)30177-2

This European multi centre cohort study recruited from participating centres from the Paediatric Tuberculosis Network European Trials Groups, to look at 582 cases of paediatric (<18 years old) SARS-CoV-2 infection in 21 countries with 77 healthcare centres. Centres from five additional countries reported no SARS-CoV-2 cases at the time of the study. The breakdown of centres included 454 (78%) tertiary, 54 (9%) secondary and 74 (13%) primary healthcare providers.

Cases were collected retrospectively from known cases prior to 1st April and prospectively between 1-24th April. Diagnosis was made on RT-PCR of SARS-CoV-2 alone. The age group of the population was young, with a median age of 5 (IQR 0.5-12) and 230 (40%) under 2 years of age. Just over half were male (n=311, 53%).

Index case data from history was included, with parents being the suspected index case for 324 patients (56%) and siblings accounting for 24 cases (4%). However a large number of cases (n=234, 40%) were either from someone outside of the immediate family or of unknown transmission.

The most common symptoms patients presented in were fever (n=379, 65%) and respiratory symptoms (n=313, 54% URTI and n=143, 25% LRTI). 128 (2%) had gastrointestinal (GI) symptoms and 40 (7%) had GI symptoms without respiratory symptoms. Asymptomatic patients accounted for 16% of all cases (92). There was confirmed viral co-infection in 5% (n=29) of patients. The study did not capture laboratory values. Chest x-ray was performed in 34% (n=198) of patients. Almost half of the x-rays showed findings consistent with pneumonia and ten (5%) of ARDS.

Of the patients in the study, a quarter (145) had pre-existing medical conditions. Twenty nine patients had pre-existing respiratory conditions (asthma accounting for 16) and malignancy was known in 27 patients. The study collected data on antiviral treatments administered however numbers were small and depended on local practice.

Across the cohort 363 patients (62%) required hospital admission, 48 (8%) required ICU admission. Factors increasing risk of ICU admission (n=48) were found to be age <1 month (n=7/48, 14.6%) the presence of any pre-existing medical condition (n=25/48 52%) and presence of lower respiratory tract infection signs at time of presentation (n=35/48, 73%). Mechanical ventilation was required by 25 patients (4%) and echo was used for 1 patient. Data on treatments given included antivirals: hydroxychloroquine (n=40, 7%), remdesivir (n=17, 3%), lopinavir-ritonavir (n=6, 1%) and oseltamivir (n=3, 1%). Other immunomodulators used were corticosteroids in 22 (4%), IvIG in 7 (1%), tocilizumab (n=4, 1%), anakinra (n=3, 1%) and siltuximab (n=1).

There were 4 deaths (0.69%), all of which were in children >10 years of age. Of the four deaths, one was an out of hospital cardiac arrest and two had pre-existing medical conditions; one patient had a stem cell transplant 15 months prior and another patient was managed palliatively due to their pre-existing illness. By time of end study 553 patients had made a full recovery and 25 patients had ongoing symptoms.

Overall, this is one of the first multi-national European studies of SARS-CoV-2 in children. Common symptoms included respiratory and fever but gastrointestinal symptoms were present in over one fifth of cases. Although eight percent of children required ICU admission, the case fatality rate was low at 0.69%. Children at greater risk of intensive care admission had pre-existing medical conditions, were less than 1 month old, or presented with lower respiratory tract symptoms. Asymptomatic infection occurred in 16% of cases. Given that at the time of the study, there were varying practices for screening criteria, it is likely that the true proportion of asymptomatic patients is higher (and true case fatality rate lower)

Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al. Prevalence of SARSCoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet 2020. https://doi.org/10.1016/ S0140-6736(20)31483-5

Introduction: Spain was one of the countries in Europe hit hardest by the Covid 19 pandemic. These are the first wave results from the Seroepidemiological Survey of SARS-CoV-2 Virus Infection in Spain (Encuesta Seroepidemiológica de la Infección por el Virus SARS-CoV-2 en España; ENE-COVID). This is an epidemiological study with an aim to estimate the sero-prevalence of Sars Cov2 in Spain through symptom checking, point of care antibody testing, and serology.

Methods: 35 883 households across Spain were selected through stratified two stage sampling and invited to take part. This is the result of the first wave of sampling which was conducted from April 27 to May 11, 2020. Participants within selected households answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors. “Asymptomatic” was no symptoms, “paucisymptomatic” (1–2 symptoms without anosmia or ageusia), and symptomatic (anosmia or ageusia, or at least three symptoms among fever; chills; severe tiredness; sore throat; cough; shortness of breath; headache; or nausea, vomiting, or diarrhoea). Participants were contacted by phone and then invited to go to local primary care centre for testing or have a home visit. All participants were offered point-of-care antibody test (Orient Gene Biotech COVID-19 IgG/IgM Rapid Test Cassette; Zhejiang Orient GeneBiotech, Zhejiang, China, SARS-CoV-2 spike protein) and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay (SARS-CoV-2 IgG for use with ARCHITECT; Abbott Laboratories, Abbott Park, IL, USA, SARS-CoV-2 nucleoprotein). Sensitivity of the test was deemed any test positive (point of care/ serum), with specificity both tests positive. Of note Spain was under lockdown at the time of this study.

Results: Of 95 699 eligible individuals, 66 805 study participants took part, with 61 075 receiving point of care testing and 51 958 the immunoassay. Overall seroprevalence was 5.0% (CI 4.7–5.4) by the point-of-care test and 4.6% (CI 4.3–5.0) by immunoassay. In 7 provinces in the central part of Spain, including Madrid, seroprevalence was greater than 10% by both methods. Seroprevalence was similar for females and males. Seroprevalence was lower in the oldest age groups (≥85 years) compared with other adults. With regards occupation it was highest in health-care workers, 10.2% (7.9 – 13) than in other occupations these results were supported by the immunoassay.
In those who reported a contact with a confirmed case, seroprevalence was greater in those
who had a confirmed case in their household (range 31.4% to 37.4% between the two tests), in their workplace 9.9–10.6%, among their non-cohabitating family members and friends 13.2–13.7%, or among their caregivers and cleaning staff 12.4–13.5%

Symptoms: For both tests seroprevalence was highest in those with a confirmed Sars-CoV-2 PCR more than 14 days before testing (88·6–90·1%). Among those with a positive test, the proportion of individuals who reported anosmia or three or more symptoms compatible with COVID-19 was 49.1%
for the point-of-care test and 54. 2% for the immunoassay. In 32.7% (CI 30.2–35.4) of point-of-care test and 28.5% (CI 25.6–31.6) participants were asymptomatic.

Results in children: 11,422 children (<19 years) had a point of care test, with 6,527 also having an immunoassay. The proportion of paediatric participants having serology was lower than that of adults, though not unsurprising given the need for extra phlebotomy. Overall seroprevalence for those < 19 years was 3·4% (2·9–3·9) for point of care testing, and 6527 3·8% (3·2–4·6) for immunoassay.
Looking at specific age ranges for point-of-care test seroprevalence was < 1 year, 1.1% (0.3–3.5): 1- 4 years 2.1 %(1.3–3.4); 5 – 9 years 3.1% (2.2–4.2); 10-14 years 4.0% (3.1–5.0); and 15 – 19 years, 3.7% (2.9–4.8). The same pattern but slightly higher percentages were seen with immunoassay <1 year 0.0% (0.0–11.9); 1- 5 years 3.5% (1.7–6.8): 5 – 9 years 3.6% (2.3–5.7); 10 – 14 years 4.1% (3.1–5.5); and 15 – 19 years 3.8 (2.8–5.0). This paper did not give data on symptoms separately in age groups.

Conclusion: Population seroprevalence is lower than expected in areas of high endemic SARS-CoV-2, and is lowest in children. Close contact with people, particularly in the same household increases viral transmission. Over 30% of those with seroprevalence were asymptomatic. This highlights the importance of rapid identification and isolation with those with confirmed SARS-CoV-2, however isolation and separation for other household members may not be realistic in poorer or urban areas.

Yung, C. F., Kam, K., Nadua, K. D. et al. Novel coronavirus 2019 transmission risk in educational settings. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa794

A study of contact tracing of 3 clusters of confirmed COVID-19 within schools in Singapore. Only close contacts of the affected students were placed into quarantine for 14 days, not complete year groups/schools/or classes. Target health measures implemented included terminal cleaning and interventions to reduce mixing (examples were cancelling of extra-curricular activities and staggered break times). For 3rd incident in day care, the school was closed due to increasing cases amongst staff, and all students were tested regardless of exposure/symptoms.

Case 1: 12yr male in secondary school infected at home (sibling of case 2). Attended on day 1 of symptom and subsequently quarantined. 8 classmates developed compatible symptoms, all tested negative.
Case 2: 5yr male in primary school. Attended on day 1 of symptoms and quarantined. 34 classmates developed compatible symptoms, all tested negative.
Case 3: Multiple adult staff members in pre-school involved in cluster. 70% of all students tested, all negative.


These findings are consistent with the small number of other studies of transmission within a school setting so far, which have demonstrated infrequent transmission from children.

Lanyon, N., P. du Pré, T. Thiruchelvam, S. Ray, M. Johnson and M. J. Peters (2020). “Critical paediatric COVID-19: varied presentations but good outcomes.” Arch Dis Child. http://dx.doi.org/10.1136/archdischild-2020-319602

In this letter from Great Ormond Street Hospital for Children, London, 24 children, who tested positive for Covid-19, were admitted to the intensive care unit between 26th March 2020 and 31st May 2020. Thirteen of these had PIMS-TS. This letter describes the clinical features of the remaining 11.


These 11 had a median age of 5 years (range 0.4-11), 9 were boys, 9 had pre-existing medical conditions, and 4 came from the BAME community. The primary presenting feature was cough 6, apnoea 3, fever 10, gastrointestinal 6 and seizures 3

In all 11 inflammatory markers were raised, median ferritin 898 (range 254-1991), CRP 158 (27-449), LDH 1594 (802-4264) D-Dimer 158 (27-449). 4 children fulfilled the criteria for paediatric acute respiratory distress syndrome, the remaining 7 were admitted to PICU for other reason than respiratory failure. A variety of different forms of respiratory support were provided, invasive mechanical ventilation 9, prone position 4, inhaled pulmonary vasodilators 4, HFOV 2 and ECMO none. 5 children received remdesivir and 6 prophylactic anticoagulation.

All 11 children survived to hospital discharge. The authors conclude “While children can present to PICU with a pattern of illness similar to adult COVID-19 disease this is rare and three quarters of them had risk factors for respiratory infection. A larger number were found to be SARS-COV-2 coincidentally.”

L’Huillier, A. G., G. Torriani, F. Pigny, L. Kaiser and I. Eckerle (2020). “Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents.” Emerg Infect Dis 26(10). https://doi.org/10.3201/eid2610.202403

In this study from Switzerland, nasopharyngeal samples of 23 children with PCR confirmed SARS-CoV-2 infection were inoculated into a cell culture to determine the presence or absence of of viable virus. All children aged <16 years, daignsosed at the Geneva University Hospital laboratory between January 25th

Of the 23 children with SARS-CoV-2 +ve PCR, median age was 12 years (range 7 days to 15.9 years), the majority (13/23 – 57%) had symptoms of upper respiratory tract infection and 7/23 (30.4%) were admitted to hospital. All samples were taken within 5 days of symptom onset (20/20 where reported), median 2 days (IQR 1-3 days). Median viral load was 3.0 x 10^6 copies / mL (IQR 6.9 x 10^3 – 4.4 x 10^8).

Viable SARS-CoV-2 virus was isolated in half (12/23 – 52%) of children including an infant diagnosed at 7 days of age. Virus isolation was associated with higher viral load (median 1.7 x 10^8 vs 6.9 x 10^3 in culture negative patients).

The results here demonstrate that children with symptomatic SARS-CoV-2 infection have similar viral loads to those seen in adults. Similar to adults, children, particularly those with high viral loads, can also shed viable virus particles early in the course of illness. These findings confirm that transmission of SARS-CoV-2 by children is plausible. It remains however that children appear less susceptible to infection compared with adults in the first instance and when infected tend to experience milder symptoms and therefore as a whole are unlikely to be major drivers of transmission. Indeed, this study identified only 23 paediatric cases of SARS-CoV-2 infection in a region severely affected by the pandemic.

Whilst children with symptomatic SARS-CoV-2 infection can shed viable virus, the small proportion of paediatric cases observed globally indicate a limited role of symptomatic children in disease transmission.

Felstein, L.R. et al (2020) Multisystem Inflammatory Syndrome in U.S. Children and Adolescents, NEJM. epub 29 June 2020, DOI:10.1056/NEJMoa2021680.

This retrospective and prospective multi-centre cohort study from 53 participating hospitals in 26 states looked at 234 patients under 21 years of age that met criteria for multi system inflammatory syndrome in children (MIS-C), between March 15 and May 20th

The median age of the patients was 8.3years old and 62% (115) were male. Fifty one patients (27%) had an underlying medical condition. In terms of confirmation of SARS_CoV-2 infection – 70% were positive for RT-PCR and/or antibody testing.  Of a small subgroup of 14 patients with Covid-19 symptoms before MIS-C, the median time between Covid-19 sysmptom to MIS-C was 25 days (6-51 days).
Criteria for MIS-C were based on CDC guidelines (in brief, requiring hospitalisation, at least two systems involved, fever of at least 24 hours and either lab confirmed SARS_CoV-2 infection (via RT-PCR or antibody testing) or an epidemiological link to a person with Covid-19 within 4 weeks before onset of symptoms).
Although MIS-C criteria was at least 2 system involvement, 71% had involvement of four organ systems or more. The most frequent systems in order were gastrointestinal (92%) followed by cardiovascular (80%), haematological (76%) and respiratory (70%). Blood changes observed included lymphocytopaenia in 80% of patients, and an elevated CRP in 91%.
Looking at similarity and overlap with Kawasaki disease, 40% of patients had either fever for at least 5 days and 4-5 of Kawasaki’s disease-like features or 2-3 Kawasaki’s disease-like features with additional lab or echocardiographic findings. Common symptoms similar to Kawasaki disease bilateral conjunctival infection in 103 (55%), oral mucosal changes in 78 (42%), peripheral extremity change in 69 (37%), rash in 110 (59%), cervical lymphadenoapthy (>1.5cm diameter) in 18 (10%). Differences between MIS-C and Kawasaki’s disease groups include an older age group and a different cardiovascular involvement (more likely myocardial dysfunction) in MIS-C patients.
The majority of patients required ICU admission (n=148, 80%) with one in five patients needing invasive mechanical ventilation. Eight patients received ECMO support. Treatment included IVIG in 77% and systemic glucocorticoids in 49%. There were four deaths (two of which had received ECMO). At the time of writing the paper, 70% of patients had fully recovered with 28% still in hospital.

Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. DOI: 10.1056/NEJMoa2021756.

This is a case series of 99 children (<21 years of age) from New York State with multisystem inflammatory syndrome in children (MIS-C). Of note some of these cases have been reported in small series (Cheung et al JAMA 2020). New York State Department of Health required hospitals that provide paediatric medical or surgical care to report potential cases of Kawasaki’s disease, toxic shock syndrome, or myocarditis or who were suspected to have MIS-C among persons younger than 21 years of age admitted since March 1, 2020, through the NYSDOH Health Emergency Response Data System. The clinical and laboratory characteristics of these reports were studied. Between March 1 and May 10 2020 191 cases were reported of which 95 met the criteria for MIS-C and 4 further were suspected.

Case definition: Confirmed cases were defined by the presence of both clinical and laboratory criteria. Suspected cases had clinical and epidemiological criteria.

Clinical criteria was children <21 years of age with fever  and needing hospitalisation with either;  1 or more of hypotension or shock, features of severe cardiac illness, or other severe organ failure. Or 2 or more of; maculopapular rash, non purulent conjunctivitis, mucocutaneous inflammatory signs or acute GI symptoms with an absence of other cause.

Laboratory criteria:

  1. General Criteria; Two or more of raised inflammatory markers and
  2. Either positive SARS CoV2 RNA at time of presentation or within 4 weeks or detection of specific antibody.

Epidemiological criteria: In 6 weeks prior to exposure close contact with a person with confirmed or clinically consistent Sars CoV2 infection or travel to or resident in an area with ongoing community transmission.

Baseline characteristics: 53 (54%) were male. Age range was 0-5 years (31%), 6 to 12 year (42%) and  13 to 20 years (26%). 78 patients had data on race with 29 (37%) were white, 31 (40%) were black, 4 (5%) were Asian, and 14 (18%) were of other races. 36 patients had a preexisting condition, 29 had obesity.  24  (24%) had a Covid-19–compatible illness a median of 21 days (interquartile range, 10 to 31) before hospitalization, 38 (38%) had exposure to a person with confirmed Covid-19, and 22 (22%) had direct contact with a person who had clinical Covid 19.

Symptoms : Described in detail in the study. Prevalence of dermatologic symptoms was highest among children 0 to 5 years of age, and the prevalence of myocarditis (diagnoses and clinical) was highest among the adolescents.

Treatment : Of 99 patients, 79 were treated in ICU. 69 had IVIG, 63 received systemic glucocorticoids, 48  received both systemic glucocorticoids and IVIG. 9 patients had coronary aneurysm

Outcome : As of May 15, a total of 76 patients (77%) had been discharged and 21 (21%) were still hospitalised. Unfortunately 2 patients died in the hospital. Both were intubated and ventilated, once received ECMO. Neither received IVIG, systemic glucocorticoids, or immunomodulators.

González Cortés, R., García-Salido, A., Roca Pascual, D. et al. A multicenter national survey of children with SARS-CoV-2 infection admitted to Spanish Pediatric Intensive Care Units. Intensive Care Med (2020). https://doi.org/10.1007/s00134-020-06146-8

The Spanish Paediatric Intensive Care Society have published their findings of 50 children admitted to 47 PICUs in Spain between 1st March 2020 and 1st May 2020 with SARS-CoV-2. More than 90% of PICUs in Spain were represented in this national database. During the study period there were no deaths from SARS-CoV-2 in children admitted to PICU in the participating PICUs.

The authors divided the children into two groups: those requiring ventilation and those not requiring ventilation, to assess for different characteristics between these groups. Fourteen (28%) of the children were ventilated.  Twenty-seven (54%) of the 50 children in the study had suspected PIMS-TS; these children were less likely to require mechanical ventilation (4 of the 27 required ventilation) than those without PIMS-TS. Statistical significance between the two groups was found for age (median age of 2.8 years in the ventilated group, compared to 8.6 years in the non-ventilated group); co-morbidities (12, 24%, of the 50 children had comorbidities; 8 of these were ventilated); and clinical presentation with respiratory difficulties or an ARDS-type picture.

Overall, of the 50 children, 23 (46%) had haemodynamic instability, 20 (40%) had respiratory difficulties and 1 (2%) had neurological symptoms. Shock was present in half of the children (25, 50%), renal failure in 8 (15%) and cardiac dysfunction in 17 (34%).

Across the 50 children, white cell count (median 9.26, IQR 5.64-14.46), lymphocytes (median 1.02, IQR 0.42-2.59) and CRP (median 13.9, IQR 4.9-27) were not statistically different between ventilated and non-ventilated children.

These are the preliminary findings from this national registry of children with SARS-CoV-2 admitted to PICU in Spain. Further results and analysis will provide more information regarding critically unwell children with COVID-19.

Riollano-Cruz, M., E. Akkoyun, E. Briceno-Brito, S. Kowalsky, R. Posada, E. M. Sordillo, M. Tosi, R. Trachtman and A. Paniz-Mondolfi (2020). “Multisystem Inflammatory Syndrome in Children (MIS-C) Related to COVID-19: A New York City Experience.” J Med Virol. June 25th 2020, https://doi.org/10.1002/jmv.26224

This retrospective case series describes 15 patients presenting to Mount Sinai Hospital in New York between 24th April and 19th June 2020. Patients were identified by presentation to hospital with clinical features meeting the criteria for MIS-C (known in the UK as PIMS-TS) as defined by the Centers for Disease Control and Prevention Emergency Preparedness and Response, and the New York City Health Department. The mean age of the 15 patients was 12 years, with a range of 3 to 20 years. 11 patients (73%) were male, and 10 patients (66%) identified as Hispanic or Latino.

Clinical features: All patients had a fever at admission and 13/15 (87%) had gastrointestinal symptoms including abdominal pain, vomiting and diarrhoea. Respiratory symptoms were far less common, with cough or sore throat only occurring in 3/15 (20%) of cases. Other features at admission included rash in 7/15 (47%), conjunctivitis in 4/15 (27%) and swollen hands and feet in 4/15 (27%).

COVID-19 status: 7/15 (47%) tested positive for SARS-CoV-2 from a nasopharygeal or respiratory specimen during admission, and 2/15 (13%) had a positive test in the month prior to admission. 15/15 (100%) of patients were positive for COVID-19 antibodies.

Radiology: CXR at admission showed non-specific findings in 7/15 (47%), reactive airway disease in 4/15 (27%), pleural effusions in 4/15 (27%) and were normal in 3/15 (20%). Echocardiogram was abnormal in 12/15 (80%): 4/15 (27%) had reduced LV function, 3/15 (20%) had reduced biventricular function and 3/15 (20%) had coronary artery abnormalities.

Bloods: 13/15 patient (87%) presented with lymphopenia, and 14/15 (93%) had elevated fibrinogen. During admission 15/15 cases (100%) had a raised CRP and D-dimer, 14/15 (93%) had a raised ESR and 13/15 (87%) had a raised ferritin. IL-6 and IL-8 were elevated in 15/15 patients (100%) whereas 0/15 (0%) had an elevated IL-1 (which tends to be raised in Kawasaki disease).

Treatment: 15/15 patients (100%) received prophylactic enoxaparin until 2 weeks post-discharge. 12/15 patients (80%) received tocilizumab (anti-IL-6 antibody), 12 (80%) were given IVIG, 3 (20%) received steroids, 2 (13%) initially received Anakinra (IL-1 receptor antagonist),and 2 (13%) patients were treated with Remdesivir. Outcomes were not analysed according to treatment received.

Outcomes: 14/15 patients (93%) were admitted to PICU. 3 patients (20%) needed mechanical ventilation, another 5 patients (33%) required non-invasive ventilation, and 8 patients (53%) needed inotropic support. At the time of publication 13 patients had been discharged, 1 was still an inpatient and 1 had died.

Gabriele Pagani, Federico Conti, Andrea Giacomelli et al, Seroprevalence of SARS-CoV-2 IgG significantly varies with age: results from a mass population screening (SARS-2-SCREEN-CdA). medRxiv June 24th 2020, https://doi.org/10.1101/2020.06.24.20138875

In this brief report of a SARS-CoV-2 serosurvey from Castiglione D’Adda in Italy, the results of a logistic regression model based on the random sampling of 509 subjects from the region (total population 4550) following the peak of transmission in the region are detailed. Prior to this serosurvey testing was limited to severely symptomatic cases.

The exact number of children included is not provided but the age related prevalence was significantly lower in children – 9.1% (0-5yo), 10.1% (5-10yo), 11.2% (10-15yo), 12.5% (15-20yo) – compared with overall seroprevalence of 22.6%.

The methodological details are limited in this report but the data are consistent with serosurvey data from elsewehere in Europe suggesting that children are less susceptible to SARS-CoV-2 infection compared with adults.

Xiong, X., G. T. Chua, S. Chi et al. A Comparison Between Chinese Children Infected with COVID-19 and with SARS. J Pediatr. June 18th 2020, https://dx.doi.org/10.1016%2Fj.jpeds.2020.06.041

In this study, 244 children with SARS-CoV-2 infection from Wuhan, China are compared to 44 children diagnosed with SARS (SARS-CoV-1) in in Hong Kong in 2003.

The clinical details of this series of patients from Wuhan, previously described elsewhere, are compared with those of those of children with SARS-CoV-1. Overall children with SARS-CoV-2 were younger than those with SARS-CoV-1 (median age 82 montsh vs 160 months). Compared with SARS-CoV-1 patients, children with SARS CoV-2 were less likely to have symptoms (20.9% asymptomatic vs 0% of SARS-CoV-1), including fever (40.2% vs 97.7%), myalgia (37.6% vs 0.8%), and chills (32.6% vs 3.7%).

Fewer children with SARS-CoV-2 required supplemental oxygen (4.7% vs 18.6%) and few in either cohort required mechanical ventilation (1.6% vs 2.3%). A single death occurred in a patient with SARS-CoV-2 (a 10 mo with intussusspection) and no cases of PIMS-TS / MIS-C were identified amongst the 244 SARS-CoV-2 infected children from Wuhan.

The most striking difference is the milder clinical illness and relative lack of symptoms in children with SARs-CoV-2 compared with those with SARS-CoV-1. The lack of asymptomatic infections in SARS-CoV-1 is also notable, similar to findings in adults. Whilst the role of asymptomatic patients in the spread of SARS-CoV-2 is unresolved, the milder clinical illness in the majority of patients along with the demonstrated earlier peak in viral shedding relative to symptom onset and resultant role of pre-symptomatic transmission are likely major reasons for the continuing widespread transmission of SARS-CoV-2, where the outbreak of SARS-CoV-1 in 2003 was more readily contained.

Gampel, B. Troullioud Lucas, AG. Broglie, T. et al. (2020 Jun 26). “COVID-19 disease in New York City pediatric hematology and oncology patients.” Pediatr Blood Cancer: e28420. June 26th 2020, https://doi.org/10.1002/pbc.28420

This retrospective observational study provides some insight into the impact of COVID-19 on haematology/oncology patients. There were some limitations in the data collection process as testing was performed for different reasons at the two different sites that are considered. However, we see that between 10/03/2020 – 06/04/2020,  19 out of 174 tested children (each of whom had underlying haematological/oncological disorder or were undergoing haematopoietic stem cell transplantation) tested positive for COVID-19. Of these, 11 required hospitalisation. Five required PICU and one sadly died.
Method: All patients 21 years old or younger who underwent clinical laboratory COVID‐19 testing at two New York haem/onc centres were included. All patients had underlying haematological/oncological disorder or were undergoing haematopoietic stem cell transplantation. Informed consent was waived.
The two centres tested differently: “MSK tested all symptomatic patients and screened all patients prior to admission, procedures requiring sedation, and planned myelosuppressive chemotherapy. NYP tested only those patients for whom a positive test would alter management, including those who were symptomatic, likely COVID‐19 exposed, or with planned disposition to a chronic care facility.”
Features specific to children:19 out of 174 tested positive. Of these: 68% had fever, 47% had cough and 37% had dyspnea. 11 patients required hospitalisation and 4 patients required supplemental oxygen. 2 patients required mechanical ventilation and a further 3 were also admitted to PICU (all male). 3 patients received ‘COVID-19-directed therapy’ (with hydroxychloroquine and azithromycin)
1 patient died (“a child with sickle cell disease without a significant history of prior complications. Although this patient demonstrated pulmonary disease, his death may have been preceded by an acute cardiac event. Autopsy was refused…”). The authors make note that 64% of COVID+ oncology patients experienced treatment delays, showing the harms to these patients may not come primarily from COVID-19 disease itself

Denina, M., C. Scolfaro, E. Silvestro, G. Pruccoli, F. Mignone, M. Zoppo, U. Ramenghi and S. Garazzino (2020). “Lung Ultrasound in Children With COVID-19.” Pediatrics. 21. https://doi.org/10.1542/peds.2020-1157

Between March 18th and 26th 2020 8 children (age range 3 months to 10 years), 5 of whom were boys were admitted to Regina Margherita Children’s Hospital, Turin with Covid 19 respiratory tract infections. All 8 children had linear array chest ultrasound during routine medical examination. Although the number of patients analysed was small, the high concordance between radiologic and LUS findings suggested that ultrasound may be a reasonable method to detect lung abnormalities in children with COVID-19. The advantage of LUS was that the investigation could be done at the bedside, thus preventing transport of a potential infectious patient through a hospital

Colmenero, I., C. Santonja, M. Alonso-Riano, et al. “SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultraestructural study of 7 paediatric cases.” The British journal of dermatology. June 20th 2020, https://doi.org/10.1111/bjd.19327

Anecdotally, chilblains seem to be associated with Covid-19 in children and young adults. This case series from Madrid describes 7 children (age 11-17) presenting with chilblains on their toes during the pandemic. None had underlying conditions likely to cause chilblains, and in Spain, cold weather wasn’t responsible. The chilblains looked typical, caused only minor pain and itching, and all resolved spontaneously. All had skin biopsies, which showed a variety of inflammatory and vasculitic changes on histology, typical of chilblains: they also looked specifically for SARS-CoV-2 particles in the endothelium of the dermal vessels using immunohistochemistry and electron microscopy and found the virus in all of them.

What is remarkable is that all the children were systemically well, had either mild or no respiratory symptoms; and of the 6 that had nasal and pharyngeal swabs, all were negative for SARS-CoV-2 PCR. Only 4/7 had Covid-19 positive household contacts.

The implication is that children can harbour demonstrably invasive coronavirus with minimal symptoms and negative swabs. This has epidemiological as well as clinical significance.

In conclusion, the presence of SARS-CoV-2 in the endothelium of dermal vessels in skin biopsies of children and adolescents with acute chilblains confirms that these lesions are a manifestation of COVID-19.  Their clinical and histopathological features are similar to those of chilblains of other aetiologies, and virus-induced vascular damage could explain their pathophysiology.  Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a role in the pathogenesis of severe forms of the disease. More studies are needed to understand the reasons why previously healthy children, adolescents and young adults present

McDevitt KEM, Ganjoo N, Mlangeni D, Pathak S. Outcome of universal screening of neonates for COVID-19 from asymptomatic mothers [published online ahead of print, 2020 Jun 19]. J Infect. 2020;S0163-4453(20)30418-7. doi:10.1016/j.jinf.2020.06.037

This study is reported as a letter to the Editor.

The North West Anglia NHS Foundation Trust based in Peterborough, UK, introduced universal screening for SARS-CoV-2 of all in-patients, including asymptomatic newborn infants, on 27th April 2020. The testing method was naso-pharyngeal RT-PCR of nasopharyngeal swabs.

Between 27th April and 21st May 2020 481 infants were delivered, of whom 418 were screened. Nine infants (2.2%) tested positive within the first 24 hours of life, three within three hours. The gestational ages ranged from 364 to 422 weeks and birthweights from 2815 to 4420 g. Only one infant developed signs of illness – an oxygen requirement for 2 hours and high flow humidified nasal cannulae for 22 hours, a chest X-ray showing streaky hila and hazy consolidation in both lower lobes. Seven babies were re-tested at one to seven days of age and all were negative.

With regard to mode of delivery, three babies were born by ELCS elective caesarean section, three by EMCS and three by SVD. No details concerning membrane rupture-delivery interval are provided. All mothers were asymptomatic and only one tested positive to SARS-CoV-2. Five mothers who tested negative were re-tested at un-specified times and all were again negative.

The authors considered the following explanations for the positive tests:

Contamination of the specimens – this was considered to be unlikely as the specimens were taken on different days by different members of staff, all of whom were wearing PPE.

False positive results – this was also considered unlikely as the CT values of the RT-PCR were 29-31 and the specificity was 100% at a CT of 35, with a positive predictive value of 100%.

Maternal false negative results – these could not be rules out but were unlikely as all mothers were asymptomatic and three of the positive swabs were taken within three hours.

The mothers might have been positive previously and, although they were no longer shedding viral RNA in the nasopharynx, they had shed RNA or RNA fragments into the amniotic fluid and these were still within the newborns’ nasopharynx on the first day of life but cleared by the second test. Possible confirmation of this by maternal/infant serology was not available at the time.

This paper is published as the first report of the outcome of universal screening of newborn infants for SARS-CoV-2. The explanation for the finding of 2.2% positive naso-pharyngeal swab RT-PCR tests in the babies of asymptomatic mothers is currently not certain.

Chambers, P. Krogstad, K. Bertrand et al. Evaluation of SARS COV-2 in breastmilk from 18 infected women. MedRxiv. 16th June 2020, https://doi.org/10.1101/2020.06.12.20127944

This is a letter to the editor of the journal in which the authors report their finding on detection of SARS COV-2 in the breast milk of 18 infected mothers in the USA. A total of 64 breastmilk samples were collected between 27/03 and 06/05, pre and post the mothers testing positive for COVID. All samples were tested with quantitative RT-PCR for SARS Cov-2. 26 of these samples (from 9 mothers) also underwent tissue culture for the replication component of SARS Cov-2. The researchers also tested the Holder Pasteurization technique in eliminating the virus. They spiked 2 donor breast milk samples with the virus and then testing the samples with RT-PCR and the tissue culture method after the spiked samples had been subjected to the pasteurisation.

Of the 64 samples of breastmilk which were tested for viral RNA, only one sample tested positive and this was noted to have been on the day of symptom onset in that mother. All 26 samples which underwent tissue culture for the replication component of the virus, including the sample which tested positive for the viral RNA, were negative. Both donor milk samples were negative on RT-PCR and tissue culture following pasteurisation.

It is a very small sample and there is no standardisation of when the milk was collected from each woman and how frequently it was collected (varying between only one sample contributed to 12 samples from the same mother). It would have also been useful to know the COVID swab and/or antibody status of the infants. The merits of this study lie in the use of the tissue culture for replication components of the SARS CoV 2 which has not been used by the previous case studies which only looked for viral RNA in breast milk. The tissue culture is likely to be a more clinically meaningful way of analysing the breastmilk to determine infection risk to infant. It is reassuring that Holder pasteurisation method (also commonly used by milk banks in the UK) in donor breast milk can neutralise the virus. Further large-scale study is required to draw firm conclusions.

Top 10 Neonatal Papers

Knight, K. Bunch, N. Vousden et al. Characteristics and outcomes of pregnant women hospitalised with confirmed SARS-CoV 2 infection in the UK: A national cohort study using UK obstetric surveillance system. Nuffield Department of Population Health, UKOSS Publications 11th May 2020, https://doi.org/10.1101/2020.05.08.20089268

As a pre print this study should be interpreted with caution until it has undergone peer review.

This is a prospective observational national cohort study carried out across all 194 consultant-led maternity units in the UK. It captured data from women admitted to hospital with confirmed SARS CoV 2 between 01/03/20 and 14/04/20, with tests having been carried out only if the woman was symptomatic. 427 women were studied and compared to a historical control sample of 694 women admitted between 01/11/17 – 31/10/18 (a historical sample was chosen to avoid confounding by including asymptomatic or minimally symptomatic carriers of COVID). The total number of maternities in the study period was 86293 and therefore the incidence of admission the SARS CoV 2 confirmed women was 4.9 per 1000 maternities. The median gestation at admission was 34 weeks (IQR 29-38 weeks), with 81% of admissions in the 3rd trimester. The results showed that there was a statistically significant risk of admission with SARS CoV 2 patients who had the following factors:

From a Black and Minority Ethnicity group: adjusted OR 4.49 (3.37-6.00). Even after sensitivity analysis which excluded women from London, West Midlands and North West England which had high rates of general infection OR 3.67 (2.55-5.28)

Overweight: adjusted OR 1.91 (1.37-2.68)

Obese: adjusted OR 2.20 (1.56-3.10)

Pre-existing medical condition (asthma, hypertension, cardiac disease or diabetes): adjusted OR 1.52 (1.12-2.06)

Maternal age ≥ 35: adjusted OR 1.35 (1.01-1.81)

Being a current smoker reduced the risk of admission, with adjusted OR 0.3 (0.17-0.51).

The odds ratio for each significant factor outlined above was adjusted for the other significant factors which became confounding variables. There were 40 admission to level 3 critical care with 4 requiring ECMO. There were 5 maternal deaths recorded, 3 of whom had been admitted to critical care. SARS CoV 2 associated maternal mortality was 5.6 (1.3-13.1) per 100,000. Only 9 women were treated with antivirals (oseltamivir, lopinavir/ritonavir and/or remdesivir). 61 women were given corticosteroids for the maturation of fetal lung.

247 women in this cohort gave birth (singleton/multip proportion not stated) to a live infant (n=243) or had a pregnancy loss (n=4). 59% of women gave birth via c-section with 20% under general anaesthetic compared to 29% of the control group with 7% of women delivering under GA. There were 63 (26%) preterm births (<37 weeks) and 29 of these were documented as being secondary to COVID 19 infection; the other reasons stated were iatrogenic, fetal compromise and other obstetric conditions. This is compared to 8.9% of births in the control group being born preterm. There were 5 neonatal deaths, including 3 stillbirth; in two of the cases of stillbirths, it is unclear whether COVID 19 infection contributed to death. The rate of pregnancy loss, still birth, livebirth and neonatal death was not statistically different between the groups. The NICU admission rate was 26% (majority for prematurity) and 5% in the cohort and comparison groups, respectively. 12 infants tested positive for SARS CoV 2, with 6 being within the first 12 hours of life (early). 1 in the early positive and 5 in the later positive groups were admitted to NICU.

This is a national study reporting on the largest cohort of SARS CoV 2 positive pregnant women admitted to hospitals with symptoms. There is likely to be an underestimation of the true effect size presented in this report as analysis was carried out in only those patient in whom data was returned and not on the entire cohort of admissions in the specified time period.  The results convincingly show important risk factors (maternal age, black and minority ethnicity, BMI, and pre-existing medical condition) for admission and thus confers the severe of infection in these risk groups. The black and minority ethnicity risk factor, which existed even after the sensitivity analysis, requires urgent further analysis and study as it was the biggest risk factor and one which has not been demonstrated to be the case in other coronavirus strains. The supposed protective factor of current smoker status is not explained in this report but could reflect lower current prevalence of smoking in pregnancy in general compared to the prevalence at the time of the historical sample. The report also highlights that most of the admission with SARS CoV 2 was in the second and third trimester thus providing weight for the precautions currently being taken in this group of women. However, they also correctly identify that there may be a sampling bias as those in the first trimester may be being admitted to hospital via routes other than the maternity services. There was a higher rate of preterm deliveries (statistical significance unknown) which is difficult to interpret but raises questions as to what extent the maternal infection may cause fetal compromise triggering preterm birth.

2% of babies tested positive for SARS CoV 2 suggesting a risk of vertical transmission, especially since 3 of the positive cases were pre-labour, c-section delivered babies. However, the IgG or IgM status of the infants is unknown and there were no placental, umbilical cord, etc samples taken/reported. The discussion states that mothers and infants were kept together with infection control measures (surgical face masks) and the low rates of neonatal infection supports continuation of this practice. However, 6 of the 12 infants testing positive for SARS CoV2 required neonatal unit admission, majority of whom were classed as late infections as they tested positive after 12 hours of life. There is no information provided on the reason for these admissions and what support and/or treatment was required during this time. It is important to point out that the report does not specially say that all other infants born to this cohort of mothers were tested for SARS CoV 2 and found to be negative. Further questions are raised in the two cases of stillbirth which may have been caused by COVID 19. There is also no clarification on the characteristics of the cases of neonatal death (e.g. were they preterm, was mother critically ill in ITU, etc) which would have added greatly to the analysis of this report.

Although this study does not provide enough detail to draw firm conclusions, it provides an important basis for further avenues where research is needed.

Zeng L, Xia S, Yuan W et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. Published online March 26, 2020. doi:10.1001/jamapediatrics.2020.0878

This is a cohort study following 33 neonates born to COVID-19 positive mothers, recruited Wuhan Children’s Hospital, Hubei Province, China, between January 2020 and February 2020. The authors describe three cases of early-onset neonatal COVID-19, which they suggest implies vertical transmission. However, amniotic fluid, cord blood and maternal breast milk of the mothers of all 3 positive neonates were negative for SARS-CoV-2, therefore it is unclear whether the infection was transmitted vertically or environmentally.

Three of the 33 neonates tested positive for COVID-19 on day 2 of life (positive nasopharyngeal or anal swabs). All 3 were born by caesarean section, two at term and the third at 31+2 for premature rupture of membranes and foetal distress.

Clinical features: The two term COVID-19 positive neonates had fever, although the authors don’t define what temperature they consider fever. These two neonates were also lethargic, but neither had respiratory distress. Neonate 3 was the most unwell, although this may be due to prematurity, poor condition at birth and sepsis rather than COVID-19. He was born at 31+2, required resuscitation at birth and had poor Apgars of 3, 4 and 5 at 1, 5 and 10 minutes, requiring non-invasive ventilation for respiratory distress. His blood cultures were positive for Enterobacter agglomerates.

Bloods: Neonate 1 (fever and lethargy) had normal bloods except raised procalcitonin (0.09 microgram/L). Neonate 2 (fever, lethargy and vomiting) had a leucocytosis, lymphocytopenia and elevated CK. Neonate 3 (premature with sepsis) had leucocytosis, thrombocytopenia and coagulopathy with prolonged PT (21 sec) and APTT (81.9 sec).

Radiology: All 3 had radiological evidence of pneumonia on CXR.

The authors state that because strict infection control and infection prevention procedures were implemented during delivery, SARS-CoV-2 isolated from their upper respiratory tracts or anuses was therefore maternal in origin. However, although it is stated in the illustration that one neonate was immediately quarantined after birth, it’s not clear whether this was the case for the other two babies. Plus, the negative amniotic fluid and cord blood does raise the question as to whether these neonates were truly infected in utero or not.

Yu, Nan et al Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study, The Lancet Infectious Diseases, Volume 0, Issue 0, Published:March 24, 2020 DOI:https://doi.org/10.1016/S1473-3099(20)30176-6

This is a retrospective study of 7 pregnant mothers infected with COVID-19 between Jan 1st and Feb 8th at Tongji Hospital in Wuhan, China. They were all at term (range 37/40 – 41+2/40). The mothers were all symptomatic, mainly with fever, cough, shortness of breath and diarrhoea. They all delivered via emergency caesarian section. All mothers did well.

The babies were all born with normal apgars. 4 babies were discharged home and not tested for SARS-CoV-2 and never developed symptoms (including at 28d follow up phone call. 3 children were tested, of which one was positive at age 36hrs (reported in separate study, Wang et.al Clinical infectious Diseases, but did well with no fever or cough and mild shortness of breath). The other 2 tested negative and were later discharged without complication.

Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395 :809–15. doi:10.1016/S0140-6736(20)30360-3

This retrospective case series looks at 9 pregnant women who were positive for COVID19 in Wuhan University Hospital between Jan 20th and Jan 31st. They all underwent a caesarean section (between 36 and 39+4 gestation). All newborn babies were well with good APGARS and, importantly, tests from 6 (3 not tested) patients were negative for SARS-CoV-2 in all amniotic fluid, cord blood, neonatal throat swabs, and breastmilk samples. There was no evidence of vertical transmission.

Dong L, Tian J, Songming H et al. Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4621

This is a case report that would suggest that vertical transmission of COVID-19 can occur. A 34+2 primiparous woman was diagnosed with COVID-19 (she was symptomatic with fever and respiratory difficulty and had classic CT chest findings and a positive nasopharyngeal swab for SARS-CoV-2). She was treated with antiviral medications, antibiotics and corticosteroids.

Her female infant was delivered by caesarean section 4 weeks after the onset of her mother’s symptoms in good condition with Apgars of 9 and 10. Although the infant’s nasopharyngeal swabs were negative, her IgM antibodies against SARS-CoV-2 were raised at 2 hours post delivery and cytokine levels were elevated. The risk of environmental infection was minimised: the caesarean was performed in a negative pressure room, the mother wore an N95 mask and did not hold her infant and the infant was immediately isolated in NICU. Maternal vaginal secretions were negative for SARS-CoV-2, which would also suggest the infection did not happen at birth. As IgM antibodies do not cross the placenta, the infant’s elevated IgM antibody levels suggest that she was infected in utero. Moreover, IgM antibodies usually do not appear until 3 to 7 days after infection. The infant also had raised IgG antibodies, but IgG is transferred placentally so this may reflect maternal or infant infection. The mother’s breast milk was negative for SARS-CoV-2 1 week following delivery.

Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4861

This report outlines the course of 6 mothers who were symptomatic for COVID-19 in their last trimester, and gave birth to 6 liveborn infants. This study is notable for antibody testing of both mothers and infants. The accuracy of the antibody tests are suspiciously high given current struggles to produce adequate tests around the world, and should be treated with a high degree of caution.

All 6 infants were born in good condition, and all tested negative for SARS-CoV-2 viral throat swabs and blood PCR. Unsurprisingly all infants had elevated IgG or SARS-CoV-2 (as this crosses the placenta), but notably 2 infants had raised IgM (39.9AU/ml and 16.25AU/ml). This raises the possibility of intrauterine infection, similar to another case of an infant with raised IgM (Dong et al JAMA). Issues with cross reactivity of IgM are well described, and so whilst full validation of these tests is awaited internationally, this should be treated with caution.

Liu, Yangli et al. Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy.Journal of Infection, Volume 0, Issue 0 https://doi.org/10.1016/j.jinf.2020.02.028

This is a small case series of 13 pregnant women with confirmed SARS-CoV-2 infection between December 8 2019 and February 25 2020, in China. Two women were <28 weeks at presentation, the remainder were in the third trimester. One infant was stillborn, the 12 remaining infants (92%) were well at birth with no complications. None were positive for SARS-CoV2 or had ‘serological evidence’ of vertical transmission. The method of testing neonates was not clearly defined. The stillborn neonate had a mother who was severely unwell on Extracorporeal Membrane Oxygenation (ECMO) at the time of delivery.

Five of the 10 patients (50%) were delivered by emergency cesarean section due to pregnancy complications including fetal distress (30%), premature rupture of the membrane (10%) and stillbirth (10%). Interestingly, six patients (46%) had preterm labour between 32- 36 weeks of gestation.

Han, M. S., M. W. Seong, E. Y. Heo, J. H. Park, N. Kim, S. Shin, S. I. Cho, S. S. Park and E. H. Choi (2020). “Sequential analysis of viral load in a neonate and her mother infected with SARS-CoV-2.” Clin Infect Dis. https://doi.org/10.1093/cid/ciaa447

This is a case report of a 27 day-old female neonate with confirmed SARS-CoV-2 infection. Over the course of a short and reasonably mild illness, samples were tested from the nasopharynx, oropharynx, plasma, urine, stool and saliva. SARS-CoV-2 RNA was detected in all samples. Early in the infection, viral load was highest in the nasopharynx and oropharynx, decreasing to undetectable at day 17. Viral load in stool, however, remained high throughout, despite cessation of gastrointestinal symptoms. This was in contrast to the mother’s stool sample in which viral load was undetectable earlier.

Groß, C. Conzelmann, J. A. Müller, S. Stenger, K. Steinhart, F. Kirchhoff and J. Münch. Detection of SARS-CoV-2 in human breastmilk. Lancet, May 21st 2020, https://doi.org/10.1016/S0140-6736(20)31181-8

This report is presented as a letter.

The study primarily relates to the SARS­CoV­2 content of the breast milk of two “nursing mothers” who shared a room postnatally, with their babies, and who developed swab-positive mild Covid-19 infection after birth – three days and six days respectively. The gestation and birthweights of the babies are not reported but they seem to have been full term, well at birth and initially well for the first few days following delivery.

The babies developed abnormal respiratory signs, one with jaundice, at 8 days and 11 days respectively, both becoming swab positive for SARS­CoV­2 at about the same ages and both being admitted to a Neonatal Unit. One infant, who also tested positive for RSV, subsequently required mechanical ventilation. It is stated that one infant recovered but the outcome for the ventilated infant is not given.

The patient identification and recruitment processes are not described.

Breast milk was collected, after feeds and after nipple disinfection, from each mother starting at eight days and four days respectively after development of Covid-19 symptoms. Samples were collected on postnatal days 12-15 for the first mother and 10, 12, 13, 14 and 25 for the second. Testing for SARS­CoV­2 RNA was performed using RT­qPCR.  Information on the method of nipple disinfection is not provided.

A separate laboratory-based study investigated the effect of breast milk on viral recovery rates by “spiking” breast milk with serial dilutions of a SARS­CoV­2 stock.

The main findings of potential importance are:

  1. The breast milk of one of the mothers tested positive for SARS­CoV­2 RNA at 10-13 days after birth. Testing of breast milk from the other mother was negative.
  2. Quantification using Ct values corresponded to 1∙32 × 10⁵ copies per mL in whole milk and 9∙48 × 10⁴ copies per mL in skimmed milk.
  3. An 89∙2% reduction in recovery rate in whole milk and 51∙5% in skimmed milk, suggesting that the actual viral loads in whole milk of the mother could be even higher than detected.

This study provides the first report of the detection of viral RNA in human breast milk collected from a mother who had clinical signs of Covid-19 confirmed by PCR testing of swabs. This does not provide evidence that the RNA was indicative of infectious virus or that transmission of the virus to the baby occurred via breastmilk. Further studies will be necessary to attempt to culture virus from breast milk and assess risk of transmission, which to date has seemed low.

Li, M., L. Chen, J. Zhang, C. Xiong and X. Li (2020). “The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study.” PLoS One 15(4): e0230295. https://doi.org/10.1371/journal.pone.0230295

The study explores the presence of Angiotensin-converting enzyme 2 (ACE2) within the placenta and the developing baby. It demonstrates significant expression of RNA coding the for ACE2 protein at several points of the maternal-foetal interface, as well as variable expression in a number of foetal organs. This theoretically provides a potential route for vertical transmission, placental dysfunction and pregnancy complications. The authors call for further clinical analysis to establish this potential.

Top 10 Clinical Papers

Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med 2020;:NEJMc2005073. doi:10.1056/NEJMc2005073

This retrospective study examines the clinical characteristics of children with confirmed COVID-19 diagnosed at Wuhan Children’s hospital. There were 1391 children tested between Jan 28th and Feb 26th 2020 due to known contact with a case of COVID-19, of these 171 were confirmed to have SARS-CoV-2.  Median age was 6.7yrs, and there was a relatively even spread amongst age groups. Children were predominantly male (104/171, 60.8%).

Clinical features: 83/171 had cough, 79/171 had pharyngeal inflammation (sore throat), 71/171 had fever. 15/171 had diarrhoea and 13/171 had rhinorrhoea. 49/171 were tachypnoeic on admission and 72/171 were tachycardia. Only 4/171 had Oxygen saturations <92% during hospitalisation. 0/31 infants <1yr were asymptomatic in this cohort, with rates of asymptomatic infection increasing with age. There were higher rates of pneumonia in infants (25/6), but the definition of this is unclear. We also have no information regarding co-infection with other viruses or bacteria.

Radiology: Not delineated into CXR or CT, but descriptions sound like CT findings. The most common was bilateral ground glass opacity (56/171) followed by unilateral patchy shadowing (32/171) and bilateral patchy shadowing (21/171). There were several children with radiographic pneumonia who were asymptomatic.

Bloods: The supplementary appendix contains lab results. Only 6/171 patients had lymphopaenia, the vast majority were in normal range (Med 2.9×109/L, IQR 2.2 – 4.4). CRP was elevated (>10mg/L) in 33/171 (Med 4, IQR 1.3 – 8) of which 27/33 had pneumonia.

Outcomes: 3 patients required ITU admission and intubation. All 3 had comorbidities, including hydronephrosis, leukaemia and intussusception. The child with intussusception suffered multiorgan failure and died after 4 weeks. The cause of death is not clear from the report. As of writing 149 patients had been discharged with 21 stable in the general wards.

Parri N, Lenge M, Buonsenso D; Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) Research Group. Children with Covid-19 in Pediatric Emergency Departments in Italy [published online ahead of print, 2020 May 1]. N Engl J Med. doi:10.1056/NEJMc2007617

This report is of confirmed COVID-19 infections in children under 18 years of age who presented to a research collaboration of 17 paediatric emergency departments in Italy between March 3rd and March 27th. The median age was 3.3 years and 57/100 were male. Children under 1 year were overrepresented (40%) followed by children >10yrs (24%).

Helpfully they categorise their patients according to criteria from Dong et. al (see review in Epidemiology top 10): Asymptomatic 21%, Mild 58%, Moderate 19%, Severe 1% and Critical 1%. Only 12% of patients appeared ill on assessment. Interestingly only 4% of patients had Oxygen saturations <94%. Only 38% of children needed admission for severity of illness. There were no deaths. The supplementary appendix includes a huge amount of detailed analysis of the cases, which are summarised below

Clinical features: Fever 54%, Cough 44%, Feeding difficulty 23%, Sore throat 4%, Rhinorrhoea 22%, Diarrhoea 9%, vomiting 10%.

Bloods: Largely unremarkable (although reports of lymphopenia unclear – state 14 patients lymphopenic but that this is 28%? – perhaps only 50 children had bloods, but this is not reported). Procalcitonin <0.5ng/L in 29/23 patients.

Radiology: Chest x-rays performed for 35 children, of which 14/35 had interstitial abnormalities, 6/35 consolidation and 1/35 pleural effusion: remaining 15/35 normal.

Comorbidities: There were 27/100 children with comorbidities – although it appears most had mild illness (did not require respiratory support). This included 6 with cystic fibrosis, 4 neurological, 4 haematological, 4 with a syndrome, 3 with prematurity, 2 with cardiac conditions, 2 immunological, 2 oncological and 1 metabolic disease.

Of the few patients who required respiratory support (9/100) a significant number had comorbidities (6/9), although the rage was broad. This included 2 children with “epileptic encephalopathy”, one of whom also had CHARGE syndrome, a child with autism, a child with a VSD, a child with propionic acidemia, and a child with thrombocytopenia and frequent respiratory infections.

One of the strengths of this study is comparisons across other studies of clinical features of COVID-19 in children. In comparison to Dong et al, CDC data and Lu et al, most features are broadly comparable. Some notable differences are a significantly larger number of infants in the Italian data (40% <1yr compared to 18% in Lu, 12% in Dong and 15.5% in CDC) and a slightly higher number of asymptomatic children (21% compared to 16% Lu, 13% Dong and 1.3% CDC). This most likely represents differences in which population cohorts presented for testing among the different studies – comparisons between cohorts is always difficult currently due to broad differences in the denominators used. Notably there is no apparent difference in severity according to age in this Italian data, whereas CDC noted increased hospitalisation in children <1yr and Don’t et al noted higher rates of severe or critical illness in infants <1yr.

Broadly speaking this study confirms findings from China and the USA regarding significantly milder illness in children than adults with COVID-19, including many asymptomatic children. Note is made of overrepresentation of children with comorbidities in this cohort (similar to CDC data), although most of these still had mild illness – it is unclear if these children become more unwell, or are more likely to present to be tested.

Qiu, Haiyan et al, Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. The Lancet Infectious Diseases, Volume 0, Issue 0 DOI:https://doi.org/10.1016/S1473-3099(20)30198-5

Qui and colleagues retrospectively identified 36 children with an EMR diagnosis of COVID-19, during the period Jan 17 through March 1st, at three hospitals in Zhejiang, China, a province 900km to the east of Wuhan.

Diagnosis was made by COVID-19 RT PCR for all patients presenting with fever, cough and radiographic presentation, or if there was a history of exposure to an infected individual.

The paper provides reasonably clear definitions of Mild, Moderate, Severe and Critical illness, with asymptomatic patients identifying as Mild. For this cohort, 28% of patients were asymptomatic, with Moderate cases more likely to have fever of 38degC or higher (47%), cough (24%), vomiting or diarrhoea (10%) or headache (10%). More than half (53%) of patients had ground-glass opacities on CT scan, meeting the case definition for Moderate illness.

Key laboratory values of note include lymphopaenia, leukocytopaenia and increased procalcitonin as all associated with moderate illness. No patients in this cohort were hypoxaemic as a result of their pneumonia.

The authors further analyse their cohort as 1-5yo and 5-16yo, in general noting that the older children were more likely to be lymphopaenic and would shed virus for a longer period (11 vs 9 days).

The authors also draw comparisons between adults and children with COVID-19 (less severe illness, less likely to have abnormal investigations), as well as comparing the clinical features and severity of COVID-19 with SARS (milder symptoms and severity) and H1N1 influenza (fewer symptoms, more frequent pneumonia) in children.

Wisely, Qui & colleagues note the high rate of findings that are not clinically obvious, and the high proportion of asymptomatic cases make for very challenging case identification in the absence of clear epidemiologic information. “This finding suggests a dangerous situation if community- acquired infections occur.”

Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. Published online May 11, 2020. doi:10.1001/jamapediatrics.2020.1948

This is a cross-sectional study of children admitted to 46 PICUs in North America. 48 children were admitted during the collection period (March 14 to April 3 2020). All had confirmed COVID-19 infection on PCR from a nasal swab.

Most patients presented with respiratory symptoms, but there were other presentations – three with DKA, and one with vaso-occlusive crisis (sickle cell). 86% of these patients had at least one comorbidity. 69% were severely or critically ill on admission, and 25% needed vasoactive drugs. 81% of patients needed respiratory support that exceeded their baseline.
61% had a range of therapies, including Hydroxychloroquine, Azithromycin, Remdisivir, and Tocilizumab. These were used as single agents or in combination with other therapies.
The overall mortality rate was 4.2% (both patients who died had pre-existing comorbidities and developed multisystem organ failure). 32% were still hospitalised at the time of publication (including one patient still receiving ECMO). 65% had been discharged.

This study reinforces what is known about the decreased burden of disease from COVID-19 in children compared with adults. Critically ill children had a less severe course of illness and better hospital outcomes than in adults. Children commonly had medically complex comorbidities. Overall the mortality is much lower in children (4.2%) than has been reported in adults (50-62%).

Riphagen, Shelley et al., Hyperinflammatory shock in children during COVID-19 pandemic, The Lancet, May 7th 2020, https://doi.org/10.1016/S0140-6736(20)31094-1

This is the first case series to describe a cluster of children presenting with hyperinflammatory shock during the COVID-19 pandemic.
Eight children aged 4 to 14 years were identified by a paediatric retrieval service based in London in mid-April 2020. Interestingly, of the 8 children, 7 had weights >75th centile. Notably 6 were of Afro-Caribbean descent and 2 were Asian, with no Caucasian children in this cohort. 5/8 were boys. 4 children had exposure to family members with COVID-19.

The clinical presentation was similar to Kawasaki disease, with unrelenting fever, rash, conjunctivitis, peripheral oedema, and extremity pain, in addition to gastrointestinal symptoms. All children developed warm, vasoplegic shock and required inotropic support. Seven children required mechanical ventilation.

Small pleural, pericardial and ascitic effusions, also consistent with a diffuse inflammatory process were also observed. Vascular involvement was demonstrated with echo-bright coronary arteries seen in all children, with a giant coronary aneurysm in one patient. One child died from a large cerebrovascular infarct. Myocardial enzymes were significantly elevated.

A range of investigations were done in all children, and despite this no causative pathogen was identified. Adenovirus and enterovirus were isolated in one child. Four children had known exposures to SARS-CoV-2 in family members, but only two tested positive for SARS-CoV-2 (1 was positive only postmortem).

In addition to other supportive therapies, all children received IVIG and broad-spectrum antibiotics (ceftriaxone, clindamycin). Six children have been given aspirin.

This clinical presentation may represent a new phenomenon associated with SARS-CoV-2 infection in children and has remarkable similarities to Kawasaki Disease. Following publication of this case series, Evelina London Children’s Hospital has managed >20 similar cases in children. Ten of these children were SARS-CoV-2 antibody positive (unclear which antibody or which test was used).

These findings have garnered particular interest due to the fact that children have otherwise been relatively spared from severe disease due to COVID-19, and here both the temporal association and high proportion of children with seemingly positive serology suggests a possible association with this hyperinflammatory syndrome. Anecdotally, clusters have also been noted in the USA (particularly NYC) and some centres in Spain and Italy. Reports are conspicuously absent from Asia, most notable as Kawasakis disease is more common amongst this population normally. Even more striking is the gross overrepresention of children with an Afro-Carribean background, which given current investigations into the increased incidence of severe adult disease in these communities seems even more pertinent.

As so little is currently known about “garden variety” Kawasakis, it will make defining this disease and its associated with COVID-19 that bit more difficult, but studies are currently ongoing to assess the nature and mechanism of this disease (https://www.diamonds2020.eu/). Three points are worth noting at this stage:

  • Kawasakis disease has been theorised to be triggered by viral infections. One could imagine if this is the case, then COVID-19 could also trigger a similar syndrome
  • It is well documented that some adults experience a systemic inflammatory response to COVID-19 (including cytokine storm) and whilst children generally suffer a much milder course, it seems within reason that a subset of children may develop a similar illness
  • Reports from a paper in 2005 suggested a link between human coronaviruses in Kawasakis disease. A case control study found significantly higher rates of coronavirus in children with Kawasakis (72.7%) than a matched control group without Kawasakis (4.2%)

For now, this cohort doesn’t change the management of childhood COVID-19, nor does it change the management of hyperinflammatory shock or Kawasakis – although the RCPCH have produced excellent guidance for suggested investigations and processes to include these patients in ongoing research.

Julie Toubiana, Clement Poirault, Alice Corsia et al. Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France medRxiv 2020.05.10 doi: https://doi.org/10.1101/2020.05.10.20097394

As a pre print this study should be interpreted with caution until it has undergone peer review.

This retrospective cohort study looks at a cluster of patients diagnosed with Kawasakis disease at a hospital in Paris between April 27th and May 7th. During this time they admitted 17 children with a diagnosis of Kawasakis or incomplete Kawasakis, with a mean age of 7.5yr and 10/17 (59%) female.

Clinical features: All children presented with persistent fever and with initial GI symptoms (vomiting and diarrhoea) with nearly half fulfilling complete KD criteria (8/17, 47%). The majority were irritable (11/17, 65%) and myocarditis was common (12/17, 71%). Coronary artery dilation was seen in 5/17 but no aneurysms seen. 6/14 who had chest imaging had lung changes.

Bloods: Inflammatory markers were significantly raised, with a median CRP of 219, PCT 23.3 and IL-6 218. Interestingly mean platelet count was 432 (but up to 838). Median troponin 136 and D dimer 4762 (up to 19330). Ferritin not reported.

COVID-19 status: 7/17 tested positive on swab and 15/17 had positive serology

Treatment: All were given IVIg, following which 5/17 still had fever 36hrs afterwards. They were given a second dose of IVIg and steroids. 10/17 required inotropic support and the same number required intubation/ventilation.

Outcomes: Median length of stay was 8 days (rage 5 – 17). There were no deaths.

Three subsequent studies have confirmed very similar presentations of this hyperinflammatory syndrome (PIMS-TS) in children, with initial abdominal pain, fever, diarrhoea and vomiting, progressing to a picture similar to Kawasakis disease but with a significant number developing shock and significant cardiac involvement.

Piccolo, V., I. Neri, C. Filippeschi, T et al (2020). “Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients.” J Eur Acad Dermatol Venereol published online 24th April 2020 https://doi.org/10.1111/jdv.16526

This is a report of chilblain like lesions observed during the COVID-19 pandemic, collected through a survey issued to Italian dermatologists and Paediatricians. This is a preliminary report as data collection still ongoing.

Importantly – very few patients in this cohort were tested for COVID-19 (11/63) and only 2 of these patients were positive. It is therefore difficult to extrapolate these findings to paediatric COVID-19 specifically, but is worth being aware of.

63 patients have been reported on with a median age of 14 years (IQR 12 – 16yrs) with feet alone being bar far the most commonly affected area (85/7%) followed by feet and hands together (7%). In uploaded pictures from 54 patients, erythematous-oedematous lesions were most common (31/54) followed by blistering lesions (23/54) and pain and itch were common, although a quarter of lesions were “asymptomatic”. Median time of onset of rash to diagnosis was 10 days. The lesions were generally stable and no other cutaneous signs observed. GI symptoms were the most common co-existing (11.1%) with surprisingly low levels of respiratory symptoms (7.9%).

This is basically a description of a common skin manifestation which coincided with COVID-19, and looked like it could be infectious in origin. Few patients tested, and even fewer positive. An interesting series worth bearing in mind given increasing reports of skin manifestation of COVID-19.

Lazzerini, Marzia et al, Delayed access or provision of care in Italy resulting from fear of COVID-19, The Lancet Child & Adolescent Health, Volume 0, Issue 0, Published April 9th 2020, https://doi.org/10.1016/S2352-4642(20)30108-5

This is a report of case studies during the COVID-19 pandemic in Italy of children whose presentations were thought to have been delayed due to parental fears of coming to the hospital. They report from 5 hospitals between March 1st and March 27th 2020, where paediatric presentations were reduced between 73 – 88%

During this period, in the week of March 23rd to 27th 12 children are identified whose parents reported avoiding accessing hospital due to concerns over SARS-CoV-2 infection . 6 of these were admitted to PICU and there were 4 deaths. The cases include 2 children with DKA, 2 with acute leukaemia, 2 children with cerebral palsy and complex needs, 1 with pneumonia and febrile convulsions, 1 with pyelonephritis, 1 with pyloric stenosis, 1 with a Wilm’s tumour, 1 with vomiting and hypoglycaemia and 1 with a congenital syndrome on dialysis.

This case series highlights the concerns of many paediatricians that more deaths will be seen in children from collateral damage born from the COVID-19 response, than will die of COVID-19. Delayed presentations is a major concern around the world currently, and whilst these cases certainly raise concerns, evidence is needed to ascertain the true presence and extent of this problem.

Turner D, Huang Y, Martín-de-Carpi J, et al. COVID-19 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto group of ESPGHAN [published online ahead of print, 2020 Mar 31]. J Pediatr Gastroenterol Nutr. 2020; doi:10.1097/MPG.0000000000002729

This article outlines the experience from Asia and Europe so far of children with inflammatory bowel disease given the COVID-19 pandemic. This is of particular interest because many of these children receive immunosuppression as part of their treatment, and so could be considered high risk for complications of the disease.

It appears to have been routine practice to suspend treatment for IBD during the outbreak of COVID-19, which resulted in a large number of relapses. No children with IBD contracted COVID-19 in China in the period covered by the survey.

In  South Korea treatment for IBD was not suspended. They also have had no cases of COVID-19 in children with IBD.

In the PORTO IBD group of ESPGHAN (covering Europe, some centres in Canada and Israel) treatment was not suspended in 31/32 centres. 7 children with IBD, who were on immunosuppression, had COVID-19. They all suffered a mild illness with no flare of their IBD. There is an additional child case from an international IBD database identified who also experiences mild symptoms (no hospitalisation required).

This survey provides further reassurance that treatment with immunosuppression does not appear to significantly increase the risk of severe disease from COVID-19 in children.

Boulad F, Kamboj M, Bouvier N, Mauguen A, Kung AL. COVID-19 in Children With Cancer in New York City. JAMA Oncol. Published online May 13, 2020. doi:10.1001/jamaoncol.2020.2028

This research letter reports the results of SARS-CoV-2 screening of patients and caregivers from one of the largest paediatric cancer centres in the US (Memorial Sloan Kettering Cancer Center, New York) in a region with very high levels of community SARS-CoV-2 transmission.

From March 10th to April 12th 2020, inpatients and outpatients with either symptoms of or exposure to SARS-CoV-2 infection underwent RT-PCR testing. Asymptomatic patients were also tested prior to admission, deep sedation and or myelosuppressive chemotherapy, as were caregivers of children being admitted.

Overall 11% (20/178) of paediatric patients returned a positive SARS-CoV-2 result; including 29.3% in the symptomatic / exposed group and 2.5% in the asymptomatic group. In contrast 14.7% (10/76) of asymptomatic caregivers were positive. Despite close contact, 5 of the 10 children of caregivers with SARS-CoV-2 were uninfected.
Only 1 of the 20 paediatric patients required hospitalisation for COVID-19 symptoms, without need for critical care.

This data provides reassurance that children with cancer may not be more vulnerable to complications of SARS-CoV-2 infection compared to other children. The lack of specific clinical detail in this report limits the ability to draw more definitive conclusions regarding risk.
The lower rate of asymptomatic carriage in children relative to their caregivers provides further evidence that children, including paediatric cancer patients, may be less susceptible to SARS-CoV-2 infection compared with adults.
Clearly infection control strategies must consider the risk of nosocomial spread from infected caregivers as well as paediatric patients, particularly in areas with high levels of community transmission.

Top Papers on Co-morbidities

Mixed co-morbidities

Issitt R, Booth J, Bryant W, Spiridou A, Taylor A, DuPre P, Ramnarayan P, Hartley J, Borja MC, Moshal K, Dunn H. Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population. medRxiv. 2020 Jan 1. Doi https://doi.org/10.1101/2020.05.20.20107904

A retrospective cohort study published by Great Ormond Street Hospital (GOSH), London, UK suggested children who are defined as vulnerable in the COVID-19 pandemic era do not appear to be at significantly increased risk of being admitted to hospital with COVID-19. In addition, the vulnerable group have similar outcomes to those who are COVID-19 negative. However, the authors do identify children undergoing chemotherapy or radiotherapy are ‘over-represented’ in the vulnerable group.

Data was collected from the institution’s electronic health record system. The inclusion criteria were any patient admitted between 01/03/2020 and 15/05/2020 who was admitted with features suggestive of COVID-19 based on the attending clinician’s interpretation, of undefined grade, including fever, cough and “systemic symptoms”. Children were defined as COVID-19 positive by a positive PCR test for nucleic acid in respiratory or blood specimens performed at the referring or presenting hospital or a documented positive familial test. Patients were classified as vulnerable if they fulfilled the high risk shielded list from NHS digital or the institutions local policy that was not provided. Due to the nature of the specialist paediatric services the population of children were highly selected.

166 children fulfilled the criteria; 65 (38.7%) were COVID positive and 101 (60.8%) were negative. The average age for COVID positive group was 9 years [IQR 0.9-14] with 38 (58.5%) males. This compared to the COVID-19 negative group with an average age of 1 year [0.1-5.75], 58 (55.4%) male. The COVID-19 positive patients were significantly older (p<0.001). Differences in ethnicity frequency was statistically significant for Asian ethnicity: 12 (8.5%) COVID-19 positive compared to 6 (5.9%) in the COVID-19 negative group (p=0.02).

The number of vulnerable children who were COVID-19 positive totalled 31 (47.7%) compared to 73 who were COVID-19 negative (72.3%), demonstrating a lower number of vulnerable children were positive for COVID-19, (p=0.002).    

Clinical features: Breakdown of symptoms were not provided

Radiology: N/A

Bloods (For those COVID-19 positive):

ALT 41.5 U/L [IQR 29-74], Albumin 32 g/L [IQR 27-36], AntiDNAse 310U/mL [80.8-402], AntiStreptolysin O 285 IU/mL [134-384], AST 70 U/L [43-100], CRP 28 mg/L [10-74], CK 63.5 U/L [35-214], Creatinine 23 umol/L [14-46], D-dimer 1876 ug/L [1043-3618], Ferritin 788 ug/L [445-1863], Fibrinogen 3.65 g/L [2.4-4.8], Interleukin-6 50 pg/ml [50-152], Interleukin-10 50pg/mL, LDH 848 U/L [654-1136],  BNP 3550 pg/ml [626-6992], Lymphocytes 1.44 X10^9/L [0.64-2.49], Neutrophils 3.90X10^9/L [1.46-8.6], WBC 8X10^9/L [3.38-13.2], Troponin I 54 ng/L [13-157], Prothrombin time 12 seconds [11.3-13],  bilirubin 6 umol/L [3-10], Triglycerides 2.48 mmol/L [1.65-3.56].

The results highlight the difference in results between the COVID positive and negative groups but do not define further differences between vulnerable and non-vulnerable groups. These include a statistically higher average CRP (p=0.002, fibrinogen (p<0.001), albumin (p0.02) neutrophil (p<0.001) and white blood cell count (p<0.001) and a lower LDH (p=0.002),

Treatments: Patient were treated following national or speciality specific guidance. No further information was provided.

Outcomes: Mortality for those who were COVID-19 was 1 (1.5%) who was in the vulnerable group. Additional comments described the primary focus of treatment was aspiration pneumonia. This compared to 4 (4%) in the non-COVID-9 group, all of whom were in the vulnerable group. The difference in mortality rates was not statistically significant.

There was no difference in the proportion of vulnerable patients based on their COVID-19 status: 61% of vulnerable patients who were COVID-19 positive compared to 64.3% who were negative, (p = 0.84). Overall, comparing all patients, a significantly lower proportion of COVID-19 positive patients required mechanical ventilation (27.7%) than COVID-19 negative patients (57.4%), (p<0.001). The individual number of patients were not provided.

The average ICU length of stay for those with COVID-19 was 4 days [2.4-10.6]. For those in the vulnerable subgroup the average was 11 days [3.7-15.1]. The significance of the difference between the vulnerable and non-vulnerable group was not described. However, vulnerable non-COVID-19 patients had a 6 [2.8-12.2] day stay in ICU. The difference between vulnerable COVID-19 positive and negative groups demonstrated no significance (p=0.3). 

The average total hospital stay for vulnerable patients with COVID-19 was 16.2 days [3.8-20.8]. This compared to vulnerable COVID-19 negative patient were in hospital for 12.3 days [5.2-19.8]. The difference in duration was not significant (p=0.94). 

Other salient features: Breaking down conditions that comprises vulnerable children there was a significant increased number of children with cancer undergoing active chemotherapy or radiotherapy who were admitted to hospital with symptoms and COVID-19 positive status compared to with symptoms but COVID-19 negative [7 VS 3 (p=0.01)].  There was no statistical differences between the COVID-19 positive and negative categories with on the national transplant, transplant medication, haematological cancer, respiratory and rare genetic, metabolic and autoimmune conditions lists or local severe respiratory conditions, rare diseases immunosuppressive therapies and other potential factors lists.

Oncology

Gampel, B. Troullioud Lucas, AG. Broglie, T. et al. (2020 Jun 26). “COVID-19 disease in New York City pediatric hematology and oncology patients.” Pediatr Blood Cancer: e28420. June 26th 2020, https://doi.org/10.1002/pbc.28420

This retrospective observational study provides some insight into the impact of COVID-19 on haematology/oncology patients. There were some limitations in the data collection process as testing was performed for different reasons at the two different sites that are considered. However, we see that between 10/03/2020 – 06/04/2020,  19 out of 174 tested children (each of whom had underlying haematological/oncological disorder or were undergoing haematopoietic stem cell transplantation) tested positive for COVID-19. Of these, 11 required hospitalisation. Five required PICU and one sadly died.


Method of data collection: All patients 21 years old or younger who underwent clinical laboratory COVID‐19 testing at two New York haem/onc centres were included. All patients had underlying haematological/oncological disorder or were undergoing haematopoietic stem cell transplantation. Informed consent was waived.


The two centres tested differently: “MSK tested all symptomatic patients and screened all patients prior to admission, procedures requiring sedation, and planned myelosuppressive chemotherapy. NYP tested only those patients for whom a positive test would alter management, including those who were symptomatic, likely COVID‐19 exposed, or with planned disposition to a chronic care facility.”
Features specific to children:19 out of 174 tested positive. Of these: 68% had fever, 47% had cough and 37% had dyspnea. 11 patients required hospitalisation and 4 patients required supplemental oxygen. 2 patients required mechanical ventilation and a further 3 were also admitted to PICU (all male). 3 patients received ‘COVID-19-directed therapy’ (with hydroxychloroquine and azithromycin)
1 patient died (“a child with sickle cell disease without a significant history of prior complications. Although this patient demonstrated pulmonary disease, his death may have been preceded by an acute cardiac event. Autopsy was refused…”). The authors make note that 64% of COVID+ oncology patients experienced treatment delays, showing the harms to these patients may not come primarily from COVID-19 disease itself

Ferrari, A., M. Zecca, C. Rizzari, F. et al (2020). “Children with cancer in the time of COVID-19: An 8-week report from the six pediatric onco-hematology centers in Lombardia, Italy.” Pediatr Blood Cancer: e28410. 

This letter to the editor describes the findings of 6 paediatric haematology and oncology centres in Lombardy during the 8 weeks after the COVID-19 pandemic began in Italy. Between 20th February 2020 and 15th April 2020. 286 patients were tested for COVID-19 when accessing services at these centres: 74 were symptomatic, 25 had close contact with a diagnosed case and 187 were tested for screening purposes. Of these, 21 cases tested positive for COVID-19, with a median age of 6 years (range 1-17 years) and 48% were male.

Of the 21 cases 10 had leukaemia, 5 had soft tissue or bone sarcoma, 2 had lymphoma, two had hepatoblastoma, 1 had a CNS tumour and 1 had colon carcinoma. 15 patients were currently receiving treatment while 6 had completed treatment and were receiving follow up.

Clinical features: 1 patient (who had existing neurological respiratory impairment) developed aspiration pneumonia requiring respiratory support, and 1 developed atypical bilateral pneumonia with mild symptoms.

Outcomes: There were no deaths related to COVID-19 infection. Cancer treatment was modified in 10 cases (delaying chemotherapy, reducing drug doses and postponing surgery).

The authors observe that despite the overwhelming rate of COVID-19 in the general population in the region at the time, relatively few paediatric cancer patients were symptomatic, or tested positive for the virus, and that severe illness was rare. They suggest that these results may indicate that paediatric anti-cancer treatments could continue without major adjustments, especially as alterations may reduce their efficacy.

Of note, these centres experienced a reduction in newly diagnosed cancer cases to 55% of the expected rate, which may reflect delayed access to healthcare services.

Boulad F, Kamboj M, Bouvier N, Mauguen A, Kung AL. COVID-19 in Children With Cancer in New York City. JAMA Oncol. Published online May 13, 2020. doi:10.1001/jamaoncol.2020.2028

This research letter reports the results of SARS-CoV-2 screening of patients and caregivers from one of the largest paediatric cancer centres in the US (Memorial Sloan Kettering Cancer Center, New York) in a region with very high levels of community SARS-CoV-2 transmission.

From March 10th to April 12th 2020, inpatients and outpatients with either symptoms of or exposure to SARS-CoV-2 infection underwent RT-PCR testing. Asymptomatic patients were also tested prior to admission, deep sedation and or myelosuppressive chemotherapy, as were caregivers of children being admitted.

Overall 11% (20/178) of paediatric patients returned a positive SARS-CoV-2 result; including 29.3% in the symptomatic / exposed group and 2.5% in the asymptomatic group. In contrast 14.7% (10/76) of asymptomatic caregivers were positive. Despite close contact, 5 of the 10 children of caregivers with SARS-CoV-2 were uninfected.
Only 1 of the 20 paediatric patients required hospitalisation for COVID-19 symptoms, without need for critical care.

This data provides reassurance that children with cancer may not be more vulnerable to complications of SARS-CoV-2 infection compared to other children. The lack of specific clinical detail in this report limits the ability to draw more definitive conclusions regarding risk.
The lower rate of asymptomatic carriage in children relative to their caregivers provides further evidence that children, including paediatric cancer patients, may be less susceptible to SARS-CoV-2 infection compared with adults.
Clearly infection control strategies must consider the risk of nosocomial spread from infected caregivers as well as paediatric patients, particularly in areas with high levels of community transmission.

Cesaro, S., F. Compagno, D. Zama, L. Meneghello, N. Giurici, E. Soncini, D. Onofrillo, F. Mercolini, R. Mura, K. Perruccio, R. De Santis, A. Colombini, A. Barone, L. Sainati, V. Baretta and M. G. Petris (2020). “Screening for SARS-CoV-2 infection in pediatric oncology patients during the epidemic peak in Italy.” Pediatr Blood Cancer: e28466, https://doi.org/10.1002/pbc.28466

Observational study of nasopharyngeal presence of SARS-CoV-2 in a cohort of 282 paediatric oncology patient presenting for scheduled care at 14 specialist centres in Italy between 20/02/20 and 19/04/20.  Median age for oncology cases (n=247) was 7 years (range 0-17.9) and for stem cell transplant (SCT) patients (n=35) was 9.6 years (range 0.3-17.6). 10/334 swabs from the oncology group were +ve and 0/56 from the SCT group. Only 2/10 NPS +ve patients had any symptoms (both “mild fever”). Chemotherapy was paused for all NPS +ve patients until 2 clear swabs were obtained 24 hours apart.  No adverse outcomes were recorded up to the study end but follow up was only reported up to 30/04/20. This study demonstrates that paediatric oncology patients can remain asymtomatic whilst carrying SARS-CoV-2 in the nasopharynx, and recover spontaneously, without any apparent increased rate of adverse outcomes. Researchers raise the question of whether routine chemotherapy needs to be paused for asymptomatic NP carriage of SARS-CoV-2 but present no evidence for the safety of this course of action.

Flores V, Miranda R, Merino L, et al. SARS-CoV-2 infection in children with febrile neutropenia [published online ahead of print, 2020 Jun 12]. Ann Hematol. 2020;1-2. doi:10.1007/s00277-020-04115-1

This letter to Annals of Hematology offers a brief description of three children with ALL who presented with febrile illness and were found to be SARS-CoV2 PCR positive. The letter is of note as sadly one of the children died during this illness following cardiac arrest; the authors offer the paper to highlight the occurrence of SARS CoV2 in febrile neutropenic patients; however it prompts further analysis of those cases of severe infection in the context of immunosuppression.

The patients were identified at a centre in Mexico however the time period is not known. The three patients were aged 4yrs, 8yrs and 9yrs. All had ALL, two receiving consolidation chemotherapy and one on immunosuppression with mycophenolate and prednisolone. The latter patient had undergone HSCT for ALL, the time since HSCT was not provided, however this patient was admitted from the community suggesting she wasn’t in the immediate post-transplant period. All patients developed neutropenia either at time of fever or quickly following it and similarly evolved to have ‘respiratory symptoms’. All had negative blood cultures however results of other virology is not provided. Over-all pre-covid health status is not provided within the letter and this might be helpful in understanding the severity of symptoms in the patient who died.

The child who died was 8 years old and presented with febrile neutropenia, they were on mycophenolate and prednisolone following HSCT for ALL. The child quickly developed respiratory distress and required invasive mechanical ventilation; a heamodynamic deterioration led to cardiac arrest and resuscitation measures failed.

The distinguishing features of this child was her immunosuppression and history of HSCT, she was also more profoundly lymphopenic and thrombocytopenic. All other laboratory values were variable between all three patients. Further information on her overall cardiorespiratory status pre-SARS-CoV-2 would be helpful to understand her vulnerabilities and to guide management of children presenting with similar comorbidities in the future.

Sieni, E. Pegoraro, F. Casini, T. Tondo, A. Bortone, B. Moriondo, M. Azzari, C. Galli, L. Favre, C. Favourable outcome of Coronavirus‐19 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced immunosuppression. British Journal of Haematology. 2020 May 5. https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16781

This retrospective single case report discusses the progression and treatment of a child with high risk acute myeloid leukaemia having undertaken the third chemotherapy cycle of the induction phase following AIEOP LAM 2013 protocol.

13-month-old female patient attended routine clinic at Myers Hospital, Florence, Italy following completion of the chemotherapy. Routine investigations revealed a low white cell count, haemoglobin and platelet count which necessitated admission for transfusions. The need for admission was the initial reason for testing for SARS-CoV-2. RT-PCR was performed for nasal and pharyngeal swabs. Faecal PCR testing was also positive.   

Clinical features: Fever starting on day 3 (the combination of fever and low WCC suggested neutropenic sepsis), vomiting and diarrhoea with negative stool culture.

Radiology: CXR on day 3 showed bilateral reticular markings. A repeat prior to discharge demonstrated “no significant modification from baseline”.

Bloods: Day 0 showed low WCC (80/mmc), haemoglobin (7.9g/dL) and platelet (5000/mmc) count. The elevated CRP was highest at day 5 (7.2mg/dL) and normalised by day 10 (<0.5mg/dL). Additional laboratory investigations included LDH which was highest by day 13 (401  IU/L) and ferratin maximally raised on day 9 (3000 mg/mL). Immunoglobulins were low throughout the illness. On day 3 the results were: IgG 258 mg/dL, IgA 18.7 mg/dL, IgM 7 mg/dL. IL-1β, IL-6, IL-10, TNFα and cardiac enzymes were normal.

Blood microbiology was negative.

Additional  laboratory  investigations, including  cytokines  (IL-1β,  IL-6,  IL-10  and  TNFα)  and  cardiac  enzymes,  were  normal;  lactate dehydrogenase  slightly  increased  (up  to  401  IU/L  at  day  13),  whereas  ferritin  values  showed moderate elevation from day 9

Treatments: Treatment for neutropenic sepsis with piperacillin-tazobactam and fluconazole was commenced on day 3 due to fever. Hydroxychloroquine day 3-11. On day 4 lopinavir/ritonavir stopping day 12

Outcomes: Was treated on a hospital ward without supplemental oxygen until discharge. 

Other features of interest: There was a undetectable viral plasma load by day 16, however nasal swab for SARS-CoV-2  remained positive beyond discharge at day 26. There is no data to suggest a negative test to publication date. 

It is unclear if the low WCC, anaemia and thrombocytopenia requiring transfusion was due to the chemotherapy, underlying acute myeloid leukaemia or COVID-19 infection, however, on discharge these values had normalised and were maintained by day 26.   

Summary: This case describes a high-risk young patient with acute myeloid leukaemia undergoing chemotherapy presenting with febrile neutropenia. Whilst the symptoms were initially vague, subsequent investigations suggested the underlying cause was SARS-CoV-2. Early anti-viral treatments were commenced. Given the patient’s immunosuppression the authors discuss fears regarding seroconversion, viral dissemination and inflammatory responses which did not occur.  

Hrusak, O., T. Kalina, J. Wolf, A. et al. (2020). “Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment.” European Journal of Cancer 132: 11-16. https://doi.org/10.1016/j.ejca.2020.03.021

This is the report of a data from an international survey of paediatric haematology and oncology clinicians to assess the frequency and severity of SARS-CoV-2 infection amongst children with cancer. The survey, conducted from 16th-17th March 2020, had over 35 respondents from 25 countries. Of an estimated 10,000 patients at risk and over 200 tested, 9 children were positive for SARS-CoV-2. Clinical details are provided for 8 cases, 6 of whom had solid tumours and 2 with acute lymphoblastic leukaemia. 7 had mild or asymptomatic disease, 1 patient required low flow oxygen. Fever was the presenting symptom in 6 patients and one patient also had diarrhoea. All 7 patients with outcome data available made a full recovery.

The interpretation of these data is clearly limited by the study design as well as the relatively early stage of the pandemic during which the survey was conducted. Notwithstanding these limitations, the absence of severe COVID-19 cases in this report provides some early reassurance. More detailed clinical studies are needed to draw firm conclusions about the risk of severe disease in children receiving chemotherapy.

D’Antiga L. (2020), Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl. Accepted Author Manuscript. doi:10.1002/lt.25756

This letter is from a liver transplant centre in Lombardy, Italy, reporting their experience of patients (including children) with immunosuppression and COVID-19. They have had 3 children post liver transplant test positive for SARS-CoV-2, and none have developed clinical pulmonary disease. They believe due to the widespread nature of infection that many other of their patients may also be infected, but not developed clinically apparent disease.

This provides the first official reports of vulnerable paediatric populations with COVID-19, which so far does not appear to be any more severe than the rest of the population in that age bracket. Further data is awaited.

Balduzzi, A, Brivio, E, and Rovelli, A et al, Lessons After the Early Management of the COVID-19 Outbreak in a Pediatric Transplant and Hemato-Oncology Center Embedded within a COVID-19 Dedicated Hospital in Lombardia, Italy. Estote Parati. (Be Ready.) (3/19/2020). Available at SSRN: https://ssrn. com/abstract=3559560 or http://dx.doi.org/10.2139/ssrn.3559560

This report from a paediatric haematology unit in Lombardia, Italy, includes the Italian experience of COVID-19 in children with malignancy so far. At their particular unit, they have had no children with malignancy test positive for COVID-19 (they admit this is dependent on testing criteria, requiring hospitalisation at their institute). They are aware of 5 cases of paediatric cancer patients who have had COVID-19 and have all suffered a mild course, with 3 managed at home and 2 in hospital.

This small case series provides further reassurance for at risk paediatric populations.

Cardiac disease

Lee, H., B. S. Mantell, M. E. Richmond, S. P. Law, W. A. Zuckerman, L. J. Addonizio, T. M. Lee and I. D. Lytrivi (2020). “Varying Presentations of COVID-19 in Young Heart Transplant Recipients: A Case Series.” Pediatr Transplant: e13780. https://doi.org/10.1111/petr.13780

This is a peer reviewed prepublication case report on the experience of Covid-19 among a population of young heart transplant patients from a tertiary centre, Columbia University Irving Medical Centre, New York.

Period Covered: first 3 months of the New York Covid pandemic

Hospital/Region Covered: the tertiary transplantation programme is one of the largest in the USA covering “hundreds” of patients.

Identification of Patients: 4 patients under the care of the hospital for heart transplantation are included. Case 1 was admitted after referral from secondary care with Covid symptoms and an oxygen requirement.. Cases 2 and 4 presented from home and case 3 was diagnosed during a planned admission for heart biopsy.

Age/Gender:  there is a wide age range: case 1 (F)15 years, case 2 (F)25 years, case3 (M)13 months, case 4(F) 29 months.

Comorbidities and immunosuppression: The authors highlight the questions of whether the comorbidities (including immunosuppression) associated with heart transplantation lead to worse outcomes with Covid infection? Also whether immunosuppression has a protective or aggravating effect on outcome and how regimes should be managed?

Two patients (1 and2)also had renal transplants. Case 2 had connective tissue disease (elevated IL-2).

All patients were on various combinations of immunosuppressants (1,2 and 3 on steroids).In only one case (1) was this withheld during infection because of neutropenia.

Clinical Features: 3 patients (1,2,3) had  symptoms of acute Covid-19 and were nasal/nasopharyngeal positive. Case 1 required supplemental oxygen but no other treatment for 3 days and was then discharged.Cases 2 and 3 did not require admission. Cough: 3/3. Fever: 3/3.Sore throat: 1/3. Abdominal pain: 1/3. All remained well on follow up.

Patient 4 is likely to have had Covid-19 4 weeks prior to admission (symptoms and family history). She presented with a probable post Covid anaemia and hepatitis. She had a rash (acral papular) She was negative on nasal and hepatic Covid assay. Her liver biopsy was consistent with viral hepatitis. Her Covid serology was positive and other viral hepatitis serology negative. She received a blood transfusion

Reported Imaging: CXR:1/4. Normal. Cardiac echo:2/4. No deterioration.

Laboratory: Case1: WCC low 1460/ul, neutropenia (800/ul). ?secondary to immunosuppression or Covid.  Elevated inflammatory markers: CRP, ferritin.  D-dimer, pro- BNP elevated.

Case 2:  no report. Case 3: normal FBC, CRP and LFTs.

Case 4: Hb 6.2 g/dl. Peak ALT elevated 1807 U/L. Peak AST 1070 U/L.

Comment: The centre maintains surveillance (telehealth) of most of it’s patients. Despite possible risk factors of comorbidities and immunosuppression only 4 cases presented. In the acute cases the illness was either mild (2,3) or moderate (1). This is the first report from a paediatric transplant centre and it will be necessary to examine the experience in other centres worldwide.

Case 4 developed hepatitis, anaemia and a rash 4 weeks after probable Covid infection. It is possible that this was Covid related.  Viral hepatitis has been reported in a child post liver transplant with acute Covid infection.

Respiratory disease

Poli, P., S. Timpano, M. Goffredo, R. Padoan and R. Badolato. “Asymptomatic case of Covid-19 in an infant with cystic fibrosis.” Journal of Cystic Fibrosis, April 14th 2020, https://doi.org/10.1016/j.jcf.2020.03.017

This is the first case report of confirmed SARS-CoV-2 infection in a child with cystic fibrosis. The 1 month-old, from Italy, was diagnosed with CF on newborn screening. SARS-CoV-2 infection was confirmed on nasopharyngeal swab PCR as part of contact tracing following exposure to COVID-19 through his grandfather.
The infant remained asymptomatic throughout follow up and did not require hospital admission.
This is one of a limited number of reports of SARS-CoV-2 infection in people with CF. A better understanding of the course of illness in this group will likely emerge with data from ongoing collaborative studies.

Inflammatory Bowel Disease

Turner D, Huang Y, Martín-de-Carpi J, et al. COVID-19 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto group of ESPGHAN [published online ahead of print, 2020 Mar 31]. J Pediatr Gastroenterol Nutr. 2020; doi:10.1097/MPG.0000000000002729

This article outlines the experience from Asia and Europe so far of children with inflammatory bowel disease given the COVID-19 pandemic. This is of particular interest because many of these children receive immunosuppression as part of their treatment, and so could be considered high risk for complications of the disease.

It appears to have been routine practice to suspend treatment for IBD during the outbreak of COVID-19, which resulted in a large number of relapses. No children with IBD contracted COVID-19 in China in the period covered by the survey.

In South Korea treatment for IBD was not suspended. They also have had no cases of COVID-19 in children with IBD.

In the PORTO IBD group of ESPGHAN (covering Europe, some centres in Canada and Israel) treatment was not suspended in 31/32 centres. 7 children with IBD, who were on immunosuppression, had COVID-19. They all suffered a mild illness with no flare of their IBD. There is an additional child case from an international IBD database identified who also experiences mild symptoms (no hospitalisation required).

This survey provides further reassurance that treatment with immunosuppression does not appear to significantly increase the risk of severe disease from COVID-19 in children.

Brenner, E. J., R. C. Ungaro, R. B. Gearry et al “Corticosteroids, but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry.” Gastroenterology https://doi.org/10.1053/j.gastro.2020.05.032

This is a pre-proof article and therefore has not yet undergone final editing and review.

This is an article from America (Carolina) aiming to characterise the clinical course of COVID-19 on patients with inflammatory bowel disease (IBD) and evaluate the association between demographics, clinical characteristics and immunosuppressant treatments of COVID-19 outcomes.

The authors created a surveillance database and healthcare providers were encouraged to voluntarily report all cases of Polymerase Chain Reaction (PCR)-confirmed COVID-19 patients with IBD.  A website was developed to enable international contributions. Contributors were asked to report cases a minimum of 7 days from symptom onset and after sufficient time had passed to observe disease course through to resolution of acute illness or death.

525 patients from 33 countries were reported. 7% had severe COVID-19, 31% were hospitalised, 3% of patients died.  The median age of patient was 41 years (from 5 to 90). The majority of patients had Crohns Disease (59.4%) and IBD disease activity was classed as remission in 58.9% of cases. The most common class of treatment was TNF antagonist therapy (43.4% of patients).

63.5% of patients had no comorbidities other than IBD. Most patients who died had other co-morbidities.  Only 3 paediatric patients (10% of paediatric cases) required hospitalization. After controlling for all other covariates use of systemic corticosteroids and ASA/sulfasalazine use were strongly associated with more serious outcomes after infection with COVID-19 but there was no significant association seen between TNF antagonist use and adverse outcomes.

The authors observed an age-standardized mortality ration of approximately 1.5-1.9 as compared to the general populations of China, Italy and the U.S.

They state it is reassuring that the most commonly used treatment- TNF antagonists- appears not to lead to increased adverse outcome for patients infected with COVID-19.

This study has strength in that it includes data from many countries although how comparable that data can be between countries is debatable. The authors did not look at dosing regimens or what was done in terms of continuing or postponing treatment which may well have varied from one country to another. There may also be some bias towards patients who were unwell enough to present to hospital, there may have been other patients who were infected but not unwell enough to require hospital treatment/testing  for COVID-19 who would not have been included in this study population.

Renal disease

Schwierzeck, V., J. C. Konig, J. Kuhn, A. Mellmann, C. L. Correa-Martinez, H. Omran, M. Konrad, T. Kaiser and S. Kampmeier (2020). “First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit.” Clin Infect Dis, https://doi.org/10.1093/cid/ciaa491

This paper presents the results of an outbreak investigation following a member of staff on a paediatric dialysis unit developing confirmed COVID-19. Detailed contact tracing was carried out and found that 48 cases in total were involved – this included 13 patients, 28 healthcare workers and seven ‘accompanying persons’. Of note, of the 3 traced who children tested positive for SARS-CoV-2, only one had symptoms; given these children’s high-risk status, their asymptomatic presentations are noteable. The paper discusses hygiene measures put in place to avoid further spread.

Transplant related disease

Lagana SM, De Michele S, Lee MJ, Emond JC, Griesemer AD, Tulin-Silver SA, Verna EC, Martinez M, Lefkowitch JH. COVID-19 Associated Hepatitis Complicating Recent Living Donor Liver Transplantation. Archives of Pathology & Laboratory Medicine. 2020 Apr 17. doi: 10.5858/arpa.2020-0186-SA.

This retrospective single case report examines the histopathological features of liver associated COVID-19 in a child admitted to Columbia University Medical Centre, USA. The female child, 6 months old, was admitted for a liver transplant for treatment of biliary atresia. COVID-19 was diagnosed in the donor on post-operative day 2 and confirmed in the patient day 4 post-operatively. The type of test used was not described.

Clinical features: Increased work of breathing requiring CPAP, fever and diarrhoea were developed on post-operative day 4.

Radiology: CXR on post-operative day 4 was described as “no significant changes compared to prior exam with only patchy areas of atelectasis in irregularly aerated lungs”. CXR on day 6 demonstrated “patchy lung opacities bilaterally, mildly increased in the right upper lobe and left lung base”.

Bloods: Deranged LFTs exacerbated from baseline on post-operative day 1: AST (maximum 908U/L from 163U/L), ALT (maximum 980U/L from 215U/L), GGT (maximum 473U/L from 174U/L), ALP (maximum 578U/L from 388U/L).

Treatments: Treated with hydroxychloroquine from day 4 post-operative. She required CPAP for an undefined time period. Undefined immunosuppressant treatment was provided for acute transplant rejection, however liver enzymes worsened when commenced.

Outcomes: Remains on a hospital ward without supplemental oxygen.

A liver biopsy was performed on post-operative day 7 demonstrating portal tract expansion through a mixed inflammatory infiltrate which consisted of lymphocytes, rare plasma cells, and interspersed eosinophils, lymphocytic cholangitis, reactive changes in the interlobular bile ducts and mild portal venulitis. These were interpreted as acute cellular rejection.

Other findings of moderate acute hepatitis including an “azonal pattern of clusters of apoptotic hepatocytes” and singly dispersed apoptotic hepatocytes. Other features of interest include large fragments of cytoplasmic debris described as “crumbling” hepatocytes, few mitotic figures, regions of Kupffer cell prominence with sinusoidal and central vein endotheliitis. The authors commented that the extent of hepatocyte apoptosis and large clusters were unusual and not a usual feature of acute cellular rejection (ACR). Central endotheliitis may also be a feature of COVID-19 hepatitis, with the presence of more Kupffer cells and less plasma cells than ACR.

Summary: COVID-19 hepatitis likely presents as a moderate acute hepatitis with prominent clusters of “crumbling” apoptotic hepatocytes. Other features may be lymphohistiocytic inflammation of sinusoidal and central vein endothelium, with the presence of more Kupffer and less plasma cells when compared to ACR.

Angeletti, A., A. Trivelli, A. Magnasco, S. Drovandi, F. Sanguineri, M. Santaniello, G. Ferrando, R. Forno, G. Cipresso, G. Tripodi, L. V. Riella, P. Cravedi and G. M. Ghiggeri (2020). “Risk of COVID-19 in young kidney transplant recipients. Results from a single-center observational study.” Clin Transplant. 2020 May 12. doi: 10.1111/ctr.13889. [Epub ahead of print]

Giannina Gaslini Children’s Hospital, Italy undertook this prospective observational study of patients, who received a kidney transplant between January 2010 and March 2020, with stable graft function and were taking chronic immunosuppressant therapy. They were interviewed weekly between 24th February and 12th April 2020 for 7 weeks, using a 12-point structure questionnaire contained in the appendix, to evaluate the health status of themselves and their cohabitants. The data for adults and children were combined presenting a median age of 20 (2-30) years. The demographics were reported as a combined total; 93 were male.

2 patients, an adult (information not included) and 1 girl aged 13, had co-habitants who were positive for SARS-CoV-2. The 13-year-old had a kidney transplant aged 9 years old. At the time of study, she was taking a combination of steroid, calcineurin inhibitor (CNI and mycophenolate mofetil (MMF) and had investigations including a white cell count and haemoglobin within normal limits.

She tested negative for SARS-CoV-2 using a nasopharyngeal swab (test not declared) and did not develop any symptoms in the subsequent 21 days, declared as the incubation period. Anti-SARS-CoV-2 antibodies were also negative at an undefined time point.

Clinical features: No patients developed any clinical symptoms.

Radiology: None discussed.

Bloods: None discussed for patients who were positive for SARS-CoV-2.

Treatments: None.

Outcomes: None.

Other salient features: The authors recommend avoiding altering the immunosuppressive therapy in young transplant recipients who do not have symptoms of SARS-CoV-2 including those who are exposed to positive close contact. Despite observing a relatively large population of kidney transplant recipients, a small number, 2 (1 child) were exposed to SARS-CoV-2, upon which has the conclusions are based.

Morand, A., B. Roquelaure, P. Colson, S. Amrane, E. Bosdure, D. Raoult, J. C. Lagier and A. Fabre (2020). “Child with liver transplant recovers from COVID-19 infection. A case report.” Archives de Pediatrie. https://doi.org/10.1016/j.arcped.2020.05.004

This a case report form France of a 2-and-a-half-year-old girl who recovered from COVID-19 infection, 5 months after a liver transplant; she had co-infection with Epstein-Barr virus (EBV).

The child had received a living donor transplant (father) as she had developed portal hypertension post Kasai portoentemrostoy performed at 53 days of age for biliary atresia.

She had been discharged home 20 days post procedure on tacrolimus immunosuppression therapy and had no immunization against EBV before transplantation.

On day 96 post transplant she was found to have primary EBV infection linked to the transplant- her father was EBV positive- but was asymptomatic of this.

The first developed rhinitis which developed into a fever, cough and tachypnoea.  In the few days before this her mother had been hospitalized with pneumonia and found to be COVID-19 positive on nasopharyngeal swab. On day three of the illness the child was referred to hospital where she was found to be positive for COVID-19 on NPA.

On admission she was tachypnoeic with no other signs of respiratory distress, her CRP was low (3). A chest CT showed focal alveolar condensation of the ligula and a stable mediastinal enlargement. Her liver function tests had deteriorated (GGT and AST). An US of the liver showed aggravation of the transplanted biliary tract stenosis and an elevated EBV blood viral load. She was managed symptomatically, and she did not receive any COVID-19 specific treatment.

She recovered from COVID-19 infection despite the high level of immunosuppression caused by her tacrolimus treatment.  NPA test samples became negative on day 11. The authors report they reduced the dose of tacrolimus but do not state at which point in the illness nor for how long. They do not state how long it took for her LFTs to return to previous levels nor if there were any consequences of the raised EBV viral load.

The authors suggest liver transplantation is not associated with COVID-19 symptom severity development even when there is high level immunosuppression on tacrolimus. Moreover COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.

It is difficult to draw conclusions based on one case study. Particularly as other studies have shown the severity of COVID-19 is increased when present with other co-morbidities. This particular patient, due to the nature of her original liver insult and the fact that she is a young patient, did not have other co-morbidities, this is often not the case for other patients who have required a liver transplantation.

 Other co-morbidities

Genovese, G., Colonna, C. and Marzano, A.V. (2020), Varicella‐like exanthem associated with COVID‐19 in an 8‐year‐old girl: A diagnostic clue?. Pediatr Dermatol. Accepted Author Manuscript. doi:10.1111/pde.14201

This single case report describes an 8 year old girl presenting on a hospital in Milan, Lombardy region, Italy, on 21 March 2020 with a painless, non-pruritic papulovesicular rash on the trunk developing 3 days after onset of a mild cough. The rash was predominantly papular with  some vesicles with crusting, similar in appearance to chickenpox. Limbs, face, genitalia and mucous membranes were spared. She developed a mild fever 5 days after the onset of the rash, and tested positive for SARS-CoV-2. She had bloods including FBC, renal function, liver function and CRP, all of which were normal with the exception of a mild thrombocytopenia with platelets of 105 x 109/L, which subsequently normalised. The rash lasted 7 days, by which time systemic symptoms had resolved. The young girl had a history of varicella infection a year previously.

The authors quote other case reports of cutaneous manifestations associated with COVID-19: petechial rash, widespread urticaria and varicella-like rash predominantly involving the trunk. Although unable to confirm that the rash was definitely associated with COVID-19, they feel it is likely given the child’s previous history of varicella infection and lack of pruritis to suggest the lesions were insect bites. They suggest papulovesicular eruptions be included in the spectrum of exanthems possibly associated with COVID-19.

Top 10 Epidemiological Papers on Transmission

Yung, C. F., Kam, K., Nadua, K. D. et al.  Novel coronavirus 2019 transmission risk in educational settings. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa794

A study of contact tracing of 3 clusters of confirmed COVID-19 within schools in Singapore. Only close contacts of the affected students were placed into quarantine for 14 days, not complete year groups/schools/or classes. Target health measures implemented included terminal cleaning and interventions to reduce mixing (examples were cancelling of extra-curricular activities and staggered break times). For 3rd incident in day care, the school was closed due to increasing cases amongst staff, and all students were tested regardless of exposure/symptoms.

Case 1: 12yr male in secondary school infected at home (sibling of case 2). Attended on day 1 of symptom and subsequently quarantined. 8 classmates developed compatible symptoms, all tested negative.

Case 2: 5yr male in primary school. Attended on day 1 of symptoms and quarantined. 34 classmates developed compatible symptoms, all tested negative.

Case 3: Multiple adult staff members in pre-school involved in cluster. 70% of all students tested, all negative.

These findings are consistent with the small number of other studies of transmission within a school setting so far, which have demonstrated infrequent transmission from children.

Heavey, L., G. Casey, C. Kelly, D. Kelly and G. McDarby (2020). “No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020.” Euro Surveill 25(21). May 28th 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.21.2000903

This is an epidemiological study describing cases of Covid-19 in Irish school setting in March 2020. Cases were identified by screening all cases of SARS-CoV-2 notified to public health departments in the Republic of Ireland, to identify children under the age of 18 years, and adults who had attended the school setting.

Six cases were identified, 3 school going children, and 3 adults (1 a teacher, and 2 who conducted educational session in a school). 5 out of 6 cases presented symptomatically with fever or cough, the final case was asymptomatic and screened due to a household cluster.  Contact-tracing records were reviewed to identify cases of secondary transmission.

A total of 1155 contact of these six cases were identified. In the school setting, among 924 child contacts and 101 adult contacts identified, there were no confirmed cases of COVID-19. The only documented transmission that occurred from this cohort was from an adult case to other adults working environment outside school.

In conclusion no case of onward transmission to other children or adults within the school occurred. In the case of children, no onward transmission was detected at all.  Furthermore, no onward transmission from the three identified adult cases to children was identified.

Limitations of the study, was only symptomatic contacts were tested, and so asymptomatic secondary cases were not captured. Also, in Ireland, when a case was identified, all children and staff within the school were excluded thus limiting the potential for further transmission within the school setting once a case was identified. All Irish schools closed on March 12th 2020 and remain closed.

Somekh, E., A. Gleyzer, E. Heller, M. Lopian, L. Kashani-Ligumski, S. Czeiger, Y. Schindler, J. B. Lessing and M. Stein (2020). “The Role of Children in the Dynamics of Intra Family Coronavirus 2019 Spread in Densely Populated Area.” Pediatr Infect Dis J. doi: 10.1097/INF.0000000000002783

This is a brief study of the transmission dynamics within households in Bnei Brak, an area of Isreal with high population density and high proportion of young people (almost 50% of its population are <18yrs). They assessed 13 family clusters and tested every member of their households by PCR, regardless of the presence or absence of symptoms. The index case was identified by date of onset of symptoms (this is standard practice but does leave open the possibility of mis-classifying the index case if they were truly asymptomatic).

The results were as follows; Excluding index cases, 58.3% of adults tested positive, 32.5% of children aged 5 – 17 tested positive, and 11.8% of children aged <5yrs tested positive. In 12/13 families the index case was an adult. The other case was a 14yr old male.

This evidence is consistent with almost all other household contact tracing studies which have demonstrated a significantly lower secondary attack rate in children compared to adults. A strength is the clear documentation that all household members were tested regardless of symptoms, and for clarity the index case was not included in the rates of infection making secondary AR better defined.

Qin-Long Jing, Ming-Jin Liu, Jun Yuan et al, Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study, The Lancet, June 17th 2020, https://doi.org/10.1016/S1473-3099(20)30471-0

This is study from Guangzhou, China documenting the attack rate amongst 1964 close contacts and 134 secondary or tertiary cases of 215 confirmed COVID-19 cases from January 7th to February 18th 2020.

There were 103 non-primary cases amongst 784 household contacts giving an attack rate of 13.1% overall. Notably children (<20yo) had a lower non-primary household attack rate of 5.2%.
In statistical transmission modelling to estimate true secondary attack rates, children (<20yo) had a lower odds of infection compared with adults >60yo (OR 0.23, 95% CI 0.11-0.46)

Only 10/215 (5%) of primary cases were children.

Although the criteria for testing contacts in this study are not entirely clear, the results suggests that children are less susceptible to SARS-CoV-2 infection compared with adults with similar exposure. This is in keeping with other reports from Asia (Zhang), Israel (Somekh) and the USA (Rosenberg).

Eli S Rosenberg, Elizabeth M Dufort, Debra S Blog et al. New York State Coronavirus 2019 Response Team, COVID-19 Testing, Epidemic Features, Hospital Outcomes, and Household Prevalence, New York State—March 2020, Clinical Infectious Diseases, ciaa549, https://doi.org/10.1093/cid/ciaa549

This epidemiological study examined the first 229 positive cases diagnosed in New York State outside of the city of New York from 2nd March to 12th March 2020 and described their outcomes. In addition, from the 5th March to the 17th March, they screened any household contacts of the positive patient. There was one ‘source’ patient under 5 years of age and 7 ‘source’ patients from 5 to <18 years of age. Household screening identified a further 42 children with COVID-19. No children <18 years of age required hospitalisation but it appears they only had complete data on 18/50 positive children.

Household contact with positive patients of any age found that likelihood of the contact being positive for SARS-CoV-2 increased with the contact’s age. Of the 25 children screened <5 years of age, 5 (20%) were positive and of the 131 screened age 5 to <18 years 37 (28.2%) were positive, compared to 16/29 (55%) of contacts aged 65+ years (p 0.002). This supports previous studies which shows a lower prevalence of SARS-CoV-2 infection in children <18 years. Unfortunately it does not described whether the household contacts of the 50 source children were positive for the infection too which could contribute to the discussion about whether children spread SARS-CoV-2 as effectively as adults and would require completion of the missing data and more in-depth analysis of the findings.

Zhang J, Litvinova M, Liang Y, et al, Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China, Science, 29th April 2020, DOI: 10.1126/science.abb8001

This fascinating study assesses contacts and infection risk in China (Wuhan and Shanghai) using 3 arms:

Surveys conducted within cities studying contacts between individuals, finding that during lockdown all contact except for those within households ceased – backing up evidence that about 90% of infections during this period occurred by household transmission

Most importantly for us – an age stratified model of susceptibility to acquiring infection was produced by assessing the data from the Hunan CDC, whereby every positive case found in Hunan had recent contacts placed under quarantine for 14 days and was tested for COVID-19. They estimated odds ratios for age groups to become infected, and performed statistical adjustment for clustering and correlation structures of contacts exposed t the same index case (generalized linear mixed model regression). Their finding was that susceptibility to infection increased with age, lowest in children 0-14 years (OR 0.34, 95% CI 0.24 – 0.49 – reference participants aged 15 – 64yrs).

Finally using the above data they estimated the effects of non-pharmceutical interventions on reducing spread of COVID-19. They found that closing schools was likely to significantly impact the R0 but not enoght to be a useful measure on its own. They describe social distancing as implemented in China, to be a sufficient measure to control COVID-19

This is the latest, and one of the most comprehensive of a number of studies to demonstrate significantly lower attack rate in children to adults, suggesting decreased susceptibility to infection.

Li, W., B. Zhang, J. Lu, S. Liu, Z. Chang, P. Cao, X. Liu, P. Zhang, Y. Ling, K. Tao and J. Chen (2020). “The characteristics of household transmission of COVID-19.” Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 17. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281

This retrospective study calculated secondary attack rates of COVID-19 amongst 392 household contacts of 105 SARS-CoV-2 RT-PCR positive index cases hospitalised at Zaoyang First People’s Hospital (250 km from Wuhan) and Chibi People’s Hospital (150 km from Wuhan) between 1st January and 20th February 2020.

Study design:  Households were eligible for the study if the index case was the only member of the household with a clear history of exposure to Wuhan, its residents or high-risk sites in the 14 days before onset of illness (the assumption then being that the only exposure of household contacts to SARS-CoV-2 was via the index case).  Once index cases were confirmed, household contacts were quarantined for 14 days in local government sites and monitored daily, with at least 2 nasopharyngeal swabs (taken at the beginning and mid-point of quarantine).  Variables analysed retrospectively in this study (using medical notes and telephone interviews) included household size, age/gender/symptoms of index cases and household contacts, time between onset of illness of the index case and hospitalisation (range 0-11 days) and spouse/non-spouse relationships. 

Key paediatric findings:  100 of the 392 household contacts were under 18 years of age (median 6.5 yrs, IQR 4-11 yrs); of these, only 4 children became infected (all male, 1 aged 0-5 yrs, 3 aged 6-17 yrs).  This secondary attack rate of 4% for children compares with 21% for the adult household contacts (60 out of 292 infected) and 16% overall (64 out of 392).

Of interest:  14 of the 105 index cases self-quarantined within the home immediately after onset of symptoms before hospitalisation (wearing masks, eating and residing separately from the rest of the household); in these households there was a 0% secondary attack rate, versus 18% in those households where the index case didn’t self-quarantine before hospitalisation.  In households where the index case was afebrile, 13% of household contacts became infected, versus 19% where the index case had fever.  In households where the index case had no cough, approximately the same proportion of household contacts became infected as in households where the index case had a cough (17% vs 16%).  9 of the infected household contacts were asymptomatic (14%), but this figure isn’t broken down by age in the article.  [Note: there are some discrepancies between calculations in the text and data tables; data from tables used here.

This article provides further reassurance to the growing body of evidence of lower attack rates of COVID-19 in children as compared to adults, as well as a signal that symptomatic patients are higher risk of transmitting the virus than those who do not develop symptoms.

Wang, Z., W. Ma, X. Zheng, G. Wu and R. Zhang (2020). “Household Transmission of SARS-CoV-2.” The Journal of infection. 10. https://doi.org/10.1016/j.jinf.2020.03.040

This is a retrospective case series of 85 patients admitted to Union Hospital in Wuhan City, Hubei Province, China and their households, one household per index case.  The aim was to attempt to determine the transmission rate of SARS-CoV-2 among household members.

All patients were confirmed infected with SARS-CoV-2 with real-time reverse transcription polymerase chain reaction (RT-PCR) assays on throat swabs. The admission dates were February 13 and February 14, 2020. The city had been under lockdown measures since the 23rd of January.

The composition of these 85 households was 107 (45%) male adults, 115 (48%) female adults and 18 (7%) children.

64 (60%) of 107 male adults and 66 (58%) of 115 female adults were confirmed infected with SARS-CoV-2, only 2 (11%) of 18 children became positive. As a whole, there were totally 240 cases in these 85 households, with 132 (55%) of them were confirmed with SARS-CoV-2 infection and 57 (24%) cases were negative in RT-PCR assays.

The researchers found there was a secondary transmission rate of 30% and this increased to 50% for households with 2 contacts, they compared this to previous studies on other two coronavirus pneumonia epidemics which reported secondary transmission rates among household contacts of 5% for Middle East respiratory syndrome coronavirus (MERS-CoV) and 10.2% for severe acute respiratory syndrome coronavirus (SARS-CoV). The researchers concluded this demonstrated the need for stringent quarantining of household contacts.

This research did have some limitations. The researchers did not clarify what criteria they were using to guide testing nor did they quantify exactly how long they followed up household contacts for. It reproduces similar studies which have found significantly lower attack rates in children.

Zhu Y, Bloxham CJ, Hulme KD, et al. Children are unlikely to have been the primary source of household SARS-CoV-2 infections. medRxiv 2020;:2020.03.26.20044826. doi:10.1101/2020.03.26.20044826

A pre-print, the information should be treated with caution until it has undergone peer review.

This study includes a review of symptom frequency in children, but most interestingly examines available case series in the literature of family clusters of COVID-19 to determine what contribution is made of children to the chain of transmission. Clusters were taken from China, Singapore, the USA, South Korea and Vietnam, totalling 31 household transmission clusters. Of these cases, only 3 (9.7%) had a child as the index case. Considering a worst case scenario (whereby ALL infected children were the index case in their family and had been mislabelled as a secondary in some studies), still children would only account for 6/28 (21%) infection clusters. They compare this to the H5N1 epidemic where children were the index case in 54% of household clusters. This provides further evidence that children appear to have a fairly limited role in the transmission of COVID-19, which has implications for non-pharmaceutical interventions such as school closures.

Bi Q, Wu Y, Mei S, et al. Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study, Lancet Infectious Disease, April 27th 2020, https://doi.org/10.1016/S1473-3099(20)30287-5

This was a fairly impressive study looking at contact tracing of 1286 contacts of 391 patients with COVID-19. Only 20 (5.1%) of the initial 391 cases were children, of which 2/3 were asymptomatic. They discovered a secondary attack rate of 15% for household contacts and 9.6% overall. The most important finding is that the rate of infection in children <10 years (7.4%) was similar to the population average (7.9%). The findings of this study suggested that children were becoming infected at a similar rate to adults but were much less likely to be asymptomatic. As no repeat testing was performed, it is unclear if these children were truly asymptomatic, or presymptomatic. Subsequent studies have consistently shown lower attack rates in children, and the reason for this discrepancy is unknown.

Top Epidemiological Papers on Disease Burden

Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al. Prevalence of SARSCoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet 2020. https://doi.org/10.1016/ S0140-6736(20)31483-5

Introduction: Spain was one of the countries in Europe hit hardest by the Covid 19 pandemic. These are the first wave results from the Seroepidemiological Survey of SARS-CoV-2 Virus Infection in Spain (Encuesta Seroepidemiológica de la Infección por el Virus SARS-CoV-2 en España; ENE-COVID). This is an epidemiological study with an aim to estimate the sero-prevalence of Sars Cov2 in Spain through symptom checking, point of care antibody testing, and serology.

Methods: 35 883 households across Spain were selected through stratified two stage sampling and invited to take part. This is the result of the first wave of sampling which was conducted from April 27 to May 11, 2020. Participants within selected households answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors. “Asymptomatic” was no symptoms, “paucisymptomatic” (1–2 symptoms without anosmia or ageusia), and symptomatic (anosmia or ageusia, or at least three symptoms among fever; chills; severe tiredness; sore throat; cough; shortness of breath; headache; or nausea, vomiting, or diarrhoea). Participants were contacted by phone and then invited to go to local primary care centre for testing or have a home visit. All participants were offered point-of-care antibody test (Orient Gene Biotech COVID-19 IgG/IgM Rapid Test Cassette; Zhejiang Orient GeneBiotech, Zhejiang, China, SARS-CoV-2 spike protein) and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay (SARS-CoV-2 IgG for use with ARCHITECT; Abbott Laboratories, Abbott Park, IL, USA, SARS-CoV-2 nucleoprotein). Sensitivity of the test was deemed any test positive (point of care/ serum), with specificity both tests positive. Of note Spain was under lockdown at the time of this study.

Results: Of 95 699 eligible individuals, 66 805 study participants took part, with 61 075 receiving point of care testing and 51 958 the immunoassay. Overall seroprevalence was 5.0% (CI 4.7–5.4) by the point-of-care test and 4.6% (CI 4.3–5.0) by immunoassay. In 7 provinces in the central part of Spain, including Madrid, seroprevalence was greater than 10% by both methods. Seroprevalence was similar for females and males. Seroprevalence was lower in the oldest age groups (≥85 years) compared with other adults. With regards occupation it was highest in health-care workers, 10.2% (7.9 – 13) than in other occupations these results were supported by the immunoassay.
In those who reported a contact with a confirmed case, seroprevalence was greater in those
who had a confirmed case in their household (range 31.4% to 37.4% between the two tests), in their workplace 9.9–10.6%, among their non-cohabitating family members and friends 13.2–13.7%, or among their caregivers and cleaning staff 12.4–13.5%

Symptoms: For both tests seroprevalence was highest in those with a confirmed Sars-CoV-2 PCR more than 14 days before testing (88·6–90·1%). Among those with a positive test, the proportion of individuals who reported anosmia or three or more symptoms compatible with COVID-19 was 49.1%
for the point-of-care test and 54. 2% for the immunoassay. In 32.7% (CI 30.2–35.4) of point-of-care test and 28.5% (CI 25.6–31.6) participants were asymptomatic.

Results in children: 11,422 children (<19 years) had a point of care test, with 6,527 also having an immunoassay. The proportion of paediatric participants having serology was lower than that of adults, though not unsurprising given the need for extra phlebotomy. Overall seroprevalence for those < 19 years was 3·4% (2·9–3·9) for point of care testing, and 6527 3·8% (3·2–4·6) for immunoassay.
Looking at specific age ranges for point-of-care test seroprevalence was < 1 year, 1.1% (0.3–3.5): 1- 4 years 2.1 %(1.3–3.4); 5 – 9 years 3.1% (2.2–4.2); 10-14 years 4.0% (3.1–5.0); and 15 – 19 years, 3.7% (2.9–4.8). The same pattern but slightly higher percentages were seen with immunoassay <1 year 0.0% (0.0–11.9); 1- 5 years 3.5% (1.7–6.8): 5 – 9 years 3.6% (2.3–5.7); 10 – 14 years 4.1% (3.1–5.5); and 15 – 19 years 3.8 (2.8–5.0). This paper did not give data on symptoms separately in age groups.

Conclusion: Population seroprevalence is lower than expected in areas of high endemic SARS-CoV-2, and is lowest in children. Close contact with people, particularly in the same household increases viral transmission. Over 30% of those with seroprevalence were asymptomatic. This highlights the importance of rapid identification and isolation with those with confirmed SARS-CoV-2, however isolation and separation for other household members may not be realistic in poorer or urban areas.

Gabriele Pagani, Federico Conti, Andrea Giacomelli et al, Seroprevalence of SARS-CoV-2 IgG significantly varies with age: results from a mass population screening (SARS-2-SCREEN-CdA). medRxiv June 24th 2020, https://doi.org/10.1101/2020.06.24.20138875

In this brief report of a SARS-CoV-2 serosurvey from Castiglione D’Adda in Italy, the results of a logistic regression model based on the random sampling of 509 subjects from the region (total population 4550) following the peak of transmission in the region are detailed. Prior to this serosurvey testing was limited to severely symptomatic cases.

The exact number of children included is not provided but the age related prevalence was significantly lower in children – 9.1% (0-5yo), 10.1% (5-10yo), 11.2% (10-15yo), 12.5% (15-20yo) – compared with overall seroprevalence of 22.6%.

The methodological details are limited in this report but the data are consistent with serosurvey data from elsewehere in Europe suggesting that children are less susceptible to SARS-CoV-2 infection compared with adults. 

Stringhini, S., A. Wisniak, G. Piumatti, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.” Lancet. June 11th 2020, https://doi.org/10.1016/S0140-6736(20)31304-0

Methods: This study takes a representative population sample from Geneva, Switzerland (already identified by a pre-existing health study) and invites them to attend blood tests looking for antibodies against the SARS-CoV-2 virus over time. The purpose is to monitor what proportion of the population are infected and see how it changes during the course of the pandemic (5 weeks in this study). Participants could only attend once, and were invited by email with a telephone follow up. The only exclusion criteria was living in a prison or care home. Antibodies were measured using a commercial assay (ELISA for S1 domain of spike protein IgG). They performed in house validation of the assay using a couple of techniques (the results of the immunofluorescence validation were factored in to the sensitivity analysis of the model used later in the study)

Analysis: The statistical analysis performed was a Bayesian regression which had a random effect for households and factored in age/sex as well as the test performance to extrapolate the sample results on to population estimates of seropositivity. They calculated the relative risk (RR) of age groups having been infected with age 20 – 49yrs as the reference group.

Results: 5492 people were invited and the final analysis included 2766 people (3426 of the rest were non-responders or awaiting an appointment). 455 children participated. Seropositivity in the population increased between weeks 1 and 2 (4.8% to 8.5%), with no statistically significant difference thereafter (final estimate 10.8%).

The most significant result is that of the children<10yrs in the study, only 1/115 children tested positive (although a further 8 had an equivocal result). This made the RR of infection for children <10yrs 0.32 (0.11 – 0.63) compared to adults aged 20 – 49yrs. There was no statistically significant difference between children aged 10 – 19 yrs (OR 0.86, 0.57–1.22). Another important factor was strong association between household contacts (unsurprisingly). This is important, as there were also lower rates of infection seen in the elderly (>65 yrs OR 0.5, 0.28–0.78) but only 3% of these participants had a positive household contact. Of the 123 children aged 5-9yrs, 17% of them had a positive household contact.

This study adds to a growing body of evidence that younger children (particularly those under 10yrs) may be less susceptible to acquiring infection than adults. The RR of 0.3 despite a relatively high proportion having positive household contacts is in contrast to the elderly, whose low infectivity rate may be explained by reduces exposure (additionally, a relatively high number of elderly will have been hospitalised or passed away from infection during the study, meaning they will not be counted in these statistics).

Considerations: Schools were closed for the duration of this study period which will have reduced community exposure of young children. In addition, almost all validation of antibody assays has been in adults so far. There were a notable number of equivocal results in the young children, but the significance of this is unclear. The results are however consistent with the largest seroprevalence study to date, from Spain.

Lavezzo, E., Franchin, E., Ciavarella, C. et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature (2020). https://doi.org/10.1038/s41586-020-2488-1

This paper outlines the strategy of a small town in Italy which immediately shutdown for 14 days following their first death from COVID-19 on Feb 21st 2020. They subsequently screened 86% of the population for SARS-CoV-2 using nasopharyngeal swabs, then screened again 2 weeks later (71.5% of the population).

At the start of the lockdown 2.6% (95% CI 2.1 – 3.3%) of the population tested positive, but 0 of 217 children aged 0 – 10 tested positive (0%), and only 3/250 aged 11 – 20 (1.2%) tested positive. By the end of the lockdown, 0/157 (0%) children aged 0 – 10 tested positive, and 2/210 (1%) children aged 11- 20 tested positive. Many of the children aged 0 -10 lived with infected individuals. They also noted >40% of people who tested positive were asymptomatic. They note a significant number of infections appeared to have come from asymptomatic individuals during contact tracing. They also note these asymptomatic individuals never developed symptoms, and had similar viral loads to symptomatic patients (as determined by the cycle threshold from RT-PCR). It should be noted the definition of symptoms was restricted to ECDC definitions of COVID-19 related symptoms, and given the wide variation of non-classic symptoms which have been described (rashes, malaise, joint aches, rhinorroea, GI symptoms etc), this likely significantly undercounts the number of patients who truly developed symptoms.

This study has relatively small numbers, but again appears to provide evidence for several important features of paediatric infection: primarily that children appear significantly less likely to become infected than adults. It presents evidence for asymptomatic transmission, and against the theory of viral load correlation with symptom burden.

Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, et al. Spread of SARS-CoV-2 in the Icelandic Population. N Engl J Med, Published April 14th 2020, doi:10.1056/NEJMoa2006100.

This study describes the entry and spread of SARS-CoV-2 through Iceland. Importantly, this is the first epidemiological report to include SARS-CoV-2 screening of the general population and likely represents the most complete national epidemiological data published to date.

Study design: This report includes all confirmed SARS-CoV-2 infections in Iceland identified through either: targeted testing (January 31st to March 31st 2020) – 9199 predominantly symptomatic patients with travel to a high risk country or contact with a confirmed case; population screening (March 13th to April 1st 2020) – 13080 volunteers screened from the general population (without high-risk travel or contact with a confirmed case). Most patients in the population screening cohort were asymptomatic, with a minority with predominantly mild URTI symptoms. A subsequent period of random population screening from April 1st-4th excluded children.

SARS-CoV-2 real-time PCR was performed on combined oropharyngeal and nasopharyngeal samples. All confirmed cases were isolated and close contacts placed in quarantine for 14 days.

Key paediatric findings – there is comparative data provided on the 1412 children <10 years of age tested: of 564 children <10 years old tested in the targeted testing cohort, 6.7% (38) were positive – compared with 13.7% of persons >10 years old; of 848 children <10 years old tested in the population screening cohort, 0% (0) were positive – compared with 0.8% of persons >10 years old.

Details on severity of infection, hospitalisation rates and age specific symptom profiles are not included.

Discussion: The first SARS-CoV-2 infection in Iceland was confirmed on 28th February 2020. The dynamics of new cases has transitioned from imported infections initially to ongoing community spread. To date just over 0.5% of the population have had confirmed infection. Whilst physical distancing measures have been put into place including limiting gatherings to a maximum of 20 people, elementary schools have remained open. Iceland has amongst the highest national rates of SARS-CoV-2 testing per capita, with 6% of the population tested as described here. As a result this report provides the most accurate and complete national epidemiological data published to date.

The lower rate of positive tests in childen <10 year olds adds support the hypothesis that children are less susceptible to SARS-CoV-2 infection compared to adults. Similarly the lack of positive tests amongst >800 children screened goes against the theory that the low reported rates of COVID-19 in children are due to a large number of undocumented/asymptomatic paediatric cases. This finding, particularly, has important implications in decision-making around patient flow and isolation in general paediatric care, suggesting that routine testing and isolation of asymptomatic children may be of low yield in similar settings. Clearly a single PCR screening test at one time point has an insufficient negative predictive value to exclude infection. As such, serological studies will be important in providing a clearer picture of the extent of SARS-CoV-2 infection in children.

Conclusion: Children under 10 yo appear to be less likely to develop SARSCoV-2 infection compared with people >10 yo. In settings with moderate levels of SARS-CoV-2 infection (0.5% population with confirmed infection in this setting), screening of asymptomatic children without overseas travel or contact with a known case is of very low yield.

Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020. MMWR Morb Mortal Wkly Rep. ePub: 6 April 2020. DOI: http://dx.doi. org/10.15585/mmwr.mm6914e4

This is the first USA CDC report of COVID-19 looking specifically at children, examining confirmed cases nationally between FEbruary 12th and April 2nd. Due to the extremely disparate nature of public health reporting in the USA, the data quality and availability for this report is highly variable. There is no information as to the basis on which tests were performed, whether for presentation to hospital, symptomology or due to contact tracing. This cohort is therefore likely extremely heterogeneous. Of the nearly 150,000 confirmed cases in the US at this time, 2,572 (1.7%) were in children. New York City had 33% of paediatric cases. The median age was 11y and males account for 57%. Nearly 33% of cases were in children aged 15 – 17yrs, 15% in children <1y, 11% in children ages 1 – 4y and 15% in children 5 – 9y. 91% of cases had xposure to a known COVID-19 case.

Data on signs/symptoms was only available for 11% of cases. Fever, cough OR shortness of breath were present in 73% of cases, with fever in 56%, cough in 54%, shortness of breath in 13%, rhinorrhoea 7.2%, sore throat 24%, vomiting 11% and diarrhoea 13%. They have not reported on “asymptomatic” cases due to incomplete reporting on symptoms.CU admission was documented for 2% of cases. Hospitalisation was most common in infants (62%), with little difference between other age groups in regards to hospitalisation or ICU admission. From low numbers infants id not appear significantly more likely to be admitted to ICU. Underlying conditions were present in 23% of cases, most commonly respiratory (such as asthma), followed by cardiac conditions and immunosuppression. There are 3 deaths reported, but review is ongoing to determine whether COVID-19 was the cause. This patchy data from the US is useful as it closely resembles data from Chinese cohorts of children in regards to low frequency of severity and adverse outcomes. It confirms available data suggesting lower frequency of common symptoms in children as compared to adults.

Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China. Pediatrics 2020:e20200702. doi:10.1542/peds.2020-0702

This landmark paper is a retrospective epidemiological study of 2143 pediatric patients with suspected or confirmed COVID-19 (Jan 16 – Feb 8 2020) from in and around Hubei province in China. Confirmed cases were diagnosed by PCR of NPA or blood or genetic sequencing from the respiratory tract or blood highly homologous with SARS-CoV-2. To be a suspected case you needed to be high risk (based on community exposure) with any 2 of: fever, respiratory symptoms or diarrhoea/vomiting; normal or lower white cell count +/- raised CRP; abnormal CXR. If you were medium/low risk for community exposure, you could still be a suspected case if you met any 2 of the above criteria and had other respiratory viruses excluded. Patients were classed according to severity.

There were 731 (34.1%) laboratory-confirmed and 1412 (65.9%) suspected cases. The median age was 7 years. There were 94 (4.4%) asymptomatic, 1091 (50.9%) mild and 831 (38.8%) moderate, accounting for 94.1% of all cases. Of note, the youngest patients (under 1yr) had the highest proportion of severe and critical illness (10.6%). However, this group also had the highest proportion of “suspected” disease (293/379) – of which we do not know how many had an infection with RSV, HPMV or Flu. This was peak bronchiolitis season. There was one death in a 14yr old boy, for which there are no clinical details available. The highest proportion of asymptomatic cases was in the 6-10yr olds (31.9%), for whom there was no recorded critical illness. Critical illness was uncommon in general (0.6% of all cases). The median time from illness onset to diagnosis was 2 days. Chest imaging was emphasized in delineating the severity (CXR and CT). There are also  some interesting epidemiology graphs which essentially map to the well-described adult prevalence of disease and demonstrate Hubei as the epicentre.

This large cohort study provides reassuring data about the severity of illness of COVID-19 in children. There is an indication that younger infants may be most likely to be affected most severely, however, this cohort is highly likely to contain children with normal, severe, winter viral infections such as bronchiolitis. Critical illness was extremely rare.

Top 10 PIMS-TS / MIS-C Papers

Felstein, L.R. et al (2020) Multisystem Inflammatory Syndrome in U.S. Children and Adolescents, NEJM. epub 29 June 2020, DOI:10.1056/NEJMoa2021680.

This retrospective and prospective multi-centre cohort study from 53 participating hospitals in 26 states looked at 234 patients under 21 years of age that met criteria for multi system inflammatory syndrome in children (MIS-C), between March 15 and May 20th

The median age of the patients was 8.3years old and 62% (115) were male. Fifty one patients (27%) had an underlying medical condition. In terms of confirmation of SARS_CoV-2 infection – 70% were positive for RT-PCR and/or antibody testing.  Of a small subgroup of 14 patients with Covid-19 symptoms before MIS-C, the median time between Covid-19 symptom to MIS-C was 25 days (6-51 days).
Criteria for MIS-C were based on CDC guidelines (in brief, requiring hospitalisation, at least two systems involved, fever of at least 24 hours and either lab confirmed SARS_CoV-2 infection (via RT-PCR or antibody testing) or an epidemiological link to a person with Covid-19 within 4 weeks before onset of symptoms).
Although MIS-C criteria was at least 2 system involvement, 71% had involvement of four organ systems or more. The most frequent systems in order were gastrointestinal (92%) followed by cardiovascular (80%), haematological (76%) and respiratory (70%). Blood changes observed included lymphocytopaenia in 80% of patients, and an elevated CRP in 91%.
Looking at similarity and overlap with Kawasaki disease, 40% of patients had either fever for at least 5 days and 4-5 of Kawasaki’s disease-like features or 2-3 Kawasaki’s disease-like features with additional lab or echocardiographic findings. Common symptoms similar to Kawasaki disease bilateral conjunctival infection in 103 (55%), oral mucosal changes in 78 (42%), peripheral extremity change in 69 (37%), rash in 110 (59%), cervical lymphadenoapthy (>1.5cm diameter) in 18 (10%). Differences between MIS-C and Kawasaki’s disease groups include an older age group and a different cardiovascular involvement (more likely myocardial dysfunction) in MIS-C patients.
The majority of patients required ICU admission (n=148, 80%) with one in five patients needing invasive mechanical ventilation. Eight patients received ECMO support. Treatment included IVIG in 77% and systemic glucocorticoids in 49%. There were four deaths (two of which had received ECMO). At the time of writing the paper, 70% of patients had fully recovered with 28% still in hospital.

Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. DOI: 10.1056/NEJMoa2021756.

This is a case series of 99 children (<21 years of age) from New York State with multisystem inflammatory syndrome in children (MIS-C). Of note some of these cases have been reported in small series (Cheung et al JAMA 2020). New York State Department of Health required hospitals that provide paediatric medical or surgical care to report potential cases of Kawasaki’s disease, toxic shock syndrome, or myocarditis or who were suspected to have MIS-C among persons younger than 21 years of age admitted since March 1, 2020, through the NYSDOH Health Emergency Response Data System. The clinical and laboratory characteristics of these reports were studied. Between March 1 and May 10 2020 191 cases were reported of which 95 met the criteria for MIS-C and 4 further were suspected.

Case definition: Confirmed cases were defined by the presence of both clinical and laboratory criteria. Suspected cases had clinical and epidemiological criteria.

Clinical criteria were children <21 years of age with fever and needing hospitalisation with either; 1 or more of hypotension or shock, features of severe cardiac illness, or other severe organ failure. Or 2 or more of; maculopapular rash, non-purulent conjunctivitis, mucocutaneous inflammatory signs or acute GI symptoms with an absence of other cause.

Laboratory criteria:

1. General Criteria; Two or more of raised inflammatory markers and

2. Either positive SARS CoV2 RNA at time of presentation or within 4 weeks or detection of specific antibody.

Epidemiological criteria: In 6 weeks prior to exposure close contact with a person with confirmed or clinically consistent Sars CoV2 infection or travel to or resident in an area with ongoing community transmission. 

Baseline characteristics: 53 (54%) were male. Age range was 0-5 years (31%), 6 to 12 year (42%) and  13 to 20 years (26%). 78 patients had data on race with 29 (37%) were white, 31 (40%) were black, 4 (5%) were Asian, and 14 (18%) were of other races. 36 patients had a preexisting condition, 29 had obesity.  24  (24%) had a Covid-19–compatible illness a median of 21 days (interquartile range, 10 to 31) before hospitalization, 38 (38%) had exposure to a person with confirmed Covid-19, and 22 (22%) had direct contact with a person who had clinical Covid 19.

Symptoms : Described in detail in the study. Prevalence of dermatologic symptoms was highest among children 0 to 5 years of age, and the prevalence of myocarditis (diagnoses and clinical) was highest among the adolescents.

Treatment : Of 99 patients, 79 were treated in ICU. 69 had IVIG, 63 received systemic glucocorticoids, 48  received both systemic glucocorticoids and IVIG. 9 patients had coronary aneurysm

Outcome : As of May 15, a total of 76 patients (77%) had been discharged and 21 (21%) were still hospitalised. Unfortunately 2 patients died in the hospital. Both were intubated and ventilated, once received ECMO. Neither received IVIG, systemic glucocorticoids, or immunomodulators.

Kaushik, S., S. I. Aydin, K. R. Derespina et al, “Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multi-institutional Study from New York City.” J Pediatr.  https://doi.org/10.1016/j.jpeds.2020.06.045

This retrospective observational study details clinical characteristics, therapies and outcomes of a multicentre cohort of 33 children with Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 admitted to PICUs at 3 tertiary care children’s hospitals in New York City between 23 April and 23 May 2020.

Study design:  Patients aged 1 month to 21 years admitted to 3 NYC PICUs (at Children’s Hospital at Montefiore, Mount Sinai Kravis Children’s Hospital and Jacobi Medical Center) with confirmed SARS-CoV-2 infection (positive nasopharyngeal swab RT-PCR or antibody assay) meeting criteria for MIS-C (US CDC case definition, formalised on 14 May 2020, used: age < 21 yrs presenting with fever, laboratory evidence of inflammation and evidence of clinically severe illness requiring hospitalisation, with ³ 2 organ involvement, plus no alternative plausible diagnosis, plus positive for current/recent SARS-CoV-2 infection or COVID-19 exposure within 4 wks prior to onset of symptoms).  During the study period there were additional suspected patients with similar presentations and management without confirmed SARS-CoV-2 infection/exposure who were excluded; only cases with confirmed infection by RT-PCR/antibody assay were included. 

Study population:  33 children met the inclusion criteria at the 3 centres.  Median age 10 years (IQR 6-13), 20/33 male (61%), median BMI 18.6 kg/m2 (IQR 15.9-22.9), 2/33 obese (6%, BMI > 30 kg/m2).  15/33 Hispanic/Latino (45%), 13/33 black (39%), 3/33 white (9%), 1/33 Asian (3%), 1/33 other (3%).  16/33 comorbidities (48%) (most common comorbidity was asthma).  8/33 (24%) had had contact with an ill person, 5/33 (15%) had had contact with a confirmed COVID-19 case.

Clinical features:  Fever 31/33 (94%), mucocutaneous involvement 7/33 (21%), conjunctivitis 12/33 (36%), rash 14/33 (42%), abdominal pain 21/33 (64%), nausea/vomiting 23/33 (70%), diarrhoea 16/33 (48%), dyspnoea 11/33 (33%), dizziness 3/33 (9%).  Duration of symptoms prior to admission 4.5 days (IQR 3-6).  21/33 (64%) were hypotensive on admission.

Admission blood results:  Medians (IQR in brackets): WBC 11,000/mL (8450-14,400), lymphocytes 1,100/mL (600-1,300), CRP 250 mg/L (156-302), ESR 53 mm/hr (28-77), procalcitonin 5.4 ng/mL (1.8-16.7), ferritin 568 ng/mL (340-954), fibrinogen 627 mg/dL (455-782), D-dimer 3.7 mg/mL FEU (2.4-5.1), BNP 388 pg/mL (75-1086), pro-BNP 4328 pg/mL (2117-13370), troponin T 0.08 ng/mL (0.02-0.17), IL-6 200 pg/mL (56.4-330), IL-8 41.7 pg/mL (25.1-54.4), creatinine 0.6 mg/dL (0.4-1.1).

CXRs:  Cardiomegaly 10/33 (30%), focal or bilateral pulmonary opacities 11/33 (33%).

Echocardiograms:  Performed in 32/33 (97%).  Pericardial effusion 15/32 (47%), median LVEF 47% (IQR 40-53).  LVEF < 30% 4/32 (13%), LVEF 30-50% 17/32 (53%), LVEF > 50% 11/32 (34%).  24/32 had a second echocardiogram prior to discharge: of those with initial LVEF < 50%, 20/21 (95%) had recovery of ventricular function with normal EF.  Median pre-discharge LVEF 58% (IQR 55-62).  A detailed table is supplied for the 21 patients with LVEF < 50%, including BNP/troponin levels, drug treatment by patient and the 8/21 who had prominent coronary arteries on echo.

Treatment in PICU:  18/33 received IVIg (55%), 17/33 corticosteroids (52%), 12/33 tocilizumab (35%), 7/33 remdesivir (21%), 4/33 Anakinra (12%), convalescent plasma therapy 1/33 (3%), 17/33 vasopressor/inotropes (52%) (median duration of vasopressor use 72 hrs (IQR 48-110), norepinephrine most commonly used agent), 8/33 aspirin (24%), 21/33 diuretics (64%).  Anticoagulation was used in all patients:  prophylactic dose enoxaparin 5/33 (15%), therapeutic dose enoxaparin 27/33 (82%), therapeutic dose unfractionated heparin 1/33 (3%).  Empiric antibiotic coverage for < 48 hrs in 14/33 (42%) and > 48 hrs in 15/33 (45%).  5/33 (15%) required invasive mechanical ventilation.  2/33 (6%) required mechanical circulatory support: 1 ECMO (5-yr-old) and 1 intra-aortic balloon pump (20-yr-old).

Outcomes:  32/33 (97%) patients were discharged home with median PICU stay of 4.7 days (IQR 4-8) and hospital stay of 7.8 days (IQR 6-10).  1/33 (3%) died (ischaemic brain infarction with subarachnoid haemorrhage on day 6 of ECMO).

The authors conclude that rapid, complete clinical and myocardial recovery was almost universal in their study.  They hypothesise that this novel COVID-19 MIS-C is predominantly an antibody-mediated or other immune cell-mediated cytokine storm, with some contribution from direct myocardial injury.  They note the lower morbidity in their cohort relative to recent European studies

Capone, C. A., A. Subramony, T. Sweberg, J. et al. “Characteristics, Cardiac involvement, and Outcomes of Multisystem Inflammatory Disease of Childhood (MIS-C) Associated with SARS-CoV-2 Infection.” J Pediatr. https://dx.doi.org/10.1016%2Fj.jpeds.2020.06.044

This is a single-centre retrospective case series of 33 sequentially hospitalized febrile paediatric patients with CDC case definition for Multisystem Inflammatory Disease of Childhood (MIS-C) and WHO criteria for Multisystem Inflammatory Syndrome (MIS) admitted to Cohen Children’s Medical Center, Queens, NY from April 17, 2020 through May 13, 2020. All cases were positive for SARS-CoV-2 by detection of serum antibodies or nucleic acid from a nasopharyngeal specimen. Patients with COVID-like lower respiratory tract involvement were excluded. The peak of hospitalizations occurred approximately five weeks after the peak of hospitalizations with acute COVID-19. Patients were predominantly male (20, 61%) and non-Hispanic (24, 73%) with a median age of 8.6 years (IQR 5.5-12.6). Most patients were previously healthy but a higher proportion were overweight (2,6%) or obese (12, 39%) compared with the regional childhood obesity rate of 18%. 

Patients presented with a median of 4 days (IQR 3-5) of fever and almost all (32, 97%) had gastrointestinal symptoms (including diarrhoea, vomiting and abdominal pain) as well as other organ system involvement. 21 (64%) patients fulfilled complete criteria for KD and most patients with complete KD criteria, had shock (16, 76%). 

All patients had negative blood cultures and multiplex nucleic acid amplification test for multiple respiratory pathogens except 1 patient in whom influenza virus detected. 26 (79%) patients needed intensive care and 6 (18%) required mechanical ventilation. 58% had myocardial dysfunction and 76% required vasoactive medications. Coronary artery aneurysm was identified in 5 (15%) and dilation was detected in 3 (9%) patients. 

All patients were treated with IVIG, 88% received aspirin, and 70% were given a corticosteroid and 42% were given Enoxaparin. 24% of patients exhibited a partial response to these treatments and received a biologic modifying medication (Anakinra, Tocilizumab, Infliximab). Most patients demonstrated rapid clinical improvement. No patients died. Median length of hospital stay was 4 days (IQR 4, 8). At hospital discharge, mild cardiac dysfunction was still present in 9 of 19 patients. 

This case series shares similarities with smaller international case series reported as Kawasaki-like disease and hyperinflammatory shock syndrome. In all these studies, most patients had antibodies against SARS-COV2 virus, suggestive of a post-infectious, immunologically mediated pathophysiology. The authors suggest that the latent period between the peak of paediatric cases of COVID-19 and MIS-C suggests that MIS-C has a post-infectious, possibly immunologically mediated pathogenesis.

Despite clinical similarities with KD, differences include the predominance of gastrointestinal symptoms, an older age range (8.6 year in MIS-C patients compared with a median age of 2.5 years for patients with KD), markedly elevated inflammatory markers, higher proportion of patients with shock and/or impaired cardiac function (76%) than in other KD studies (less than 3% shock reported), and the lack of thrombotic events in the case series patients. This suggests that MIS-C may be a syndrome distinct from KD. Acute COVID-19 with “cytokine storm” further complicates differentiation of these presentations.  

Further study is needed to shed light on the pathophysiology, treatment options, and outcomes of MIS-C.

Whittaker, E., A. Bamford, J. Kenny, et al. “Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2.” Jama. doi:10.1001/jama.2020.10369

This paper provides a detailed description of the clinical and laboratory features of 58 children diagnosed with PIMS-TS from 8 hospitals in England between March 23rd and May 16th 2020. All children fulfilling the UK, WHO or CDC criteria for PIMS-TS / MIS-C were included; evidence of SARS-CoV-2 infection was not required for inclusion. Features of this group were compared with previous data from children with Kawasaki Disease (KD), KD shock syndrome (KDSS) and toxic shock syndrome (TSS).

Of the 58 patients, 45 (78%) had evidence of SARS-CoV-2 infection (RT-PCR (15) and or IgG (40)). 33 (57%) were female. 22 (38%) were of black race, 18 (31%) asian. The majority were previously well; only 7 had co-morbidities (3 with asthma, 1 epilepsy, 1 neuro-disability, 1 sickle cell trait, 1 alopecia)

All patients had fever (range 3-19 days). Gastrointestinal symptoms were common (abdominal pain (53%), diarrhoea (52%), vomiting (45%)) whilst respiratory symptoms were relatively uncommon (21%) and 15 (26%) had headache. 

Only 13 (22%) of patients fulfilled criteria for KD; 8 (14%) had coronary artery aneurysm, 26 (45%) conjunctival injection, 30 (52%) rash, 17 (29%) mucous membrane changes, 9 (16%) lymphadenopathy, and 9 (16%) swollen hands and feet. Half of patients developed shock. 

Laboratory findings were consistent with marked inflammation (mean CRP 229 mg/L (IQR 156-338), ferritin 610 μg/L (359-1280), fibrinogen 5.7 g/L (4.4-7), D-dimer 3578 ng/mL (2085-8235)) with neutrophilia (13 x 10^9 (10-19)). Evidence of myocardial injury was common with troponin elevated in 34/50 (68%) and NT ProBNP in 24/29 (83%). Low haemaglobin (92 g/L (83-103)), lymphocyte (0.8 x 10^9 (0.5-1.5) and platelet levels (151 x 10^9 (104-210)) were also observed. 

Half of patients were admitted to a critical care unit; 25 (43%) requiring mechanical ventilation, 27 (47%) inotropes and 3 (5%) ECMO. A range of treatments were given including IVIG (71%), steroids (64%), anakinra (5%) and infliximab (14%). 13 (22%) recovered without immunomodulatory treatment, whilst 60% received >/= 2 and  16% >/= 3 agents. To the last date of follow up only one child had passed away. 

The authors suggest three clinical patterns of PIMS-TS based on the patients included in this series: 

  (1) persistent fever and elevated inflammatory markers (without KD, shock or organ failure) – 23 patients here

  (2) fever and shock, often with myocardial dysfunction – 29 patients 

  (3) children fulfilling criteria for KD – 7 patients (13 if aneurysm included in criteria). 

Compared with children with KD, KDSS and TSS, children with PIMS-TS were older (median age 9 (IQR 5.7-14)) with higher CRP and lower haemaglobin. Compared with those with KD and KDSS, PIMS-TS patients in this series had higher neutrophil count, ferritin and troponin with lower platelet and lymphocyte counts. Compared with pre-COVID-KD cases children with PIMS-TS KD were older and had higher markers of inflammation and myocardial injury. 

This is the most detailed clinical report of PIMS-TS to date. The findings here demonstrate a syndrome with a wide spectrum of signs, symptoms and severity with some overlap with KD, KDSS and TSS. PIMS-TS is characterised by marked inflammation with myocardial dysfunction and often shock necessitating ICU admission for inotropic support, mechanical ventilation and, in a small number of patients, ECMO. Treatment with immunomodulatory agents similar to those used in KD has been employed and only one death had occurred at the time of the report. Differences in clinical and laboratory profile compared with KD, KDSS and TSS, suggests= that PIMS-TS is a unique entity, potentially arising from a maladaptive acquired immune response to SARS-CoV-2 infection. 

Cheung EW, Zachariah P, Gorelik M, et al. Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City. JAMA. Published online June 08, 2020. doi:10.1001/jama.2020.10374

This is a case series of 17 children, admitted to a hospital in New York city, between April 18th and May 5th 2020 with features of Multisystem Inflammatory Syndrome Related to COVID-19.

Patients included in this series were i. less than 21 years old, ii. presented with a clinical syndrome characterized by prolonged fever, systemic inflammation, shock, end-organ dysfunction, or symptoms reminiscent of Kawasaki Disease or Toxic Shock Syndrome and iii. had evidence of recent (SARS-CoV-2) infection. The baseline characteristics of these children were; median age 8 years (1.8-16), 8 were male (47%); 12 were classified white (70.1%), 4 black (23.5%), 1 Asian (5.9%).

Presentation: All had fever, with median duration of 5 days. 14/17 had GI symptoms. Mucocutaneous findings were common (12 rash, 11 conjunctivitis, 9 lip redness/swelling). 3 were hypoxic at presentation, and 13 had shock. 8 met criteria for KD and 5 for incomplete KD.

Investigations: 8 patients tested positive for SARS-CoV-2 by RT-PCR and 9 by serology.

Xrays: 14 had abnormal chest radiograph findings, most commonly bilateral, interstitial opacities.

Bloods: mean values for a wide variety of investigations shown in paper in table 2. Mainly group were lymphopenic with raised ferritin, d dimers, clotting times, and troponin.

Cardiac: ECG of 16 patients showed nonspecific ST/T-wave abnormalities in 10 and attenuated QRS voltage in 1. Dysrhythmias were noted in 3. Admission echos showed normal to mildly decreased left ventricular function in 11,  or moderate or more ventricular dysfunction in 6.  All patients had normal coronary arteries by measurement, though coronary arteries were described as prominent or echogenic in 7. However one patient (aged 4 years) developed a medium-sized aneurysm (z score, 5.2) of the left anterior descending coronary artery. This patient presented with fever, diarrhea, and shock, with no additional features of KD.

Treatment: 15/17 patients were admitted to PICU; vasoactive support was required in 10. Treatment was varied, 14 received steroids (either methylprednisone or hydrocortisone, prednisolone numbers of each not given). 13/17 received IVIG including 3 patients who did not receive steroids and 8 who met criteria for KD. One patient received tocilizumab.

Outcome: All patients discharged home with no fatalities.

Comparison with other PIMS TS cohorts:

Reports of hyperinflammatory syndrome in children during the Sars CoV2 outbreak has been reported in France, Italy, UK and US. (see https://dontforgetthebubbles.com/pims-ts/)

This cohort used the CDC definition, which is broadly similar to RCPCH and WHO, though in the US paediatrics < 21 years of age.

Like the other cohorts, the age range is older than typically seen in Kawasaki Disease. Fever and GI symptoms are very common. Mucocutaneous signs were also common. Children presented very unwell, with many needing PICU care (88% in this study). Treatment used included IVIG and steroids.

Unlike other cohorts where black ethnicity was pronounced, 70% of this cohort was classified as white. It would be useful to know the demographic breakdown of the local paediatric population who attend this hospital.

Belot, A., D. Antona, S. Renolleau, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.” Euro Surveill 25(22). June 4th 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.22.2001010

The first epidemiological surveillance study of SARS-CoV-2-related paediatric inflammatory multisystem syndrome (also known as PIMS-TS).  Carried out in France (population: 67 million) this was a nationwide study through the French public health agency.  156 cases were reported between 1st March and 17th May 2020 through both prospective and retrospective case identification.

Case definition required one or more of the following symptoms: seritis (serositis), characteristics of macrophage activation syndrome (MAS), myocarditis and/or Kawasaki-like disease (KLD).  Cases were divided according to associated Covid status into confirmed, probable or possible CoV and non-CoV.  Comparison was undertaken between non-CoV PIMS and CoV PIMS.

Of note, this definition differs marginally from the UK RCPCH definition of PIMS-TS which is a child with persistent fever, inflammation (neutrophilia, elevated CRP and lymphopaenia) and evidence of single or multi-organ dysfunction.

Age distribution showed a median of 8 years and an interquartile range of 5–11 years.  Peak incidence was week of 18th to 27th April, which was 4-5 weeks behind the peak of the Covid-19 epidemic in France. 

95 of the 156 reported cases were confirmed or probable Covid, supporting a causal link between Covid-19 infection and PIMS.

CoV-PIMS cases (n=108) compared with non-CoV PIMS cases (n=48) had a higher median age (8 vs 3) and showed higher rates of myocarditis (70% vs 10%), macrophage-activation syndrome (23% vs 2%), seritis (22% vs 10%) and ITU admission (67% vs 8%). Rates of Kawasaki-like disease (KLD) were higher in the non-CoV group (81% vs 61%0) supporting the idea that these are ‘classic’ Kawasaki Disease presentations. In the CoV-PIMS groups 73% required vasopressors, 43% were ventilated and one child died.

This is the first epidemiological surveillance study of PIMS-TS indicating rates across a population. It supports a causal link with Covid following 4-5 weeks behind the clinical illness.

Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020 May 17. doi: 10.1161/CIRCULATIONAHA.120.048360

A multi-centred retrospective case series studied the early outcomes for children admitted to intensive care for cardiogenic shock, left ventricular dysfunction and severe inflammatory state. The study involved 14 centres in France and Switzerland. The inclusion criteria were admission between 22nd March and 30th April 2020 with fever (>38.5°C), cardiogenic shock or left ventricular dysfunction (left ventricular ejection fraction<50% in the presence of an inflammatory state (CRP> 100 mg/mL).

In summary, left ventricular systolic dysfunction was present in all patients who experienced a low systolic blood pressure. The authors contrast this to Kawasaki disease, in which diastolic dysfunction predominates and only a third of patients experience left ventricular systolic dysfunction.

The authors suggest the rapid resolution of systolic dysfunction in conjunction with a mild to moderate troponin rise implies the mechanism of cardiac impairment associated with SARS-CoV2 in the paediatric population differs to that seen in the adult population. Due to the high BNP levels present in the case series a mechanism of myocardial oedema or stunning is suggested. Very high levels of Interleukin-6 were also seen and may be related to vasoplegia. It was hypothesised these significantly raised results could be caused by stretched cardiomyocytes and cardiac fibroblasts in conjunction with macrophage activation. However, further research would be required to determine the immune mechanisms involved and potentially guide treatment choices.

35 patients were included with a median age of 10 years (IQR 2-16 years), 18 were male. 31 patients were confirmed SARS-CoV2 positive by either a nasopharyngeal RT-PCR, faecal RT-PCR, tracheal swab, or serology using Chemiluminescent Microplate Immunoassay-CMIA technique. 2 other patients were SARS-CoV2 negative, however, had CT chest appearances consistent with SARS-CoV2 changes.

10 of the patients had an identified co-morbidity: 3 (8.5%) had asthma, 1 (3%) had lupus and 6 (17%) were overweight with a BMI greater than 25. There was no data regarding ethnic origin included.

Clinical features: 35 (100%) had fever, 35 (100%) Asthenia, GI symptoms 29 (83%), rhinorrhoea 15 (43%), respiratory distress 23 (65%), adenopathy 21 (60%), rash 20 (57%), meningism 11 (31%), chest pain 6 (71%), cardiogenic shock 28 (80%), ventricular arrhythmia 1 (3%). A large proportion of the patients had shock with low systemic blood pressure with limited information.

Radiology: 2 patients had CT chest appearances “typical” for those with SARS-CoV2.

Bloods: CRP 241 mg/mL (IQR150-311) mg/mL, Troponin I 347 (IQR 186-1267) ng/L (normal <26ng/L), Creatinine Kinase 174 U/L (IQR 110-510), NT-proBNP 41484 pg/mL (IQR 35811-52475) (normal <300 pg/mL), BNP 5743 pg/mL (IQR 2648-11909) normal <100 pg/mL), D-Dimer 5284 ng/ml (IQR 4069-9095), Procalcitonin 36 ng/ml (IQR 8-99), WCC 16 X 10^3/L (IQR 12-23), Neutrophil count 13 X 10^3/L (IQR 8-19), Interleukin 6 135 pg/mL (IQR 87-175) (normal <8.5 pg/mL) 

Treatments: All patients required intensive care management with 10 (28%) needing V-A ECMO for an average of 4.5 days (range 3-6), 28 (80%) needing inotropic medication, 22 (62%) invasive ventilation and 11 (32%) non-invasive ventilation.

25 (71%) were given intravenous immune globulin with 1 (3%) patient given repeated IVIG due to persistent fever 48 hours after the first dose. 12 (34%) received intravenous steroids, dose unclear, due to grading them high-risk with symptoms similar to an incomplete form of Kawasaki disease and 3 patients received interleukin 1 receptor antagonist (anakinra) due to a persistent severe inflammatory state. 23 patients received therapeutic heparin.

Outcomes: No patients died. All 10 patients requiring V-A ECMO were weaned off successfully. The average hospital stay was 8 days (IQR 8-14) with ICU duration of 7 days (3.7-10 days). At the time of publication 7 (20%) patients remained as an inpatient or had residual left ventricular dysfunction.

Complete recovery of left ventricular function, [left ventricular ejection fraction > 60% at day 7] was seen in 25 patients (71%) by an average of 2 days after admission. 5 (14%) had residual mild to moderate left ventricular systolic dysfunction with a left ventricular ejection fraction greater than 45%. This was measured on the last follow up, an average of 12 days after admission.

Other investigations were undertaken to assess cardiac function.

ECG: 1 patient (3%) had ST elevation on ECG.

Echocardiography results: 10 (29%) of patients had an ejection fraction below 30% on admission whilst 25 (71%) had an ejection fraction between 30 and 50%. Global hypokinesis was seen in 31 (89%) with an additional 3 (9%) patients had segmental wall hypokinesis. 1 (3%) patient had Takotsubo syndrome presentation with akinesis of the apical segment Pericardial effusions were diagnosed in 3 (9%) patients.

Coronary artery dilatation, defined as Z-score >2 adjusted for body temperature, was present in 6 patients (17%): 5 patients (14%) had dilatation of the left main stem and 1 (3%) had dilatation of the right coronary artery. Right ventricular function was normal, and no thrombi were seen. No coronary aneurysms have been seen, however, ongoing follow up is planned.

Data was not presented regarding SARS-CoV2 antibodies, however, within the discussion it was noted that those who were serologically positive for SARS-CoV2 already had IgG antibodies suggesting the patients included within the study had contact with the virus “more than 3 weeks before admission”.   

Toubiana Julie, Poirault Clément, Corsia Alice, Bajolle Fanny, Fourgeaud Jacques, Angoulvant François et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study BMJ 2020; 369 :m2094

This cohort study looks at a cluster of patients diagnosed with Kawasakis disease at a hospital in Paris between April 27th and May 11th. During this time they admitted 21 children with a diagnosis of Kawasakis or incomplete Kawasakis, with a median age of 7.9yr and 12/21 female.

Clinical features: All children presented with persistent fever and with initial GI symptoms (vomiting and diarrhoea) with over half fulfilling complete KD criteria (11/21, 52%). The majority were irritable (12/21, 57%) and myocarditis was common (16/21, 76%). Coronary artery dilation was seen in 5/21 (24%) but no aneurysms seen. 8/18 who had chest imaging had lung changes.

Bloods: Inflammatory markers were significantly raised, with a median CRP of 253, PCT 22.5 and IL-6 170. Interestingly mean platelet count was 499 (but up to 838). Median troponin 282 and D dimer 4025 (up to 19330). Ferritin not reported.

COVID-19 status: 8/21 tested positive on swab and 19/21 had positive serology

Treatment: All were given IVIg, following which 5/21 still had fever 36hrs afterwards. They were given a second dose of IVIg and steroids. 15/21 required inotropic support and 11/21 required intubation/ventilation.

Outcomes: Median length of stay was 8 days (rage 5 – 17). There were no deaths.

Three subsequent studies have confirmed very similar presentations of this hyperinflammatory syndrome (PIMS-TS) in children, with initial abdominal pain, fever, diarrhoea and vomiting, progressing to a picture similar to Kawasakis disease but with a significant number developing shock and significant cardiac involvement.

Riphagen, Shelley et al., Hyperinflammatory shock in children during COVID-19 pandemic, The Lancet, May 7th 2020, https://doi.org/10.1016/S0140-6736(20)31094-1

This is the first case series to describe a cluster of children presenting with hyperinflammatory shock during the COVID-19 pandemic.
Eight children aged 4 to 14 years were identified by a paediatric retrieval service based in London in mid-April 2020. Interestingly, of the 8 children, 7 had weights >75th centile. Notably 6 were of Afro-Caribbean descent and 2 were Asian, with no Caucasian children in this cohort. 5/8 were boys. 4 children had exposure to family members with COVID-19.

The clinical presentation was similar to Kawasaki disease, with unrelenting fever, rash, conjunctivitis, peripheral oedema, and extremity pain, in addition to gastrointestinal symptoms. All children developed warm, vasoplegic shock and required inotropic support. Seven children required mechanical ventilation.

Small pleural, pericardial and ascitic effusions, also consistent with a diffuse inflammatory process were also observed. Vascular involvement was demonstrated with echo-bright coronary arteries seen in all children, with a giant coronary aneurysm in one patient. One child died from a large cerebrovascular infarct. Myocardial enzymes were significantly elevated.

A range of investigations were done in all children, and despite this no causative pathogen was identified. Adenovirus and enterovirus were isolated in one child. Four children had known exposures to SARS-CoV-2 in family members, but only two tested positive for SARS-CoV-2 (1 was positive only postmortem). 

In addition to other supportive therapies, all children received IVIG and broad-spectrum antibiotics (ceftriaxone, clindamycin). Six children have been given aspirin.

This clinical presentation may represent a new phenomenon associated with SARS-CoV-2 infection in children and has remarkable similarities to Kawasaki Disease. Following publication of this case series, Evelina London Children’s Hospital has managed >20 similar cases in children. Ten of these children were SARS-CoV-2 antibody positive (unclear which antibody or which test was used).

These findings have garnered particular interest due to the fact that children have otherwise been relatively spared from severe disease due to COVID-19, and here both the temporal association and high proportion of children with seemingly positive serology suggests a possible association with this hyperinflammatory syndrome. Anecdotally, clusters have also been noted in the USA (particularly NYC) and some centres in Spain and Italy. Reports are conspicuously absent from Asia, most notable as Kawasakis disease is more common amongst this population normally. Even more striking is the gross overrepresention of children with an Afro-Carribean background, which given current investigations into the increased incidence of severe adult disease in these communities seems even more pertinent.

As so little is currently known about “garden variety” Kawasakis, it will make defining this disease and its associated with COVID-19 that bit more difficult, but studies are currently ongoing to assess the nature and mechanism of this disease (https://www.diamonds2020.eu/). For now, this cohort doesn’t change the management of childhood COVID-19, nor does it change the management of hyperinflammatory shock or Kawasakis – although the RCPCH have produced excellent guidance for suggested investigations and processes to include these patients in ongoing research.

Paediatric COVID data

First authorLast authorJournalArticle titleDate of PublicationCountryRegion(n) childrenStudy typePaper linkReview summary
Wardell, HDixit, AJ Pediatr Infect DisSARS-CoV-2 Infection in Febrile Neonates09 JUL 2020USANorth America4Clinical - Clinical Featureshttps://academic.oup.com/jpids/article/doi/10.1093/jpids/piaa084/5869489
Denina,MGarrazino,SPEDIATRICSLung Ultrasound in Children With COVID-191 Jul 2020ItalyEurope8Clinical - Clinical Features https://pediatrics.aappublications.org/content/early/2020/06/12/peds.2020-1157
Wu, QXing, QPediatricsCo-infection and Other Clinical Characteristics of COVID-19 in Children1 Jul 2020ChinaAsia74Clinical - Clinical Featureshttps://pediatrics.aappublications.org/content/early/2020/05/04/peds.2020-0961
Li, JDai, XJ Med Internet ResIdentification of Symptoms Prognostic of COVID-19 Severity: Multivariate Data Analysis of a Case Series in Henan Province30 Jun 2020ChinaAsia12Clinical - Clinical Featureshttps://www.jmir.org/2020/6/e19636/pdf
Götzinger, FTebruegge, MLancetCOVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study25 Jun 2020Europe (Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the UK)Europe582Clinical - Clinical Featureshttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30177-2/fulltext
Zheng, G. Guo, Y.Pediatric PulmonologyClinical Characteristics of Acute Respiratory Syndrome with SARS-CoV-2 Infection in Children in South China.24 Jun 2020ChinaAsia52Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/full/10.1002/ppul.24921
Rossoff, JMuller, WJPediatric blood and cancerBenign course of SARS‐CoV‐2 infection in a series of pediatric oncology patients23 Jun 2020USNorth America6Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/10.1002/pbc.28504
Gonzales Cortes, Rde Carlos-Vicente, JCIntensive Care MedA multicenter national survey of children with SARS-CoV-2 infection admitted to Spanish Pediatric Intensive Care Units22 Jun 2020SpainEurope50Clinical - Clinical Featureshttps://link.springer.com/article/10.1007/s00134-020-06146-8
Rosenzweig, JKaicker, SPediatric Blood and CancerSARS‐CoV‐2 infection in two pediatric patients with immune cytopenias: A single institution experience during the pandemic21 Jun 2020USANorth America2Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1002/pbc.28503
Hildenwall HHerleniusActa PaediatricaPaediatric COVID‐19 admissions in a region with open schools during the two first months of the pandemic21 Jun 2020SwedenEurope63Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303651/
Colmenero ITorello ABritish Journal of DermatologySARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: histopathological, immunohistochemical and ultraestructural study of 7 paediatric cases20 Jun 2020SpainEurope7Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/bjd.19327
Heinz, NMartinez, MPaediatr TransplantA Case of an Infant with SARS-CoV-2 hepatitis early afterLiver Transplantation19 Jun 2020USANorth America1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/petr.13778
Xiong, XIp, PJ Pediatr.A Comparison Between Chinese Children Infected with COVID-19 and with SARS18 Jun 2020ChinaAsia244Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301144/
Del Barba, P.Barera, G.Pediatr PulmonolCOVID-19 cardiac involvement in a 38-day old infant18 Jun 2020ItalyEurope1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/full/10.1002/ppul.24895
Meethal, LBKociolek, LKj.pedsSARS-CoV-2 Infection in Infants Less than 90 Days Old17 Jun 2020USANorth America18Clinical - Clinical Featureshttps://www.jpeds.com/article/S0022-3476(20)30750-2/fulltext
Ekbatani, M. S.Mamishi, S.British Journal of Biomedical ScienceAtypical and novel presentations of Coronavirus Disease 2019: a case series of three children.16 Jun 2020IranAsia3Clinical - Clinical Featureshttps://www.tandfonline.com/doi/full/10.1080/09674845.2020.1785102?scroll=top&needAccess=true
Li, YLi, Jpaediatric pulmunologyImmune-related factors associated with Pneumonia in 127 children with Coronavirus Disease in 2019 in Wuhan.16 Jun 2020chinaAsia127Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1002/ppul.24907
Stewart, DStojanovic, JLancet. Child & adolescent healthRenal dysfunction in hospitalised children with COVID-1915 Jun 2020UKEurope52Clinical - Clinical Featureshttps://www.thelancet.com/pdfs/journals/lanchi/PIIS2352-4642(20)30178-4.pdf
Ranabothu, SVeerapandiyan, AActa Paediatr.Spectrum of COVID‐19 in Children15 Jun 2020USANorth America1353Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/apa.15412
Lanyon, NPeters, MArch Dis ChildhCritical paediatric COVID-19: varied presentations but good outcomes15 Jun 2020United KingdomEurope11Clinical - Clinical Featureshttps://adc.bmj.com/content/early/2020/06/28/archdischild-2020-319602
Kanthimathinathan, KJyothish, DHospital PediatricsCOVID-19 - a UK Children's Hospital Experience15 Jun 2020UKEurope45Clinical - Clinical Featureshttps://hosppeds.aappublications.org/content/hosppeds/early/2020/06/06/hpeds.2020-000208.full.pdf
Pan, YZhang, LJIDEpidemiological and Clinical Characteristics of 26 Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Carriers15 Jun 2020ChinaAsia26Clinical - Clinical Featureshttps://academic.oup.com/jid/article/221/12/1940/5823633
Lee,HLytrivi,IPediatr TransplantVarying Presentations of COVID-19 in Young Heart Transplant Recipients:a Case Series15 Jun 2020United States of AmericaNorth America4Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/abs/10.1111/petr.13780?af=R
Colonna, C.Gelmetti, C.Pediatric dermatologyChilblains in children in the time of Covid‐19: new evidence with serology assay13 Jun 2020ItalyEurope8Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/pde.14269
Kesici,SBayracki,BESCFulminant COVID 19 related Myocarditis in an infant12 Jun 2020TurkeyAsia1Clinical - Clinical Featureshttps://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa515/5856627
Zeng, QLYu, ZJTransbound Emerg DisClinical course and treatment efficacy of COVID-19 near Hubei Province, China: a multicentre, retrospective study12 Jun 2020ChinaAsia3Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/tbed.13674
Jafari, RJavanbakht, MTravel Med Infect DisA 6 months old infant with fever, dyspnea and poor feeding, diagnosed with COVID-1911 Jun 2020IranMiddle East1Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S1477893920302799
Marhaeni, WR. S. Mapianto,Indian J PediatrThalassemic Child Presenting with Anosmia due to COVID-19.9 Jun 2020IndonesiaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281692/pdf/12098_2020_Article_3370.pdf
González-Dambrauskas, SKarsies, TPediatricsPediatric Critical Care and COVID199 Jun 2020InternationalInternational17Clinical - Clinical Featureshttps://pediatrics.aappublications.org/content/pediatrics/early/2020/06/05/peds.2020-1766.full.pdf
Cen YLiu Y HClin Infect Dis.Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019 -- a multi-centre observational study.8 Jun 2020ChinaAsia5Clinical - Clinical Features https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30341-4/fulltext
MAK, PQKwan, MPediatr.Infect.Dis.J.Anosmia and Ageusia : not an uncommon presentation of COVID-19 infection in children and adolescents.8 Jun 2020USANorth America3Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/.
Trogen, BShust, GPed. Infectious Disease J.COVID-19-Associated Myocarditis in an Adolescent8 Jun 2020USANorth America1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/COVID_19_Associated_Myocarditis_in_an_Adolescent.96126.aspx
Du, WQ. LiJ Infect Public HealthPersistence of SARS-CoV-2 virus RNA in feces: A case series of children7 Jun 2020ChinaAsia10Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S1876034120304913
Chen, YXiao, XJ Infect Public HealthRe-evaluation of retested nucleic acid-positive cases in recovered COVID-19 patients: Report from a designated transfer hospital in Chongqing, China7 Jun 2020ChinaAsia4Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275981/
Foster, CCampbell, JJ Pediatric Infect Dis Soc.Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Initial Clinical Characteristics and Outcomes6 Jun 2020USANorth America57Clinical - Clinical Featureshttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa072/5854294
Xing, CXu, ZWorld J Clin CasesSerial computed tomographic findings and specific clinical features of pediatric COVID-19 pneumonia: A case report6 Jun 2020ChinaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281042/
Li, C.Wu, B MedicineA 3-month-old child with COVID-19: A case report.5 Jun 2020ChinaAsia1Clinical - Clinical Featureshttps://journals.lww.com/md-journal/fulltext/2020/06050/a_3_month_old_child_with_covid_19__a_case_report.92.aspx
Sun, D., XLiu, Z., SWorld Journal of PediatricsSARS-CoV-2 infection in infants under 1 year of age in Wuhan City, China5 Jun 2020ChinaAsia36Clinical - Clinical Featureshttps://link.springer.com/article/10.1007%2Fs12519-020-00368-y
Gorkem,SCetin,BDiagn Interv RadiolCOVID-19 pneumonia in a Turkish child presenting with abdominal complaints and reversed halo sign on thorax CT5 Jun 2020TurkeyEurope1Clinical - Clinical Featureshttps://www.dirjournal.org/en/covid-19-pneumonia-in-a-turkish-child-presenting-with-abdominal-complaints-and-reversed-halo-sign-on-thorax-ct-167964
Mohammadi, A Mirza‑Aghazadeh‑Attari, MJpn J RadiolClinical and radiological characteristics of pediatric patients with COVID-19: focus on imaging findings4 Jun 2020IranMiddle East27Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293432/
Kerber, AYoussef, MIntnl J of DermatologyChilblains-like dermatologic manifestation of COVID-19 diagnosed by serology via multidisciplinary virtual care4 Jun 2020USANorth America1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/10.1111/ijd.14974
Lin, EShah, AJAMA SurgeryIncidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children’s Hospitals4 Jun 2020USANorth America12Clinical - Clinical Featureshttps://jamanetwork.com/journals/jamasurgery/fullarticle/2766924
Zachariah, PSalman, LJAMA PediatricsEpidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children’s Hospital in New York City, New York3 Jun 2020USANorth America50Clinical - Clinical Featureshttps://jamanetwork.com/journals/jamapediatrics/fullarticle/2766920
Wu, HXiang, YJAMA Netw OpenClinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China3 Jun 2020ChinaAsia157Clinical - Clinical Featureshttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2766670
Parri,NLazzerini,MEur J Pediatr Characteristic of Covid-19 infection in paediatric patients: early findings from two Italian Pediatric Research Networks3 Jun 2020ItalyEurope130Clinical - Clinical Features https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269687/pdf/431_2020_Article_3683.pdf
Pandey UDien Bard JMedRxIVPediatric COVID-19 in Southern California: clinical features and viral genetic diversity2 Jun 2020CaliforniaNorth America35Clinical - Clinical Featureshttps://www.medrxiv.org/content/10.1101/2020.05.28.20104539v2.full.pdf
Frauenfelder, CBamford APediatricsInfant With SARS-CoV-2 Infection Causing Severe Lung Disease Treated With Remdesivir1 Jun 2020United KingdomEurope1Clinical - Clinical Featureshttps://pediatrics.aappublications.org/content/early/2020/06/16/peds.2020-1701
Escalera-Antezana, JP Rodríguez-Morales, AJLe Infezioni in MedicinaRisk factors for mortality in patients with Coronavirus Disease 2019 (COVID-19) in Bolivia: An analysis of the first 107 confirmed cases1 Jun 2020BoliviaInternational9Clinical - Clinical Featureshttps://www.infezmed.it/media/journal/Vol_28_2_2020_15.pdf
Manzoni, P Polastri, RoThe Pediatric Infectious Disease Journal:Uncommon Presentation of Coronavirus Disease 2019 Infection in a Child1 Jun 2020italyEurope1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Citation/9000/Uncommon_Presentation_of_Coronavirus_Disease_2019.96134.aspx
Jones, B. A. ." . Slater, B. J.Journal of Pediatric Surgery Case ReportsNon-operative management of acute appendicitis in a pediatric patient with concomitant COVID-19 infection31 May 2020USANorth America1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261356/
Alsofayan, YAssiri, AJ Infect Public HealthClinical characteristics of COVID-19 in Saudi Arabia: A national retrospective study31 May 2020Saudi ArabiaMiddle East74Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S1876034120304925
Valente, PBuzzonetti, LJournal of AAPOSOcular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report30 May 2020ItalyEurope27Clinical - Clinical Featureshttps://jaapos.org/article/S1091-8531(20)30115-4/fulltext?rss=yes
Olisova, OYShnakhova, LMDermatol TherCutaneous manifestations in COVID‐19: a skin rash in a child30 May 2020RussiaEastern Europe and Northern Asia1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/dth.13712
Cai, JHe, GJ Med VirolClinical features and the treatment of children with COVID-19: a case series from Wenzhou, China30 May 2020ChinaAsia3Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26092
Kakuya, FKinebuchi, TJapanese Journal of Infectious DiseasesThe first pediatric patients with coronavirus disease 2019 (COVID-19) in Japan; The risk of co-infection with other respiratory viruses29 May 2020JapanAsia3Clinical - Clinical Featureshttps://www.jstage.jst.go.jp/article/yoken/advpub/0/advpub_JJID.2020.181/_pdf
Zhao, WZhang, FClin PediatrCharacteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge28 May 2020ChinaAsia14Clinical - Clinical Featureshttps://journals.sagepub.com/doi/full/10.1177/0009922820928057
Oualha, MRenolleau, SArchives de PédiatrieSevere and fatal forms of COVID-19 in children28 May 2020FranceEurope27Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S0929693X20301172
Zhao, WZhang, FClin PediatrCharacteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge28 May 2020ChinaAsia15Clinical - Clinical Featureshttps://journals.sagepub.com/doi/full/10.1177/0009922820928057
Garcia-Salido, ASerrano-Gonzalez, APediatr Crit Care MedChildren in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital27 May 2020SpainEurope7Clinical - Clinical Featureshttps://journals.lww.com/pccmjournal/Abstract/9000/Children_in_Critical_Care_Due_to_Severe_Acute.98028.aspx
Kumar, KJayanthi, CRIJOPresence of viral RNA of SARS-CoV-2 in conjunctival swab specimens of COVID-19 patients25 May 2020IndiaAsia4Clinical - Clinical Featureshttp://www.ijo.in/temp/IndianJOphthalmol6861015-4225372_114413.pdf
Gefen, AMSethna, CPediatric NephrologyPediatric COVID-19-associated rhabdomyolysis: a case report23 May 2020USANorth America1Clinical - Clinical Featureshttps://link.springer.com/article/10.1007/s00467-020-04617-0
Torrelo AColmenero IPaediatric DermatologyErythema multiforme-like lesions in children and COVID-1923 May 2020ItalyEurope4Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/abs/10.1111/pde.14246
Armann, J.Berner, R.Dtsch Arztebl IntHospital Admission in Children and Adolescents With COVID-1922 May 2020GermanyEurope128Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271745/
Docherty, ASemple, MBMJFeatures of 20133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study22 May 2020United KingdomEurope310Clinical - Clinical Featureshttps://www.bmj.com/content/bmj/369/bmj.m1985.full.pdf
de Ceano-Vivas, MCalvo CArch Dis ChildSARS-CoV-2 infection in ambulatory and hospitalised Spanish children22 May 2020SpainEurope58Clinical - Clinical Featureshttps://adc.bmj.com/content/archdischild/early/2020/05/22/archdischild-2020-319366.full.pdf
Scheier, EBalla, UEur Rev Med Pharmacol SciLung ultrasound cannot be used to screen for Covid-19 in children21 May 2020IsraelMiddle East1Clinical - Clinical Featureshttps://www.europeanreview.org/wp/wp-content/uploads/4623-4624.pdf
Li, BYu, CIndian PediatricsRadiographic and Clinical Features of Children With Coronavirus Disease (COVID-19) Pneumonia21 May 2020ChinaAsia22Clinical - Clinical Featureshttps://link.springer.com/content/pdf/10.1007/s13312-020-1816-8.pdf
Leung, CLeung, CPediatric PulmonologyClinical characteristics of COVID‐19 in children: Are they similar to those of SARS?21 May 2020ChinaAsia43Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/10.1002/ppul.24855
Zachariag, PGreen, DClin Infect DisSymptomatic Infants have Higher Nasopharyngeal SARS-CoV-2 Viral Loads but Less Severe Disease than Older Children20 May 2020USANorth America57Clinical - Clinical Featureshttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa608/5841161
Venturini, EGalli, LJ PaediatrSevere neutropenia in infants with severe acute respiratory syndrome caused by the novel coronavirus 2019 infection19 May 2020ItalyEurope2Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236669
Xiong XTam, PGutComparative study of the clinical characteristics and epidemiological trend of 244 COVID-19 infected children with or without GI symptoms19 May 2020chinaAsia244Clinical - Clinical Featureshttps://gut.bmj.com/content/early/2020/05/19/gutjnl-2020-321486.info
Dallan, CSahyoun, CLancetSeptic shock presentation in adolescents with COVID -1919 May 2020SwitzerlandEurope3Clinical - Clinical Featureshttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30164-4/fulltext
Venturini, EGalli, LJ PaediatrSevere neutropenia in infants with severe acute respiratory syndrome caused by the novel coronavirus 2019 infection19 May 2020ItalyEurope2Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236669
Giacomet, VZuccotti, GPIDJAcute inflammation and elevated cardiac markers in a two-month-old infant with severe acute respiratory syndrome coronavirus 2 infection presenting with cardiac symptoms19 May 2020ItalyEurope1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/ACUTE_INFLAMMATION_AND_ELEVATED_CARDIAC_MARKERS_IN.96157.aspx
Dugue, RMishra, NNeurologyNeurologic manifestations in an infant with COVID-1919 May 2020USANorth America1Clinical - Clinical Featureshttps://n.neurology.org/content/neurology/early/2020/05/18/WNL.0000000000009653.full.pdf
Shaw, RYuki, KJ Pediatr Surg Case Rep.Intubation precautions in a pediatric patient with severe COVID-1918 May 2020USANorth America1Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S2213576620301299
Guarneri, CNunnari, GThe Lancet, Infection diseasesSilent COVID-19: what your skin can reveal18 May 2020Italy (assumed)Europe3Clinical - Clinical Featureshttps://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30402-3/fulltext#coronavirus-linkback-header
Yoo, SKim, D Pediatrics InternationalReactivation of SARS-CoV-2 after Recovery18 May 2020KoreaAsia1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/ped.14312
Li, YWu, BBMC PediatricsChest CT imaging characteristics of COVID-19 pneumonia in preschool children: a retrospective study18 May 2020ChinaAsia8Clinical - Clinical Featureshttps://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-020-02140-7
Turbin, RNimchimsky, EOrbitOrbital cellulitis, sinusitis and intracranial abnormalities in two adolescents with COVID-1918 May 2020USANorth America2Clinical - Clinical Featureshttps://www.tandfonline.com/doi/full/10.1080/01676830.2020.1768560
Wang, Y.Li, L.The Journal of Infectious DiseasesClinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China17 May 2020ChinaAsia15Clinical - Clinical Featureshttps://academic.oup.com/jid/article/221/11/1770/5807958
Voinsky, IGurwitz,DJ Infect.Effects of age and sex on recovery from COVID-19: Analysis of 5769 Israeli patients16 May 2020IsraelMiddle East933Clinical - Clinical Featureshttps://www.journalofinfection.com/article/S0163-4453(20)30303-0/fulltext
Duramaz, BTurel, ODermatol TherAppearance of Skin Rash in Pediatric Patients with COVID-19: Three Case Presentations15 May 2020TurkeyWestern Asia, Southeastern Europe20Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/full/10.1111/dth.13594
Diotallevi, FOffidani, AJ Med VirolSkin Involvement in SARS-CoV-2 Infection: Case Series15 May 2020ItalyEurope2Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/10.1002/jmv.26012
He, GCai, JIndian PediatricsSerial Computed Tomography Findings in a Child with Coronavirus Disease (COVID-19) Pneumonia15 May 2020ChinaAsia1Clinical - Clinical Featureshttps://link.springer.com/content/pdf/10.1007/s13312-020-1824-8.pdf
Mastrolonardo, MFoti, CDermatologic TherapyThe management of the outbreak of acral skin manifestationsin asymptomatic children during COVID-19 era14 May 2020ItalyEurope38Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/dth.13617
Craver, RFinger, LFetal Pediatr PatholFatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c)13 May 2020USANorth America1Clinical - Clinical Featureshttps://www.tandfonline.com/doi/full/10.1080/15513815.2020.1761491
Cordoro, KMMcCalmont, THPediatric DermatologyClustered Cases of Acral Perniosis: Clinical Features, Histopathology and Relationship to COVID‐1912 May 2020USNorth America6Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/abs/10.1111/pde.14227
DeBiasi, RWessel, DJ Pediatr.Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region12 May 2020United StatesNorth America177Clinical - Clinical Featureshttps://www.jpeds.com/article/S0022-3476(20)30581-3/fulltext
Bai, KLi, CPIDJClinical analysis of 25 Novel Coronavirus Infections in Children12 May 2020ChinaAsia25Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/Clinical_Analysis_of_25_Novel_Coronavirus.96172.aspx
Brambilla, IMarseglia, GLThe Pediatric Infectious Disease JournalCOVID-19 in the Pediatric Population Admitted to a Tertiary Referral Hospitap in Northern Italy: Preliminary Clinical Data12 May 2020ItalyEurope17Clinical - Clinical Featureshttps://journals.lww.com/pidj/Citation/9000/COVID_19_in_the_Pediatric_Population_Admitted_to_a.96177.aspx
Brambilla, I.Ciprandi, G.Obesity: A research journalSpecial Issues for COVID‐19 in Children and Adolescents12 May 2020ItalyEurope1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/abs/10.1002/oby.22878
Meslin, PZemouri, NThe Pediatric Infectious Disease JournalCoronavirus Disease 2019 in Newborns and Very Young Infants a Series of Six Patients in France12 May 2020FranceEurope6Clinical - Clinical Featureshttps://journals.lww.com/pidj/Fulltext/2020/07000/Coronavirus_Disease_2019_in_Newborns_and_Very.33.aspx
Cai, XLi, WFront. PediatrClinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children12 May 2020ChinaAsiaClinical - Clinical Featureshttps://www.frontiersin.org/articles/10.3389/fped.2020.00258/full
Shekerdemian, LSBurns, JPJAMA PediatricsCharacteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units11 May 2020USA & CanadaNorth America48Clinical - Clinical Featureshttps://jamanetwork.com/journals/jamapediatrics/fullarticle/2766037
Chao, JMedar, SJ. Pediatr.Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City11 May 2020USNorth America46Clinical - Clinical Featureshttps://www.jpeds.com/article/S0022-3476(20)30580-1/pdf
Wehl, G..Rauchenzauner, MKlin PadiatrCo-infection of SARS CoV-2 and influenza A in a Pediatric Patient in Germany.11 May 2020GermanyEurope1Clinical - Clinical Featureshttps://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-1163-7385
Oberweis, MGarcia, IPediatr. Infect. Dis. J.Pediatric Life-Threatening Coronavirus Disease 2019 With Myocarditis11 May 2020LuxembourgEurope1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/Pediatric_Life_Threatening_Coronavirus_Disease.96160.aspx
Zhang, NZheng, XTransl PediatrAnalysis and suggestions for the preview and triage screening of children with suspected COVID-19 outside the epidemic area of Hubei Province10 May 2020ChinaAsia36Clinical - Clinical Features http://dx.doi.org/10.21037/tp.2020.03.08
Andina, D.Torello, A.Paediatric DermatologyChilblains in children in the setting of COVID-19 pandemic9 May 2020SpainEurope22Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/pde.14215
Locatelli, ASena, PJ Eur Acad Dermatol VenereolHistologic features of long lasting chilblain‐like lesions in a pediatric COVID‐19 patient9 May 2020ItalyEurope1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.16617
Diercks, GRKwolek, CJInternational Journal of Pediatric OtorhinolaryngologyAsymptomatic COVID-19 infection in a child with nasal foreign body8 May 2020USANorth America1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205643/pdf/main.pdf
Fu, BFu, XMed Clin (Barc)Clinical characteristics of 11 asymptomatic patients with COVID-198 May 2020ChinaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205640/pdf/main.pdf
Ma, Y.Zhang, Z.Microbes and InfectionCharacteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China7 May 2020ChinaAsia10Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204664/pdf/main.pdf
Zhang, YSun, BCell Mol ImmunolProtective humoral immunity in SARS-CoV-2 infected pediatric patients7 May 2020ChinaAsia6Clinical - Clinical Featureshttps://www.nature.com/articles/s41423-020-0438-3
Papa, AVarrassi, GPain TherImages in Practice: Painful Cutaneous Vasculitis in a SARS-Cov-2 IgG-Positive Child6 May 2020ItalyEurope1Clinical - Clinical Featureshttps://link.springer.com/content/pdf/10.1007/s40122-020-00174-4.pdf
Ma, H.Shao, J.BMC MedicineA single-center, retrospective study of COVID-19 features in children: a descriptive investigation6 May 2020ChinaAsia158Clinical - Clinical Featureshttps://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01596-9
Zhang, BZhang SJ InfectionChildren hospitalized for coronavirus disease 2019 (COVID-19): A multicenter retrospective descriptive study6 May 2020ChinaAsia46Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204760/pdf/main.pdf
Wang, YSun, DPediatr Infect Dis JThe Risk of Children Hospitalized With Severe COVID-19 in Wuhan6 May 2020ChinaAsia43Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/research/coronavirus/publication/32384397
Colonna, C.Gelmetti, C.Paediatric DermatologyChilblains-like lesions in children following suspected Covid-19 infection6 May 2020ItalyEurope4Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/pde.14210
Li, J.Song, S.Q.The Brazilian Journal of INFECTIOUS DISEASEAn infant with a mild SARS-CoV-2 infection detected only by anal swabs: a case report6 May 2020ChinaAsia1Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S141386702030043X
Xiong, X.Tam, P.Med archivesAre COVID-19 infected children with gastrointestinal symptoms different from those without symptoms? A comparative study of the clinical characteristics and epidemiological trend of 244 pediatric cases from Wuhan5 May 2020ChinaAsia244Clinical - Clinical Featureshttps://www.medrxiv.org/content/10.1101/2020.04.29.20084244v1
Lu, YDu, HPed Infectious Disease JSymptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan5 May 2020ChinaAsia110Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/Symptomatic_Infection_is_Associated_with_Prolonged.96181.aspx
Garcia-Lara, G.Ruiz-Villaverde, R.Dermatologic TherapyChilblain-like lesions in pediatrics dermatological outpatients during the COVID-19 outbreak5 May 2020SpainEurope27Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/dth.13516
Merza, MAbdulah, D.Diabetes Metab SyndrCOVID-19 outbreak in Iraqi Kurdistan: The first report characterizing epidemiological, clinical, laboratory, and radiological findings of the disease5 May 2020Iraqi KurdistanMiddle East4Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199697/
Hong-Rui, C.Wan-Xin, C.The Pediatric Infectious Disease Journal:A CASE OF CHILDHOOD COVID-19 INFECTION WITH PLEURAL EFFUSION COMPLICATED BY POSSIBLE SECONDARY MYCOPLASMA PNEUMONIAE INFECTION5 May 2020ChinaAsia1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/A_CASE_OF_CHILDHOOD_COVID_19_INFECTION_WITH.96183.aspx
Peng, HXu, HJ Clin VirologyCoronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes4 May 2020ChinaAsia75Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204737/table/tbl0010/
Rahmanzade, RHashemian, SA A PractRespiratory Distress in Postanesthesia Care Unit: First Presentation of Coronavirus Disease 2019 in a 17-Year-Old Girl: A Case Report4 May 2020IranAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227797/pdf/acc-14-e01227.pdf
Morey-Olive, MGarcia-Patos, VAnales de pediatriaCutaneous manifestations in the current pandemic of coronavirus infection disease (COVID 2019)4 May 2020SpainEurope2Clinical - Clinical Featureshttps://www.analesdepediatria.org/en-cutaneous-manifestations-in-current-pandemic-avance-S2341287920300673
Nirenberg, M.Herrera, MDMRJ Am Podiatr Med Assoc.Foot Manifestations in a COVID-19 Positive Patient, A case study4 May 2020SpainEuropeClinical - Clinical Featureshttps://www.japmaonline.org/doi/pdf/10.7547/20-088
Zheng, ZLiu, JJ Cent South Univ (Med Sci)Chest CT findings and clinical features of coronavirus disease 2019 in children3 May 2020ChinaAsia9Clinical - Clinical Featureshttp://xbyxb.csu.edu.cn/xbwk/fileup/PDF/202003236.pdf
Sun, JWang, YJ Infect Dev CtriesDifferent outcome of COVID-19 in members of a family3 May 2020ChinaAsia1Clinical - Clinical Featureshttps://jidc.org/index.php/journal/article/download/12792/2248
Steinberger, SLittle, B PAm J RoentgenolCT Features of Coronavirus Disease (COVID-19) in 30 Pediatric Patients1 May 2020ChinaAsia30Clinical - Clinical Featureshttps://www.ajronline.org/doi/10.2214/AJR.20.23145
Qiu, LLuo, XPediatr Infect DisA Typical Case of Critically Ill Infant of Coronavirus Disease 2019 With Persistent Reduction of T Lymphocytes1 May 2020ChinaAsia1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/9000/A_Typical_Case_of_Critically_Ill_Infant_of.96189.aspx
Tsao, HSFearon, DMPediatricsThrombocytopenia (ITP) in a SARS-CoV-2 Positive Pediatric Patient1 May 2020USANorth America1Clinical - Clinical Featureshttps://pediatrics.aappublications.org/content/pediatrics/early/2020/05/19/peds.2020-1419.full.pdf
Zhu, XCiu, LVirusResCo-infection with respiratory pathogens among COVID-2019 cases30 Apr 2020ChinaAsia11Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S0168170220303531
Yu, X.Fu, C.Transboundary and Emerging diseasesEpidemiological and clinical characteristics of 333 confirmed cases with coronavirus disease 2019 in Shanghai, China29 Apr 2020ChinaAsia10Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/10.1111/tbed.13604
Casas, CGarcia-Doval, IBr J DermatologyClassification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases29 Apr 2020spainEurope0Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/bjd.19163This report is of confirmed COVID-19 infections in children under 18 years of age who presented to a research collaboration of 17 paediatric emergency departments in Italy between March 3rd and March 27th. The median age was 3.3 years and 57/100 were male. Children under 1 year were overrepresented (40%) followed by children >10yrs (24%). Helpfully they categorise their patients according to criteria from Dong et. al (see review in Epidemiology top 10): Asymptomatic 21%, Mild 58%, Moderate 19%, Severe 1% and Critical 1%. Only 12% of patients appeared ill on assessment. Interestingly only 4% of patients had Oxygen saturations <94%. Only 38% of children needed admission for severity of illness. There were no deaths. The supplementary appendix includes a huge amount of detailed analysis of the cases, which are summarised below Clinical features: Fever 54%, Cough 44%, Feeding difficulty 23%, Sore throat 4%, Rhinorrhoea 22%, Diarrhoea 9%, vomiting 10%. Bloods: Largely unremarkable (although reports of lymphopenia unclear – state 14 patients lymphopenic but that this is 28%? – perhaps only 50 children had bloods, but this is not reported). Procalcitonin <0.5ng/L in 29/23 patients. Radiology: Chest x-rays performed for 35 children, of which 14/35 had interstitial abnormalities, 6/35 consolidation and 1/35 pleural effusion: remaining 15/35 normal. Comorbidities: There were 27/100 children with comorbidities – although it appears most had mild illness (did not require respiratory support). This included 6 with cystic fibrosis, 4 neurological, 4 haematological, 4 with a syndrome, 3 with prematurity, 2 with cardiac conditions, 2 immunological, 2 oncological and 1 metabolic disease. Of the few patients who required respiratory support (9/100) a significant number had comorbidities (6/9), although the rage was broad. This included 2 children with “epileptic encephalopathy”, one of whom also had CHARGE syndrome, a child with autism, a child with a VSD, a child with propionic acidemia, and a child with thrombocytopenia and frequent respiratory infections. One of the strengths of this study is comparisons across other studies of clinical features of COVID-19 in children. In comparison to Dong et al, CDC data and Lu et al, most features are broadly comparable. Some notable differences are a significantly larger number of infants in the Italian data (40% <1yr compared to 18% in Lu, 12% in Dong and 15.5% in CDC) and a slightly higher number of asymptomatic children (21% compared to 16% Lu, 13% Dong and 1.3% CDC). This most likely represents differences in which population cohorts presented for testing among the different studies – comparisons between cohorts is always difficult currently due to broad differences in the demoninators used. Notably there is no apparent difference in severity according to age in this Italian data, whereas CDC noted increased hospitalisation in children <1yr and Dong et al noted higher rates of severe or critical illness in infants <1yr. Broadly speaking this study confirms findings from China and the USA regarding significantly milder illness in children than adults with COVID-19, including many asymptomatic children. Note is made of overrepresentation of children with comorbidities in this cohort (similar to CDC data), although most of these still had mild illness - it is unclear if these children become more unwell, or are more likely to present to be tested.
Chacon-Aguilar, R.Perez-Moneo, B.An Padiatric (Engl Ed)COVID-19: Fever syndrome and neurological symptoms in a neonate27 Apr 2020SpainEurope1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183976/
Nathan, NCorvol, HLancetAtypical presentation of COVID-19 in young infants27 Apr 2020FranceEurope5Clinical - Clinical Featureshttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30980-6/fulltext
Piccolo, VBassi, AJournal of the European Academy of Dermatology and VenereologyChillblain-like lesions during COVID-19 pandemic: a preliminary study on 63 patients24 Apr 2020ItalyEurope63Clinical - Clinical Featureshttps://doi.org/10.1111/jdv.16526
Racalcati, SFantini, FJ Eur Acad Dermatol VenereolAcral cutaneous lesions in the time of COVID-1924 Apr 2020ItalyEurope11Clinical - Clinical Featureshttps://doi.org/10.1111/JDV.16533
Landa, NAguirre, TInternational Journal of DermatologyChillblain-like lesions on feet and hands during the COVID-19 pandemic24 Apr 2020SpainEurope2Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/ijd.14937
Wu, PNie, SGraefes Arch Clin Exp OphthalmolA child confirmed COVID-19 with only symptoms of conjunctivitis and eyelid dermatitis24 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://link.springer.com/article/10.1007/s00417-020-04708-6
Zhang, BZhang SJ InfectPositive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19)23 Apr 2020ChinaAsia3Clinical - Clinical Featureshttps://www.journalofinfection.com/article/S0163-4453(20)30233-4/fulltext
Huang, LZhou, JClin ImagInitial CT imaging characters of an imported family cluster of COVID-1923 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175903/#!po=31.2500
Kan, MJGreenhow, TLJ Ped Inf Dis SocFever without a source in a young infant due to SARS-CoV-222 Apr 2020United StatesNorth America1Clinical - Clinical Featureshttps://doi.org/10.1093/jpids/piaa044
Carrabba, GLocatelli, MLancetNeurosurgery in an infant with COVID-1922 Apr 2020ItalyEurope1Clinical - Clinical Featureshttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30927-2/fulltext
Kan, M. JGreenhow, T. LJ Pediatric Infect Dis Soc.Fever without a source in a young infant due to SARS-CoV-222 Apr 2020USANorth America1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188112/
Genovese, GMarzano, AVPediatr DermatolVaricella-like exanthem associated with COVID-19 in an 8-year-old girl: A diagnostic clue?21 Apr 2020ItalyEurope1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/pde.14201
Li, HXu, QJ InfectThe Profile of Peripheral Blood Lymphocyte Subsets and Serum Cytokines in Children With 2019 Novel Coronavirus Pneumonia20 Apr 2020ChinaAsia40Clinical - Clinical Featureshttps://www.sciencedirect.com/science/article/pii/S0163445320302073?via%3Dihub
Richardson, SDavidson, KJAMA networkPresenting Characteristics, Comorbidities and Outcomes among 5700 patients hospitalized with COVID-19 in the New York City area20 Apr 2020USANorth America34Clinical - Clinical Featureshttps://jamanetwork.com/journals/jama/fullarticle/2765184
Li, HXu, JJournal of Medical VirologyPositive result of SARS-CoV-2 in faeces and sputum from discharged patient with COVID-19 in Yiwu, China20 Apr 2020ChinaAsia0Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25905
Du, AZhang, ZInfectionClinical characteristics of COVID-19 in children compared with adults in Shandong Province, China16 Apr 2020ChinaAsia14Clinical - Clinical Featureshttps://link.springer.com/article/10.1007%2Fs15010-020-01427-2
Xing, YXing, QJ InfecDynamics of faecal SARS-CoV-2 in infected children during the convalescent phase16 Apr 2020ChinaAsia3Clinical - Clinical Featureshttps://www.journalofinfection.com/article/S0163-4453(20)30177-8/fulltext
Jiang, SYu, XClin Chem Lab MedCoinfection of SARS-CoV-2 and multiple respiratory pathogens in children16 Apr 2020ChinaAsia2Clinical - Clinical Featureshttps://www.degruyter.com/view/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0434/article-10.1515-cclm-2020-0434.xml
See, K CIbrahim Hinternational journal of infectious diseasesCOVID-19: Four paediatric cases in Malaysia15 Apr 2020malaysiaAsia4Clinical - Clinical Featureshttps://www.ijidonline.com/article/S1201-9712(20)30181-8/fulltext
Shi, BXu, HClin PediatrSevere pneumonia due to SARS-CoV-2 and respiratory syncytial virus infection: a case report15 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://journals.sagepub.com/doi/full/10.1177/0009922820920016?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#articleCitationDownloadContainer
Chen, JHuang, AGenes Dis.The clinical and immunological features ofpediatric COVID-19 patients in China14 Apr 2020ChinaAsia12Clinical - Clinical Featureshttps://reader.elsevier.com/reader/sd/pii/S2352304220300507?token=631DD2FAEE11F02D80D1CC96D2AB2621AA7960348DA5FFDD2FAB802D188A0726E724273D5014403A376291F4BD637C50
liu, J.Lu, B.JMVDetection of SARS‐CoV‐2 by RT‐PCR in anal from patients who have recovered from coronavirus disease 201914 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25875
Shen, LLan, JJournal of InfectionClinical and laboratory-derived parameters of 199 hospitalized patients with coronavirus disease 2019 in Xiangyang, Hubei Province, China10 Apr 2020ChinaAsia7Clinical - Clinical Featureshttps://doi.org/10.1016/j.jinf.2020.03.038
He, GCai, JIndian PaediatricsSerial Computed Tomography Findings in a Child with Coronavirus Disease (COVID-19) Pneumonia9 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240233/pdf/13312_2020_Article_1824.pdf
Wang, H.Lu, XiaoxiaPediatric Infectious Disease JournalRehospiatlization of a recovered coronavirus disease 19 (COVID-19) child with positive nucleic acid detection9 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://journals.lww.com/pidj/Abstract/onlinefirst/Rehospitalization_of_a_Recovered_Coronavirus.96214.aspx
Lazerrini, MTrobia, GLancet Child and Adolescent HealthDelayed access of provision of care in Italy resulting from fear of COVID-199 Apr 2020ItalyEurope12Clinical - Clinical Featureshttps://doi.org/10.1016/S2352-4642(20)30108-5
Zhu, CZhu, LPediatric PulmonologyClinical characteristics of a case series of children with coronavirus disease 20198 Apr 2020ChinaAsia10Clinical - Clinical Featureshttps://doi.org/10.1002/ppul.24767
Yuan, JLiu, LClinical Infectious DiseasesPCR assays turned positive in 25 discharged COVID-19 patients8 Apr 2020ChinaAsia6Clinical - Clinical Featureshttps://doi.org/10.1093/cid/ciaa398
Shen, QZhou, ZPediatric PulmonologyNovel coronavirus infection in children outside of Wuhan, China7 Apr 2020ChinaAsia9Clinical - Clinical Featureshttps://doi.org/10.1002/ppul.24762
Lei, PJiao, JJournal of X-ray Science and TechnologyClinical and computed tomographic (CT) images characteristics in the patients with COVID-19 infection: what should radiologists need to know?7 Apr 2020ChinaAsia1Clinical - Clinical Featureshttps://content.iospress.com/articles/journal-of-x-ray-science-and-technology/xst200670
Han, YFang, YJournal of Medical VirologyA comparative-descriptive analysis of clinical characteristics in 2019-coronavirus-infected children and adults6 Apr 2020ChinaAsia7Clinical - Clinical Featureshttps://doi.org/10.1002/jmv.25835
Graselli, GPasenti, AJAMABaseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy6 Apr 2020ItalyEurope4Clinical - Clinical Featureshttps://jamanetwork.com/journals/jama/fullarticle/2764365
Lai, WLiu, JPediatr RadiolComputed tomography of the lungs in novel corona virus (COVID-19) infection6 Apr 2020ChinaAsia2Clinical - Clinical Featureshttps://doi.org/10.1007/s00247-020-04664-7
Canarutto, DBarera, GPediatric PulmonologyCOVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings6 Apr 2020ItalyEurope1Clinical - Clinical Featureshttps://doi.org/10.1002/ppul.24754
Lin, LShan, HGutGastrointestinal symptoms of 95 cases with SARS-CoV-2 infection2 Apr 2020ChinaAsia5Clinical - Clinical Featureshttps://gut.bmj.com/content/early/2020/04/02/gutjnl-2020-321013
Xing, YXing, QJournal of Microbiology, Immunology and Infection.Prolonged viral shedding in feces of pediatric patients with coronavirus disease 201928 Mar 2020ChinaAsia3Clinical - Clinical Featureshttps://dx.doi.org/10.1016%2Fj.jmii.2020.03.021
Yin XLi HRadiology of Infectious DiseasesA mild type of childhood COVID-19 - a case report27 Mar 2020ChinaAsia1Clinical - Clinical Featureshttps://doi.org/10.1016/j.jrid.2020.03.004
Qui, HLancet: Infectious DiseasesClinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study25 Mar 2020ChinaAsia36Clinical - Clinical Featureshttps://doi.org/10.1016/S1473-3099(20)30198-5
Su, LGai, ZEmerging Microbes and InfectionsThe different clinical characteristics of corona virus disease cases between children and their families in China - the character of children with COVID-1925 Mar 2020Asia9Clinical - Clinical Featureshttps://www.tandfonline.com/doi/full/10.1080/22221751.2020.1744483
Zheng, FJin, RCurrent Medical ScienceClinical characteristics of children with coronavirus disease 2019 in Hubei, China24 Mar 2020ChinaAsia25Clinical - Clinical Featureshttps://doi.org/10.1007/s11596-020-2172-6
Lou, XTian, YJournal of Paediatrics and Child HealthThree children who recovered from novel coronavirus 2019 pneumonia22 Mar 2020ChinaAsia3Clinical - Clinical Featureshttps://doi.org/10.1111/jpc.14871
Liu HLan WJournal of InfectionClinical and CT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children21 Mar 2020ChinaAsia4Clinical - Clinical Featureshttps://doi.org/10.1016/j.jinf.2020.03.007
Lu, XWong, GWKNEJMSARS-CoV-2 infection in children18 Mar 2020ChinaAsia171Clinical - Clinical Featureshttps://www.nejm.org/doi/full/10.1056/NEJMc2005073
Cui, YZha, YJournal of Infectious DiseasesA 55-day-old female infant infected with 2019 novel coronavirus disease: presenting with pneumonia, liver injury, and heart damage17 Mar 2020ChinaAsia1Clinical - Clinical Featureshttps://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa113/5807961
Zhang, CZhou, XMedRxIVClinical characteristics of 34 children with coronavirus disease-2019 in the West of China: a multiple-center case series16 Mar 2020ChinaAsia34Clinical - Clinical Featureshttps://www.medrxiv.org/content/10.1101/2020.03.12.20034686v1
Ji, LJian, RWorld Journal of PediatricsClinical features of pediatric patients with COVID-19: a report of two family cluster cases16 Mar 2020ChinaAsia2Clinical - Clinical Featureshttps://dx.doi.org/10.1007/s12519-020-00356-2
Xu, YGong, SNature MedicineCharacteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding13 Mar 2020ChinaAsia10Clinical - Clinical Featureshttps://doi.org/10.1038/s41591-020-0817-4
Liu, WLiu, YNEJMDetection of COVID-19 in children in early January 2020 in Wuhan, China12 Mar 2020ChinaAsia6Clinical - Clinical Featureshttps://doi.org/10.1056/NEJMc2003717
Li, WLi, SPediatric RadiologyChest computed tomography in children with COVID-19 respiratory infection11 Mar 2020ChinaAsia5Clinical - Clinical Featureshttps://doi.org/10.1007/s00247-020-04656-7
Xu, R.Hu, XQuantit Imag Med and SurgCT imaging of one extended family cluster of corona virus disease 2019 (COVID-19) including adolescent patients and "silent infection"10 Mar 2020ChinaAsia1Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136726/
Xia, WHu, DPediatric PulmonologyClinical and CT features in pediatric patients with COVID-19 infection: different points from adults5 Mar 2020ChinaAsia20Clinical - Clinical Featureshttps://doi.org/10.1002/ppul.24718
Lan, L.Xu, H.Korean J RadiolEarly CT Findings of Coronavirus Disease 2019 (COVID-19) in Asymptomatic Children: A Single-Center Experience.4 Mar 2020ChinaAsia4Clinical - Clinical Featureshttps://kjronline.org/Synapse/Data/PDFData/0068KJR/kjr-21-919.pdf
Zhu, YFeng, SJournal of InfectionClinical and CT imaging features of 2019 novel coronavirus disease (COVID-19)3 Mar 2020ChinaAsia1Clinical - Clinical Featureshttps://doi.org/10.1016/j.jinf.2020.03.033
Kai-qian, KThoon, KCClinical Infectious DiseasesA well infant with coronavirus disease 2019 with high viral load28 Feb 2020SingaporeAsia1Clinical - Clinical Featureshttps://doi.org/10.1093/cid/ciaa201
Cai, JZeng, MClinical Infectious DIseasesA case series of children with 2019 novel coronavirus infection: clinical and epidemiological features28 Feb 2020ChinaAsia10Clinical - Clinical Featureshttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa198/5766430
Chen, CWang, FLancet pre-print serverCoronavirus disease-19 among children outside Wuhan, China25 Feb 2020ChinaAsia31Clinical - Clinical Featureshttp://dx.doi.org/10.2139/ssrn.3546071
Xu, XWLi, LJBMJClinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-CoV-2) outside of Wuhan, China: a retrospective case series19 Feb 2020ChinaAsia2Clinical - Clinical Featureshttps://www.ncbi.nlm.nih.gov/pubmed/32075786
Wei, MLiu, YJAMANovel coronavirus infection in hospitalized infants under 1 year of age in China14 Feb 2020ChinaAsia9Clinical - Clinical Featureshttps://doi.org/10.1001/jama.2020.2131
Wilkes, MRapaport RJ of PediatricsSevere COVID-19 in Children and Young Adults.23 Jun 2020USANorth America10Clinical - Comorbiditieshttps://www.jpeds.com/article/S0022-3476(20)30764-2/pdf
Kulkarni, RKJadhav, TIndian Journal of PaediatricsFatal Covid-19 in a Malnourished Child with Megaloblastic Anemia17 Jun 2020IndiaAsia1Clinical - Comorbiditieshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297666/
Yuksel, MAriKan, CEur J Gastroenterol HepatolImmune monitoring of a child with autoimmune hepatitis and type 1 diabetes during COVID-19 infection16 Jun 2020TurkeyMiddle East1Clinical - Comorbiditieshttps://journals.lww.com/eurojgh/Abstract/9000/Immune_monitoring_of_a_child_with_autoimmune.97545.aspx
Akcabelen, Y. M.Yarali, N.Pediatr Blood Cancer: e28443.COVID‐19 in a child with severe aplastic anemia15 Jun 2020TurkeyMiddle East1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28443?af=R
Cesaro, S.Petris, MGPaediatr Blood CancerScreening for SARS-CoV-2 infection in pediatric oncology patients during the epidemic peak in Italy15 Jun 2020ItalyEurope282Clinical - Comorbiditieshttps://doi.org/10.1002/pbc.28466
Flores, VLenica A, CAnn Hematol.SARS-CoV-2 infection in children with febrile neutropenia12 Jun 2020MexicoSouth America3Clinical - Comorbiditieshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289627/
Gine, CLopez, MJ Laparoendosc Adv Surg Tech A .Thoracoscopic Bullectomy for Persistent Air Leak in a 14-Year-Old Child With COVID-19 Bilateral Pulmonary Disease11 Jun 2020SpainEurope1Clinical - Comorbiditieshttps://www.liebertpub.com/doi/abs/10.1089/lap.2020.0289
Anurathapan, U.Hongeng, S.Bone Marrow Transplantation; www.nature.com/bmt/Hematopoietic stem cell transplantation from an infected SARS-CoV2 donor sibling11 Jun 2020ThailandAsia2Clinical - Comorbiditieshttps://www.nature.com/articles/s41409-020-0969-3
Du, HGao, YAllergyClinical characteristics of 182 pediatric COVID‐19 patients with different severities and allergic status10 Jun 2020ChinaAsia183Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/10.1111/all.14452
Sabatino, JDi Salvo, GJ Clin MedCOVID-19 and Congenital Heart Disease: Results from a Nationwide Survey8 Jun 2020ItalyEurope4Clinical - Comorbiditieshttps://www.mdpi.com/2077-0383/9/6/1774
Alloway, B. C.Hardy, G.Radiology Case reportsSuspected case of COVID-19-associated pancreatitis in a child.6 Jun 2020USANorth America1Clinical - Comorbiditieshttps://reader.elsevier.com/reader/sd/pii/S1930043320302569?token=2F2186726A3F368F41FAC9F6CCCAB2CE9CB00D44308E9ADA898D0795CFDBF9CC12EE79807C3C0390C107B51CF81D49EA
Jones, B. A.Slater, B. J.Journal of Pediatric Surgery Case ReportsNon-operative management of acute appendicitis in a pediatric patient with concomitant COVID-19 infection.6 Jun 2020USANorth America1Clinical - Comorbiditieshttps://reader.elsevier.com/reader/sd/pii/S1930043320302569?token=2F2186726A3F368F41FAC9F6CCCAB2CE9CB00D44308E9ADA898D0795CFDBF9CC12EE79807C3C0390C107B51CF81D49EA
Wahlster, LSankaran, VG Pediatr Blood CancerCOVID-19 presenting with autoimmune hemolytic anemia in the setting of underlying immune dysregulation.3 Jun 2020USANorth America1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28382?af=R
Tennuri, UMiyatani, HClinics (Sao Paulo)Low Incidence of COVID-19 in Children and Adolescent Post-Liver Transplant at a Latin American Reference Center3 Jun 2020BrazilSouth America6Clinical - Comorbiditieshttps://www.scielo.br/pdf/clin/v75/1807-5932-clin-75-e1986.pdf
Mirzaree, SMMVossough, ARadiologyFocal Cerebral Arteriopathy in a COVID-19 Pediatric Patient2 Jun 2020IranMiddle East1Clinical - Comorbiditieshttps://pubs.rsna.org/doi/pdf/10.1148/radiol.2020202197
Harman KGupta ALancetEthnicity and COVID-19 in children with comorbidities28 May 2020UKEurope12Clinical - Comorbidities https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30167-X/fulltext
Ferrari, ABalduzzi, APediatr Blood CancerChildren with cancer in the time of COVID-19: An 8-week report from the six pediatric onco-hematology centers in Lombardia, Italy26 May 2020ItalyEurope286Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28410
Issitt, RWSebire, NJmedRxivCoronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population25 May 2020UKEurope166Clinical - Comorbiditieshttps://www.medrxiv.org/content/10.1101/2020.05.20.20107904v1
Barsoum, ZSN Comprehensive Clinical MedicinePediatric Asthma & Coronavirus (COVID-19)-Clinical Presentation in an Asthmatic Child—Case Report19 May 2020Northern IrelandEurope1Clinical - Comorbiditieshttps://link.springer.com/content/pdf/10.1007/s42399-020-00310-3.pdf
Hains, DKrammer, FJAMAAsymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit14 May 2020USANorth America3Clinical - Comorbiditieshttps://jamanetwork.com/journals/jama/fullarticle/2766215
Boulad, FBouvier, NJAMA Oncol.COVID-19 in Children With Cancer in New York City13 May 2020USNorth America20Clinical - Comorbiditieshttps://jamanetwork.com/journals/jamaoncology/fullarticle/2766112
Marlais, MTullus KLancet Child Adolesc HealthThe severity of COVID-19 in children on immunosuppressive medication13 May 2020Multi-countryMulti-region18Clinical - Comorbiditieshttps://www.thelancet.com/pdfs/journals/lanchi/PIIS2352-4642(20)30145-0.pdf
Bush, R.Upadhyay, K.Am J TransplantMild COVID-19 in a Pediatric Renal Transplant Recipient13 May 2020USANorth America1Clinical - Comorbiditieshttps://pubmed.ncbi.nlm.nih.gov/32406181/
Zhao, YGao, GPediatr Infect Dis JFIRST CASE OF CORONAVIRUS DISEASE 2019 IN CHILDHOOD LEUKEMIA IN CHINA12 May 2020ChinaAsia1Clinical - Comorbiditieshttps://journals.lww.com/pidj/Abstract/9000/FIRST_CASE_OF_CORONAVIRUS_DISEASE_2019_IN.96166.aspx
Angelletti, AForno, RClin TransplantRisk of COVID-19 in young kidney transplant recipients. Results from a single-center observational study12 May 2020ItalyEurope64Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.13889
Koczulla, RAKneidinger, NAmerican Journal of TransplantationSARS-CoV-2 infection in two patients following recent lung transplantation12 May 2020GermanyEurope1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.15998
Blanchon, SRochat, IPediatr PulmonolCOVID-19: A Message of Hope From a Young Girl With Severe Cystic Fibrosis11 May 2020SwitzerlandEurope1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/epdf/10.1002/ppul.24812
brenner, EUngaro RGastroenterologyCorticosteroids but not TNF Antagonists are Associated with Adverse COVID-19 Outcomes in Pateitns with Inflammatory Bowel Disease: Results from an International Registry.8 May 2020USANorth America30Clinical - Comorbidities https://www.sciencedirect.com/science/article/pii/S0016508520306557
de Rojas, TPerez-Martinez, APediatric Blood and CancerCOVID-19 Infection in children and adolescents with cancer in Madrid8 May 2020ItalyEurope15Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28397
Andre, NGandemer, VPediatr Blood CancerCOVID-19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms?8 May 2020FranceEurope33Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28392
morand, AFabre AArchives de PediatrieChild with liver transplant recovers from COVID-19 infection. A case report.6 May 2020franceEurope1Clinical - Comorbidities https://www.sciencedirect.com/science/article/pii/S0929693X2030110X
Michelena, XMarsal, S.Med archivesIncidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs5 May 2020SpainEuropeClinical - Comorbiditieshttps://www.medrxiv.org/content/10.1101/2020.04.30.20086090v1.full.pdf
Sieni, EFavre, CBritish Journal of HaematologyFavourable outcome of Coronavirus‐19 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced immunosuppression5 May 2020ItalyEurope1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16781
Melgosa, MPerez-Beltran, VPed NephrolSARS-CoV-2 infection in Spanish children with chronic kidney pathologies1 May 2020SpainEurope16Clinical - Comorbiditieshttps://link.springer.com/content/pdf/10.1007/s00467-020-04597-1.pdf
Odièvre, MCorvol, HAm J HematologyDramatic improvement after Tocilizumab of a severe COVID-19 in a child with sickle cell disease and acute chest syndrome1 May 2020FranceEurope1Clinical - Comorbiditieshttps://onlinelibrary.wiley.com/doi/10.1002/ajh.25855
Inci Yildirim, ATurkmen Karaagac, AIndian PediatricsCOVID-19 in a Young Girl with Restrictive Cardiomyopathy and Chronic Lung Disease30 Apr 2020TurkeyWestern Asia, Southeastern Europe1Clinical - Comorbiditieshttps://www.indianpediatrics.net/june2020/577.pdf
Russell M.Reardon LThe Journal of Heart and Lung TransplantationCOVID-19 in a paediatric heart transplant recipient: Emergence of donor-specific antibodies29 Apr 2020UKEurope1Clinical - Comorbidities https://www.jhltonline.org/article/S1053-2498(20)31532-1/fulltext
Climent, F. J.Pérez-Martínez, ARev Esp Cardiol (Engl Ed).Fatal outcome of COVID-19 disease in a 5-month infant with comorbidities27 Apr 2020SpainEurope12Clinical - Comorbiditieshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183979/pdf/main.pdf
Schwierzeck, VKampmeier, SClin Infect DisFirst reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit27 Apr 2020GermanyEurope13Clinical - Comorbiditieshttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa491/5825509
Chen, YHuang, KDiabetes CareClinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication24 Apr 2020ChinaAsia3Clinical - Comorbiditieshttps://care.diabetesjournals.org/content/early/2020/05/13/dc20-0660
Poli, PBadolato, RJ. Cyst FibrosAsymptomatic case of COVID-19 in an infant with cystic fibrosis14 Apr 2020ItalyEurope1Clinical - Comorbiditieshttps://www.cysticfibrosisjournal.com/article/S1569-1993(20)30096-5/fulltext#%20
Hrusak, OSchrappe, MEur J CancerFlash survey on SARS-CoV-2 infections in pediatric patients on anti-cancer treatment7 Apr 2020International (first author from Czechia)International9Clinical - Comorbiditieshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141482/
Balduzzi, ABiondi, ALancet pre-print serverLessons after the early management of the COVID-19 outbreak in a pediatric transplant and hemato-oncology center embedded within a COVID-19 dedicated hospital in Lombardia, Italy2 Apr 2020ItalyEurope5Clinical - Comorbiditieshttps://dx.doi.org/10.2139/ssrn.3559560
Lagana, SMLefkowitch, JHArchives of Pathology & Laboratory MedicineCOVID-19 associated hepatitis complicating recent living donor liver transplantation2 Apr 2020USANorth America1Clinical - Comorbiditieshttps://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2020-0186-SA
Turner, DRussel, RJournal of Pediatric Gastroenterology and NutritionCOVID-19 and paediatric inflammatory bowel diseases31 Mar 2020InternationalInternational8Clinical - Comorbiditieshttps://doi.org/10.1097/MPG.0000000000002729
D'Antiga, LLiver transplantationCoronaviruses and immunosuppressed patients: the facts during the third epidemic20 Mar 2020ItalyEurope3Clinical - Comorbiditieshttps://doi.org/10.1002/lt.25756
Davies, PRamnarayan, PLancetIntensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study8 July 2020UKEurope78Clinical - PIMS-TShttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30215-7/fulltext#%20
Dufort, EZucker, HNEJMMultisystem Inflammatory Syndrome in Children in New York State29 Jun 2020USANorth America99Clinical - PIMS-TShttps://www.nejm.org/doi/full/10.1056/NEJMoa2021756?query=featured_coronavirus
Feldstein, LRRandolph, AGNEJMMultiststem Inflammatory Syndrome in U.S. Children and Adolescents29 Jun 2020USANorth America186Clinical - PIMS-TShttps://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.nejm.org%2Fdoi%2Ffull%2F10.1056%2FNEJMoa2021680&data=01%7C01%7CA.Munro%40soton.ac.uk%7C44a8f00e84024fc3091408d81ce42e9c%7C4a5378f929f44d3ebe89669d03ada9d8%7C0&sdata=bQRL8Sx61R5%2FkQST67%2FVl9CZj8puJPfyKJCftB6Q9ec%3D&reserved=0
Hameed, SJogeesvaran, K HRadiologySpectrum of Imaging Findings on Chest Radiographs, US, CT, and MRI Images in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.25 Jun 2020UKEurope35Clinical - PIMS-TShttps://pubs.rsna.org/doi/10.1148/radiol.2020202543
Riollano-Cruz, MPaniz-Mondolfi, AJ Med VirolMultisystem Inflammatory Syndrome in Children (MIS‐C) Related to COVID‐19: A New York City Experience25 Jun 2020USANorth America15Clinical - PIMS-TShttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.26224
Chiu, J. S., Samuels-Kalow, MPediatr Cardiol.Kawasaki Disease Features and Myocarditis in a Patient with COVID-1915 Jun 2020USANorth America1Clinical - PIMS-TShttps://link.springer.com/article/10.1007/s00246-020-02393-0
Capone, CDavidson, KJ. PediatrCharacteristics, Cardiac involvement, and Outcomes of Multisystem Inflammatory Disease of Childhood (MIS-C) Associated with SARS-CoV-2 Infection14 Jun 2020USNorth America33Clinical - PIMS-TShttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293762/
Foong Ng, KTang, JWTJournal of Medical VirologyCOVID-19 Multisystem Inflammatory Syndrome in Three Teenagers with Confirmed SARS-CoV-2 Infection13 Jun 2020UKEurope3Clinical - PIMS-TShttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.26206
Kaushik, SMedar, SJ PediatricsMultisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection: A Multi-institutional Study from New York City13 Jun 2020USANorth America33Clinical - PIMS-TShttps://www.jpeds.com/action/showPdf?pii=S0022-3476%2820%2930747-2
Schnapp, AMolho-Pessach, VJ Eur Acad Dermatol VenereolIntroductory histopathologic findings may shed light on COVID19 pediatric hyperinflammatory shock syndrome13 Jun 2020IsraelMiddle East1Clinical - PIMS-TShttps://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.16749
Ramcharan, TChikermane, APediatr Cardiol.Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital12 Jun 2020UKEurope15Clinical - PIMS-TShttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289638/
Pouletty, AMelki, IAnn Rheum DisPaediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort11 Jun 2020FranceEurope16Clinical - PIMS-TShttps://ard.bmj.com/content/annrheumdis/early/2020/06/11/annrheumdis-2020-217960.full.pdf
Blondiaux EDucou le Pointe HRadiologyCardiac MRI of Children with Multisystem Inflammatory Syndrome (MIS-C) Associated with COVID-19: Case Series9 Jun 2020FranceEurope4Clinical - PIMS-TShttps://pubs.rsna.org/doi/10.1148/radiol.2020202288
Cheung, EMilner, JJAMAMultisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City8 Jun 2020USANorth America17Clinical - PIMS-TShttps://jamanetwork.com/journals/jama/fullarticle/2767207?appId=scweb
Whittaker, ELevin, MJAMAClinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-28 Jun 2020UKEurope58Clinical - PIMS-TShttps://jamanetwork.com/journals/jama/fullarticle/2767209
Toubiana, JAllali, SBMJKawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study3 June 2020FranceEurope21Clinical - PIMS-TShttps://www.bmj.com/content/369/bmj.m2094
Grimaud, MOualha, MAnnals of Intensive careAcute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.1 Jun 2020FranceEurope20Clinical - PIMS-TS https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-020-00690-8
Wolfler, AndreaZuccotti, GianvincenzoLancet Child Adolescent Health 2020Acute myocardial injury: a novel pattern in children with Covid-191 Jun 2020ItalyEurope9Clinical - PIMS-TShttps://doi.org/10.1016/s2352-4642(20)30168-1
Greene, ASinert, RAJEMToxic shock-like syndrome and COVID-19: A case report of multisysteminflammatory syndrome in children (MIS-C)31 May 2020USANorth America1Clinical - PIMS-TShttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274960/pdf/main.pdf
Miller, JMargolis, KGastroeneterologyGastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children (MIS-C) that is related to COVID-19 a single center experience of 44 cases30 May 2020USANorth America44Clinical - PIMS-TShttps://www.gastrojournal.org/article/S0016-5085(20)34753-3/pdf
Choitos, KJohn, AJ Pediat Inf Dis SocMultisystem Inflammatory Syndrome in Children during the COVID-19 pandemic: a case series26 May 2020AmericaNorth America6Clinical - PIMS-TShttps://watermark.silverchair.com/piaa069.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAo0wggKJBgkqhkiG9w0BBwagggJ6MIICdgIBADCCAm8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMAzYAZY35QjPArFumAgEQgIICQK8-sXGxb39yAfl4ik-mwJjbAXvX7bOyyGhieI8jCQWnMyNMkHicNgxkAQ1IDQcEsF-HEqz1vHIOQ_Y0L0B7ifNaZCSyZC85BaKZ2opuUBPV-RSkeD6GePxzShamADHXegYfJwSjOFrqfQPgXHO-cAJgcDH2mzPTO8OhjBb-LmbwvLjDWTFA7ZG1nhrCywE0Cv7nYcrCjKpRNicI7_-nVueyWTxweYJp20-ShvmZvyTWmsgN5TywY-dhMu2dcsHU2gbsML77SiooWvCBL1VQGgmCJ07SzwIujblXDu9OjZL-7X5i-CXRX0UJQH1GroCjBZBLpsQQzArTaw_zNC5m3412awRE1nHHNl9cYZhYkqb_19id-XNXeZOg4toLFl-qDzusvGrnag3l3KCjDuYKxvUGyf6WqNK5tmm2ERHvOi3_Sj-kTLQXYM5Q0KoA1h1C8xug9rARJvtko54zlWJIpsJpE5iym--8Ow3TZPoCckrL8tD4jozdw-np4GGf2UOe8gugXm0dZnI1s1iqniJejKKcCQsSjIjGCo5muutOT-BMvYzsqEdftG-fN7dIJ2Wqmh0LMzSkOrocCNplzr3iYxKlnFffWgvYNHhag4l6KGfGTgsNs7IsAMXUOS2QygtZ4rRmgrBs403i4mol8TEUSiWu7DZsf69CbVihRL6mCA1Gh8HTlgFApPkL4ocVlbpJj50B5bTPv60kPtf991srx0pntK-Iof3mWXdkvwiqUvHnrQm5ziWHs1_yRQFKKExdlw
Chang, AHicar, MmedRxivKawasaki Disease serum responses against SARS-CoV-2.26 May 2020United StatesNorth America14Clinical - PIMS-TShttps://www.medrxiv.org/content/10.1101/2020.05.24.20111732v1
Labe, PMahe, EJ Eur Acad Dermatol VenereolErythema multiforme and Kawasaki disease associated with COVID-19 infection in children26 May 2020FranceEurope2Clinical - PIMS-TShttps://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.16666
Waltuch, TGill, PAm J Emerg MedFeatures of COVID-19 post-infectious cytokine release syndrome in children presenting to the emergency department23 May 2020North AmericaNorth America4Clinical - PIMS-TShttps://www.ajemjournal.com/article/S0735-6757(20)30403-4/fulltext#t0005
Acharyya, BDas, DIndian PediatrNovel Coronavirus Mimicking Kawasaki Disease in an Infant22 May 2020IndiaAsia1Clinical - PIMS-TShttps://www.indianpediatrics.net/COVID29.03.2020/CCL-00184.pdf
Deza Leon, MAsmar, BJPIDSCOVID-19–Associated Pediatric Multisystem Inflammatory Syndrome22 May 2020USANorth America1Clinical - PIMS-TShttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa061/5842067
Tullie, LCurry, JThe Lancet. Child & adolescent healthGastrointestinal features in children with COVID-19: an observation of varied presentation in eight children19 May 2020EnglandEurope8Clinical - PIMS-TShttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30165-6/fulltext#articleInformation
Licciardi,FMontin, DPediatricsSAR-Cov2-Induced Kawasaki -Like Hperinflamatory Syndrome: A novel Covid Phenotype in Children19 May 2020ItalyEurope2Clinical - PIMS-TShttps://pediatrics.aappublications.org/content/pediatrics/early/2020/05/19/peds.2020-1711.full.pdf
Belhadjer, ZWacker, JCirculationAcute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic17 May 2020France and SwitzerlandEurope35Clinical - PIMS-TShttps://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.13889
Pain, CHedrich, CLancet RheumatolNovel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms15 May 2020United KingdomEurope1Clinical - PIMS-TShttps://www.thelancet.com/action/showPdf?pii=S2665-9913%2820%2930137-5
Cabrero-Hernandez, MSerrano-Gonzalez, APediatr Infect Dis JSevere SARS-CoV-2 Infection in Children With Suspected Acute Abdomen: A Case Series From a Tertiary Hospital in Spain10 May 2020SpainEurope5Clinical - PIMS-TShttps://journals.lww.com/pidj/Abstract/9000/Severe_SARS_CoV_2_Infection_in_Children_With.96141.aspx
Balasubramanian, SRamanan, AIndian PediatrHyper-inflammatory Syndrome in a Child With COVID-19 Treated Successfully With Intravenous Immunoglobulin and Tocilizumab10 May 2020IndiaAsia1Clinical - PIMS-TShttps://www.indianpediatrics.net/COVID29.03.2020/CCL-00180.pdf
Rivera-Figueroa, ESimpson. SIndian PediatrIncomplete Kawasaki Disease in a Child With Covid-199 May 2020USANorth America1Clinical - PIMS-TShttps://www.indianpediatrics.net/COVID29.03.2020/CCL-00179.pdf
Riphagen, STheocharis, PLancetHyperinflammatory shock in children during COVID-19 pandemic1 May 2020LondonEurope8Clinical - PIMS-TShttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31094-1/fulltext
Jones, VMathew, RHospital PediatricsCOVID-19 and Kawasaki Disease: Novel virus and novel case7 Apr 2020AmericaNorth America1Clinical - PIMS-TShttps://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/hpeds.2020-0123.full.pdf
Pollan, MYotti, RLancetPrevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study6 Jul 2020spainEurope6527Epidemiology - Disease Burdenhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31483-5/fulltext
Gampel, BRoberts, SSPediatr Blood CancerCOVID‐19 disease in New York City pediatric hematology and oncology patients26 Jun 2020USANorth America174Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/10.1002/pbc.28420
Pagani, GGalli, MmedRxivSeroprevalence of SARS-CoV-2 IgG significantly varies with age: results from a mass population screening (SARS-2-SCREEN-CdA)24 Jun 2020ItalyEurope000Epidemiology - Disease Burdenhttps://www.medrxiv.org/content/10.1101/2020.06.24.20138875v1
Rha, BLangley,GJ Pediatric Infect DisSARS-CoV-2 Infections in Children - Multi-Center Surveillance, United States, January-March 2020."18 Jun 2020USANorth America4Epidemiology - Disease Burdenhttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa075/5859277?searchresult=1
Hua, CFu, JJ Med VirolEpidemiological features and viral shedding in children with SARS-CoV-2 infection15 Jun 2020ChinaAsia43Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.26180
Stringhini, SGuessous, IThe LancetSeroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study11 Jun 2020SwitzerlandEurope455Epidemiology - Disease Burdenhttps://doi.org/10.1016/S0140-6736(20)31304-0
Alvarez-Roman, MTJimenez-Yuste, VHaemophiliaREGISTRY OF PATIENTS WITH CONGENITAL BLEEDING AND COVID-19 IN MADRID10 Jun 2020SpainEurope84Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.14089
Belot, ALevy-Bruhl, DEurosurveillanceSARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 20204 Jun 2020FranceEurope156Epidemiology - Disease Burdenhttps://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.22.2001010#t1
Jie QuanYuan LiClin Inect DisAge-dependent gender differences of COVID-19 in mainland China: comparative study30 May 2020ChinaAsia0Epidemiology - Disease Burdenhttps://doi.org/10.1093/cid/ciaa683
Choe, PKim, NKJIMSelecting coronavirus disease 2019 patients with negligible risk of progression: early experience from non-hospital isolation facility in Korea29 May 2020KoreaAsia0Epidemiology - Disease Burdenhttp://kjim.org/upload/kjim-2020-159.pdf
Bandi, SMahdavinia, MPediatr Allergy ImmunolAfrican American children are at higher risk for COVID-19 infection29 May 2020USANorth America474Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/abs/10.1111/pai.13298
Zheng, XChen, JJ. InfectionCo-infection of SARS-CoV-2 and Influenza virus in Early Stage of the COVID-19 Epidemic in Wuhan, China28 May 2020ChinaAsia1Epidemiology - Disease Burdenhttps://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.journalofinfection.com%2Farticle%2FS0163-4453(20)30319-4%2Fpdf&data=02%7C01%7Cdr98%40leicester.ac.uk%7C1a70a2a944e24723c11108d807052900%7Caebecd6a31d44b0195ce8274afe853d9%7C0%7C0%7C637267066036624572&sdata=sL1i5FVbIszDDJ6an2gzf9kXbJakQIakOv4kzeTtDSw%3D&reserved=0
Yang, LLei, YJ Clin VirolEpidemiological and clinical features of 200 hospitalized patients with corona virus disease 2019 outside Wuhan, China: A descriptive study26 May 2020ChinaAsia3Epidemiology - Disease Burdenhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250074/pdf/main.pdf
Phaksy, AGabbie, SEMAResponse to "SARS-CoV-2 Testing and Outcomes in the First 30 Days after the first case of COVID-19 at an Australian Children's Hospital23 May 2020UKEurope18Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/abs/10.1111/1742-6723.13560
Buonsenso, DValentini, PLancet Inf DisToward a clinically based classification of disease severity for paediatric COVID-1915 May 2020ItalyEurope0000Epidemiology - Disease Burdenhttps://doi.org/10.1016/S1473-3099(20)30396-0
Lusignan, SHobs, FLancet Infect DisRisk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study15 May 2020UKEurope23Epidemiology - Disease Burdenhttps://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930371-6
Deng, XYu, HClin Infect DisCase fatality risk of the first pandemic wave of novel coronavirus disease 2019 (COVID-19) in China15 May 2020ChinaAsia996Epidemiology - Disease Burdenhttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa578/5837356
COVID-19 National Incident Room Surveillance TeamCommun Dis IntellCOVID-19, Australia: Epidemiology Report 1515 May 2020AustraliaAustralasia172Epidemiology - Disease Burdenhttps://doi.org/10.33321/cdi.2020.44.43
Yanover, C.Mizrahi, B.Med archivesWhat factors increase the risk of complications in SARS-CoV-2 positive patients? A cohort study in a nationwide Israeli health organization13 May 2020IsraelMiddle East647Epidemiology - Disease Burdenhttps://www.medrxiv.org/content/10.1101/2020.05.07.20091652v2.full.pdf+html
Talarico, VRaiola, GActa Biomed .Preliminary Epidemiological Analysis on Children and Adolescents With Novel Coronavirus Disease (2019-nCoV) in a Central Area of Calabria Region11 May 2020ItalyEurope173Epidemiology - Disease Burdenhttps://www.mattioli1885journals.com/index.php/actabiomedica/article/view/9550/8798
Das, AGopalan, SMedrxivEpidemiology of CoVID-19 and predictors of recovery in the Republic of Korea11 May 2020Republic of KoreaAsia202Epidemiology - Disease Burdenhttps://www.medrxiv.org/content/10.1101/2020.05.07.20094094v1.full.pdf+html
Garazzino, SItalian SITIP-SIP Paediatric Infection Study GroupEurosurveillanceMulticentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 20207 May 2020ItalyEurope168Epidemiology - Disease Burdenhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219028/
Lounis, MElectron J Gen MedA Descriptive Study of the Current Situation of COVID-19 in Algeria6 May 2020AlgeriaAfrica79Epidemiology - Disease Burdenhttps://www.ejgm.co.uk/download/a-descriptive-study-of-the-current-situation-of-covid-19-in-algeria-8287.pdf
Lian, JYang, YWileyEpidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID‐19) from Zhejiang province in China4 May 2020ChinaAsia3Epidemiology - Disease Burdenhttps://onlinelibrary.wiley.com/doi/10.1111/irv.12758
COVID-19 National Incident Room Surveillance TeamCommun Dis IntellCOVID-19, Australia: Epidemiology Report 13 (Reporting Week to 23:59 AEST 26 April 2020)1 May 2020AustraliaInternationalEpidemiology - Disease Burdenhttps://www1.health.gov.au/internet/main/publishing.nsf/Content/1D03BCB527F40C8BCA258503000302EB/$File/epidemiology_report_13_reporting_week_ending_23_59_aest_26_april_2020.pdf
Li, HHe, YFront Med (Lausanne) 7: 190.Age-Dependent Risks of Incidence and Mortality of COVID-19 in Hubei Province and Other Parts of China30 Apr 2020ChinaAsia260Epidemiology - Disease Burdenhttps://www.frontiersin.org/articles/10.3389/fmed.2020.00190/full
Goldstein, ELipsitch, MEurosurveillanceTemporal rise in the proportion of younger adults and older adolescents among coronavirus disease (COVID-19) cases following the introduction of physical distancing measures, Germany, March to April 202030 Apr 2020GermanyEuropeEpidemiology - Disease Burdenhttps://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.17.2000596
Chen, PXu, YJournal of Formosan Medical AssociationEpidemiological and clinical characteristics of 136 cases of COVID-19 in main district of Chongqing29 Apr 2020ChinaAsia4Epidemiology - Disease Burdenhttps://www.sciencedirect.com/science/article/pii/S0929664620301558
Sun, YWang, FJournal of AutoimmunityCharacteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience24 Apr 2020ChinaAsia3Epidemiology - Disease Burdenhttps://www.sciencedirect.com/science/article/pii/S0896841120300895
Nikpouraghdam, MBagheri, MJournal of Clinical VirologyEpidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in iran: A single center study21 Apr 2020IranMiddle East10Epidemiology - Disease Burdenhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172806/pdf/main.pdf
Wang, PChen, SInt. J. Infect. DisStatistical and network analysis of 1212 COVID-19 patients in Henan, China18 Apr 2020ChinaAsia31Epidemiology - Disease Burdenhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180361/pdf/main.pdf
Lavezzo, ECrisanti, AmedRXivSuppression of COVID-19 outbreak in the municipality of Vo, Italy17 Apr 2020ItalyEurope468Epidemiology - Disease Burdenhttps://doi.org/10.1101/2020.04.17.20053157
Randhawa A KJerome K RJAMAChanges in SARS-CoV-2 Positivity Rate in Outpatients in Seattle and Washington State, March 1-April 16, 202015 Apr 2020USANorth America909Epidemiology - Disease Burdenhttps://jamanetwork.com/journals/jama/fullarticle/2766035
Gujski, MPinkas, JMed Sci MonitEpidemiological Analysis of the First 1389 Cases of COVID-19 in Poland: A Preliminary Report15 Apr 2020PolandEurope231Epidemiology - Disease Burdenhttps://www.medscimonit.com/download/index/idArt/924702
Gudbjartsson, FStefansson, KNEJMSpread of SARS-CoV-2 in the Icelandic Population14 Apr 2020IcelandEurope1412Epidemiology - Disease Burdenhttps://www.nejm.org/doi/full/10.1056/NEJMoa2006100
Amira, YWakita, TEmerg Infect DisSevere Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 202010 Apr 2020JapanAsia10Epidemiology - Disease Burdenhttps://wwwnc.cdc.gov/eid/article/26/7/20-0994_article
Santacroce, LDel Prete, REJGMCOVID-19 in Italy: An Overview from the First Case to Date8 Apr 2020ItalyEurope1Epidemiology - Disease Burdenhttps://www.ejgm.co.uk/article/covid-19-in-italy-an-overview-from-the-first-case-to-date-7926
Tagarro, AJAMA PedScreening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain8 Apr 2020SpainEurope365Epidemiology - Disease Burdenhttps://jamanetwork.com/journals/jamapediatrics/fullarticle/2764394
CDCMMRWCoronavirus Disease 2019 in Children — United States, February 12–April 2, 20206 Apr 2020USANorth America2572Epidemiology - Disease Burdenhttp://dx.doi.org/10.15585/mmwr.mm6914e4
Bialek, SSauber-Schatz, ECDC + Morb Mortal Wkly RepSevere Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 202018 Mar 2020USAAmerica123Epidemiology - Disease Burdenhttps://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm?s_cid=mm6912e2_w
LivingstonBucherLancetCoronavirus Disease 2019 (COVID-19) in Italy17 Mar 2020ItalyEurope250Epidemiology - Disease Burdenhttps://jamanetwork.com/journals/jama/fullarticle/2763401
Choe, YMedRxIVCoronavirus disease-19: The First 7,755 Cases in the Republic of Korea15 Mar 2020South KoreaAsia480Epidemiology - Disease Burdenhttps://doi.org/10.1101/2020.03.15.20036368
Dong, YTong, SPediatricsEpidemiology of COVID-19 Among Children in China1 Mar 2020ChinaAsia2135Epidemiology - Disease Burdenhttps://pediatrics.aappublications.org/content/early/2020/03/16/peds.2020-0702
Wu, ZMcGoogan, JJAMACharacteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China; Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention24 Feb 2020ChinaAsia1400Epidemiology - Disease Burdenhttps://jamanetwork.com/journals/jama/fullarticle/2762130
Yung CFThoon KCJ PediatrHousehold Transmission of SARS-CoV-2 from Adults to Children2 Jul 2020SingaporeAsia213Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334921/
L'Huillier, AEckerle, IEmerg Infect Dis.Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents30 Jun 2020SwitzerlandEurope23Epidemiology - Transmissionhttps://wwwnc.cdc.gov/eid/article/26/10/20-2403_article#suggestedcitation
Fontanet, AHoen, BmedRxivSARS-CoV-2 infection in primary schools in northern France: A retrospective cohort study in an area of high transmission29 Jun 2020FranceEurope510Epidemiology - Transmissionhttps://www.medrxiv.org/content/10.1101/2020.06.25.20140178v2
Yung, CNg, KClincal infectious diseasesNovel coronavirus 2019 transmission risk in educational settings25 Jun 2020SingaporeAsia119Epidemiology - Transmissionhttps://doi.org/10.1093/cid/ciaa794
Wongsawat, JDisthakumpa, AJ Paediatr Child HealthRisk of novel coronavirus 2019 transmission from children to caregivers: A case series22 Jun 2020ThailandAsia3Epidemiology - Transmissionhttps://onlinelibrary.wiley.com/doi/full/10.1111/jpc.14965
Ferraiolo AArioni CMedicinaReport of Positive Placental Swabs for SARS-CoV-2 in an Asymptomatic Pregnant Woman with COVID-1922 Jun 2020ItalyEurope1Epidemiology - Transmissionhttps://doi.org/10.3390/medicina56060306
Tomb, RGunson, RJ InfectRetrospective screening for SARS-CoV-2 in Greater Glasgow and Clyde ICUs between December 2019 and February 202015 Jun 2020ScotlandEurope23Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295493/
Rovida, F.Cereda, D.Clin Microbiol InfectLow risk for SARS-CoV2 symptomatic infection and early complications in paediatric patients during the ongoing CoVID19 epidemics in Lombardy12 Jun 2020ItalyEurope27Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289743/
Kayem, G.Winer, N.J Gynecol Obstet Hum ReprodA snapshot of the Covid-19 pandemic among pregnant women in France4 Jun 2020FranceEurope181Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270811
Han, MChoi, EEmerg Infect DisViral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul4 Jun 2020South KoreaAsia12Epidemiology - Transmissionhttps://wwwnc.cdc.gov/eid/article/26/10/20-2449_article
Gao, Y.Xu, R.Indian J Pediatr.Clinical Features and Treatment Protocol in Eleven Chinese Children with Mild COVID-194 Jun 2020ChinaAsia11Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269701/
Nassih, HSab, IIndian J PediarAbsence of Evidence of Transmission of Coronavirus Disease 2019 from a Young Child to Mother Despite Prolonged Contact1 Jun 2020MoroccoNorth Africa1Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292798/pdf/12098_2020_Article_3382.pdf
Somekh, EStein, MPaediatric infectious disease journalThe Role of Children in the Dynamics of Intra Family Coronavirus 2019 Spread in Densely Populated Area1 Jun 2020IsraelMiddle East58Epidemiology - Transmissionhttps://journals.lww.com/pidj/Abstract/9000/The_Role_of_Children_in_the_Dynamics_of_Intra.96128.aspx
Behera, P.Parameswaran, G.F1000Research 9 (no pagination)(315)SARS-CoV-2 epidemic in India: epidemiological features and in silico analysis of the effect of interventions30 May 2020IndiaAsia109Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262570/
Wong, JChaw, L Influenza Other Respir VirusesAsymptomatic transmission of SARS‐CoV‐2 and implications for mass gatherings30 May 2020MalaysiaAsia2Epidemiology - Transmissionhttps://onlinelibrary.wiley.com/doi/full/10.1111/irv.12767
Yang, MSu, WPublic HealthA three-generation family cluster with COVID-19 infection: should quarantine be prolonged?30 May 2020TaiwanAsia1Epidemiology - Transmissionhttps://www.sciencedirect.com/science/article/pii/S0033350620302055
Heavy, LMcDarby, GEuro Surveill No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 202028 May 2020IrelandEurope3Epidemiology - Transmissionhttps://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.21.2000903
Chen, MZhao, DJournal of Infection and Public HealthA SARS-CoV-2 familial cluster infection reveals asymptomatic transmission to children27 May 2020ChinaAsia2Epidemiology - Transmissionhttps://doi.org/10.1016/j.jiph.2020.05.018
Posfay-Barbe, KL'Huillier, APediatrCOVID-19 in Children and the Dynamics of Infection in Families26 May 2020SwitzerlandEurope40Epidemiology - Transmissionhttps://doi.org/10.1542/peds.2020-1576
De Ioris, MRaponi, MJ Pediatric Infect Dis SocDynamic viral SARS-CoV-2 RNA shedding in children: preliminary data and clinical consideration of Italian regional center23 May 2020ItalyEurope22Epidemiology - Transmissionhttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa065/5842265?searchresult=1
Wolf, GProtzer, UJ Paed Inf Dis SocClinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic SARS-CoV-2 Infection22 May 2020GermanyEurope3Epidemiology - Transmissionhttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa060/5842074
Yuan, CXiao, HEmerging microbes & infectionsViral loads in throat and anal swabs in children infected with SARS-CoV-218 May 2020ChinaAsia2138Epidemiology - Transmissionhttps://www.tandfonline.com/doi/pdf/10.1080/22221751.2020.1771219?needAccess=true
Zhao FLiu YJ GastroThe Time Sequences of Oral and Fecal Viral Shedding of Coronavirus Disease 2019 (COVID-19) Patients16 May 2020ChinaAsia30Epidemiology - Transmission https://www.gastrojournal.org/article/S0016-5085(20)30663-6/pdf
Rosenberg, ENew York State Coronavirus 2019 Response TeamClinical Infectious DiseasesCOVID-19 Testing, Epidemic Features, Hospital Outcomes and Household Prevalence, New York State - March 20208 May 2020USANorth America50Epidemiology - Transmissionhttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa549/5831986
Mao, LYuan, ZBMJ Infect DisA child with household transmitted COVID-197 May 2020ChinaAsia1Epidemiology - Transmissionhttps://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05056-w
Zhang, JYu, HScienceChanges in contact patterns shape the dynamics of the COVID-19 outbreak in China29 Apr 2020ChinaAsia756Epidemiology - Transmissionhttps://science.sciencemag.org/content/early/2020/04/28/science.abb8001
Jiang XQiu JJ Med VirolAsymptomatic SARS‐CoV‐2 infected case with viral detection positive in stool but negative in nasopharyngeal samples lasts for 42 days24 Apr 2020ChinaAsia1Epidemiology - Transmissionhttps://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25941
Luo, YXiao, WEmerg Infect DisAsymptomatic SARS-CoV-2 infection in household contacts of a healthcare provider, Wuhan, China.24 Apr 2020ChinaAsia2Epidemiology - Transmissionhttps://wwwnc.cdc.gov/eid/article/26/8/20-1016_articlehttps://dontforgetthebubbles.com/wp-content/uploads/2020/05/Salvatori-2.png
Song, RLi, XJ. Infect.Clinical and epidemiological features of COVID-19 family clusters in Beijing, China23 Apr 2020ChinaAsia7Epidemiology - Transmissionhttps://www.journalofinfection.com/article/S0163-4453(20)30229-2/pdf
Liu, SKuo, HJ Med VirolThree Taiwan's domestic family cluster infectionsof coronavirus disease 201923 Apr 2020TaiwanAsia1Epidemiology - Transmissionhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25949
Jiang, XMa, MJ. Infect.Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China22 Apr 2020ChinaAsia1Epidemiology - Transmissionhttps://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa206/5823691
Li, WChen, JClinical Infectious DiseasesThe characteristics of household transmission of COVID-1917 Apr 2020ChinaAsia100Epidemiology - Transmissionhttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa450/5821281
Jing, QYang, YmedRxiv (preprint)Household secondary attack rate of COVID-19, and associated determinants15 Apr 2020ChinaAsia254Epidemiology - Transmissionhttps://www.medrxiv.org/content/10.1101/2020.04.11.20056010v1
Danis, KSaura, CClinical Infectious DiseasesCluster of coronavirus disease 2019 (Covid-19) in the French Alps, 202011 Apr 2020FranceEurope1Epidemiology - Transmissionhttps://doi.org/10.1093/cid/ciaa424
Pan, AWang, CJAMAAssociation of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China10 Apr 2020ChinaAsia536Epidemiology - Transmissionhttps://jamanetwork.com/journals/jama/fullarticle/2764658
Xiao, ZZheng, TJ Infect Dev CountrExamining the incubation period distributions of COVID-19 on Chinese patients with different travel histories8 Apr 2020ChinaAsiaEpidemiology - Transmissionhttps://jidc.org/index.php/journal/article/view/32379707/2227
Zhu, YShort, KMedRxivChildren are unlikely to have been the primary source of household SARS-CoV-2 infections30 Mar 2020InternationalInternational19Epidemiology - Transmissionhttps://doi.org/10.1101/2020.03.26.20044826
Davies, NJit, MMedRxivAge-dependent effects in the transmission and control of COVID-19 epidemics24 Mar 2020UKEuropeEpidemiology - Transmissionhttps://doi.org/10.1101/2020.03.24.20043018
wang, ZZhang, RJournal of infectionHousehold transmission of SARS-CoV-221 Mar 2020chinaAsia18Epidemiology - Transmission https://www.journalofinfection.com/article/S0163-4453(20)30169-9/pdf
COVID-19 National Emergency Response Center, Epidemiology and Case Management Team, Korea Centers for Disease Control and PreventionOsong Public Health Res PerspectCoronavirus Disease-19: Summary of 2,370 Contact Investigations of the First 30 Cases in the Republic of Korea20 Mar 2020South KoreaAsia155Epidemiology - Transmissionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104686/pdf/ophrp-11-81.pdf
Mizumoto, KNishiura, HMedRxIVAge specificity of cases and attack rate of novel coronavirus disease (COVID-19)13 Mar 2020JapanAsia176Epidemiology - Transmissionhttps://doi.org/10.1101/2020.03.09.20033142
Bi, QFeng, TMedRxIVEpidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts24 Feb 2020ChinaAsia20Epidemiology - Transmissionhttps://doi.org/10.1101/2020.03.03.20028423
Pan, XLiu, JLancet: Infectious DiseasesAsymptomatic cases in a family cluster with SARS-CoV-2 infection19 Feb 2020ChinaAsia1Epidemiology - Transmissionhttps://doi.org/10.1016/S1473-3099(20)30114-6
Fuk-Woo Chan, JYuen, KYLancetA familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster24 Jan 2020ChinaAsia1Epidemiology - Transmissionhttps://doi.org/10.1016/S0140-6736(20)30154-9
Hantoushzadeh, S.Aagaard, K.American Journal of Obstetrics and GynecologyMaternal death due to COVID-191 Jul 2020IranMiddle East9Neonatalhttps://www.sciencedirect.com/science/article/pii/S0002937820305160
Chhabra, A.Subramaniam, RIndian Journal of AnaesthesiaAnaesthetic management of a COVID-19 parturient for caesarean section - Case report and lessons learnt.23 Jun 2020IndiaAsia1Neonatalhttp://www.ijaweb.org/article.asp?issn=0019-5049;year=2020;volume=64;issue=14;spage=141;epage=143;aulast=Chhabra
NawsherwanWang, SIndian J PediatrImpact of COVID-19 Pneumonia on Neonatal Birth Outcomes22 Jun 2020ChinaAsia7Neonatalhttps://link.springer.com/content/pdf/10.1007/s12098-020-03372-2.pdf
Nyholm, SDiderholm, BActa PaediatricaInvasive mechanical ventilation in a former preterm infant with COVID‐1922 Jun 2020SwedenEurope2Neonatalhttps://onlinelibrary.wiley.com/doi/epdf/10.1111/apa.15437
Deng, G.Yin, M.J HepatolCharacteristics of pregnant COVID-19 patients with liver injury.20 Jun 2020ChinaAsia6Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305728/
MMcDevitt, KPathak, S.J InfectOutcome of universal screening of neonates for COVID-19 from asymptomatic mothers19 Jun 2020UKEurope9Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303651/
Dong, YChen, WEmerging Microbes & InfectionsAntibodies in the breast milk of a maternal woman with COVID-1918 Jun 2020ChinaAsia1Neonatalhttps://www.tandfonline.com/doi/full/10.1080/22221751.2020.1780952
Khoury, RDolan, SObstet GynecolCharacteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers16 Jun 2020USANorth America245Neonatal https://journals.lww.com/greenjournal/Abstract/9000/Characteristics_and_Outcomes_of_241_Births_to.97310.aspx
Blitz, MNimaroff, MAm J Obstet GynecolMaternal mortality among women with coronavirus disease 2019 admitted to the intensive care unit15 Jun 2020USANorth America7Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294262/pdf/main.pdf
Sentiles, LDeruelle, PAm J Obstet GynecolCOVID-19 in pregnancy was associated with maternal morbidity and preterm birth15 Jun 2020FranceEurope21Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294260/pdf/main.pdf
Griffin, ISchenkman, AAm J PerinatolThe Impact of COVID-19 Infection on Labor and Delivery, Newborn Nursery, and Neonatal Intensive Care Unit: Prospective Observational Data from a Single Hospital System13 Jun 2020USANorth America62Neonatal https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0040-1713416
Bani Hani, D. A.Aleshawi, A. J.Am J Case ReportsSuccessful Anesthetic Management in Cesarean Section for Pregnant Woman with COVID-19.12 Jun 2020JordonMiddle East1Neonatalhttps://www.amjcaserep.com/download/index/idArt/925512
Preßler, JWellmann, SPediatric Allergy & ImmunologyPostnatal SARS-CoV-2 Infection and Immunological Reaction: A Prospective Family Cohort Study9 Jun 2020GermanyEurope61Neonatalhttps://onlinelibrary.wiley.com/doi/epdf/10.1111/pai.13302
Kmietowicz, Z.Kmietowicz, Z.BMJCharacteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study8 Jun 2020UKEurope12Neonatalhttps://doi.org/10.1136/bmj.m2107
Martínez-Perez, OBaud, DJAMAAssociation Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain8 Jun 2020SpainEurope78Neonatal https://jamanetwork.com/journals/jama/fullarticle/2767206
Gregorio-Hernandez, RMartinez-Gimeno, AEur J PediatrPoint-of-care lung ultrasound in three neonates with Covid-195 Jun 2020SpainEurope3Neonatalhttps://link.springer.com/article/10.1007/s00431-020-03706-4
Silverstein, J. S.Penfield, C. AAJPAcute Respiratory Decompensation Requiring Intubation in Pregnant Women with SARS-CoV-2 (COVID-19)4 Jun 2020USANorth America2Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272216/
White ADietz RNeonatologyNeonates Hospitalized with CommunityAcquired SARS-CoV-2 in a Colorado Neonatal Intensive Care Unit4 Jun 2020USANorth America3Neonatalhttps://www.karger.com/Article/Abstract/508962
San-Juan, RAguado, JLancetIncidence and clinical profiles of COVID-19 pneumonia in pregnant women: A single-centre cohort study from Spain1 Jun 2020SpainEurope6Neonatalhttps://www.thelancet.com/action/showPdf?pii=S2589-5370%2820%2930151-6
Luo, QChen, HPre printSafety of Breastfeeding in Mothers with SARS-CoV-2 Infection1 Jun 2020ChinaAsia23Neonatalhttps://www.medrxiv.org/content/10.1101/2020.05.30.20033407v1
Piersigilli, FDanhaive, OThe Lancet, Child & Adolescent HealthCOVID-19 in a 26-week preterm neonate1 Jun 2020BelgiumEurope1Neonatalhttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30140-1/fulltext
Zhu, CXia, YJ InfectRisk from Detectable Severe Acute Respiratory Syndrome Coronavirus 2 in Breastmilk1 Jun 2020ChinaAsia5Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270809/
Breslin, ND'Alton, MGynecology MFMCoronavirus disease 2019 in pregnancy: early lessons27 May 2020USANorth America2Neonatalhttps://reader.elsevier.com/reader/sd/pii/S2589933320300410?token=4C959DDF7EB12D7B76B1E63FA1F96A0989263A0BB2CECE20E5FCBFB628A46B1701A439F7D08AD5DEFCC46CCEBD5E24F0
Yilmaz, RUzun, STJ Clin AnesthAnesthetic management for cesarean birth in pregnancy with the novel coronavirus (COVID-19)27 May 2020TurkeyEurope1Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250746/pdf/main.pdf
Fontanella, F.t Baalman, J. H. Eur J Obstet Gynecol Reprod Biol.COVID-19 infection during the third trimester of pregnancy: Current clinical dilemmas.26 May 2020Netherlands and Ireland, UKEurope2Neonatalhttps://www.ejog.org/article/S0301-2115(20)30337-7/fulltext
Campbell, KPettker, CMJAMAPrevalence of SARS-CoV-2 Among Patients Admitted for Childbirth in Southern Connecticut26 May 2020USANorth America30Neonatalhttps://jamanetwork.com/journals/jama/fullarticle/2766650
Salik, IMehta, BJournal of Clinical AnesthesiaTetralogy of Fallot palliation in a COVID-19 positive neonate25 May 2020USANorth America1Neonatalhttps://www.sciencedirect.com/science/article/pii/S0952818020308540?via%3Dihub
Carvalho, WJohnston, CClinicsNeonatal SARS-CoV-2 infection25 May 2020BrazilSouth America1Neonatalhttps://www.clinicsjournal.com/wp-content/uploads/articles_xml/1807-5932-clin-75-e1996/1807-5932-clin-75-e1996.pdf
Tang, MWBiermond, BJAm J HematolImmune Thrombocytopenia during Pregnancy due to COVID-1923 May 2020NetherlandsEurope1Neonatalhttps://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.25877
McLaren, RAMinkoff, HLAJOGDelivery for respiratory compromise among pregnant women with coronavirus disease 201923 May 2020USANorth America9Neonatalhttps://www.ajog.org/action/showPdf?pii=S0002-9378%2820%2930567-6
Precit, MBard, JJ Paediatric Infect Dis SocA Case Report of Neonatal Acute Respiratory Failure Due to SARS-CoV-222 May 2020USANorth America1Neonatalhttps://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa064/5842097
Pereira, APerez-Medina, TActa Obstetricia et Gynecologica ScandinavaClinical course of coronavirus disease‐2019 in pregnancy22 May 2020SpainEurope23Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.13921
Alsharaydeh, IObeidat, NInt J Gynaecol ObstetChallenges and solutions for maternity and gynecology services during the COVID-19 crisis in Jordan22 May 2020JordanMiddle East2Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/ijgo.13240
Groß, RMünch, JLancetDetection of SARS-CoV-2 in human breastmilk21 May 2020GermanyEurope2Neonatal https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31181-8.pdf
Perrone, SEsposito, SJ Med VirolLack of viral transmission to preterm newborn from a COVID‐19 positive breastfeeding mother at 11 days postpartum21 May 2020ItalyEurope1Neonatalhttps://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26037
Zeng, YChen, DObstetrics & GynaecologyUpdate on clinical outcomes of women with COVID‐19 during pregnancy21 May 2020ChinaAsia16Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/ijgo.13236
Qadri, FMariona, FJ Matern Fetal Neonatal MedPregnancy affected by SARS-CoV-2 infection: a flash report from Michigan20 May 2020USANorth America16Neonatalhttps://www.tandfonline.com/doi/full/10.1080/14767058.2020.1765334
Joudi, NLyell, DAmerican Journal of Obstetrics & Gynecology MFMPreeclampsia treatment in severe acute respiratory syndrome coronavirus 220 May 2020AmericaNorth America1Neonatalhttps://www.sciencedirect.com/science/article/pii/S2589933320300902
Du, YLv, JJ Anesth.Anesthesia and protection in an emergency cesarean section for pregnant woman infected with a novel coronavirus: case report and literature review.19 May 2020ChinaAsia1Neonatalhttps://link.springer.com/article/10.1007/s00540-020-02796-6
Savasi, VCetin, IObstetrics & GynecologyClinical Findings and Disease Severity in Hospitalized Pregnant Women with Coronavirus Disease 2019 (COVID-19)19 May 2020ItalyEurope57Neonatalhttps://journals.lww.com/greenjournal/Abstract/9000/Clinical_Findings_and_Disease_Severity_in.97347.aspx?sessionEnd=true
Yu, YShen, Y Int J Gynecol ObstetSevere COVID‐19 in a pregnant patient admitted to hospital in Wuhan19 May 2020ChinaAsia1Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13232
Lokken E. M.Rah, SAmerican Journal of Obstetrics and GynecologyClinical Characteristics of 46 Pregnant Women with a SARS-CoV-2 Infection in Washington State19 May 2020USANorth America8Neonatalhttps://www.sciencedirect.com/science/article/pii/S0002937820305585
Yang, HXiong, GArchivesEffects of SARS-CoV-2 infection on pregnant women and their infants: A retrospective study in Wuhan, China19 May 2020ChinaAsia24Neonatalhttps://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2020-0232-SA
London, VMinkoff, HAM J PerinatolThe Relationship between Status at Presentation and Outcomes among Pregnant Women with COVID-1919 May 2020USANorth America55Neonatalhttps://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0040-1712164.pdf
Ahmed, I.Tan, B.K.British Journal of HaematologyFirst Covid‐19 maternal mortality in the UK associated with thrombotic complications18 May 2020United KingdomEurope1Neonatalhttps://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.16849?af=R
Patane, LCornolti, GAJOG MFMVertical transmission of Covid-19: SARS-CoV-2 RNA on the fetal side of the placenta in pregnancies with Covid-19 positive mothers and neonates at birth18 May 2020ItalyEurope2Neonatalhttps://www.sciencedirect.com/science/article/pii/S2589933320300896
Panichaya, PUthaisan, JEur J Obstet Gynecol Reprod BiolProlonged viral persistence in COVID-19 second trimester pregnant patient18 May 2020ThailandAsia1Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233222/pdf/main.pdf
Fang, HDunjin, CObstetrics & GynaecologyBe aware of misdiagnosis—Influenza A H1N1 in a pregnant patient with suspected COVID‐1918 May 2020ChinaAsia1Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/ijgo.13183
2. Dumpa, VNoor, ACureusNeonatal Coronavirus 2019 (COVID-19) Infection: A Case Report and Review of Literature17 May 2020USANorth America1Neonatalhttps://www.cureus.com/articles/32203-neonatal-coronavirus-2019-covid-19-infection-a-case-report-and-review-of-literature
Mehta, HRezai, FElsevierNovel coronavirus-related acute respiratory distress syndrome in a patient with twin pregnancy: A case report16 May 2020USANorth America2Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229956/pdf/main.pdf
Cooke, WSoulsby, KEur J Obstet Gynecol Reprod Biol.SARS-CoV-2 infection in very preterm pregnancy: Experiences from two cases15 May 2020United KingdomEurope2Neonatalhttps://www.ejog.org/article/S0301-2115(20)30276-1/pdf
Doria, MSilva, PTEur J of O&G & Reproductive BiolCovid-19 during pregnancy: a case series from an universally tested population from the north of Portugal15 May 2020PortugalEurope11Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227580/pdf/main.pdf
Calderaro AChezzi CInt J Infect DisSARS-CoV-2 infection diagnosed only by cell culture isolation before the local outbreak in an Italian seven-week-old suckling baby14 May 2020ItalyEurope1Neonatalhttps://www.ijidonline.com/article/S1201-9712(20)30342-8/fulltext
Kirtsman, MSha, PcmajProbable congenital SARS-Cov-2 infection in a neonate born to a woman with active SARS-Cov-2 infection14 May 2020CanadaNorth America1Neonatalhttps://www.cmaj.ca/content/cmaj/early/2020/05/14/cmaj.200821.full.pdf
Taghizadieh, A Valizadeha, HRespiratory Medicine Case ReportsAcute kidney injury in pregnant women following SARS-CoV-2 infection: A case report from Iran.13 May 2020IranMiddle East1Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219375/
Baergen, RHeller, DPediatr Devel PatholPlacental Pathology in Covid-19 Positive Mothers: Preliminary Findings.12 May 2020United statesNorth America20Neonatalhttps://journals.sagepub.com/doi/pdf/10.1177/1093526620925569
Lorenz, NGrober, KThe Pediatric Infectious Disease JournalNeonatal Early-Onset Infection With SARS-CoV-2 in a Newborn Presenting With Encephalitic Symptoms12 May 2020GermanyEurope1Neonatalhttps://journals-lww-com.libproxy.ucl.ac.uk/pidj/Citation/9000/Neonatal_Early_Onset_Infection_With_SARS_CoV_2_in.96175.aspx
Liu, PZhang, YJ Allergy Clin ImmunolThe immunologic status of newborns born to SARS-CoV2-infected mothers in Wuhan, China11 May 2020ChinaAsia51Neonatalhttps://www.sciencedirect.com/science/article/pii/S0091674920306400
Polonia-Valente, RRodriguez, TEur J Obstet Gynecol Reprod Biol.Vaginal delivery in a woman infected with SARS-CoV-2 – The first case reported in Portugal11 May 2020PortugalEurope1Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211642/
Perrone, SEsposito, SActa BiomedReport of a series of healthy term newborns from convalescent mothers with COVID-19.11 May 2020ItalyEurope4Neonatalhttps://europepmc.org/article/med/32420961
Liu, PZhang, YJACIThe immunologic status of newborns born to SARS-CoV-2–infected mothers in Wuhan, China11 May 2020ChinaAsia51Neonatalhttps://www.sciencedirect.com/science/article/pii/S0091674920306400
Kuhrt, KShennan, AAm J Obstet Gynecol MFMPlacental abruption in a twin pregnancy at 32 weeks’ gestation complicated by coronavirus disease 2019 without vertical transmission to the babies8 May 2020UKEurope2Neonatalhttps://www.sciencedirect.com/science/article/pii/S2589933320300781
Algarroba, GVintzileos, AAJOGVizulaisation of SARS-CoV-2 virus invading the human placenta using electron microscopy8 May 2020USANorth America1Neonatalhttps://www.sciencedirect.com/science/article/pii/S0002937820305494
Blauvelt, CGaw, SObstet Gynecol.Acute Respiratory Distress Syndrome in a Preterm Pregnant Patient With Coronavirus Disease 2019 (COVID-19)8 May 2020USANorth America1Neonatalhttps://journals.lww.com/greenjournal/Abstract/9000/Acute_Respiratory_Distress_Syndrome_in_a_Preterm.97348.aspx
Vallejo, V.Ilagan, J.G.Obstetrics & GynecologyA Postpartum Death Due to Coronavirus Disease 2019 (COVID-19) in the United States.8 May 2020USANorth America1Neonatalhttps://journals.lww.com/greenjournal/Abstract/9000/A_Postpartum_Death_Due_to_Coronavirus_Disease_2019.97350.aspx
Lang, G.JZhao, H Zhejiang Univ-Sci B (Biomed & Biotechnol)Can SARS-CoV-2-infected women breastfeed after viral clearance?*8 May 2020ChinaAsia1Neonatalhttps://link.springer.com/content/pdf/10.1631/jzus.B2000095.pdf
Fox, APowell, RmedRxivEvidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-198 May 2020USANorth America15Neonatalhttps://www.medrxiv.org/content/10.1101/2020.05.04.20089995v1.full.pdf
Munoz, A CBoukas, KNEJMLate-onset neonatal sepsis in a patient with covid-197 May 2020USANorth America1Neonatalhttps://www.nejm.org/doi/full/10.1056/NEJMc2010614
Govind, AYoong, WEur J Obstet Gynecol Reprod Biol .Re: Novel Coronavirus COVID-19 in Late Pregnancy: Outcomes of First Nine Cases in an Inner City London Hospital7 May 2020United KingdomEurope9Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204671/pdf/main.pdf
Ochiai, D.Tanaka, MInt J Gynaecol Obstet.Universal screening for SARS-CoV-2 in asymptomatic obstetric patients in Tokyo, Japan6 May 2020JapanAsia52Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/ijgo.13252
An, P.Ye, Y.CMAJPostpartum exacerbation of antenatal COVID-19 pneumonia in 3 women6 May 2020ChinaAsia3Neonatalhttps://www.cmaj.ca/content/cmaj/early/2020/05/06/cmaj.200553.full.pdf
Ng, KTang, JPediatr Infect DisCOVID-19 in Neonates and Infants: Progression and Recovery6 May 2020UKEurope8Neonatalhttps://journals.lww.com/pidj/Abstract/9000/COVID_19_in_Neonates_and_Infants__Progression_and.96180.aspx
Li, JChen, DInt J Gynaecol ObstetCritically ill pregnant patient with COVID-19 and neonatal death within two hours of birth5 May 2020ChinaAsia1Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/ijgo.13189
Wu, YHuang, HBJOGCoronavirus disease 2019 among pregnant Chinese women: Case series data on the safety of vaginal birth and breastfeeding5 May 2020ChinaAsia5Neonatalhttps://pubmed.ncbi.nlm.nih.gov/32369656/
Hirshberg, A.Srinivas, S. K.Am J Obst & GynCare of critically ill pregnant patients with coronavirus disease 2019: a case series.3 May 2020USANorth America3Neonatalhttps://www.ajog.org/action/showPdf?pii=S0002-9378%2820%2930515-9
De Socio, G. V.Francisci, DMed J Hematol & Infect disDelivery in Asymptomatic Italian Woman with SARS-CoV-2 Infection.1 May 2020ItalyEuropeNeonatalhttps://www.mjhid.org/index.php/mjhid/article/view/2020.033/3768
Baud, DPomar, LJAMASecond-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection30 Apr 2020SwitzerlandEurope1Neonatalhttps://jamanetwork.com/journals/jama/fullarticle/2765616
Xu, L.Wang, L.Sci Bull (Beijing)Clinical presentations and outcomes of SARS-CoV-2 infected pneumonia in pregnant women and health status of their neonates28 Apr 2020ChinaAsia5Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186128/
Sun, MZhang, JBJAEvidence of mother-to-newborn infection with Covid-1927 Apr 2020ChinaAsia3Neonatalhttps://bjanaesthesia.org/article/S0007-0912(20)30281-6/fulltext
Ferrazzi, ECetin, IBJOGVaginal delivery in SARS‐CoV‐2 infected pregnant women in Northern Italy: a retrospective analysis27 Apr 2020ItalyEurope42Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.16278
Buonsenso, D.Moro, F.Ultrasound in Obstetrics & GynecologyClinical role of lung ultrasound for the diagnosis and monitoring of COVID ‐19 pneumonia in pregnant wome26 Apr 2020ItalyEurope2Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/uog.22055
JustinMulveyAnn. Diagn. Pathol.Analysis of Complement Deposition and Viral RNA in Placentas of COVID-19 Patients25 Apr 2020USANorth America5Neonatalhttps://www.sciencedirect.com/science/article/pii/S1092913420300708?via%3Dihub
Lu, DYang, XJ Med VirolAsymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission24 Apr 2020ChinaAsia1Neonatalhttps://onlinelibrary.wiley.com/doi/10.1002/jmv.25927
Zhou, C. G. Caughey, A. B.J Matern Fetal Neonatal MedAntenatal corticosteroids for pregnant women with COVID-19 infection and preterm prelabor rupture of membranes: a decision analysis.24 Apr 2020USANorth America0Neonatalhttps://www.tandfonline.com/doi/full/10.1080/14767058.2020.1763951
Lu, DYang, XJ of Med VirologyAsymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission24 Apr 2020ChinaAsia1Neonatalhttps://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25927
Hu, XChen, LObstet GynecolSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vertical Transmission in Neonates Born to Mothers With Coronavirus Disease 2019 (COVID-19) Pneumonia24 Apr 2020ChinaAsia7Neonatalhttps://journals.lww.com/greenjournal/Citation/9000/Severe_Acute_Respiratory_Syndrome_Coronavirus_2.97384.aspx
Sharma TBhatla NInt J Gynaecol ObstetManagement of the first patient with confirmed COVID‐19 in pregnancy in India: From guidelines to frontlines23 Apr 2020IndiaAsia1Neonatalhttps://doi.org/10.1002/ijgo.13179
salvatori Gcampana ABreastfeeding medicineManaging COVID-19-Positive Maternal–Infant Dyads: An Italian Experience22 Apr 2020ItalyEurope2Neonatalhttps://www.liebertpub.com/doi/full/10.1089/bfm.2020.0095?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Al-Kuraishy, HAli, ZAsian Pacific Journal of Reproduction 9(3): 156-158.COVID-19 pneumonia in an Iraqi pregnant woman with preterm delivery21 Apr 2020IraqMiddle East1Neonatalhttp://www.apjr.net/preprintarticle.asp?id=282984
Lyra, JGuimaraes, MActa Med PortCesarean Section in a Pregnant Woman with COVID-19: First Case in Portugal20 Apr 2020PortugalEurope1Neonatalhttps://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/13883
Liao, J.Li, J.Gynaecology and ObstetricsAnalysis of vaginal delivery outcomes among pregnant women in Wuhan, China during the COVID‐19 pandemic19 Apr 2020ChinaAsia10Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/ijgo.13188
Zamaniyan, MAzizi, SPrenat. Diagn.Preterm delivery in pregnant women with critical COVID-19 pneumonia and vertical transmission17 Apr 2020IranMiddle East1Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/pd.5713?af=R
Parat, MRatner, AJClin Infect Dis.SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress17 Apr 2020United StatesNorth America2Neonatalhttps://doi.org/10.1093/cid/ciaa452
Koumoutsea, EVMalinowski, AKJournal of tjrombosis and haemostasisCOVID‐19 and acute coagulopathy in pregnancy17 Apr 2020CanadaNorth America2Neonatalhttps://onlinelibrary.wiley.com/doi/epdf/10.1111/jth.14856
Li, MLi, XPLoS OneThe SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study16 Apr 2020ChinaAsia0Neonatalhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230295
Han, MSChoi, EHClin Infect DisSequential analysis of viral load in a neonate and her mother infected with SARS-CoV-216 Apr 2020KoreaAsia1Neonatalhttps://academic.oup.com/cid/article/doi/10.1093/cid/ciaa447/5820869
Patek, PKhandhar, PClinical PediatricsSARS-CoV-2 Infection in a 2-Week-Old Male With Neutropenia15 Apr 2020USANorth America1Neonatalhttps://journals.sagepub.com/doi/full/10.1177/0009922820920014?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&
Lowe, BBopp, BAustralian & NZ Journal of Obstetrics & GynaecologyCOVID‐19 vaginal delivery – a case report15 Apr 2020AustraliaOceania1Neonatalhttps://doi.org/10.1111/ajo.13173
Zhoujie, PShi, YJ Infect Public HealthUnlikely SARS-CoV-2 vertical transmission from mother to child: A case report11 Apr 2020ChinaAsia1Neonatalhttps://doi.org/10.1016/j.jiph.2020.04.004
Munoz, ABoukas, KNEJMLate-Onset Neonatal Sepsis in a Patient with Covid-1911 Apr 2020USANorth America1Neonatalhttps://www.nejm.org/doi/full/10.1056/NEJMc2010614
Xiong, XPang, QJournal of Medical VirologyVaginal delivery report of a healthy neonate born to a convalescent mother with COVID­‐1910 Apr 2020ChinaAsia1Neonatalhttps://doi.org/10.1002/jmv.25857
Cao, DSun, GInt. J. Infect. Dis.Clinical analysis of ten pregnant women with COVID-19 in Wuhan, China: A retrospective study10 Apr 2020ChinaAsia11Neonatalhttps://www.ijidonline.com/article/S1201-9712(20)30263-0/fulltext
Alzamora, MCLa Rosa, MA, J PerinatolSevere COVID-19 during Pregnancy and Possible Vertical Transmission8 Apr 2020USA or Peru (not clear)Unclear1Neonatalhttps://www.thieme-connect.com/products/ejournals/html/10.1055/s-0040-1710050
Zhang, ZBi, YEuropean Respiratory JournalNovel Coronavirus Infection in Newborn Babies Under 28 Days in China8 Apr 2020ChinaAsia4Neonatalhttps://doi.org/10.1183/13993003.00697-2020
Yang, PZhao, DJournal of Clinical VirologyClinical characteristics and risk assessment of newborns born to mothers with COVID-198 Apr 2020ChinaAsia7Neonatalhttps://www.sciencedirect.com/science/article/pii/S1386653220300986
Wu, XWang, XIJGORadiological findings and clinical characteristics of pregnant women with COVID‐19 pneumonia8 Apr 2020ChinaAsia21Neonatalhttps://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13165
Yang, HJin, ZjinfClinical features and outcomes of pregnant women suspected of coronavirus disease 20197 Apr 2020ChinaAsia57Neonatalhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152867/pdf/main.pdf
Kalafat, EKoc, EUltrasound in Obstetrics and GynaecologyLung ultrasound and computed tomographic findings in pregnant woman with COVID‐196 Apr 2020TurkeyAsia1Neonatalhttps://doi.org/10.1002/uog.22034
Gidolf, SJosefsson, HActa Obstetricia et Gynecologica ScandinavicaCOVID‐19 in pregnancy with comorbidities: More liberal testing strategy is needed6 Apr 2020SwedenEurope2Neonatalhttps://doi.org/10.1111/aogs.13862
Kamali Aghdam, MEftekhari, KInfectious DiseasesNovel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report1 Apr 2020IranMiddle East1Neonatalhttps://www.tandfonline.com/doi/full/10.1080/23744235.2020.1747634
Iqbal, SRuiz, MNEJMAn Uncomplicated Delivery in a Patient with Covid-19 in the United States1 Apr 2020USANorth America1Neonatalhttps://www.nejm.org/doi/full/10.1056/NEJMc2007605
Lee, DAn, JKorean Journal of AnesthesiologyEmergency cesarean section on severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) confirmed patient.31 Mar 2020South KoreaAsia1Neonatalhttps://doi.org/10.4097/kja.20116
Chen, SShao, YJournal of Medical VirologyClinical analysis of pregnant women with 2019 novel coronavirus pneumonia28 Mar 2020ChinaAsia5Neonatalhttps://doi.org/10.1002/jmv.25789
Breslin, ND'Alton, MAmerican Journal of Obstetrics and GynecologyCOVID-19 in pregnancy: early lessons27 Mar 2020USANorth America7Neonatalhttps://doi.org/10.1016/j.ajogmf.2020.100111
Dong, LYang, JJAMAPossible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn26 Mar 2020ChinaAsia1Neonatalhttps://jamanetwork.com/journals/jama/fullarticle/2763853
Zeng, LZhou, WJAMA PedNeonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China26 Mar 2020ChinaAsia3Neonatalhttps://jamanetwork.com/journals/jamapediatrics/fullarticle/2763787
Zeng, HFan, JJAMAAntibodies in Infants Born to Mothers With COVID-19 Pneumonia26 Mar 2020ChinaAsia6Neonatalhttp://jamanetwork.com/article.aspx?doi=10.1001/jama.2020.4861
Zheng, QJin,LReprod Dev MedSingle cell RNA expression profiling of ACE2 and AXL in the human maternal-fetal interface25 Mar 2020N/AN/A0Neonatalhttp://www.repdevmed.org/article.asp?issn=2096-2924;year=2020;volume=4;issue=1;spage=7;epage=10;aulast=Zheng;type=0
Zambrano, LRodrigues-Morales, ATravel Medicine and Infectious DiseaseA pregnant woman with COVID-19 in Central America25 Mar 2020HondurasNorth America1Neonatalhttps://doi.org/10.1016/j.tmaid.2020.101639
Yu, NWu, JLancet: Infectious DiseasesClinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study24 Mar 2020ChinaAsia7Neonatalhttps://doi.org/10.1016/S1473-3099(20)30176-6
Fan, CWang, SClinical Infectious DIseasesPerinatal Transmission of COVID-19 Associated SARS-CoV-2: Should We Worry?17 Mar 2020ChinaAsia2Neonatalhttps://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa226/5809260
Lui, WWong, ZFront. Med.Clinical characteristics of 19 neonates born to mothers with COVID-1917 Mar 2020ChinaAsia19Neonatalhttps://link.springer.com/content/pdf/10.1007/s11684-020-0772-y.pdf
Chen, YLiu, YFrontiers in Paediatrics: NeonatologyInfants Born to Mothers With a New Coronavirus (COVID-19)16 Mar 2020ChinaAsia4Neonatalhttps://doi.org/10.3389/fped.2020.00104
Li, NYang, LMedRxIVMaternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study13 Mar 2020ChinaAsia17Neonatalhttps://doi.org/10.1101/2020.03.10.20033605
Wang, SFeng, LClinical Infectious DiseasesA Case Report of Neonatal 2019 Coronavirus Disease in China12 Mar 2020ChinaAsia1Neonatalhttps://doi.org/10.1093/cid/ciaa225
Mogharab, VJavdani, FJournal of the Formosan Medical AssociationThe first case of COVID-19 infection in a 75-day-old infant in Jahrom City, south of Iran8 Mar 2020IranMiddle East1Neonatalhttps://www.sciencedirect.com/science/article/pii/S0929664620301078?via%3Dihub
Ooldali, NDanis, KLancet Child Adolescent HealthEmergence of Kawasaki Disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic:a time-series analysis02 07 2020FranceEurope10Epidemiology - Disease Burdenhttps://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30175-9/fulltext#seccestitle140
Liu, DZeng, CAmerican Journal of RoentgenologyPregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: A preliminary analysis7 Mar 2020ChinaAsia11Neonatalhttps://www.ajronline.org/doi/full/10.2214/AJR.20.23072
Li, YSheng, JEmerging Infectious DiseasesLack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China5 Mar 2020ChinaAsia1Neonatalhttps://doi.org/10.3201/eid2606.200287
Liu, YGuo, YJournal of InfectionClinical manifestations and outcome of SARS-CoV-2 infection during pregnancy4 Mar 2020ChinaAsia13Neonatalhttps://doi.org/10.1016/j.jinf.2020.02.028
Wang, XChen, XClinical Infectious DiseasesA Case of 2019 Novel Coronavirus in a Pregnant Woman With Preterm Delivery28 Feb 2020ChinaAsia1Neonatalhttps://doi.org/10.1093/cid/ciaa200
Chen, HZhang, YLancetClinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records12 Feb 2020ChinaAsia9Neonatalhttps://doi.org/10.1016/S0140-6736(20)30360-3
Zhu, HZhou, WTranslational PediatricsClinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia10 Feb 2020ChinaAsia10Neonatalhttps://doi.org/10.21037/tp.2020.02.06

About Alison Boast, Alasdair Munro + Henry Goldstein

Alison is a paediatric registrar in Australia, currently embarking on her PhD in bone and joint infections. She is passionate about teaching and making the world just that little bit more organized with the help of washi tape.


Alasdair is a Paediatric registrar in the UK, currently working as a Clinical Research Fellow in Paediatric Infectious Diseases. His interests include evidence based medicine, diagnostics and antimicrobial resistance.

Henry is a paediatric trainee based in Queensland, Australia, Henry is passionate about Adolescent Medicine & General Paediatrics, with a strong interest in Medical Education & Clinical Teaching. An admitted nerd & ironman with a penchant for Rubik's Cubes & 'Dad jokes'.

Author: Alison Boast, Alasdair Munro + Henry Goldstein Alison is a paediatric registrar in Australia, currently embarking on her PhD in bone and joint infections. She is passionate about teaching and making the world just that little bit more organized with the help of washi tape. Alasdair is a Paediatric registrar in the UK, currently working as a Clinical Research Fellow in Paediatric Infectious Diseases. His interests include evidence based medicine, diagnostics and antimicrobial resistance. Henry is a paediatric trainee based in Queensland, Australia, Henry is passionate about Adolescent Medicine & General Paediatrics, with a strong interest in Medical Education & Clinical Teaching. An admitted nerd & ironman with a penchant for Rubik's Cubes & 'Dad jokes'.

58 Responses to "An evidence summary of Paediatric COVID-19 literature"

  1. Jo Mannion
    Jo Mannion 4 months ago .Reply

    Thanks for collating this Alisdair and Alison
    Really useful

    • Dr. Vicki Burneikis
      Dr. Vicki Burneikis 4 months ago .Reply

      The prolonged faecal shedding is worrying- should grandparents wear PPE to change nappies?

  2. Kylie Stark
    Kylie Stark 4 months ago .Reply

    You guys never fail to deliver
    Thankyou

  3. Claire Lundy
    Claire Lundy 4 months ago .Reply

    Absolutely brilliant thanks so much

  4. Dr Rajiv Uttam
    Dr Rajiv Uttam 4 months ago .Reply

    Very useful information
    Thanks

  5. Dr P
    Dr P 4 months ago .Reply

    Thanks. An amazing effort once again.

  6. veronica giordano
    veronica giordano 4 months ago .Reply

    Thank you so much, brilliant

  7. Shermina
    Shermina 4 months ago .Reply

    Thanks for doing this work – really helpful

  8. Johhn Kopsidas
    Johhn Kopsidas 4 months ago .Reply

    Thank you!

  9. Kelly
    Kelly 4 months ago .Reply

    We need risk and recommendation commentary on special needs paediatric population; particularly those of school age (and whose parents/Carers are front line such as health care workers)

    • Katie
      Katie 4 months ago .Reply

      Echoing your request; this cohort needs timely guidance based on what evidence we can glean. Thanks DFTB once again for educational content.

    • Steph D
      Steph D 4 months ago .Reply

      I am a NHS front line worker with a child who has severe & complex needs and recurring chest infections. Currently isolated pseudomonas in the chest. Desperate for information.

      • CER
        CER 4 months ago .Reply

        Me too. My daughter has bronchiectasis but is currently well.

      • Steph D
        Steph D 4 months ago .Reply

        Massive thanks to you all for this. Keep up the good work 🙂

    • Sarah Mudge
      Sarah Mudge 4 months ago .Reply

      Much appreciated for collating this information. Frontline ICU Nurse and Cerebral Palsy parent.

  10. Angela Luangrath
    Angela Luangrath 4 months ago .Reply

    Very appreciative of you work. Thank you!

  11. Amelia
    Amelia 4 months ago .Reply

    This is amazing – thanks!! Paeds Reg on mat leave with a newborn here. Have been wanting to look into this but too tired to tackle – I am so appreciative.

    • Annika
      Annika 4 months ago .Reply

      Me too, 6 week old daughter, father neurologist in emergency department in Germany. Thank you for summarizing!!

  12. Dr Jacinta Coleman
    Dr Jacinta Coleman 4 months ago .Reply

    Great to have some clarity about presentation in these paediatric case studies. Thank you!

  13. Larry Budd
    Larry Budd 4 months ago .Reply

    With Mycoplasms noted more than just once do Symptomatic cases earn Azithromycin or other atypical therapy while waiting for results? Would the CXR / CT chest findings be consistent with Mycoplasms?

  14. Genevieve
    Genevieve 4 months ago .Reply

    Thank you! This is great summary of really useful studies. Keep up the good work!

  15. Dave Watkin
    Dave Watkin 4 months ago .Reply

    CT’s on asymptomatic children? Why?

  16. Shilpa Shah
    Shilpa Shah 4 months ago .Reply

    this is fabulous work. you all deserve an OBE 🙂

  17. Sarah C
    Sarah C 4 months ago .Reply

    Well done, very concise

  18. Saqib
    Saqib 4 months ago .Reply

    thank you – interesting that they have unilateral opacities on some CXR considering all I knew previously was that it was bilateral ground glass – makes me wonder about the kid I sent home recently with coamox as the XR changes were unilateral…however he has not come back so I assume he is ok! no harm, no foul.

  19. sabine Hennel
    sabine Hennel 4 months ago .Reply

    thank you so much for doing this – great work !!

  20. Konstantina Karanasiou
    Konstantina Karanasiou 4 months ago .Reply

    Thank you

  21. Pilar
    Pilar 4 months ago .Reply

    Thanks! Very useful

  22. Paola
    Paola 4 months ago .Reply

    Thanks a lot for doing this excellent work. These data are confirmed in Italy. Up to Now few children admittedto the hospital, mild symptoms, NO admission di intensive care. Keep fingers crossed. Very important to apply prevention policy and . isolation. Infection rate is starting to decrease in the area where the isolation was perforned rigorously (North East of Italy meaning Veneto and Friuli Venezia Giulia where I work. Good luck to all of you and keep safe

  23. Nick Thies
    Nick Thies 4 months ago .Reply

    Thanks for a brilliant review. You deserve a koala stamp!

  24. Jose Manuel
    Jose Manuel 4 months ago .Reply

    Thank you for this useful review.

  25. Sanaa
    Sanaa 4 months ago .Reply

    Thank you so much . This is a great summary , and such a positive look at paediatric covid cases , so we can somehow reassure the panicked mothers!

  26. Simon Chiles
    Simon Chiles 4 months ago .Reply

    Thank you, really interesting

  27. Rob Millar
    Rob Millar 4 months ago .Reply

    Good to know COVID in kids is relatively mild. However, do we know anything about numbers of paediatric HCWs becoming infected?

  28. OKUYAT ROBERT
    OKUYAT ROBERT 4 months ago .Reply

    Nice good info

  29. ILHAAM Abbas
    ILHAAM Abbas 4 months ago .Reply

    Interesting read. Thank you for sharing

  30. Aurora, R
    Aurora, R 4 months ago .Reply

    Thank you for this much needed information.

  31. Angela Freydag
    Angela Freydag 4 months ago .Reply

    Dear DFTB Team, thank you for this very helpful summary!

    Please note: In Cui Y, Tian M, Huang D, et al. , A 55- day old female.. the authors write at the end of the first paragraph:
    “The nasopharyngeal swab obtained from the infant also tested positive for severe acute respiratory syndrome coronavirus (SARS-CoV-2) on real-time reverse transcription–polymerase-chain-reaction (RT-PCR) assay.”
    I find this reassuring and would like to recommend to correct this part of your summary.
    Sincerely, Angela

    • Alasdair Munro
      Alasdair Munro 4 months ago .Reply

      Thank you for pointing out this omission – we will correct this immediately. We appreciate you taking the time to comment and help us improve the post.

  32. jogender Kumar
    jogender Kumar 4 months ago .Reply

    Excellent work. Very useful, precise and to the point information.

  33. Katie
    Katie 4 months ago .Reply

    thank you so much for this summary!

  34. Judith morgan
    Judith morgan 4 months ago .Reply

    Thank you. As a paediatric anaesthetist I’m trying to keep up with all the latest information and this is a great summary and am very grateful you’ve done this review.

  35. Karen Bartholomew
    Karen Bartholomew 4 months ago .Reply

    Thanks for the excellent work from another paediatric anaesthetist

  36. Yamila Gurovich
    Yamila Gurovich 4 months ago .Reply

    Thank you for reviewing these papers a friend who is a
    Paediatric nurse sent me this information. What is interesting is that a lot of studies note fecal shedding of virus or detection of virus in fecal samples is still there after oral/nasal tests are negative for virus. This is interesting as it seems coronavirus have evolved and originated in bats and bats shed these virus in fecal matter.

  37. Narinder Kaur
    Narinder Kaur 4 months ago .Reply

    Thank you so much for putting this together. Great Work. Faecal shedding is interesting and worrysome at the same time

  38. Robert S. Greenberg MD
    Robert S. Greenberg MD 4 months ago .Reply

    Great work….linked to from PedsAnesthesia.Net
    #teamsport

  39. Sarah Berwick
    Sarah Berwick 4 months ago .Reply

    Paeds medical nurse practitioner here, amazing job on the delivery of such valuable information. Great work. Your time & effort greatly appreciated.

  40. Kgomotso Lovey Sanyane
    Kgomotso Lovey Sanyane 4 months ago .Reply

    What a wonderful post. Absolutely valuable information in these trying times. I’m a paediatrician in South Africa and we are experiencing an increasing amount of COVID-19 cases

  41. Dr Luke Jeremijenko Emergency Physician
    Dr Luke Jeremijenko Emergency Physician 4 months ago .Reply

    Thanks team. Wonderful resource. Avidly reading through the papers. Question to the DFTB brains trust. I ran Dr Ben Symons simulation today and was asked (appropriately) is there a viral filter available for the F&P airvo 2? How are people running HFNP outside a negative pressure room?

    • Andrew Tagg
      Andrew Tagg 4 months ago .Reply

      We are trying to see what the evidence is, or at least find some expert consensus on this, so watch this space. I’m not a fan of the idea at the moment so we are advocating for starting it in the place it is going to b ultimately used. You don’t want to push a patient on HF through the hospita.l

  42. Tilmann Schober
    Tilmann Schober 4 months ago .Reply

    Thanks for this wonderful tool. Just one important remark? If you sort according to the date of publication, it is no in a chronological order. It might work if you put the year first, than the month and than the day.
    Best, Tilmann

  43. Paul Van Laer
    Paul Van Laer 3 months ago .Reply

    Cui Y, Tian M, Huang D, et al. A 55-Day-Old Female Infant infected with COVID 19: presenting with pneumonia, liver injury, and heart damage. J Infect Dis
    Concerning the elevated troponin: we see a slightly elevated troponin in all our young babies (newborn and older), without any clinical or echographic signs of cardiac involvement

  44. Pratik Patel M.D.
    Pratik Patel M.D. 2 months ago .Reply

    Dear Don’t Forget the Bubbles,

    I wanted to make you aware of a critically ill previously healthy pediatric patient who we had in Atlanta (USA) in late March who had concern for hyperinflammation and was successfully treated with a variety of COVID as well as hyperinflammation treatments (remdesivir and tocilizumab). We published our case and it is available online at Pediatrics in case you were interested in including it in your future summaries/posts! https://pediatrics.aappublications.org/content/pediatrics/early/2020/04/30/peds.2020-1437.full.pdf

    Thanks,
    Pratik

  45. Khallad
    Khallad 2 months ago .Reply

    Great work … !!

  46. Solomie
    Solomie 1 month ago .Reply

    Dear Alison, Alasdair and Henry, I was looking for a nice summary of pediatrics literatures and I found yours to be very comprehensive and well organized. Thank you so much!

  47. Daniel
    Daniel 1 month ago .Reply

    Dear Alison, Alasdair and Henry, I´ve been following your updates for weeks now. Very helpful. Great work, very much appreciated! Way to go!

  48. Simon Middle
    Simon Middle 4 weeks ago .Reply

    Has there been anything said about that the children are not going out so wouldn’t be the primary source of the disease (adults doing food shop)? Also, they would rarely be the care giver if a member of household became ill, so less chance of transmission there too.

  49. Mafe Maluleke
    Mafe Maluleke 4 days ago .Reply

    Do you have DFTB iOS app?

Leave a Reply