Swann Olivia V, Holden Karl A, Turtle Lance, Pollock Louisa, Fairfield Cameron J, Drake Thomas M et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ. August 27th 2020, https://doi.org/10.1136/bmj.m3249
This large prospective observational study from 260 hospitals in the UK examines the clinical characteristics of children (<19yo) hospitalised with laboratory confirmed SARS-CoV-2 infection between 17th January and 3rd July 2020; as part of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK cohort. The main outcome measures were admission to critical care, in-hospital mortality and MIS-C.
Results; A total of 651 children admitted to 138 hospitals were included; median age was 4.6 (IQR 0.3-13.7); 35% were <12 months of age. Of patients with recorded ethnicity 57% were white, 12% south asian and 10% black. 56% were male and 42% had identified co-morbidities.
Symptoms; The most common symptoms were fever (70%), cough (35%) nausea / vomiting (32%) and dyspnoea (30%). Three distinct clusters of symptoms were identified: – a discreet respiratory illness – cough, fever, dyspnoea, coryza and wheeze – a mucocutaneous enteric illness – headache, myalgia, sore throat, vomiting, abdominal pain, diarrhoea, fatigue, rash, lymphadenopathy and conjunctivitis – a rarer neurological illness – seizures and confusion
Critical care and mortality; Critical care admission occurred in 18% (116/632); 8% received inotropic support; 9% received non-invasive and invasive ventilation respectively. Children of black ethnicity had higher odds of critical care admission (OR 2.82). Infants <1mo (OR 3.21, 95% CI 1.36-7.66) and children 10-14 yo (OR 3.23, 95% CI 1.55-6.99) were also more likely to be admitted to critical care. Co-morbidities including prematurity, respiratory and cardiac co-morbidities and obesity were more common in those with critical care admission compared with those receiving ward care. Six (1%) of patients died in hospital, all had serious comorbidities; 89% of children had been discharged alive and 10% remained in hospital at the time of reporting.
MIS-C; Based on the preliminary WHO case definition, 11% (52/456) of admitted children fulfilled diagnostic criteria for MIS-C. Children with MIS-C were older than those without (median 10.7 yo vs 1.6 yo) and were more likely to be of non-white ethnicity (64% vs 42%); obesity was also more common amongst those with MIS-C (10% vs 2%). Children with MIS-C were more likely to require critical care admission (73% vs 15%), receive inotropes (51%), invasive (27%) and non-invasive (35%) ventilation. There were no deaths due to MIS-C.
Of children with MIS-C differences were noted between those who were SARS-CoV-2 PCR positive (acute phase of infection – 56%) and those who were antibody positive (post-acute phase of infection – 44%). Antibody positive MIS-C patients were more likely to be of non-white ethnicity (90% vs 45%), less likely to be obese (0% vs 19%), and more likely to have conjunctivitis (71% vs 16%) and abdominal pain (95% vs 44%) compared to those who were PCR positive. Dyspnoea was more common in PCR positive patients (52% vs 14%). Cardiac complications were also more common in the antibody positive group (75% vs 35%).
Conclusion; The findings of this large prospective study are consistent with previous studies indicating that children represent a small proportion of hospitalised cases of COVID-19 (0.9% here), that outcomes in children are generally favourable and that death due to COVID-19 in children is rare. Similar to previous studies, fever and cough were the most common symptoms, although gastrointestinal symptoms (35%) were more common in this cohort; the identification of a mucocutaneous-enteric symptom cluster with overlap with WHO MIS-C criteria is a novel finding here. Children of black ethnicity were over-represented in overall cases, as well as amongst children admitted to critical care units, consistent with adult data from the UK. Similarly, obesity was associated with increased risk of critical care admission.
The association of MIS-C with older age and non-white ethnicity are consistent with previous studies. In addition to current WHO criteria, fatigue, headache, myalgia, sore throat and low platelet count were all associated with MIS-C. The demographic and clinical differences identified between MIS-C patients who were antibody positive compared with those who were PCR positive suggest a spectrum of clinical presentation that varies according to phase of infection and immune response.
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.
This European multicentre cohort study recruited 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 identified cases prior to 1st April and prospectively between 1-24th April. The diagnosis was made based 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 was included from the history, with parents being the suspected 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 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. A 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 included 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 for 25 patients (4%) and ECMO was needed in one 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 older than 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 the end of the study period, 553 patients had made a full recovery and 25 patients had ongoing symptoms.
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)
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 confirmed contact with a case of COVID-19. Of these, 171 were confirmed to have SARSCoV-2. The 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 hospitalization. 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 their definition 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 covered 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, the authors categorize their patients according to criteria from Dong et. al (see review in theEpidemiology 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 the 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 were 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 a 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 ontological, and 1 metabolic disease.
Of the few patients that required respiratory support (9/100) a significant number had comorbidities (6/9), although the range was broad. This included two 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.
In comparison to Dong et al, the 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 the population cohorts presenting for testing among the different studies – comparison between cohorts is always difficult due to broad differences in the denominators used. There is no apparent difference in severity according to age in this Italian data set, whereas CDC noted increased hospitalization 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 the presence of significantly milder illness in children with COVID-19, including many asymptomatic children. A note is made of overrepresentation of children with comorbidities in this cohort (similar to the 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.
DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. The Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2020.05.007
This is a retrospective cohort study, describing 177 children and young adults with confirmed SARS-CoV-2 infection treated between March 15 and April 30 2020 at the Children’s National Hospital, Washington DC US. Children and young adults were detected because of presentation with symptoms at emergency departments, ambulatory clinics, inpatient units, or by referral for admission from external facilities. Of 177 patients, 44 (25%) were hospitalized, with 9 (5%) classified as critically ill. The aim of the study was to identify if any specific epidemiological or clinical features were associated with hospitalization, or critical care.
This hospital served as a regional centre providing critical care for young adults aged 21 – 35 years, therefore not all patients would be termed “paediatric patients”. The overall patient age range was from 0.1 – 34.2 years, with a median of 9.6 years. Of the total group 12/177 were > 20 years of age, and 37/177 were between the ages of 15 – 20years.
Age: There was no significant difference in age between the hospitalized and non-hospitalized patients, however in the hospitalized cohort, the critically unwell group were significantly older than the non-critically unwell hospitalized group (17.3 years versus 3.6 years; P =.04)
Sex: There was equal representation (n = 177 52% male, 48% female), as well as in the hospitalised cohort (n=44 50% male, 50% female). However, males made up 67% of the critically ill cohort (n =9, 67% male, 33% female); but this was not statistically significant (p=0.26)
Race/ethnicity: data not provided, authors describe plans to do so in follow up analysis
Underlying conditions: 39% of positive patients had an underlying condition (classified as asthma, diabetes, neurological, obesity, cardiac, haematological, oncological). Though asthma was the most common underlying condition (35/177 20%), it was not more common in hospitalized patients (7/44 16%), nor of those admitted, or those who were critically unwell (2/9, 22%). Though the numbers were small, specific underlying conditions such as neurological, cardiac, haematological, or oncological issues were more common in the hospitalised cohort than the non hospitalised cohort. They were not more common in the hospitalized critically ill compared with the hospitalised non critically ill. The authors noted there was no underlying condition present in 96/177 (55%) of overall SARS-CoV-2 infected patients overall, 16/44 (37%) of hospitalized patients and in 2/9 (22%) of critically ill patients.
Symptoms: 76% of infected patients presented with respiratory symptoms (rhinorrhea, congestion, sore throat, cough, or shortness of breath) with or without fever. Fever was present in 116/177 (66%) but was not more common in the infected hospitalized cohort (34/44, 77%) compared with the non-hospitalized cohort (82/133, 62%; p=0.46).
Shortness of breath was more common in the hospitalized cohort (11/44, 26%) compared with non-hospitalized (16/133, 12%; p=0.04). Patients in the critically ill cohort were not more likely to have a fever or any other specific symptom compared with the non-critically ill cohort.
Critical Care: 9 patients required critical care. This represented 5% (9/177) of the total cohort and 20% (9/44) of admitted patients. 4 required intubation (3 ARDS, 2 multiple organ failure); 3 required BiPAP, 1 RAM cannula, and one high flow nasal cannula oxygenation. One patient had features consistent with the recently emerged Kawasaki disease-like presentation with hyper-inflammatory state, hypotension, and profound myocardial depression; a 4 year male with no underlying conditions.
Summary: A very clear description of 177 patients with SARS-CoV-2, in one large centre in Washington DC. 25% of patients needed hospitalisation and 5% needed critical care. Older teenagers and adults who required admission were overrepresented in requiring critical care. Though underlying conditions were more common in hospitalized patients, they were not significantly more common in the hospitalized patients who required critical care. Shortness of breath was the only symptom that was more common in hospitalized patients. No specific symptom was more apparent in patients needing critical care. One critically ill patient had features of the recently described hyperinflammatory state.
de Lusignan, S., J. Dorward, A. Correa, N et al, (2020). “Risk 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 study.” Lancet Infect Dis. May 15th 2020, https://doi.org/10.1016/S1473-3099(20)30371-6
This study examines the demographic and clinical risk factors for testing positive for SARS-CoV-2 amongst patients within a large primary care network in the UK. This included tests done through Public Health England and the UK National Health Service (NHS) between January 28th and April 4th 2020 with clinical and sociodemographic data extracted from patients’ primary care medical records.
Overall 587 of 3802 patient tests returned a positive result for SARS-CoV-2. Of children 4.6% (23/499) tested positive compared with 17.1% (564/3303) of adults.
In a multivariate logistic regression, adults had significantly higher odds of a positive test compared with children; those aged 40-64 (aOR 5.36, 95% CI 3.28-8.76) and >75 (aOR 5.23, 95% CI 3.00-9.09) were at highest risk.
Male sex (aOR 1.55, 95% CI 1.27-1.89), social deprivation (aOR 2.03, 95% CI 1.51-2.71), and black ethnicity (aOR 4.75, 95% CI 2.65-8.51) were also associated with an increased risk of a positive SARS-CoV -2 test. Of clinical factors, only chronic kidney disease (aOR 1.91, 95% CI 1.31-2.78) and obesity (aOR 1.41, 95% CI 1.04-1.91) were significantly associated with testing positive. Surprisingly, active smoking was associated with lower odds of a positive test (aOR 0.49, 95% CI 0.34-0.71) possibly due to presentation confounding (i.e. presence of cough in chronic smokers prompting increased testing in this group).
This is the first study to utilise primary care data to assess risk factors for testing positive for SARS-CoV-2 in the community. The risk factors identified are similar to those associated with severe COVID-19 in hospitalised patients including increased age, male sex and obesity. The higher odds of a positive test in adults compared with children here are consistent with other studies suggesting children are at lower risk of SARS-CoV-2 infection compared with adults.
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.
M. A. De Ioris, A. Scarselli, M. L. Ciofi Degli Atti, et al. Dynamic viral SARS-CoV-2 RNA shedding in in children: preliminary data and clinical consideration of Italian regional center. J Pediatric Infect Dis Soc. May 23rd 2020, https://doi.org/10.1093/jpids/piaa065
This study at a paediatric hospital in Rome tracked SARS-CoV-2 shedding (nasopharyngeal, faecal, urinary and conjunctival) by following a cohort of 22 children during their hospital stay, collecting clinical and microbiological data.
Study design: The study ran from 16th March to 12th April in the COVID centre at Bambino Gesu Pediatric Hospital and collected data on 22 in-patients with an initial positive nasopharyngeal swab (either prior to admission or on admission). RT-PCR for SARS-CoV-2 RNA on nasopharyngeal and conjunctival swabs and stool and urine samples were repeated every 2-3 days for each child while they were inpatients until they had two consecutive negative results in the absence of new symptoms. Kaplan-Meier analysis was used to estimate the duration of symptoms and viral shedding for symptomatic patients: patients whose last swab/sample was still positive were censored at the date of the last swab.
Study population: 15/22 (68%) male, 7/22 (32%) female. Median age 7 years (range 8 days to 17.5 years). 4/22 neonates (1/4 tested because mother positive and 3/4 tested because midwife positive). 2/22 comorbidity (Angelman syndrome, suspected genetic syndrome and autism). 13/22 patients were discharged before the end of the study period (median inpatient stay 7 days, range 3-15 days).
Symptoms: 4/22 (18%) asymptomatic (including 2/4 neonates, the other 2/4 had low-grade fever and poor feeding). 18 symptomatic patients: 15/18 (83%) fever, 10/18 (55%) respiratory symptoms, 7/18 (39%) diarrhoea and vomiting, 3/18 (17%) seizure. Symptoms had resolved in all 18 before discharge from hospital. The median duration of symptoms was 8 days (range 2-21 days). 15/22 had a positive stool sample at admission: of these 7/15 (47%) had respiratory symptoms and 3/15 (20%) had diarrhoea and vomiting.
Viral shedding: At diagnosis: 22/22 (100%) had positive nasopharyngeal swab (by definition), 15/22 (68%) had positive stool sample, 1/22 (5%) had positive urine sample (re-test 2 and 5 days later was negative; another patient had initial negative urine test but repeat 3 days later was positive) and 2/22 (9%) had positive conjunctival swab (both were negative 2-3 days later). A detailed table charting the dates of inpatient stay, onset, and end of symptoms and positive/negative swabs/samples for each patient is supplied: the full screen of faecal, urinary and conjunctival sampling was performed at variable intervals after the initial positive nasopharyngeal swab (up to 5 days later in several cases). For symptomatic patients: (1) from date of symptom onset to negative nasopharyngeal swab: median 8 days (range 2-17 days) and (2) from date of symptom onset to negative stool sample: median 14 days (range 10-15 days). The estimate of the persistence of viral shedding at day 14 from symptom onset for nasopharyngeal swab was 52% and for stool sample 31%.
The authors note the need to confirm the clinical relevance of faecal SARS-CoV-2 shedding in terms of the risk of transmission via the faeco-oral route.
Galván Casas, C., Català, A., Carretero Hernández, et al. (2020), Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. Accepted Author Manuscript. doi:10.1111/bjd.19163
This article from a team in Spain aimed to classify cutaneous manifestations of COVID-19 and relate them to other clinical findings.
From 3rd of April 2020 to 16th of April 2020 they collected 429 cases but excluded 54 leaving a sample of 375 patients. A standardised questionnaire was used, photographs were taken and the questionnaires and photographs were independently reviewed by 4 dermatologists.
Data was collected by Spanish dermatologists from across the country most of whom had been redeployed from their usual dermatology posts.
Patients with an eruption of recent onset (previous 2 weeks) and no clear explanation, plus suspected or confirmed COVID-19 were included.
They describe 5 cutaneous manifestations.
Acral areas of Erythema-oedema with some vesicles or pustules: 19% of cases. These were more likely in children.
Other vesicular eruptions: 9%. May also affect the limbs and have a haemorrhagic content, and become larger or diffuse.
Urticarial lesions: 19%. Mostly distributed in the trunk or disperse. A few cases were palmar.
Other maculopapular: 47%. Some showed perifollicular distribution and varying degrees of scaling, Some had been described as similar to pityriasis rosea.
Livedo or necrosis: 6%
Strengths of this study are the large number of patients recruited and that four dermatologists independently reviewed the images. It adds to the understanding of skin manifestations of COVID-19, which may give additional information when trying to make a clinical diagnosis of COVID-19 if other symptoms are non-specific, also the cutaneous manifestations may persist for some time once other symptoms have resolved.
A weakness is the authors did not specify the age of the patients involved so the usefulness for paediatric patients is limited. Also, in some areas, diagnosis of COVID-19 infection could only be made clinically, based on symptoms as the ability to test patients was limited during the height of the pandemic.
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 children with SARS-CoV-1. Overall children with SARS-CoV-2 were younger than those with SARS-CoV-1 (median age 82 months 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 intussusception) 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.
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Please note that whilst all papers have been reviewed for the database and consideration of the overall updates, only selected papers which added new information at the time of publication had a formal review written. The sublists below also include the top ten papers for convenience.
Larger Cohort Clinical Papers
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://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30177-2/fulltext
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)
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 SARSCoV-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 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 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.
DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. The Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2020.05.007
This is retrospective cohort study, describing 177 children and young adults with confirmed SARS-CoV-2 infection treated between March 15 and April 30 2020 at Children’s National Hospital, Washington DC US. Children and young adults were detected through symptomatic presentation at emergency departments, ambulatory clinics, inpatient units, or by referral for admission from external facilities. Of 177 patients, 44 (25%) were hospitalised, with 9 (5%) classified as critically ill. The aim of the study was to identify if any specific epidemiological or clinical features associated with hospitalisation, or critical care.
Of note this hospital served as a regional centre for providing critical care for young adults aged 21 – 35 years, therefore not all patients would be termed “paediatric patients”. Overall patient age range was from 0.1 – 34.2 years, with a median of 9.6years. Of the total group 12/177 were > 20 years of age, and 37/177 were between age of 15 – 20years.
Age: There was no significant difference in age between the hospitalised and non-hospitalised patients, however in the hospitalised cohort, the critically unwell group were significantly older than the non-critically unwell hospitalised group (17.3 years versus 3.6 years; P =.04)
Sex: There was equal representation in total cohort showed (n = 177 52% male, 48% female), as well as the hospitalised cohort (n=44 50% male, 50% female). However males made up 67% of the critically ill cohort (n =9, 67% male, 33% female); but this was not statistically significant (p=0.26)
Race/ethnicity: data not provided, authors describe plans to do so in follow up analysis
Underlying conditions: 39% of positive patients had an underlying condition (classified as asthma, diabetes, neurological, obesity, cardiac, haematological, oncological). Though asthma was the most common underlying condition (35/177 20%), it was not more common in hospitalised patients (7/44 16%), nor of those admitted, those who were critically unwell (2/9, 22%). Though the numbers where small, specific underlying conditions such as neurological, cardiac, haematological, or oncological underlying conditions were more common in the hospitalised cohort than the non hospitalised cohort. But were not more common in the hospitalised critically ill compared with the hospitalised non critically ill. The authors noted there was no underlying condition present in 96/177 (55%) of overall SARS-CoV-2 infected patients overall, 16/44 (37%) of hospitalized patients and in 2/9 (22%) of critically ill patients.
Symptoms: 76% of infected patients presented with respiratory symptoms (rhinorrhea, congestion, sore throat, cough or shortness of breath) with or without fever. Fever was present in 116/177 (66%) but was not more common in the infected hospitalized cohort (34/44, 77%) compared with the non-hospitalized cohort (82/133, 62%; p=0.46).
Shortness of breath was more common in the hospitalized cohort (11/44, 26%) compared with non-hospitalized (16/133, 12%; p=0.04). Patients in the critically ill cohort were not more likely to have fever or any other specific symptom compared with the non-critically ill cohort.
Critical Care: 9 patients required critical care; which represented 5% (9/177) of total cohort and 20% (9/44) of admitted patients. 4 required intubation (3 ARDS, 2 multiple organ failure); 3 required BiPAP, 1 RAM cannula and 1 High flow nasal cannula. One patient had features consistent with the recently emerged Kawasaki disease-like presentation with hyper-inflammatory state, hypotension and profound myocardial depression; a 4 year male with no underlying conditions.
Summary: A very clear description of 177 patients with Sars CoV 2, in one large centre in Washington DC. 25% of patients needed hospitalisation and 5 % needed critical care. Older teenagers and adults who required admission, were then overrepresented in requiring critical care. Though underlying conditions were more common in hospitalised patients, they were not significantly more common in the hospitalised patients who required critical care. Shortness of breath was the only symptom that was more common in hospitalised patients than non-hospitalised patients. No specific symptom was more apparent in patients needing critical care. One critically ill patient had features of recently described hyperinflammatory state.
de Lusignan, S., J. Dorward, A. Correa, N et al, (2020). “Risk 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 study.” Lancet Infect Dis. May 15th 2020, https://doi.org/10.1016/S1473-3099(20)30371-6
This study examines the demographic and clinical risk factors for testing positive for SARS-CoV-2 amongst patients within a large primary care network in the UK. This included tests done through Public Health England and the UK National Health Service (NHS) between January 28th and April 4th 2020 with clinical and sociodemographic data extracted from patients’ primary care medical records.
Overall 587 of 3802 patient tests returned a positive result for SARS-CoV-2. Of children 4.6% (23/499) tested positive compared with 17.1% (564/3303) of adults.
In multivariate logistic regression, adults had significantly higher odds of a positive test compared with children; those aged 40-64 (aOR 5.36, 95% CI 3.28-8.76) and >75 (aOR 5.23, 95% CI 3.00-9.09) were at highest risk.
Male sex (aOR 1.55, 95% CI 1.27-1.89), social deprivation (aOR 2.03, 95% CI 1.51-2.71) and black ethnicity (aOR 4.75, 95% CI 2.65-8.51) were also associated with an increased risk of a positive SARS-CoV -2 test. Of clinical factors, only chronic kidney disease (aOR 1.91, 95% CI 1.31-2.78) and obesity (aOR 1.41, 95% CI 1.04-1.91) were significantly associated with testing positive. Surprisingly active smoking was associated with lower odds of a positive test (aOR 0.49, 95% CI 0.34-0.71) possibly due to presentation confounding (i.e. presence of cough in chronic smokers prompting increased testing in this group).
This is the first study to utilise primary care data to assess risk factors for testing positive for SARS-CoV-2 in the community. The risk factors identified are similar to those associated with severe COVID-19 in hospitalised patients including increased age, male sex and obesity. The higher odds of a positive test in adults compared with children here are consistent with other studies suggesting children are at lower risk of SARS-CoV-2 infection compared with adults.
Parri, N., A. M. Magistà, F. Marchetti, et al, (2020). “Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks.” Eur J Pediatr: 1-9. https://doi.org/10.1007/s00431-020-03683-8
This study is published as a short communication describing the clinical presentations and outcomes in children with identified Covid-19 in 61 centres in Italy between 3rd and 26 March 2020.
Study Design: A retrospective study coordinated by the CONFIDENCE and COVID-19 Italian Paediatric Study Network’s involving 53(86.9%) hospitals and 8(13.1%) outpatient centres in 10 mainly northern regions. All children (0-18 years) diagnosed positive on screening and testing for Covid-19 by nasal/nasopharyngeal RT-PCR assay were entered into the study. Clinical, laboratory and imaging data was collected on standardised forms.
Study Population: 130 children and adolescents recruited (112 hospital;18 outpatient). <2 years 41 (31.5%), 2-9 years 35 (26.9%)’10-17 years 45 (34.6%). Male 73 (56.2%). Female 57(43.8%) p=0.47.
Comorbidities 34 (26.2%) most frequent cardiovascular, respiratory and neuromuscular. No information on ethnicity. One patients data unobtainable.
Disease Severity: The majority of subjects were categorised as being asymptomatic or having mild disease 98/130 (75.4%). 11 (8.5%) were moderate severity, 11 severe and 9 (6.9%).critical. 75 (57.7%)were hospitalised with 15.(11,5%) needing respiratory support (5 needing oxygen, 2 non invasive ventilation and 2 mechanical ventilation). 9 cases were admitted to ICU with 6 being less than 6 months. 3 of the latter were less than 2 months and did not require respiratory support. Children less than 6 months had an increased risk of critical disease than older children: 6/35 (17.1%) vs 3/86 (3.5%) p=0.34. OR 5.6 CI 1.3 to 29.1.
Symptoms: Common symptoms were fever 67(51.5%), dry cough 38(29.2%) and productive cough 16(12.3%). Other symptoms were rhinorrhoea25(19.2%), respiratory distress 17(13%), vomiting 15(11.5%);diarrhoea 10(7.6%); sore throat 9(6.9%). Thoracic pains (3%), somnolence, febrile convulsions (1.5%) and lower limb pains (1.5%) were reported as novel symptoms.
Oxygen saturation at presentation: 91-92% 1(0.8%). <90 1(0.8)
Radiology: 41 (31.5%) of children had CXRs. These were normal in 15 (36.6%). The commonest abnormalities were ground-glass opacities in 17 (41.5%). Focal consolidation was seen in 4 (9.8%).
Laboratory: 71 children were reported to have had laboratory tests. The authors report leukopenia (WCC %<5.5×109) and lymphopenia (<1.2×109) in 7/19 patients and 3/19 patients, respectively. They report elevation in aspartate transaminase >50U/l in 11/60 (18.3%) and alanine tranasaminase >45U/l in 8/68 (11.8%).
Outcomes: There were no deaths and all children were reported to have recovered.
Comment: The study obtained data on all but one child found Covid-19 positive in this largely hospital based population. The authors acknowledge that there is a bias toward more ill patients with their population than community studies and this may explain the 57.7% admission rate. Also this is reflected in the amount of comorbidity. However, the majority of patients were either asymptomatic or had mild disease and small numbers required respiratory support or ITU. The authors identify the increased likelihood of critical disease in those less than 6 months and their being the majority of ICU cases. They also comment on new presenting symptoms (thoracic pain, somnolence, febrile convulsions and lower limb pains).
de Ceano-Vivas M, Martín-Espín I, del Rosal T, et al. SARS-CoV-2 infection in ambulatory and hospitalised Spanish children, Arch Dis Child, doi:10.1136 / archdischild-2020-319366
Study design: A retrospective case series of all children seen at a tertiary centre, who were found to have positive PCR for SARS-CoV-2. Testing for SARS-CoV-2 was only conducted in those children who had respiratory symptoms and “criteria for hospitalisation” or who had “underlying chronic pathology”. Children with mild symptoms were not tested even if there was a confirmed case in the household. Comparisons were made between the characteristics of those admitted to hospital and those treated as outpatients. The study was conducted between March 11th and April 9th 2020 at Hospital La Paz, Madrid, Spain.
Inclusion criteria: All children who underwent PCR for SARS-CoV-2 in nasopharyngeal smear, N=349. Of whom 58 (16.6%) had a positive PCR and were the cases analysed.
Key findings: Of the 58 cases: Male 37 (63.8%), Median age 35.5 months (range 3.3-146), Underlying conditions 23 (39.7%), Temperature >39.7degC 41 (70.7%), Cough 42 (72.4%), Rhinorrhoea 33 (56.9%), Breathing difficulty 10 (17.2%), Vomiting 9 (15.5%), Headache 8 (13.8%), Loss of taste 1 (1.7%), Anosmia 1 (1.7%).
Radiology: 40 (69%) had a CXR of which 35 (87.5%) were abnormal: Perihilar infiltrates, ground-glass pattern, lobar or multilobar consolidation.
Bloods: 43 (74.1%) had a blood test, median WCC 9145/mm3, median lymphocyte count 2390/mm3.
Outcomes: 33 were hospitalised and 25 were treated as outpatients. Of the inpatients, 14 (42.4%) received oxygen therapy for a median of 3 days. 5 were admitted to the PICU (15% of those hospitalised): 3 with severe COVID-19, 1 with a hypertensive crisis and 1 with diabetic ketoacidosis. 31 (53.4%) were treated with hydroxychloroquine, 3 patients were treated with remdesivir. 2 patients with an inflammatory syndrome were also treated with tocilizumab. There was 1 death of a 5/12 old infant with dilated cardiomyopathy and Hurler’s syndrome. The comparisons between the inpatient and outpatient group provide almost no additional useful information.
Comment: As the authors concede, the retrospective nature of the study is a significant weakness. Patients were selected for testing on the basis of symptoms and/or underlying conditions and many other children who could have been infected were never tested. The study is useful in describing the range of symptoms, treatment and outcome in the large selected group of children who tested positive for SARS-CoV-2. It does not, however, add anything new to what is already known about the condition in children.
Chen C. Coronavirus Disease-19 Among Children outside Wuhan, China [Internet]. Lancet Child and Adolescent medicine; Available from: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3546071
A pre-print, the information should be treated with caution until it has undergone peer review. This is a prospective case series of 31 paediatric cases of COVID-19 diagnosed at the Shenzen Third Peoples hospital between Jan 16th and Feb 19th 2020. This made up 7.9% of all cases diagnosed in Shenzen. They were all confirmed by PCR. None had been exposed to the seafood market in Wuhan. The patients received nebulised interferon and, IV ribavirin or oral lopinovir/ritonavir. The median age was 6.75, with most patients (41.9%) aged 5-9. Followed by 0-4yrs (32.2%) and 10-14yrs (19.4%). 41.9% were male.
Clinical features: 12/31 Children were asymptomatic. Fever was observed in 14/31, Cough in 13/41, Sore throat in 2/31, Rhinorrhoea in 22/31 and diarrhoea in 2/31. Median duration of fever was 2 days, with a range of 1–9 days. Bloods: Lymphopaenia was not observed. Lymphocytosis occurred in 17/31 patients. CRP was elevated in 4/31 patients. Radiology: On admission 64.5% of CT were normal, with 25% having unilateral pneumonia and 9.7% having bilateral. During hospitalization one child developed a unilateral pneumonia whose radiography was initially normal. Outcome: 23 children had been discharged at the time of writing, and the remainder were well and afebrile.
Garazzino S, Montagnani C, Dona D, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2020; 25(18). https://dx.doi.org/10.2807%2F1560-7917.ES.2020.25.18.2000600
This rapid communication reports the preliminary results of an Italian multicentre study involving 11 of 13 exclusively paediatric hospitals and 51 of 390 paediatric units across Italy (mainly in central and northern Italy). Retrospective data collection began on 25 March 2020.
Study design: Data to 10 April 2020 collected by participating physicians and hospitals for all paediatric patients (aged 1 day to 17 years) with at least one RT-PCR SARS-CoV-2 positive nasal/pharyngeal swab AND adequate follow-up considered necessary by the clinician to define the final outcome (usually 2 wks).
Findings: Data collected for 168 children and adolescents with documented COVID-19:
Gender: 94/168 male (55.9%) and 74/168 female (44.1%)
Age: median 2.3 yrs (IQR 0.3-9.6 yrs, range 1 day-17.7 yrs, mean 5 yrs. <1 yr: 66/168 (39.3%), of which 15/168 neonates (6.9%). 1-5 yrs: 38/168 (22.6%). 6-10 yrs: 24/168 (14.3%). 11-17 yrs: 40/168 (23.8%)
Hospitalised: 110/168 (65.1%): <1 yr: 52/66 (78.8%). 1-5 yrs: 24/38 (63.2%). 6-10 yrs: 13/24 (54.2%). 11-17 yrs: 21/40 (52.5%)
Comorbidities: 33/168 (19.6%): chronic lung disease 7, congenital malformations or complex genetic syndromes 14, cancer 4, epilepsy 5, gastrointestinal disorders 2, metabolic disorders 1, immunosuppression 4, immunocompromise 3. The hospitalisation rate was similar between children with comorbidities (23/33, 70%) and those without (87/135, 64%).
Source of infection: Close contact with a COVID-19 infected person outside the family was rarely reported. 113/168 (67.3%) of children had at least one parent who tested positive for SARS-CoV-2 infection. Symptom onset in relatives preceded symptoms in the infected child by 1 to 14 days in 88/113 (77.8%).
Symptoms: 4/168 (2.4%) asymptomatic. Fever (37.5 to 39°C) 138/168 (82.1%), cough 82/168 (48.8%), rhinitis 45/168 (26.8%), diarrhoea 22/168 (13.1%), dyspnoea 16/168 (9.5%), pharyngitis 9/168 (5.4%), vomiting 9/168 (5.4%), conjunctivitis 6/168 (3.6%), chest pain 4/168 (2.4%), fatigue 3/168 (1.8%), non-febrile seizures 3/168 (1.8%, all 3 had a known history of epilepsy), febrile seizures 2/168 (1.2%, 1 with a history of febrile seizures and 1 with first episode of febrile seizures as onset of COVID-19).
Blood results: Of the children who had blood tests, 47/121 (38.8%) had CRP > 0.5 mg/dl. Other abnormal findings were rare.
Complications: 33/168 (19.6%) developed complications: interstitial pneumonia 26/168 (15.5%), severe acute respiratory illness 14/168 (8.3%), peripheral vasculitis 1/168 (0.6%)
No child underwent a chest CT scan; pneumonia was assessed using X-ray or ultrasound in 75/168.
Co-infection: Documented in 10/168 (5.9%), including 3 RSV, 3 rhinovirus, 2 EBV, 1 influenza A, 1 non-SARS coronavirus infection, 1 Strep pneumoniae.
Treatment: 16/168 (9.5%) required non-invasive oxygen treatment. 2 were admitted to ICU for mechanical ventilation (1 preterm neonate and a 2-month-old with congenital heart disease). 49/168 (29.2%) children (those with more severe illness) received experimental SARS-CoV-2 treatments, including lopinavir/ritonavir, hydroxychloroquine and/or azithromycin/clarithromycin, systemic steroids.
All children, including those with comorbidities, recovered fully and there were no sequelae reported at the time of submission. This paediatric data is in contrast to the high number of cases and case-fatality rate seen in adults in Italy. Children comprised a marginal percentage of those hospitalised in Italy with SARS-CoV-2 infection.
Zhang C, Gu J, Chen Q, et al. Clinical Characteristics of 34 Children with Coronavirus Disease-2019 in the West of China: a Multiple-center Case Series. doi:10.1101/2020.03.12.20034686
A pre-print, the information should be treated with caution until it has undergone peer review.
This is a further retrospective case study looking at 34 children with confirmed COVID-19 between Jan 1st and Feb 25th 2020 in 4 hospitals in Western China. They were aged 1 month to 12 years.
Clinical features: The most common symptom was fever (26/34) followed by cough (20/34), followed by vomiting (4/34) and diarrhoea (4/34). A significant number had co-infections (16/34) including Mycoplasma pneumoniae (9/34), influenza A or B (12/34) and 2/34 were mononucleosis. One child had a nephroblastoma and one had asthma. The median incubation period was 10 days (IQR 7.75 – 25.25) and median 3 days (IQ 2 – 4) from admission to fever resolution
Bloods: Lymphocytosis was most common (17/34). CRP was not significantly elevated (median 7.56ml/L, IQR 1.21 – 15.13), but was >5 for 20/34, and procalcitonin was not significantly elevated either (0.6, 0.03 – 0.07)
Radiography: On chest CT 14/34 had patchy shadows bilaterally, 14/34 unilaterally, and 6 had normal CT chest.
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.
For the mild cohort, 28% of patients were asymptomatic, with moderate cases more likely to have fever of 38oC 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 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.”
Zheng F, Liao C, Fan Q-H, et al. Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China. Curr Med Sci 2020;:1–6. doi:10.1007/ s11596-020-2172-6
This is a retrospective case series of 25 children <14 years of age hospitalised with COVID-19 from 10 hospitals across the Hubei province between February 1st and February 10th 2020. It is unclear how the cases were ascertained. 14/25 were male (54%) and the median age was 3yrs (IQR 2-9yrs). Most patients were <3 years (40%). 2 patients had a background of repaired congenital heart disease (both infants), although we have no more detail than this. Both of these children went on to develop critical illness.
Clinical features: 13/25 (52%) had fever, 11/25 (44%) had cough, 3/25 (12%) had diarrhoea, and 2/25 (8%) had nasal congestion, vomiting, breathlessness or abdominal pain.
Bloods: Inflammatory markers were not particularly raised, with a median CRP of 14.5mg/L (IQR 0.93 – 25). 10/25 (40%) patients had lymphopenia.
Radiology: CT chest was normal in 8/24 (32%) with unilateral involvement in 5/24 (20%) and bilateral in 12/24 (48%). Changes typically showed patchy shadows. Younger children appeared more likely to have bilateral lung findings than older children.
Co-infection: Other organisms identified included Mycoplasma pneumoniae (3/25, 12%), Influenza B (2/25, 8%) and one of the 2 critically ill children had Enterobacter aerogenes.
PICU Clinical Papers
González-Dambrauskas S, Vásquez-Hoyos P, Camporesi A, et al. Pediatric critical care and COVID19. Pediatrics. 2020; doi: 10.1542/peds.2020-1766
In preprint, González-Dambrauskas et al describe 17 children with COVID-19 admitted to international PICUs in Chile, Colombia, Italy, Spain and USA, in April 2020. These are interim results from the CAKE (Critical Coronavirus And Kids Epidemiologic) Study, recruiting between April and December 2020 from almost 60 PICUS in 20 countries. As well as describing the clinical details of each child in detail, this paper also describes four children with myocarditis associated with covid-19.
The 17 children predominantly presented with cough and fever (53% had cough, 76% had fever). Comorbidities were common in 71% of children, including underlying respiratory, cardiac, renal, liver or neurological disorders. Six children (35%) had gastrointestinal (GI) symptoms at presentation.
Of the four children with myocarditis, all were based in Europe, none had previous cardiac disease, and all presented with fever and GI symptoms. One also had a rash and conjunctivitis. These children all developed myocarditis early in their clinical picture, with average duration of symptoms prior to presentation of 3.5 days. All four children received IVIG. Three of these children also required inotropic support; one child also developed ARDS and acute kidney in addition to myocarditis, requiring non-invasive ventilation but not renal replacement therapy. None of the four children with myocarditis required mechanical ventilation. All four children survived to discharge home, with a mean hospital length of stay of 13.5 days.
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.
Grasselli, G et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. doi:10.1001/jama.2020.5394 Published online April 6, 2020.
This is a retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the regional ICU coordinator of the Lombardy ICU Network, and treated at one of the ICUs of the 72 hospitals in the network. Patients were recruited between 20/02/2020 and 18/03/2020 with follow-up on 25/03/2020. Data was collected via telephone. Of the nearly 1600 patients referred for ICU admission, only 4 were between 0 and 20 years of age, with a median age of 16 and interquartile range of 14 to 19 years of age. Three of the four patients (75%) were male and three of the four had comorbidities (specific details not given).
Two required mechanical ventilation. It’s important to note that the patients in this study were those admitted to ICU and not patients on medical wards, in the ED or in the community so the high percentage of ventilated patients in this study is not a reflection of the other patients in the region with SARS-CoV-2. These two patients had relatively low oxygen requirements with an FiO2 of 30% and 50%; relatively low PEEPs of 5 and 14 mmHg; and favourable PaO2/FiO2 ratios of 195 and 323, placing these two patients in the mild to moderate ARDS severity scores (for more information on PaO2/FiO2 ratios have a look at the LITFL explanation at https://litfl. com/pao2-fio2-ratio/). None of the four patients in the 0-20 year old category received ECMO. Information on disposition was only available for two of the four patients. None of these patients died. Two remained on ICU on 25/03/2020 at time of follow-up.
What can we take from this study? As the study recruited patients admitted to ICU, the numbers of adolescent patients in this case series is low at only four, with an age range of 16 to 19. The data was collected retrospectively via telephone making it difficult to draw robust conclusions. However, we can see that compared to the older groups of patients in the study, ventilation requirements were lower. Three of the four adolescent patients had comorbidities, which might suggest that children and adolescents without comorbidities in the Lombardy region were less severely unwell and did not require ICU admission.
Oualha, M., M. Bendavid, L. Berteloot, et al. “Severe and fatal forms of COVID-19 in children.” Archives de Pediatrie, June 4th 2020, https://doi.org/10.1016/j.arcped.2020.05.010
This paper describes the clinical presentation and course of the 27 children and young people with COVID who required paediatric intensive care in and around Paris at the height of the coronavirus peak in France. The total population of all ages of the Ile de France , the region for which this centre is responsible for tertiary paediatric referrals, is around 12 million. During the time covered by the study, there were around 5000 COVID deaths in France, with the Ile de France region being the hardest hit.
This study focuses on 27 children unwell enough to need high dependency care during active COVID infection. The criteria for admission were oxygen requirement > 1L/min or underlying disease. The cohort of 27 were admitted within days of onset of first symptoms and 24 were positive for COVID-19 by PCR of nasal swabs. This is consistent with active virus, rather than PIMS-TS, the Kawasaki like post-COVID syndrome.
24 had respiratory disease, mostly with radiological or CT findings consistent with COVID. 6 had cardiovascular disease and 4 renal problems.
9 required invasive ventilation with median duration 5 days. 10 received non-invasive ventilation and 23 were treated with oxygen. 4 received catecholamines, one ECMO and one renal replacement therapy. The median length of hospital stay was 6 days.
Mean laboratory findings in the group were of elevated CRP, procalcitonin, fibrinogen and D-dimers, consistent with an inflammatory and prothrombotic state. Neutrophil and lymphocyte counts were normal. T cell subsets and cytokine levels were not measured.
70% had underlying conditions, but the spectrum was different from adult experience, with neurological and respiratory problems or sickle cell disease being most common.
Three of the five who died had previously been in good health. A teenage girl whose clinical course was suggestive of the cytokine storm seen in adults died within hours of admission. A teenage boy and a 6 year old girl co-infected with other pathogens both died after long PICU stays.
This description confirms that severe illness is rare in children with COVID and shows that even those admitted for HDU care had a shorter illness and better prognosis than that seen in adults. Nonetheless, occasional children do suffer a prolonged illness with multi-organ dysfunction.
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. https://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.”
Clinical Dermatology COVID-19
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
Locatelli AG, Robustelli Test E, Vezzoli P, Carugno A, Moggio E, Consonni L, Gianatti A, Sena P. Histologic features of long-lasting chilblain‐like lesions in a pediatric COVID‐19 patient. Journal of the European Academy of Dermatology and Venereology.09 May 2020. doi: 10.1111/jdv.16617. https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.16617
This retrospective single case report describes clinical and pathological signs of chilblain-like lesions whilst the patient was asymptomatic. He did not have any signs of autoimmune conditions including on histological examination. The lesions persisted for several weeks whilst he remained positive for SARS-CoV-2 on nasopharyngeal swab. The authors highlight young people with this sign could be carriers of the virus.
A 16-year-old male patient attended Papa Giovanni XXIII Hospital, Italy. His nasopharyngeal swab was positive for SARS-CoV-2. His mother was admitted to hospital for SARS-CoV-2 management following his presentation.
Clinical features: Diarrhoea and dysgeusia were experienced 3 days prior to the onset of skin lesions described as “multiple asymptomatic erythematous oedematous partially eroded macules and plaques on dorsal aspects of the fingers”. A lesion was also noted on second toe.
Radiology: None discussed.
Bloods: “Routine bloods autoimmunity, cryoglobulins, viral serologies all negative or within normal limits”
Treatments: None
Outcomes: Was treated on a hospital ward without supplemental oxygen until discharge.
Other features of interest: Histopathological examination demonstrated oedema of the papillary dermis, superficial and deep lymphocytic infiltrate in the perivascular and strong peri-eccrine pattern. Images are provided.
Recalcati, S., T. Barbagallo, L. A. Frasin, F. Prestinari, A. Cogliardi, M. C. Provero, E. Dainese, A. Vanzati and F. Fantini (2020). “Acral cutaneous lesions in the Time of COVID-19.” J Eur Acad Dermatol Venereol.
This pre-print Letter to the Editor reports on a series of unusual dermatological manifestations presenting to the Dermatologic Unit in Alessandro Manzoni Hospital, Italy in March and April 2020. The authors observed 14 cases, of which 11 were children with a mean age of 14.4 years and a range of 13-18 years. Of the 14 cases, 6 (43%) were male. 3 pairs of cases were siblings.
None of the cases had systemic symptoms (other than mild itch in 3 cases), there was no association with cold exposure, co-morbidities or drug intake, and there was no family history of COVID-19 related symptoms. 3 cases reported cough and fever 3 weeks prior to the onset of the lesions.
The authors believe that these dermatological findings are related to COVID-19 due to the rapid outbreak and clustering of these unusual skin lesions occurring at the same time as the COVID-19 outbreak. In support of this they report multiple similar cases being described from other areas affected by the pandemic. They hypothesise that the skin lesions may represent late manifestations of COVID-19 infection in young, healthy subjects, possibly due to an immunologic response targeting the cutaneous vessels. They accept that this hypothesis cannot be tested until a reliable serological test for antibody response to COVID-19 has been developed.
Clinical features: Acral eruption of erythemato-violaceous papules and macules, with possible bullous evolution or digital swelling. Lesions were found on the feet in 8 cases, hands in 4 cases, and on both sites in 2 cases. 2 children developed erythemato-papular targetoid lesions on the hands and elbows after a few days.
Histology: Lesions on fingers showed diffuse dense lymphoid infiltrate of the superficial and deep dermis, with a prevalent perivascular pattern and signs of endothelial activation. Targetoid lesions on elbows showed mild superficial perivascular dermatitis.
Bloods: Normal FBC, CRP, LDH and D-dimer. Serology was negative for EBV, CMV, Coxsackie and Parvovirus B19.
Outcomes: In all cases the lesions resolved without treatment after 2-4 weeks.
It is worth noting that this study is limited both by the small number of cases, but more particularly by the lack of evidence linking these skin lesions with a proven COVID-19 infection.
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.
Radiology Findings COVID-19
Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults [published online ahead of print, 2020 Mar 5]. Pediatr Pulmonol. 2020;10.1002/ppul.24718. doi:10.1002/ppul.24718
A case series of 20 paediatric patients with COVID-19 infection identified with COVID-19 NAT on pharyngeal swabs from Wuhan Children’s Hospital. It reviews the clinical information and co-infections.
Clinical features: two thirds had a clear contact history. Incubation 24hrs28 days of life. 13/20 had a cough, 12/20 had a fever. Bloods: 11/20 had (N) CRP, i.e. less than 3mg/L and 80% had PCT >0.05.
Radiology: On CT: Subpleural findings were seen in all 20 patients. 50% had bilateral findings, with a further 6/20 with unilateral findings. Consolidation with a halo in 50% of cases, considered as atypical signs in paediatric patien. Chloral hydrate was the primary sedative for CTs These were predominantly mild cases in the paediatric patients, with CXR adding little diagnostically. An early chest CT exam seemed to be necessary. 9/20 had coinfection, most commonly with mycoplasma (4/9) – although the ‘flu B,’flu A or RSV accounted for almost all of the remainder
Despite this, the physical chest symptoms were mild, with retraction in one case, and another case with cyanosis.
The average length of stay 12.9 days. Some patients were managed on the basis of their CT alone. These are similar to those seen in adults.
Görkem, S. B. and B. Çetin (2020). “COVID-19 pneumonia in a Turkish child presenting with abdominal complaints and reversed halo sign on thorax CT.” Diagn Interv Radiol. June 5th 2020, DOI 10.5152/dir.2020.20361
This is a case report of a 15 year old girl with Covid-19 from Turkey in an Epublished letter ahead of print with an early description of the “reversed halo sign”(RHS) on chest CT scan in. RHS is described as a central ground glass opacity (due to septal alveolar inflammation) surrounded by denser granulomatous airspace consolidation in the shape of a crescent or ring. It was identified in adult Covid -19 patients in early studies from Wuhan.
The patient presented with abdominal pain (epigastric tenderness). She had no respiratory symptoms and was apyrexial. Covid-19 was identified on nasopharyngeal swab. WCC 4.01×109, lymphocytes 1.92×109, CRP 1.6 mg/l rising to 10 mg/l after five days. Oxygen saturation remained above 95% in air.
Initial abdominal CT identified bilateral patchy alveolar infiltrates in the lower lobes and so an unenhanced low-dose thorax CT was performed. This identified multi focal RHS lesions within bilateral upper, middle and lower lobes. There were multiple multisegmental peripherally located alveolar infiltrations and scattered ground glass opacities.
The patient received hydroxychloroquine. Interestingly, she did not develop any respiratory symptoms, making an uneventful recovery and was discharged after 8 days.
RHS is a distinctive sign on chest CT. As well as occurring in pneumonia (including community acquired pneumonia) it can also be associated with fungal infections, immunosuppression, pneumocystis, TB, sarcoidosis, pulmonary neoplasms and pulmonary infarction. Therefore it can pose diagnostic challenges and management is guided by the clinical history. Although RHS is recognised in the adult Covid-19 literature this is a first report in a paediatric patient.
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
Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection [published online ahead of print, 2020 Mar 11]. Pediatr Radiol. 2020;10.1007/s00247-020-04656-7. doi:10.1007/s00247-02004656-7
This study describes five children with confirmed COVID-19 who had CT chest scans in a large tertiary level hospital in China. Three of the five children had patchy ground-glass opacities on their CT scans but these changes were less severe than those seen in infected adults. The treatment is not detailed in the paper, so presented as published in this summary.
Case 1: 17 month old asymptomatic male. Bloods: CRP 9.4, WCC 9.2. Radiology: CT chest performed on day 4 showed patchy ground glass opacities. Repeat CT on day 9 after treatment had normalised (antiviral, anti-infective, immunoglobulin, interferon and Lianhua qingwen granules). No CXR.
Case 2: 10 month old asymptomatic female. Bloods: CRP 0.9, WCC 14.8. Radiology: Day 2 scan: normal. Not repeated. No CXR.
Case 3: 3 year old male with coryza, productive cough, sore throat and fever after 3 days. Bloods: CRP 0.7, WCC 15.0. Radiology: Day 9 CT showed patchy ground-glass opacities. Repeat CT on day 16 had normalised after treatment (antiviral, anti-infective, immunoglobulin). No CXR.
Case 4: 4 year old asymptomatic male. Bloods: CRP 0.2, WCC 6.6. Radiology: Day 2 CT chest showed patchy ground-glass opacities. Repeat CT on day 7 had normalised after treatment (montelukast, immunoglobulin). No CXR.
Case 5: 6 year old asymptomatic male. Bloods: CRP 0.6, WCC 5.3. Radiology:
Day 3 CT was normal. No CXR.
Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical and CT Imaging Features of the COVID-19 Pneumonia: Focus on Pregnant Women and Children [published online ahead of print, 2020 Mar 11]. J Infect. 2020;S0163-4453(20)30118-3. doi:10.1016/j.jinf.2020.03.007
This study is a review of CT imaging findings in children and pregnant women in a hospital in the Hubei Province. Four children with confirmed COVID-19 infection were included in the study. The bottom line is that pulmonary CT changes in children were mild, with either focal ground glass opacification or focal consolidation. Although CT has been reported as a useful screening tool in adults with suspected COVID-19 infection, the CT changes of the four children were non-specific; the authors conclude that exposure history and clinical symptoms are more helpful for screening in swab-negative children than CT. 41 pregnant women with either laboratory-confirmed or clinically-diagnosed COVID-19 infection were included in the study. All pregnant women had mild courses of their COVID-19 illnesses. Six of the 16 laboratory-confirmed pregnant women and 10 of the 25 clinically diagnosed pregnant women delivered during the study period. There were no cases of vertically transmitted COVID-19 in the neonates born to these pregnant women.
Case 1: 5 year old female with fever, cough and fatigue. No lymphadenopathy. Bloods: low WCC with raised lymphocytes and decreased neutrophil ratio. Normal CRP. CT: normal. Follow-up CT 9 days later remained normal.
Case 2: 11 month old male with fever and cough. No lymphadenopathy Bloods: normal WCC with raised lymphocyte count and decreased neutrophil ratio. Normal CRP. CT chest: single consolidation without peripheral predominance (unlike reported findings in adults).
Case 3: 9 year old female with fever but no cough. No lymphadenopathy. Bloods: normal WCC, low lymphocytes and normal neutrophil ratio. Normal CRP. CT chest: single ground glass opacity without peripheral predominance (unlike reported findings in adults).
Case 4: 2 month old male with cough but no fever. No lymphadenopathy. This infant was coinfected with RSV. Bloods: normal WCC with normal lymphocytes and normal neutrophil ratio. CRP raised (does not say how high). CT chest: multiple focal consolidations and pleural effusion. This infant’s CT findings were more severe than the other three children, thought to be due to coinfection with RSV.
Cardiology Papers
Del Barba, P., D. Canarutto, E. Sala, G. Frontino, M. P. Guarneri, C. Camesasca, C. Baldoli, A. Esposito and G. Barera (2020). “COVID-19 cardiac involvement in a 38-day old infant.” Pediatr Pulmonol. June 18th 2020, https://doi.org/10.1002/ppul.24895
First (single) case report of an infant with biochemical and echocardiographic evidence of mild cardiac involvement due to SARS-CoV-2 infection. The 38 day old male infant presented to hospital on 27/03/20. Neither the centre nor the country is identified but is likely to be in Italy. Pregnancy had been unremarkable. No delivery details given. Baby was formula fed. Both mother and father were +ve for SARS-CoV-2. He presented with a fever of 37.6oC and rhinitis but no respiratory distress and did not require oxygen therapy. Nasal and nasopharygeal swabs were +ve for SARS-CoV-2. Haemoglobin, lymphocyte count, CRP, ESR, electrolytes, liver transaminases, INR and PTT were normal. Abnormal results: LDH “mildly increased”, platelet count 525,000/μl, procalcitonin 3.28ng/ml, troponin T 8.2ng/dl, creatine kinase-MB 9.8μg/L, D-dimer 13.3 μg/ml, pro-brain natriuretic hormone 208pg/ml, fibrinogen 1.28g/L. CXR showed increased bronchovascular markings but no parenchymal changes (CT not done). A resting heart rate of 140bpm and a transient peak rate of 200bpm were the only cardiac signs (serial ECGs and 24hr recording). First echocardiogram showed no abnormalities but cardiac MR scan showed a “minimal amount” of pericardial effusion with no myocardial edema. Follow up echo 3 days after the first confirmed a 2mm effusion. A panel of other viruses linked to pulmonary and/or cardiac problems in infants was negative. He required no treatment and was discharged after 14 days. Swabs were -ve 21 and 22 days after presentation.
Selman Kesici, Hayrettin Hakan Aykan, Diclehan Orhan, Benan Bayrakci, Fulminant COVID-19-related myocarditis in an infant, European Heart Journal, June 12th 2020, ehaa515, https://doi.org/10.1093/eurheartj/ehaa515
Clinical Features: 2 year old previously healthy male in contact with Covid19, hospitalized with nausea, vomiting and lethargy. On Day 2 of admission deteriorated with Respiratory distress, filiform pulse and blood pressure was not measurable. There was hepatomegaly. Child was intubated in PICU, while preparing for ECMO went into cardiac arrest. 30 minutes of CPR was performed. During ECMO biopsy of myocardium was taken.
Radiology: Initial CXR – bilateral interstitial infiltrates. Day 2: CXR Cardiomegaly with pleural effusion. ECHO: Severe heart failure
Bloods: Initial bloods negative for inflammatory markers but Troponin was elevated 30 times normal on Day 2.
PCR for viruses were negative including RT PCR for Sars_COV_2
Myocardial Biopsy showed local inflammation, Positive for RT_PCR for COVID 19
Conclusion: Single case report showing the effect of COVID 19 causing heart failure secondary to Myocarditis without Kawasaki like Syndrome
Trogen, B., F. J. Gonzalez and G. F. Shust (2020). “COVID-19-Associated Myocarditis in an Adolescent.” The Pediatric Infectious Disease Journal. 03. June 3rd 2020, doi: 10.1097/INF.0000000000002788
This case report details the admission to PICU of a 17-year-old obese male (BMI 30kg/m2) with spondylolysis and a distant history of asthma (not requiring medication for > 5 yrs) who presented to a hospital in New York City during the third week of April with septic shock, after a week’s history of fever, GI symptoms and neck pain.
Clinical features: 7 day history of fever and neck pain and a 6 day history of diarrhoea and vomiting (non-bloody, non-bilious). No neck stiffness, headache, photophobia or respiratory symptoms. At presentation he was febrile, tachycardic and hypotensive (79/66 mmHg) with diffuse abdominal pain. His cardiovascular status remained labile after initial fluid resuscitation and he was admitted to PICU.
Initial bloods: Lymphocytes 0.9 x 103/μL, CRP 167 mg/L, ferritin 1275 ng/mL, D-dimer 1218 ng/mL, initial Troponin I level 2.97 ng/mL rising to 6.17 ng/mL 2 hrs later, brain natriuretic peptide 2124 pg/mL, sodium 128 mmol/L, creatinine 1.25 mg/dL, creatine kinase 761 U/L, LDH 346 U/L, INR 1.5, IL-6 28 pg/mL
Microbiology: Nasopharyngeal swab RT-PCR SARS-CoV-2 positive. Other respiratory and GI pathogen PCRs negative, including enterovirus, adenovirus, CMV, EBV, HHV-6, parvovirus B19.
Radiology: Abdominal USS essentially normal. CXR: low lung volumes, normal cardiothymic silhouette and mild, hazy ground glass opacities at the lower lobes bilaterally.
ECG: T-wave inversion particularly in inferior leads.
Cardiac imaging: Initial transthoracic echocardiogram: LV ejection fraction mildly depressed with no obvious intracardiac clots or pericardial effusion. Cardiac MRI: normal sized LV & RV, LVEF 40%, RVEF 39%, area of mid-wall late gadolinium enhancement at inferior LV-RV junction corresponding to area of increased T2 signal as well as an area of hypokinesia, consistent with myocarditis.
Treatment in PICU: Blood pressure normalised on day 1, but remained febrile and tachycardic until day 4. Required 2 days of oxygen via NC. Received anticoagulation, paracetamol/ibuprofen and 48 hrs of piperacillin/tazobactam until blood cultures reported negative. No other anti-inflammatories or IVIg given. Initially started on hydroxychloroquine which was stopped on day 3 when serial ECG demonstrated prolonged QTc interval not present initially. Serial Troponin I and BNP levels normalised by discharge.
Outcome: Discharged on day 5 with 2 week course of anticoagulation (apixaban). Echocardiogram at follow-up one week after discharge demonstrated normal ejection fraction (59%) with qualitatively improved function. However, tissue Doppler imaging signals of the mitral valve annulus were still abnormally diminished with low global longitudinal strain rate, consistent with residual myocardial dysfunction. Repeat ECG showed persistent T-wave inversion in lead III.
The authors conclude with a discussion of the possible mechanisms of cardiac injury secondary to COVID-19, including viral entry via the ACE2 receptor causing direct damage to myocardiocytes, immune-mediated injury secondary to cytokine release or T-cell dysregulation, microvascular damage, endothelial shedding/dysfunction, hypoxia-mediated injury and abnormal coagulation, including DIC, increasing the risk of thrombosis and ischaemic events.
Ocular Manifestation
Valente, P., G. Iarossi, M. Federici, et al. Ocular manifestations and viral shedding in tears of pediatric patients with coronavirus disease 2019: a preliminary report. J aapos. June 10th 2020, https://doi.org/10.1016/j.jaapos.2020.05.002
27 paediatric patients were identified between 16/03/2020 – 15/04/2020, from Bambino Gesù Children’s Hospital, Rome, Italy. It was not clear how patients were identified/recruited. The mean age was 84 months (range=8 days to 210 months). 74% were male (n=20); 26% were female (n=7).
Clinical features present:
– Cough and/or dyspneoa = 15 patients (56%);
– Vomiting and/or diarrhoea = 8 patients (30%);
– Ocular manifestations consistent with viral conjunctivitis = 4 patients (15%);
In the abstract it states that “At admission, all patients showed ocular manifestations”, however there is no other reference to further information in the paper.
Radiology/bloods: N/a
Other investigations:
Nasopharyngeal swab to COVID-19 tested positive in all 27 patients.
Of the 4 patients with apparent viral conjunctivitis, 1 patient resulted positive for SARS-CoV-2 on RT-PCR from conjunctival swab.
Of the other patients (n=23), two more patients had positive findings for SARS-CoV-2 in their conjunctival swab without developing clinical signs of conjunctivitis.
Outcomes: 27 (100%) discharges.
Other salient features: Some preliminary evidence to suggest that SARS-CoV-2 shedding is low in eye secretions/tears.
Testing/Viral Studies
M. A. De Ioris, A. Scarselli, M. L. Ciofi Degli Atti, et al. Dynamic viral SARS-CoV-2 RNA shedding in in children: preliminary data and clinical consideration of Italian regional center. J Pediatric Infect Dis Soc. May 23rd 2020, https://doi.org/10.1093/jpids/piaa065
This study at a paediatric hospital in Rome tracked SARS-CoV-2 shedding (nasopharyngeal, faecal, urinary and conjunctival) by following a cohort of 22 children during their hospital stay, collecting clinical and microbiological data.
Study design: The study ran from 16th March to 12th April in the COVID centre at Bambino Gesu Pediatric Hospital and collected data on 22 inpatients with an initial positive nasopharyngeal swab (either prior to admission or on admission). RT-PCR for SARS-CoV-2 RNA on nasopharyngeal and conjunctival swabs and stool and urine samples were repeated every 2-3 days for each child while they were inpatients until they had two consecutive negative results in the absence of new symptoms. Kaplan-Meier analysis was used to estimate the duration of symptoms and viral shedding for symptomatic patients: patients whose last swab/sample was still positive were censored at the date of the last swab.
Study population: 15/22 (68%) male, 7/22 (32%) female. Median age 7 years (range 8 days to 17.5 years). 4/22 neonates (1/4 tested because mother positive and 3/4 tested because midwife positive). 2/22 comorbidity (Angelman syndrome, suspected genetic syndrome and autism). 13/22 patients were discharged before the end of the study period (median inpatient stay 7 days, range 3-15 days).
Symptoms: 4/22 (18%) asymptomatic (including 2/4 neonates, the other 2/4 had low grade fever and poor feeding). 18 symptomatic patients: 15/18 (83%) fever, 10/18 (55%) respiratory symptoms, 7/18 (39%) diarrhoea and vomiting, 3/18 (17%) seizure. Symptoms had resolved in all 18 before discharge from hospital. Median duration of symptoms was 8 days (range 2-21 days). 15/22 had a positive stool sample at admission: of these 7/15 (47%) had respiratory symptoms and 3/15 (20%) had diarrhoea and vomiting.
Viral shedding: At diagnosis: 22/22 (100%) had positive nasopharyngeal swab (by definition), 15/22 (68%) had positive stool sample, 1/22 (5%) had positive urine sample (re-test 2 and 5 days later was negative; another patient had initial negative urine test but repeat 3 days later was positive) and 2/22 (9%) had positive conjunctival swab (both were negative 2-3 days later). A detailed table charting the dates of inpatient stay, onset and end of symptoms and positive/negative swabs/samples for each patient is supplied: the full screen of faecal, urinary and conjunctival sampling was performed at variable intervals after the initial positive nasopharyngeal swab (up to 5 days later in several cases). For symptomatic patients: (1) from date of symptom onset to negative nasopharyngeal swab: median 8 days (range 2-17 days) and (2) from date of symptom onset to negative stool sample: median 14 days (range 10-15 days). Estimate of persistence of viral shedding at day 14 from symptom onset for nasopharyngeal swab 52% and for stool sample 31%.
The authors note the need to confirm the clinical relevance of faecal SARS-CoV-2 shedding in terms of the risk of transmission via the faeco-oral route.
Xu, Y, Li X. Zhu, B. et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med (2020). https://doi.org/10.1038/s41591-020-0817-4
This study presents the results of widespread screening for COVID-19 in Guangzhou in China. 745 children were screened of which 10 were positive for COVID-19. Their ages ranged from 2 months to 15 years.
Clinical features: 6/10 had a fever over 38oC. 5/10 had a cough. 4/10 had a sore throat. 2/10 had rhinorrhoea and 2/10 had diarrhoea.
Radiography: 7/10 had coarse lung markings on CXR with no pneumonia, and 3/10 were normal. CT scans revealed ground glass or patchy opacities in 5/10.
Bloods: Basically normal in all cases
They made note that rectal swabs were frequently positive and that these swabs were positive for a longer duration than nasal swabs. The authors suggest on this basis that faecal-oral transmission may be possible, however this is very uncertain and will require further research to elucidate.
Yuan, C., H. Zhu, Y. Yang, X. Cai, F. Xiang, H. Wu, C. Yao, Y. Xiang and H. Xiao (2020). “Viral loads in throat and anal swabs in children infected with SARS-CoV-2.” Emerg Microbes Infect: https://doi.org/10.1080/22221751.2020.1771219
This is a retrospective review of RT-PCR testing results of 2138 paediatric patients with suspected SARS-CoV-2 infection at Wuhan Children’s Hospital in Hubei, China, from 1 January to 18 March 2020. All children were tested using throat swabs (TS); a subset of 212 were also tested using anal swabs (AS). Changes in viral load in both throat and anal swabs were monitored in 13 patients.
Findings: 217/2138 (10%) confirmed cases on EITHER throat or anal swab.
78/217 confirmed cases had both types of swab: 24/78 (31%) positive for both TS & AS, 37/78 (47%) TS pos/AS neg, 17/78 (22%) TS neg/AS pos. For those cases where the TS and AS results didn’t match (i.e. TS pos/AS neg or TS neg/AS pos):
Asymptomatic: 12/37 (32%) TS pos & 10/17 (59%) AS pos
GI symptoms: 7/37 (19%) TS pos & 6/17 (35%) AS pos
Cough: 16/37 (43%) TS pos & 4/17 (24%) AS pos
Fever: 20/37 (54%) TS pos & 5/17 (29%) AS pos
CT evidence of pneumonia: 25/37 (68%) TS pos & 10/17 (59%) AS pos
Time from positive to negative for PCR assay: 7 days for TS pos & 6 days for AS pos
The viral loads detected on throat swabs and anal swabs showed no difference.
Zhao, W., Y. Wang, Y. Tang, W. Zhao, Y. Fan, G. Liu, R. Chen, R. Song, W. Zhou, Y. Liu and F. Zhang (2020). “Characteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge.” Clin Pediatr,May 28th https://doi.org/10.1177%2F0009922820928057
In this study from Beijing, China, serial nasopharyngeal swabs were performed on children discharged between January 21st and April 18th 2020 following hospital admission with confirmed SARS-CoV-2 infection. Criteria for hospital discharge included clinical improvement and 2 negative RT-PCR tests for SARS-CoV-2 on consecutive nasopharyngeal swabs. Follow up swabs were performed fortnightly following discharge; the authors report on children with subsequent positive RT-PCR on follow up.
In total 14 children were followed, 7 of whom had a subsequent positive SARS-CoV-2 PCR result, none of whom had significant symptoms at the time (one with a temperature of 37.5). There were no significant clinical or laboratory differences between the group with subsequent positive tests compared with those who remained negative.
The authors refer to those who have subsequent positive SARS-CoV-2 PCR as having “reactivation” of infection. This is a misnomer as the persistent shedding of viral RNA has been well recognised in adult studies<https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25952>. This includes a large cohort of over 200 patients from Korea <https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030> with positive tests following negative PCR results, similar to the children in this study. Importantly no onward transmission from these “re-positive” cases was found amongst 790 contacts in the Korean cohort, suggesting the viral RNA detected in patients with prolonged shedding is not viable. Indeed in a recent in vitro study<https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa638/5842165> including 90 SARS-CoV-2 PCR positive samples, only samples taken within 8 days of symptoms onset were capable of infecting cells. This is in keeping with contact tracing data<https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2765641> suggesting peak transmissibility occurs before and immediately after symptom onset with limited transmission beyond 5 days of symptom onset.
The likely explanation of the “reactivation” described here is prolonged shedding of non-viable viral RNA with an interim “false negative” samples prior to hospital discharge. Given the available data, it is unlikely that these “re-positive” discharged patients represent an infection risk to others
Xing Y, Ni W, Wu Q, et al. Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase. doi:10.1101/2020.03.11.20033159
A pre-print, the information should be treated again with caution until it has undergone peer review.
This study of 3 paediatric patients with COVID-19 from Qingdao, China (aged 1.5, 5 and 6 years) all had fevers and none were severe. All children had elevated lymphocytes (>4.4 x 109/L) and 2 of 3 had abnormalities on chest CT (consolidation in one and ground glass changes in the other). The primary point made in the paper is that whilst respiratory swabs were negative within 2 weeks after children became afebrile, stool remained positive for over 4 weeks.
Pandey U, Yee R, Precit M, et al Pediatric COVID-19 in Southern California: clinical features and viral genetic diversity, medRXiv, June 2nd 2020, https://doi.org/10.1101/2020.05.28.20104539
A study of 35 children age range 18 days to 18.5 years (median12.5), 57% of whom were boys, seen over an 8 week period in Southern California. Patients were identified by nasopharyngeal swabs submitted to Los Angeles Children’s Hospital between 11 March 2020 and 11 May 2020. 37% were hospitalised with a median inpatient stay of 4 days. Symptoms were diverse with fever and cough being the most common, 1/3 were symptomless. Whole genome sequencing was undertaken on Covid-19 samples. There was an association between disease severity and viral load. Children < 5 years age had a higher viral load and all were symptomatic. There was limited variation in the viral genome though a calculated evolutionary rate was like other RNA viruses. No correlation was identified between disease severity and genetic variation.
Zachariah, P., K. C. Halabi, C. L. Johnson, S. Whitter, J. Sepulveda and D. A. Green (2020). “Symptomatic Infants have Higher Nasopharyngeal SARS-CoV-2 Viral Loads but Less Severe Disease than Older Children.” Clin Infect Dis, May 20th 2020, https://doi.org/10.1093/cid/ciaa608
This research letter details the viral loads of children with confirmed SARS-CoV-2 infection from Columbia University Irving Medical Centre in New York. All children admitted and discharged between March 14th to April 24th 2020 were included, timing of test relative to onset of symptoms, clinical severity along with viral load were compared between infants <1yo and children >1yo.
Of 57 patients with positive SARSCoV-2 PCR, 20 (35%) were under 1yo. Compared with older children, viral load was higher amongst infants <1yo (mean cycle threshold 21.05 vs 27.25, p<0.01 – where lower cycle threshold=greater viral load). Infants were tested earlier on average (2 vs 3.8 days from symptom onset) and fewer had severe disease compared with older children (5% vs 32.4%).
In this small hospital-based study symptomatic infants appear were found to have higher viral loads and milder disease compared with older children. This is in contrast to data from some adult studies where a higher viral load correlated with more severe illness.
Amongst several possible explanations for this observation are that:
– infants were more likely to be tested early in illness when viral load peaks<https://www.nature.com/articles/s41591-020-0869-5> – declining thereafter
– thresholds for hospital presentation may differ between infants and older children
– test performance and sample quality may differ between infants and older children
– there may possibly be differences in host biology according to age
Although some data suggest that higher SARS-CoV-2 viral load is associated with the presence of viable virus<https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa638/5842165> / in vitro infectivity, the exact implications of the findings here in terms of risk of transmission from infants compared with older children is unclear. Further studies examining SARS-CoV-2 viral load dynamics and correlation with clinical course in children are required to better understand potential variation between different age groups.
Haematology and Immunology Focus
Odièvre, M. H., C. de Marcellus, H. Ducou Le Pointe, S. Allali, A. S. Romain, J. Youn, J. Taytard, N. Nathan and H. Corvol (2020). “Dramatic improvement after Tocilizumab of a severe COVID-19 in a child with sickle cell disease and acute chest syndrome.” May 1st 2020, Am J Hematol. https://doi.org/10.1002/ajh.25855
The authors of this case study are based at two hospitals in Paris; in this correspondence they describe the treatment of a 16 year old girl with homozygous sickle cell disease (SCD) admitted to ICU with acute chest syndrome (ACS) and pulmonary emboli complicating COVID-19 pneumonia, in particular the use of Tocilizumab, a humanised anti-IL-6 monoclonal antibody (usual indications include use as immunosuppressant therapy in rheumatoid arthritis and giant cell arteritis in adults and juvenile idiopathic arthritis in children).
Course of SCD prior to admission: The patient had a history of recurrent vaso-occlusive crises and abnormal transcranial dopplers between the ages of 5 and 11 years old, necessitating treatment with exchange transfusions. At 11 years of age she was commenced on daily hydroxyurea with resolution of vaso-occlusive events. She had no history of ACS or pulmonary hypertension; respiratory function and chest radiography were previously normal.
Presentation with COVID-19-19: She presented with isolated fever, with nasophyaryngeal swabs subsequently confirmed as RT-PCR SARS-CoV-2 positive. 7 days later she developed acute chest pain associated with respiratory distress (SpO2 85%).
Radiology: CT pulmonary angiogram (CTPA) showed bilateral pulmonary emboli and bilateral consolidation with right-sided halo sign.
Treatment in ICU: Included non-invasive ventilation, anticoagulation and red cell exchange transfusion followed by simple transfusion (lowest Hb 64 g/L). Based on recent experience in adult SCD patients with COVID-19 disease she also received a single infusion of Tocilizumab (8 mg/kg). The authors report rapid clinical improvement after Tocilizumab with repeat CTPA 5 days later showing complete resolution of pulmonary emboli and consolidation on the right and decrease on the left. She was discharged from hospital 11 days after admission to continue oral anticoagulation for 6 weeks.
Conclusions: Inflammatory cytokines such as IL-6 and TNF-α are elevated in COVID-19. COVID-19 pneumonia can cause ACS in SCD patients; there have been several recent reports of successful treatment using Tocilizumab.
Tsao HS, Chason HM, Fearon DM. Immune Thrombocytopenia (ITP) in a SARS-CoV-2 Positive Paediatric Patient. Pediatrics. 2020 May 1. doi: 10.1542/peds.2020-1419. Pre-publication version.
A retrospective single case report was reported by Warren Alpert Medical School of Brown University, Rhode Island, USA, highlighting an association between SARS-CoV-2 and immune thrombocytopenia (ITP) in children. The patient was co-positive with rhinovirus and enterovirus, previously described in children managed for SARS-CoV-2.
A 10-year-old female patient was admitted for management of ITP after presenting with a petechial rash. 3 weeks prior she experienced 2 days of symptoms: cough and fever, following exposure to the SARS-CoV-2 virus. She did not have a family history of haematological or autoimmune conditions, any medical problems or medications.
A ‘respiratory panel’ was positive for rhinovirus and enterovirus and negative for coronavirus types 229E, HKU1, NL63, OC43. A Reverse transcriptase-polymerase chain reaction testing was positive for SARS-CoV-2.
Clinical features: Initial illness (3 weeks prior to ED presentation): fever, non-productive cough
Presentation to ED: petechial rash spreading from the legs to chest and neck, oral wet purpura, ecchymoses in the popliteal regions and shins.
Radiology: N/A
Bloods: At presentation: WCC 3.9 X 10^9/L (56% neutrophils, 38% lymphocytes) [Leukopenia without neutropenia or lymphopenia], haemoglobin 13.4 g/dL [normal], platelets 5 X 10^9/L [thrombocytopenia]. ANA borderline positive titers (1:40) in a speckled pattern which was considered not significant.
At 2 week follow up: WCC 6.1 X10^9/L [normal], Platelets 320 X 10^9/L [normal], ALT 56 IU/L [mildly raised], AST 28 IU/L [mildly raised].
Treatments: Intravenous immunoglobulin, paracetamol, and antihistamine to manage ITP.
Outcomes: Discharge from hospital after 1 day. Rash and oral lesions improved after 48 hours. Side effects were noted due to IVIG including headache, vomiting, abdominal pain.
At 2 week follow up platelet count was maintained, white cell count normalised and a mild transaminitis was noted.
Wu, H., H. Zhu, C. Yuan, C. Yao, W. Luo, X. Shen, J. Wang, J. Shao and Y. Xiang (2020). “Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China.” JAMA Netw Open 3(6): e2010895. doi:10.1001/jamanetworkopen.2020.10895
In this retrospective case series from Wuhan, China, the clinical and immunological characteristics of children admitted to hospital with confirmed SARS-CoV-2 infection are examined. Details are provided for the 148 children with mild or moderate disease.
The median age was 84 months (IQR 18-123). Fever (40.5%) and cough (44.6%) and vomiting or diarrhoea (21.6%) were the most common symptoms. SARS-CoV-2 PCR became negative at a median of 7 days (IQR 4-11 days).
Lymphopenia was present in only 4.5% of patients; CD 4 lymphopenia in 1.9%. Elevation in CRP (32.4%) and procalcitonin (47.3% elevated; median 0.05 (IQR 0.04-0.08)) was observed in fewer than half of patients. Liver transaminases and LDH were significantly higher in moderate versus mild cases but the vast majority of levels fell within normal range.
Levels of inflammatory cytokines including IL2, IL6, TNG-a and IFN.y were largely normal; the authors note that one patient with severe disease had elevated IL-6 (3869 pg/mL). IL-10 was increased in 14%.
No deaths occurred amongst mild and moderate cases and all 148 patients were discharged.
In this large case series of children with mild or moderated SARS-CoV-2 infection, laboratory measures of inflammation were largely normal. Specifically the significant elevations in IL-6, D-dimer, and ferritin characteristic of severe COVID-19 in adults and also PIMS-TS / MIS-C in children were absent in these milder cases. The authors postulate that the relative preservation of CD4 T-cells and the higher levels of IL-10 compared with adults with severe COVID-19 may indicate these as important components of a protective immune response.
As yet our understanding of the drivers of variation in individual immune response to SARS-CoV-2 remains incomplete.
Venturini E, Palmas G, Galli L. Severe neutropenia in infants with severe acute respiratory syndrome caused by the novel coronavirus 2019 infection. 2020 May 19. doi 10.1016/j.paeds 2020.04.051 [Epub ahead of print]
This case report from the Meyer Children University Hospital, Florence, published as a letter describes two infants with SARS-CoV-2 with transient severe neutropenia (<0.5 x109/l)
Clinical Features: The two female infants, aged 23 days and 39 days were admitted with mild respiratory symptoms and low grade fever. Nasopharyngeal swans were positive for Covid-19. There was no clinical deterioration in their condition during admission.
Radiology: not described
Treatment: not described.
Haematology: leukocytes and neutrophils normal on admission. At 5 days neutrophil counts fell to 0.244 x 109/lnand 0.482 x 109/l. Subsequently both improved.
Apart from age and gender there is no other demographic information nor any on treatments.
Although neutropenia is described in 6% of cases of Covid-19, severe neutropenia has not been described. In the report cases it was not associated with any change in clinical state. The authors suggest consideration of performing FBCs 5 to 7 days into the illness to identify neutropenia.
It requires further studies to see if these findings are replicated and whether they are clinically significant. The severity of the neutropenia could be age dependent reflecting bone marrow maturity as one patient was in the neonatal range and the other just beyond it.
Chen, J., Z. Z. Zhang, Y. K. Chen, et al (2020). “The clinical and immunological features of pediatric COVID-19 patients in China.” Genes and Diseases. https://doi.org/10.1016/j.gendis.2020.03.008
This early study from Chongqing, China describes the features of 12 children diagnosed with COVID-19. All had a mild course of illness. CT imaging was abnormal in 10 of 12 with patchy ground glass opacity the most common finding. Lymphopenia was present in 2 children.
The authors also compare the “immune profile” (including lymphocyte counts, immunoglobulins, complement, CRP and IL6 levels) of the 12 children with a group of 20 adults patients. Aside from a lower CRP in children (mean 11.5 vs 23.3mg/L) and expected age-related differences in absolute lymphocyte numbers, there were no significant differences between the groups.
Other Interesting Clinical Papers
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.
Li Y, Wang H, Wang F, Du H, Liu X, Chen P, Wang Y, Lu X, Comparison of Hospitalized Patients with pneumonia caused by COVID-19 and influenza A in children under 5 years, International Journal of Infectious Diseases (2020) https://doi.org/10.1016/j.ijid.2020.06.026
This study is from Wuhan children’s hospital, China. It is a retrospective one reviewing the clinical history, radiology and laboratory results of 57children under 5, with confirmed pneumonia on CT or radiography within 72 hours of admission, with COVID-19 diagnosed by detecting SARS-CoV-2 in throat swabs. The comparison group was 59 children aged under 5 who were admitted with influenza A pneumonia. Influenza A was diagnosed by direct immunofluorescence assay.
The 57 COVID-19 pneumonia children were consecutively admitted between 28th January and 11th March 2020; the 59 influenza A pneumonia children were consecutively admitted between 14th December 2019 and 30th February 2020(?).
The median age of the COVID-19 patients was 18.7+/- 16.7 months. The median age of the Influenza A patients was 21.8+/-16.7 months with no statistical difference. There was slightly higher proportion of males in each group 61.4% for COVID-19 vs 66.1% for the influenza A group with no statistical difference.
Clinical features: 31(54.4%) of the COVID-19 patients presented with fever compared to 50(84.7%) influenza A patients, P<0.001. 40(70.2%) of the COVID-19 patients presented with cough compared to 50(84.7%) in the influenza A group, p<0.001. Dyspnoea occurred in only 2(3.5%) COVID-19 patients and 5(8.5%) influenza A patients, p=NS. Gastrointestinal symptoms occurred in 8(14.1%) of the COVID-19 patients and 21(35.6%) of the influenza A patients, p=NS. Convulsions occurred in only 1 COVID-19 child and 3 influenza A children, p=NS. During hospitalization 1 COVID-19 child required supplementary oxygen and two required intensive care, compared to 7 influenza A children requiring supplementary oxygen and 4 intensive care, p=NS.
Radiology: CT chest imaging with ground glass appearance was more commonly found in COVID-19 pneumonia children 42.1% vs15% influenza A pneumonia children, p=0.03. Consolidation was more common in influenza A children (25%) compared to COVID-19 patients (5.2%), P = 0.02.
Haematology and Biochemistry
Haematology investigations showed COVID-19 patients had significantly lower levels of leukocytes and neutrophils but significantly higher lymphocyte levels compared with influenza A patients (7.87 vs. 9.89 ×109/L, P = 0.02; 2.43 vs. 5.16 ×109/L, P < 0.001; 4.58 vs. 3.56 ×109/L; P = 0.006.
Lower levels of C-reactive protein (CRP) were observed in COVID-19 patients than influenza A patients (3.7 vs. 15.1 mg/L, P = 0.001.
There were no significant routine biochemistry differences between the two groups except potassium which was significantly lower in the COVID-19 group.
Significantly lower levels of D-dimer and prothrombin time (PT) were found in COVID-19 patients than influenza A patients (0.34 vs. 1.94, P < 0.001; 10.8 vs. 11.2 mm/h, P = 0.014).
There were no deaths reported in this study.
Conclusion: The authors concluded that children under 5 with COVID-19 pneumonia compared to children with influenza A pneumonia showed milder clinical symptoms and a significantly increased lymphocytosis with a more prevalent ground glass CT chest appearance compared to influenza A pneumonia children under 5. There were no reported deaths or serious complications from COVID-19 in this study.
The study shows COVID-19 pneumonia is milder than influenza A pneumonia in a series children under 5. The influenza A patients were not typed and came from a different but overlapping time period during the winter months. Comorbidities were also not mentioned in either group.
Lu, Y., Y. Li, W. Deng, M. Liu, Y. He, L. Huang, M. Lv, J. Li and H. Du (2020). “Symptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan.” The Pediatric infectious disease journal. 05. doi: 10.1097/INF.0000000000002729
This retrospective study analysed demographic, clinical, laboratory, radiological and therapeutic data from the electronic medical records of 110 children hospitalised with “mild/ordinary” COVID-19 (classified as per the National Health Commission of People’s Republic of China National Recommendations for Diagnosis and Treatment of COVID-19, 7th edition) at Wuhan Children’s Hospital in Hubei, China between 30th January and 10th March 2020. Inclusion criteria: throat or nasopharyngeal swabs RT-PCR SARS-CoV-2 positive and patient discharged from hospital after recovery (an initial cohort of 127 children was reduced to 110 after exclusion of 2 critical cases and 15 children in whom the onset of disease could not be accurately determined).
Study design: Timings of onset of illness, most recent exposure (presumably to SARS-CoV-2-confirmed or symptomatic contacts, although this isn’t specified), diagnosis and discharge from hospital were recorded. Patients were discharged only once they had two consecutive RT-PCR SARS-CoV-2 negative swab results (separated by at least 24 hours). The authors calculated the duration of viral shedding for (a) symptomatic patients (81/110, 74%) as time from onset of illness to discharge and for (b) asymptomatic patients (29/110, 26%) as time from date of most recent exposure OR abnormal chest radiological imaging (reason for imaging not specified in these asymptomatic patients) to discharge. This definition of duration of viral shedding, with starting point presumably in most cases a retrospective parent-reported start of symptoms or exposure to an infectious contact, and end point two negative swabs leading to discharge from hospital, makes interpreting the duration figures problematic. Viral shedding in urine and faeces was not measured.
Clinical features: Median age of the 110 children was 6 years (IQR 2-9); 59/110 male (54%), 51/110 female (46%). Symptoms included: cough and dyspnoea 57/110 (52%), fever 56/110 (51%), GI (including diarrhoea, vomiting, poor feeding, anorexia, abdominal pain) 26/110 (24%), rhinorrhoea 10/110 (9%).
Radiology: 64/103 (62%) had unspecified chest imaging reported as demonstrating pneumonia (55/75 symptomatic (73%) and 9/28 asymptomatic (32%)).
Bloods: Leucocytes < 4.0 x 109/L in 6/110 (5%) (all 6 were symptomatic). Leucocytes > 10.5 x 109/L in 12/110 (11%) (9 symptomatic & 3 asymptomatic). Lymphocyte ranges not specified. Haemoglobin < 110 g/L in 13/110 (12%) (all 13 symptomatic). Fibrinogen < 2.0 g/L in 34/90 (38%) (20 symptomatic & 14 asymptomatic). Hs-CRP > 3.0 mg/L in 21/110 (19%) (18 symptomatic & 3 asymptomatic). Procalcitonin > 0.05 ng/mL in 52/110 (47%) (43 symptomatic & 9 asymptomatic). AST > 50.0 U/L in 19/110 (17%) (all 19 symptomatic).
Treatment: None of the patients required oxygen therapy. All of them received antiviral therapy, mostly commonly nebulised interferon-α. According to the data table 22/110 received Chinese medicine therapy, although no details are given and it’s not clear if this was pre-hospitalisation. Median duration of hospital stay was 10 days (IQR 8-13).
Conclusions: The median duration of viral shedding using the definitions above was 15 days overall (IQR 11-20 days, range 5-37 days): 17 days (IQR 12-23) in symptomatic patients and 11 days (IQR 9-13) in asymptomatic patients. Symptomatic infection, fever, pneumonia and lymphocyte counts < 2.0 x 109/L were reported to be associated with prolonged duration of shedding.
Xiao, Z., X. Xie, W. Guo, Z. Luo, J. Liao, F. Wen, Q. Zhou, L. Han and T. Zheng (2020). “Examining the incubation period distributions of COVID-19 on Chinese patients with different travel histories.” Journal of infection in developing countries 14(4): 323-327. doi:10.3855/jidc.12718
Although all ages are affected by COVID-19, this paper makes it clear that the number of infected children is tiny compared to those in adults. The authors analyse incubation periods by age, finding that this increases in length in adults from aged 20 to 70+. The findings regarding children are more difficult to interpret due to small case numbers and therefore large confidence intervals, but it appears that 6 to 20 year olds may have a longer incubation period than young adults aged 20 to 60. The results for 0-5 year olds are fairly inconclusive. The authors then examine incubation in relation to travel history, finding that those who were affected by local community spread had longer incubation periods than those who had contracted the virus directly in Wuhan. They conclude that the virulence of the virus may decrease with intergenerational transmission, but that more work is needed.
Zhang, B., S. Liu, Y. Dong, L. Zhang, Q. Zhong, Y. Zou and S. Zhang (2020). “Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19).” Journal of Infection April 23rd 2020, https://doi.org/10.1016/j.jinf.2020.04.023
In this case series from Dongguan, China, three normally fit & well children aged 14y, 13y and 10m were followed up after positive throat swab for SARS-CoV-2. All three had a subsequent negative throat swab within approximately 7 days, and fully recovered, however 7-9 days later all three had rectal swabs which were positive. These findings raise the question of whether apparently well COVID-19 patients continue to carry and possibly shed the virus. If this was found to be the case in larger and more comprehensive studies, there may be an argument for introduction of strategies to increase avoidance of transmission via the faecal-oral route.
Nathan, N., B. Prevost and H. Corvol (2020). “Atypical presentation of COVID-19 in young infants.” The Lancet 395(10235): 1481. https://doi.org/10.1016/S0140-6736(20)30980-6
This correspondence in the Lancet describes the clinical features of 5 infants with COVID-19 who were admitted to a Paris hospital during the first week after imposed population quarantine in France (from 17th March 2020). At this time at Trousseau Hospital, children needing admission with fever or respiratory symptoms (or both) were admitted to a dedicated SARS-CoV-2 infection unit: during this week 14 infants under the age of 3 months were admitted and of these 5 out of 14 were confirmed SARS-CoV-2 positive on nasopharyngeal swabs.
Age/gender of infants: All 5 of these previously healthy infants with COVID-19 were boys; ages ranged from 1.6 to 2.7 months (median 2.1). All of their parents had mild signs of viral infection (including fever, cough, rhinitis), which could have been indicative of undiagnosed COVID-19.
Clinical features at presentation: 5/5 fever (range 37.4 to 38.5 °C), 4/5 neurological signs (drowsiness/hypotonia/abnormal “moaning” cry), 4/5 mottled skin, 4/5 runny nose, 4/5 cough, 0/5 dyspnoea, 5/5 normal SpO2, 0/5 digestive symptoms.
Investigations: FBC, CRP & procalcitonin largely unremarkable, with the exception of lymphopaenia in 2/5. Lumbar punctures in 4/5 babies with abnormal neurology reported normal (including negative for RT-PCR SARS-CoV-2). Chest X-rays performed in 4/5 essentially normal.
Outcomes: All 5 showed rapid clinical improvement and received no drugs other than paracetamol. Inpatient stays ranged from 1 to 3 days and duration of fever ranged from 1 to 5 days (max 39°C). The infants were followed up for 2 weeks post-discharge with a daily phone call from a paediatrician using a standardised questionnaire.
Conclusion: This encouraging report of a small cohort of SARS-CoV-2 positive infants under the age of 3 months presenting with fever showed initially concerning signs on admisson, but rapid recovery and minimal intervention needed for all 5 infants.
Wu, Q., Y. Xing, L. Shi, W. Li, Y. Gao, S. Pan, Y. Wang, W. Wang and Q. Xing (2020). “Co-infection and Other Clinical Characteristics of COVID-19 in Children.” Pediatrics. May 1st 2020, DOI: https://doi.org/10.1542/peds.2020-0961
This retrospective study from 2 hospitals in China examines the clinical and epidemiological characteristics of 74 children with confirmed SARS CoV-2 infection. Consistent with other studies, the majority of children experienced a mild course of illness with only one severe case requiring non-invasive ventilation. All recovered.
Cough was present in 32%, fever in 27% and 40% were asymptomatic at the time of testing. Lymphopenia was present in only 5% of cases. Abnormal CT imaging was observed in 50%, but only 12% showed typical changes of COVID-19.
Of those tested for other respiratory pathogens 19 of 34 had co-infection. Mycoplasma pneumoniae (16) and RSV (3) were the most common pathogens. It is not clear how these pathogens were identified. The significance of Mycoplasma in particular is not entirely clear as asymptomatic upper respiratory tract carriage<https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001444> in children is well recognised; similarly in interpreting serology, false positives<https://onlinelibrary.wiley.com/doi/full/10.1111/j.1469-0691.2004.00993.x> can be problematic.
For cases where exposure history was available 65/68 were household contacts of a confirmed adult case. There was no evidence of transmission from children to others.
This data is consistent with larger paediatrics studies demonstrating a milder course of COVID-19 in children compared with adults. Notably co-infection was not uncommon, illustrating that the presence of another respiratory pathogen should not preclude SARS-CoV-2 testing in children.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. Published online April 22, 2020. doi:10.1001/jama.2020.6775
This is a paper from New York, USA, looking at the presenting characteristics, comorbidities, and outcomes of 5700 patients who were hospitalized with Covid-19. These were patients who were admitted to one of 12 Northwell Health acute care hospitals between 01/03/2020 and 04/04/2020. Clinical outcomes were monitored until 04/04/2020. All patients who were sufficiently medically ill to require hospital admission with confirmed severe acute respiratory syndrome coronavirus 2 infection by positive result on PCR testing of an NPA were included. The median age of patients was 63 years (IQR 52-75), 39.7% were female.
There were only 59 patients under 10yo, and 15 patients between 10-20 years of age in this study.
The results below unless specified are for patients of all ages.
At presentations, 30.7% of patients had a temperature of over 380C. 20% had oxygen saturations of less than 90%. 43.1% of patients were considered tachycardic with a heart rate of over 100.
The majority of patients white cell count and differentials were within normal range. The mean white blood cell count was 7 (IQR 5.2-9.5). Neutrophil count 5.3 (IQR 3.7-7.7), however some patients were mildly lymphopenic, median 0.88 (IQR 0.6-1.2).
Most patients had a low CRP, the mean result was 16 (IQR 6.4-26.9). Most patients had a raised ferritin, the mean result was 798 (IQR 411-1515), with 15-400 being considered normal range. Of note lactate dehydrogenase was tested in 70% of the patients and was significantly raised in most patients, the mean being 404 (IQR 300-551) with the normal considered to be 50-242.
A venous lactate was recorded in 44% of patients and all results were normal- <2.
The most common comorbidities were hypertension (56.6%), obesity (41.7%) and diabetes (33.8%).
At the study end point 2634 patients had been discharged or had died during hospitalisation. Of these 14.2% were treated in ICU, 12.2% of them received mechanical ventilation, and 21% of these patients died. At the end point of the study of those patients who had received mechanical ventilation 3.3% were discharged alive, 24.5% died, 72.2% were still in hospital. There were no deaths in the 34 patients under 18 age group out of those who had reached discharge end point. There were still 25 patients under 20 years hospitalised at the time of the paper.
Of the patients who died, those with diabetes were more likely to have received mechanical ventilation or care in the ICU compared to those who did not have diabetes. Interestingly of those who died, those with hypertension were less likely to have received invasive mechanical ventilation than those without hypertension.
As most patients were still in the hospital at the endo point of the study (53.8%) this biases rates toward including patients who died early in their hospital course. The researchers point out that as these patients complete their hospital course, reported mortality rates will decline.
This study was slightly limited by the fact that the data was collected from the electronic heath record database and not the medical notes, from which a greater level of detail may have been established, however it was using this method that allowed for such a large number of patients to have been included and reviewed over a relatively short space of time. It is also limited by the fact that the study population only included patients from within the New York metropolitan area which may underrepresent some ethnic minorities.
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%)
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.
Preßler, J., S. Fill Malfertheiner, M. Kabesch, H. Buntrock-Döpke, S. Häusler, A. Ambrosch and S. Wellmann (2020). “Postnatal SARS-CoV-2 Infection and Immunological Reaction: A Prospective Family Cohort Study.” Pediatr Allergy Immunol. 9th June 2020, https://doi.org/10.1111/PAI.13302
This letter to the editor in Pediatric Allergy and Immunology presents data on 61 deliveries where there had been varying degrees of unprotected parental contact with SARS-CoV-2-infected midwives, nurses and doctors during the first week (precontainment) of a COVID-19 outbreak affecting 36 staff members in a large maternity and perinatal centre in Bavaria, Germany. Two previous papers in the same journal, published 22 April 2020 and 15 May 2020, have reported on containment strategies, symptoms, SARS-CoV-2 RT-PCR tests and antibody responses (IgG and IgA) in hospital staff during the outbreak. The index case was a midwife returning from holiday in Ischgl, Austria on 8 March 2020, who became unwell during a nightshift on 9 March at Regensburg University Hospital obstetric clinic; the first positive SARS-CoV-2 RT-PCR test result was received on 15 March and at that point contact tracing, testing and containment measures were introduced.
Study design: 66 families were identified with an infant born at the clinic during the week of 9 to 15 March where parents had had unprotected contact with SARS-CoV-2-infected medical staff; of these, 61 families consented to a prospective cohort study involving serial symptom interview, serial SARS-CoV-2 RT-PCR screening in throat rinsing fluid (parents) and faeces (infants) and serum IgA and IgG antibody studies (parents and infants) 4-5 weeks post-partum. Serum and breast milk were also tested using a different antibody assay to verify antibody responses. The authors note in their paper of 15 May 2020 that IgM antibody testing would have been useful, but that validated and certified IgM tests were not available to them at that time.
Key neonatal findings: The median gestational age at delivery was 39.3 weeks. Infants in the study received skin-to-skin care, rooming-in and breastfeeding in line with the hospital’s usual practice. The authors state that antepartum infections can be excluded and that any neonatal infections probably occurred via postnatal horizontal transmission in the family setting. 16/61 families reported parental symptoms consistent with COVID-19 within 2 weeks postpartum (one or both parents), although only 5/16 symptomatic families had COVID-19 confirmed based on RT-PCR and antibody evidence. 3 infants of these 5 symptomatic PCR-positive families developed non-specific signs of infection, including fever, dyspnoea and compromised circulation, at 5, 10 and 26 days old, and were admitted to NICU. Details of treatment are not supplied, but symptoms resolved for all 3 within a few days. Blood cultures and tests for non-SARS-CoV-2 viruses were negative. 2/3 symptomatic neonates had PCR positive faeces (one of these still had PCR positive faeces at 4-5 weeks) and 1 asymptomatic neonate also had PCR positive faeces at 4-5 weeks. None of the 3 SARS-CoV-2 PCR positive neonates nor the uninfected neonates had elevated or even borderline antibodies [note that there is some minor disparity between results summarised in the text and the detailed figure showing results in individual families]. Only one mother had IgG-positive breast milk (serum IgG also positive at 4-5 weeks, serum IgA negative, PCR positive at 1 week but not at 4-5 weeks, infant symptomatic at day 5 with negative faecal PCR at 1 week/4-5 weeks and negative serum IgG/IgA at 4-5 weeks).
Small cohort <10 children and Single Case Reports
Ji L, Chao S, Want Y et al. Clinical features of pediatric patients with COVID-19: a report of two family cluster cases. World J Pediatr. 2020 Mar 16. doi: 10.1007/s12519-020-00356-2. [Epub ahead of print] https://dx.doi.org/10.1007/ s12519-020-00356-2
This is a review of two confirmed paediatric cases of COVID-19 (both from oropharyngeal swabs) from two family clusters with recent travel to Wuhan. One child presented with fever and the other with diarrhoea.
Case one: 15-year-old boy presenting with a one-day history of fever. Clinical features: Temperature 37.9oC, pharyngeal congestion. Normal lung auscultation. Laboratory findings: mildly elevated white cell count at 11.82 x109/L, predominantly neutrophils (67.3%) and 25.7% lymphocytes. His CRP was mildly elevated at 35 mg/L. Radiological findings: normal unenhanced CT chest. Outcome: Symptomatic treatment. Symptoms disappeared after two days. Family information: both parents also tested positive for SARSCoV2.
Case two: 9-year-old boy presented with mild diarrhoea but no cough and no fever. Normal examination. Laboratory findings: normal white cell count and normal CRP. Radiological findings: normal unenhanced CT chest. Outcome. Treated with oral probiotic and symptoms disappeared after 2 days. Family information: Family members had negative COVID-19 swabs but were symptomatic. His mother presented with fever and cough with bilateral peripheral ground glass opacifications on CT chest. The child’s father and two-year old sister had normal CT chests but had mild symptoms consistent with COVID-19: his father had a cough for four days and his twoyear-old sister had a transient two-day low-grade fever.
Liu W, Zhang Q, Chen J, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med 2020;:NEJMc2003717. doi:10.1056/ NEJMc2003717
This letter to the editor describes a case series from Tongji hospital in Wuhan, China, taken from a cohort of 366 hospitalized children between January 7th and 15th 2020. 6 children were PCR Positive for COVID-19. Of the 6 patients, age range 1-7 years. All had fever >39oC, cough and 4/6 had vomiting. All had lymphocytopenia, with 4/6 leukopenia and 3/6 with neutropenia. One child required an ICU admission, receiving pooled donor IVIG. The median recovery time was 7.5 days. Authors surmise COVID-19 occurs in children with some moderate-severe episodes of illness.
Pan X, Chen D, Xia Y, et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection, The Lancet Infectious Diseases, 2020, https://doi. org/10.1016/S1473-3099(20)30114-6.
This case study looks at another family cluster of COVID-19 involving asymptomatic patients. It involved a 3yr old boy who was positive for SARS-CoV-2 despite having no symptoms, normal bloods and a normal CT.
Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang Z. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. Published online February 14, 2020. doi:10.1001/jama.2020.2131
This is a case series of, from Dec 8 2019 to Feb 6 2020, from China of 9 infants – all of whom had been hospitalised. Clinical presentation: 4/9 fever, 2/9 mild URTI symptoms, 1/9 were asymptomatic. All had family members that were COVID-19 positive. There were no severe complications or ICU admissions.
Jiehao Cai, Jing Xu, Daojiong Lin et al, A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features, Clinical Infectious Diseases, ciaa198, https://doi.org/10.1093/cid/ciaa198
This retrospective study examines 10 children diagnosed with confirmed COVID-19 between 19th Jan and 3rd February 2020 at the Children’s hospital in Shanghai. The age range is from 3 months to 11 years. None had comorbidities. There were no severe cases.
Clinical features: The assumed incubation period (time from exposure to index case to developing symptoms) was between 2 – 10 days, but median (and mode) 7 days. With regard to symptoms, 7/10 had fever >38oC, 6/10 had a cough, 4/10 had a sore throat, 3/10 had nasal congestion, 2/10 had rhinorrhea and 2/10 were sneezing.
Radiology: The chest x-ray was normal in 6/10. The rest had unilateral opacities.
Bloods: Lymphocyte counts were normal in 9/10, raised in one case. CRP ranged from 0.5mg/L to 35mg/L but was <10 for 7/10. Procalcitonin was normal (<0.25) in all children. 2 patients had a mild elevation of ALT (100U/L) or AST (142U/L and 51U/L)
Detection of SARS-CoV-2: Virus was found in NP/throat swabs in all patients, and the duration of shedding ranged from 6-22 days (Median 12 days). Stool shedding was prolonged, over 30 days in one patient. No urine was positive, and no serum positive.
Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series BMJ 2020; 368 :m606
This study looks at a group of 62 patients with COVID-19 in a province outside of Wuhan (Hubei). 2 of these were children, aged 10 and 11. There is a lot of clinical data in the paper but it is not broken down by age, so we cannot make any inference on behalf of the paediatric patients.
Kai-Qian Kam, Chee Fu Yung, Lin Cui et al, A Well Infant with Coronavirus Disease 2019 (COVID-19) with High Viral Load, Clinical Infectious Diseases, ciaa201, https://doi.org/10.1093/cid/ciaa201
This was a case report of a single 6-month-old with a positive nasopharyngeal swab until D16 of admission to hospital. There had been household transmission. There was a positive NPA with rt-PCR on D1 of admission although the child was asymptomatic – daily swabs remained positive until D17. The child was febrile once during the course of admission although they remained asymptomatic. Blood and stool tests were positive on D2. They had essentially normal investigations except for a neutropenia.
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 Published Online First: 17 March 2020. doi:10.1093/infdis/jiaa113
This is a case report of a 55 day old with SARS-CoV-2 who was admitted to hospital in China on February 2, 2020. She was treated with inhaled intereron-alpha-1b, amoxicillin, reduced glutathione, ursodeoxycholic acid, and traditional Chinese medicine lotus qingwen. The child was initially well, although her respiratory status worsened on day 2-6, and she required supplemental oxygen via nasal cannulae. Anal swabs on day 11 and 13 were positive on day 11-13 despite negative pharyngeal swabs.
Note is made in the title of this study that the infant sustained liver injury and heart damage. This is on the basis of marginally elevated liver tranaminases and cardiac troponin measurements, for which it is unclear why the tests were performed. There is no indication of any clinical compromise demonstrated. It should be noted that a significant proportion of the child’s care (including investigations) would not be considered standard practice in UK/US/Aus paediatric medicine.
Paret M, Lighter J, Pellett Madan R, Raabe VN, Shust GF, Ratner AJ. SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress [published online ahead of print, 2020 Apr 17]. Clin Infect Dis. 2020;ciaa452. doi:10.1093/cid/ciaa452
This is a case series of two infants presenting with fever to a hospital in New York during on week in March 2020. Neither presented with respiratory symptoms, and both had Sars Cov2 infection confirmed without other aetiology despite febrile infant work ups.
First; a 25-day old full-term male infant, presented with fever, irritability and facial rash. Parents had sore throat and subjective fever but had not sought medical attention for themselves. Full routine work up with CSF, blood, urine samples and routine respiratory PCR panel was taken. SARS CoV2 PCR positive on nasal swab. Treated empirically until cultures negative at 48 hours, recovered well.
Second; a 56-day old ex 35-week male infant, presents with fever only. He had no other symptoms, and no sick contacts. Bloods, urine and routine respiratory PCR panel was taken. Infant did not have lumbar puncture. SARS CoV2 PCR was positive on nasal swab. Treated empirically until cultures negative at 36 hours.
Authors discuss the need to maintain high index of suspicion for SARS-CoV-2 infection in febrile infants during a community outbreak, and the importance of strict infection control measures in paediatric emergency department.
Zhu, L., J. Wang, R. Huang, L. Liu, H. Zhao, C. Wu and C. Zhu (2020). “Clinical characteristics of a case series of children with coronavirus disease 2019.” Pediatr Pulmonol 8th April 2020 https://doi.org/10.1002/ppul.24767
This is a case series of ten paediatrics patients aged 1 – 17 years with confirmed Covid 19. These cases were retrospectively selected from 3 hospitals in Jiangsu, a coastal province approx 700 km east of Wuhan. Cases were collect from 24th January 2020 to 22nd February 2020. All cases were confirmed by RT-PCR anal or throat swabs. 70% of children presented with symptoms, and 30% were asymptomatic, but were screened due to contact with confirmed family member.
The most common symptoms on presentation were fever (40%), cough, (20%) and headache (20%). There was no report of whether children had underlying conditions. All children had a CT chest completed. Half of the cohort had CT changes. There were 2 cases of bilateral pneumonia, and 3 cases of unilateral pneumonia, 2 of which were in asymptomatic patients. Bloods were unremarkable, one child aged 1 year had Lymphocytosis, all others had normal lymphocyte counts. CRP was not raised in any child. Only one patient in the cohort required oxygen, and there were no ICU admissions. Five children were treated with antiviral medication including lopinavir/ritonavir (n=4) interferon α‐2b (n = 4), and oseltamivir (n = 1).
Of note, 5 children were still in hospital at the end of the case series.
Canarutto, D., A. Priolo, G. Russo, M. Pitea, M. C. Vigone and G. Barera (2020). “COVID-19 infection in a paucisymptomatic infant: Raising the index of suspicion in epidemic settings.” Pediatr Pulmonol. https://doi.org/10.1002/ppul.24754
This early single case report from Milan, Italy describes an infant with a mild case of COVID-19 who recovered without need for intervention. His father, the implied household index, had an upper airway infection with conjunctivitis without confirmatory testing.
Patient: 32 day old boy, presented to hospital symptomatic
Clinical Features: Cough, fever, rhinitis
Radiology: CXR normal
Bloods: reactive lymphocytes on film, monocytosis (1400/L) and neutrpenia (900/uL), CRP normal
Outcomes: Resolution of fever by day 3 of hospitalisation, full recovery without need for supportive therapy. Breast feeding maintained.
Shen Q, Guo W, Guo T, Li J, He W, Ni S, Ouyang X, Liu J, Xie Y, Tan X, Zhou Z. Novel coronavirus infection in children outside of Wuhan, China. Pediatric pulmonology. 2020 Apr 7.p1-6 DOI: 10.1002/ppul.24762
This retrospective study examines the clinical characteristics of children admitted to Public Health centre of Changsha, Hunan, China. There were 9 children admitted during the study period 08/01/2019 and 19/02/2020 who tested positive for COVID-19. All had a confirmed contact case with COVID-19. Median age was 8 years, with a minimum age 1 year and oldest was 12 years. Children were predominantly female (6/9, 66%). There was no information provided about co-morbidities.
Clinical features: 2/9 were asymptomatic, 1/9 had cough, 4/9 had fever, 1/9 had sore throat and 2/9 had diarrhoea.
Radiology: 2 patients had chest CT that were described as ground glass opacities. No further information was provided about the indications.
Bloods: 1/9 had lymphocytosis in whom other infectious causes were excluded. 1/9 had raised CRP, 4/9 raised ESR, 1/9 raised LDH, 2/9 had raised AST with 0/9 ALT abnormalities. All abnormalities were mild.
Treatments: All (9/9) children were treated10/2.5 mg/kg lopinavir/ritonavir twice daily, orally. 5/9 children received 10 mg/kg azithromycin once a day. One child received meprednisone and immune globulin therapy for febrile convulsion. No additional information regarding treatments were provided.
All children required oxygen therapy. None required intensive care or mechanical ventilation.
Outcomes: At the end of data collection 3/9 remained under hospital care and were positive for COVID-19. The remainder (6/9) were discharged from hospital. The time spent in hospital varied between 11 and 22 days (median 13.5 IQR 10.75-14 days).
Other salient features: 6/9 children were RT-PCR negative at discharge. The time between initial contact and a negative test varied between 9 and 20 days (median 13.5 IQR 10.75-14 days).
All averages were calculated by the reviewer from the data provided within the article.
Han, Y. N., Z. W. Feng, L. N. Sun, X. X. Ren, H. Wang, Y. M. Xue, Y. Wang and Y. Fang (2020). “A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults.” J Med Virol. 6th April 2020. https://doi.org/10.1002/jmv.25835
This retrospective study compares the clinical characteristics of 25 adults and 7 children with acute respiratory disease confirmed as COVID-19. Cases were retrospectively identified from patients admitted to Xian Eighth Hospital in Shaanxi, China, between 31st January and 16th February 2020. The mean age of the children was 1.3 years with a range of 2 months to 13 years, and 4 (57%) were male. None had any co-morbidities.
Clinical features: 5/7 (71%) children had cough, 3/7 (43%) had shortness of breath, 5/7 (71%) had fever, 1/7 (14%) had sore throat and 4/7 (57%) had diarrhoea and/or vomiting.
Radiology: 5/7 (71%) children had “positive findings suggestive of pneumonia” reported on CXR and/or CT. Examples of these findings were ground glass opacities and segmental consolidation in bilateral lung fields, particularly peripherally.
Bloods: No children had a low lymphocyte count (<0.8). Raised lymphocyte counts were not mentioned but raised WCC was reported in 2/7 (29%) children. 2/7 (29%) had a raised CRP (>10). 4/7 (57%) had a raised AST (>50) or ALT (>37). 5/7 (71%) had increased Brain Natriuretic Peptide (>125). 4/7 (57%) had a raised CK Isoenzyme (>30).
Outcomes: All 7 cases in children were classified as mild and recovered within 1-2 weeks. None of the children were admitted to intensive care and none died.
Comparison of clinical characteristics in adults and children: Children were more likely than adults to have diarrhoea and/or vomiting (57% vs. 8%, p=0.012). Adults more frequently had a reduced WCC, compared to a raised WCC in children, and raised CK isoenzyme was less common in adults.
Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report [published online ahead of print, 2020 Apr 1]. Infect Dis (Lond). 2020;1–3. doi:10.1080/23744235.2020.1747 634 Accessed from: https://www.tandfonline.com/doi/full/10.1080/23744235.2 020.1747634 on 4th April
This brief case report from Iran is of a 15 day old male from Mousavi Hospital in Zanjan, Iran. Date of admission was not available. Symptoms were fever and lethargy with his parents having fever and cough. He initially appeared tachycardic and febrile with sats of 93% on RA. He was given Vancomycin, Amikacin and Oseltamivir. SARS-CoV-2 was detected on RT-PCR. His parents were not tested as they did not meet the testing criteria at the time (hospitalisation).
Radiology: Chest X-ray had nil findings
Bloods: WCC 6.7, Lymphocytes 36%, Neutrophils 42% and CRP 1 (normal).
Comorbidities: There was an incidental finding of patent foramen ovale on Echo.
Outcome: He had improvement by day 2 of admission and was cleared for discharge on day 6.
Su L, Ma X, Yu H, et al. The different clinical characteristics of coronavirus disease cases between children and their families in China – the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707–713. doi:10.10 80/22221751.2020.1744483
This study from the Jinan Infectious Disease Hospital retrospectively reviewed cases of nucleic acid-positive SARS-CoV-2 patients between 24th January to 24th February 2020 (detected using the (ORF1ab/N) nucleic acid detection kit by Bio-germ, Shanghai, China). Nine children and members of their family totalling 14 adults were included. Note that two family members missed enrollment as they were at another hospital. Of the 9 children, 6 were female (66%). The age group ranged from 11 months to 9 years and 9 months old (mean age 4.5 years). For eight of the nine children, there was history of their parents having travelled frequently, being in contact with someone from Wuhan or having worked or visited Wuhan. Of note, five of the discharged children were readmitted to hospital because their stool showed positive results in SARS-CoV-2 PCR.
Clinical Features (children): 3 of the 9 children had fever (33%) and one had cough (11.2%). Imaging (children): On chest x-ray and CT, two children had findings consistent with bronchitis (22.2%), one had bronchial pneumonia (11.1%) and a further one had pulmonary consolidation and ground glass opacity. From the two example images included,, findings appear to be bilateral but this was not specified in the body of the text. Bloods (children): 8 of 9 children (88.9%) had normal or decreased white blood cell counts. Six children (66.7%) had increased CK-MB. ALT, AST. All children had a normal CRP, PCT, ESR and IL-6. Clinical Features (adults): Of the 14 adults, 8 (57.1%) had fever, five had cough (35.7%), three had chest tightness or pain (21.4%), a further three had fatigue (21.4%) and one reported a sore throat (7.1%). Imaging (adults): Ten (71.4%) had abnormal imaging mainly pulmonary consolidation, with 7 (50%) having nodular shadow and 7 (50%) having ground glass opacities. Bloods (adults): Four (28.6%) had reduced whice cell count with seven (50%) having lymphocytopaenia.
Lou XX, Shi CX, Zhou CC, et al. Three children who recovered from novel coronavirus 2019 pneumonia. J Paediatr Child Health Published Online First: 22 March 2020. doi:10.1111/jpc.14871
This is a case series of 3 children diagnosed with COVID-19 and admitted in the Zhengzhou University Children’s hospital in Henan Province, China (dates not provided). They were 2 sisters aged 6 and 8yrs, and a 6m old infant. The children were all infected by a family member, although the family of the 6m infant had no link to Wuhan.
Clinical features: All 3 had a fever, 2 had nasal congestion and rhinitis alongside fatigue, diarrhoea, and headache. The 6yr old girl had a cough.
Radiology: All 3 patients had CT scans with bilateral infiltrates
Bloods: Not reported
Outcomes: No children required intensive care/intubation or had any severe complications. All have been discharged. The 2 sisters were treated with nebulized interferon.
