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Concomitant infection of COVID-19 and serious bacterial infection in infants less than 90 days old during the Omicron surge

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The rate of serious bacterial infection rate in febrile infants less than 90 days presenting to Emergency Departments is around 9-13%. Clinicians faced uncertainty during the COVID pandemic of how to safely and effectively manage this cohort if the SARS-CoV2 status was known as the risk of concomitant bacterial infection was unclear.

Eleven sites retrospectively reviewed case notes of infants less than 90 days presenting to ED with fever, or reported fever, from December 2021 to January 2022 and recorded disposition outcomes and bacterial and viral culture results.

237 infants met the criteria for data collection. The incidence of serious bacterial infection in this cohort was 13.5% (32/237). 86 infants were SARS-CoV2 PCR positive (36.2%). There were seven positive urine cultures in SARS-CoV2-positive infants. One was likely a contaminant. None of these patients had a positive blood or CSF culture.

In seven cases, another respiratory virus was also cultured via Polymerase Chain Reaction. SARS-CoV2 infection was relatively common in this cohort of infants presenting with potential infection with or without fever. Concomitant infection was rare but did occur. There were no specific features that could help a clinician decide not to continue investigation once COVID-19 status was known.

Background

In December 2021, there was an increase in SARS-CoV-2 cases in the United Kingdom linked to the emergence of the SARS-CoV-2 Omicron variant (GOV.UK, 2022). This led to an increase in hospital admissions in children aged 0 to 4 years with COVID (ONS, 2022). Infants under a year have the highest (PCR-confirmed) infection rates with 20% of these infections in infants less than 3 months old (Hardelid et al., 2022).

An unpublished rapid case review led by the United Kingdom Health Security Agency (UKHSA) Joint Modeling Team and the NHS England and Improvement Children and Young People’s Transformation Team identified 55 children (< 1-year-old) with confirmed SARS-CoV-2 Omicron infection who had been admitted to hospital, across 33 NHS trusts.

The majority of cases (38/55 69%) occurred in infants 90 days or under. The clinical course for these infants was characterised by a short febrile illness, and in all cases, the infants made a full recovery and were discharged home.

The NICE guidance (NICE 2019) mandates that infants in this age group presenting with a fever have some basic investigations to rule out serious bacterial infection. As the national infection rates rose, the concern was that more infants would present to EDs and Paediatric Assessment Units {PAUs} with a fever, with or without known COVID-19 infection.

This could leave clinicians in a tricky situation. I

If an infant with fever had COVID, did this mean no other tests were needed? And if large amounts of infants with fever presented and received a full spectrum of investigations, would this overwhelm services?

Ideally, you would carry about a prospective observational study from multiple sites to look at these questions. However, this would have been difficult logistically and may not have provided useful information in a meaningful time frame. Instead, we used the retrospectoscope and looked at the outcomes for all infants with fever or reported fever under 90 days old.

Methods

The Children’s Emergency Department Head of Service network identified a site lead at 11 Children’s Emergency Departments in England and Wales. They made local arrangements, with appropriate governance, to collect data on all infants less than 90 days old presenting with a fever, or reported fever (within 24 hours of presentation) or other concerns regarding sepsis between December 10th 2021 and 13th January 2022. The following data was collected

1) Age at presentation (in days)
2) Any family member positive?
3) Investigations in ED – FBC, CRP, Urine, Culture, LP, CXR
4) Admitted (Yes/No)
5) COVID PCR results (positive/negative)
6) Culture results (positive/negative)
7) Length of stay

The site leads registered the rapid service evaluation locally. Given the data collection was “usual practice in public health including health protection” as defined by the United Kingdom Health Research Authority, it did not require Research Ethics Review.

Timestamps (i.e. arrival date) were merged with no other identifying information other than days old. This meant patient identification was not possible.

Results

Data were available from eight sites on infants presenting during the five-week evaluation period. 1978 were seen across these eight sites, with an admission rate of 31.6% (626/1978). Data on infants with fever or reported fever was available from all eleven sites. 237 met the criteria for data collection (admission rate 176/237;74.3%). Attendances per week ranged from 39 to 59 (Table 1).

Table 1 – Admission rates from ED for all infants per week

The median age was 49 days, the mean was 45.1, with a range of 1 to 90 days. The COVID-19-positive status (via PCR or LFT) was before arrival in the Emergency Department in 18 cases, and 61 infants had at least one COVID-19-positive family member.

There were 28 positive urine cultures – four of these were likely contaminants – and 14 positive blood culture results. Two of these were likely contaminants. Five sets of cultures were positive with a concomitant positive urine culture. There were nine positive CSF results, six of these being enterovirus infection, one related to an E.Coli sepsis (positive blood culture and urine culture) and one contaminant. The incidence of serious bacterial infection incidence in our population was 32/237 (13.5%)

86 infants were SARS-CoV2 PCR positive (36.2%). 76 patients of these were admitted (88.3%). The peak of presentations and admissions took place in week 3 (Table 2). There were seven positive urine cultures in SARS-CoV2-positive infants, and only one of these was probably a contaminant. None of these patients had a positive blood or CSF culture. In seven cases, PCR revealed another respiratory virus.

Table 2 – Number of infants positive per week

37/86 (43%) infants had a temperature greater than 37.9 on arrival compared to 54/161 (35.7%) in the negative SARS CoV2 group. More patients had White Cell Counts < 5.0 in the SARS CoV2 positive group (16 positives versus 3 negatives). However, a greater number in the SARS CoV2 negative group (6 positives versus 24 negatives) had a WCC >15. Only two SARS-CoV2-positive infants had a CRP > 20 (53 and 229), and both had confirmed positive urine cultures.

The length of stay, by PCR result, is shown in Table 3.

Table 3 – Length of Stay by Positive and Negative PCR

Discussion

We describe the outcomes of 237 infants who were felt to be at risk of serious bacterial infection during a 5-week period of high COVID-19 rates in the UK.

The overall serious bacterial infection rate, 13.5%, is similar to other published studies (Waterfield 2021, Kupperman 2019), so this is a typical cohort of at-risk infants. Only 91 had a confirmed temperature >37.9, but this rapid evaluation was designed to also include those with fever prior to presentation and those who had an infection screen or workup.

Serious Bacterial Infection coupled with COVID-19 was uncommon, but seven infants did have urinary tract infections. While invasive bacterial infection (meningitis or septicaemia) and COVID-19 did not occur, assuming SARS-CoV2 as the only infective organism is unlikely to be a clinician’s preference. There is a low tolerance for delaying treatment of an infection that might lead to sepsis in any young infant presenting with fever or reported fever.

Further investigations probably do not help. Though, leucopenia was more common in the SARS CoV2 positive cohort, and white cell counts greater than 15 were more common in the negative group.

CRP was only raised >20 in the SARS CoV2 positive group if a urinary tract infection was present. Though a low or normal CRP did not rule out the potential for Serious Bacterial Infection regardless of SARS CoV2 status.

During this evaluation period, approximately one-third of infants had COVID-19. A significant proportion (88.3%) of these positive infants were admitted. This was higher than the total cohort admission rate (74.3%).

The COVID-19 status was only known in 18 cases on arrival, so this didn’t bias decision-making (although in some centres, a lateral flow or rapid test may have been done within the Emergency Department). Infants with COVID-19 were more likely to have a shorter stays if they were admitted (56.9% stayed less than 48 hours compared to 29.1% in the COVID-19 negative arm).

Conclusion

SARS CoV2 infection was relatively common in this cohort of infants (less than 90 days) presenting with potential infection whether they had a fever or not. Concomitant infection was rare but did occur, and there are no specific features that would help a clinician decide not to look further investigation once COVID-19 status was known.

A prospective analysis is needed to find out what features may aid safe disposition in the clinically well but COVID-positive infant.

Contributors

Dr. Chris DadnamUniversity Hospitals of Leicester NHS Trust
Dr Patrick AldridgeFrimley Health NHS Foundation Trust
Dr Richard BurridgeWatford General Hospital
Dr William KanFrimley Health NHS Foundation Trust
Dr Jordan EvansUniversity Hospital of Wales
Dr Hannah DaviesUniversity Hospitals of Wales
Dr Julia SurridgeUniversity Hospitals of Wales
Ms Vicky DavisDerby and Burton NHS Trust
Dr Cristina HearnshawDerby and Burton NHS Trust
Dr Rachel PearsonLeeds Teaching Hospitals
Dr Helen MollardLeeds Teaching Hospitals
Dr Bimal MehtaLeeds Teaching Hospitals
Dr Shanath RamachandranAlder hey Children’s Hospital
Dr. Shanath RamachandranDr Jane Bayreuther
Dr Catherine RimmerUniversity Hospital Southampton NHS Trust
Dr Phoebe SneddonSheffield Children’s Hospital
Dr David PatelSheffield Children’s Hospital
Dr. David PatelPortsmouth Hospital NHS Trust
Dr Thomas CromartyPortsmouth Hospital NHS Trust

Acknowledgements

Dr Sanjay Patel for proofreading the final version of the manuscript.

References

GOV.UK, 2022. Latest REACT-1 findings show Omicron infections rising fast, while highlighting success of vaccination programmes. [online] GOV.UK. Available at: <https://www.gov.uk/government/news/latest-react-1-findings-show-omicron-infections-rising-fast-while-highlighting-success-of-vaccination-programmes> [Accessed 13 January 2022].

Hardelid, P., Favarato, G., Wijlaars, L., Fenton, L., McMenamin, J., Clemens, T., Dibben, C., Milojevic, A., Macfarlane, A., Taylor, J., Cunningham, S. and Wood, R., 2022. Risk of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19–related hospital admissions in children and young people: birth cohort study. medRxiv, [online] Available at: <https://www.medrxiv.org/content/10.1101/2021.12.17.21267350v2.full.pdf> [Accessed 12 January 2022].

Kuppermann N, Dayan PS, Levine DA, et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019;173(4):342–351. doi:10.1001/jamapediatrics.2018.5501

NICE Fever in Under 5s: Assessment and Initial Management  (https://www.nice.org.uk/guidance/ng143)

Office for National Statistics, 2022. Coronavirus (COVID-19) latest insights – Office for National Statistics. [online] Ons.gov.uk. Available at: <https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19latestinsights/hospitals#hospital-admissions-by-age> [Accessed 13 January 2022].

Waterfield T, Lyttle MD, Munday C, Foster S, McNulty M, Platt R, Barrett M, Rogers E, Durnin S, Jameel N, Maney JA, McGinn C, McFetridge L, Mitchell H, Puthucode D, Roland D; Paediatric Emergency Research in the UK and Ireland (PERUKI). Validating clinical practice guidelines for the management of febrile infants presenting to the emergency department in the UK and Ireland. Arch Dis Child. 2021 Sep 16:archdischild-2021-322586. doi: 10.1136/archdischild-2021-322586. Epub ahead of print. PMID: 34531196.

Author

  • Damian Roland is a Paediatric Emergency Medicine and Honorary Associate Professor. His research interests include scoring systems in emergency and acute care and educational evaluation. Damian also chairs PERUKI (Paediatric Emergency Research United Kingdom and Ireland), which gives him and the team an opportunity to raise awareness of the important of research and evidence based practice at scale. The list of the many things Damian hasn’t done or achieved is far longer but through these he learns and develops new ideas.

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