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Do Febrile Neonates with COVID-19 Need a Full Workup?

January 17, 2024

Written by Sam Parnell

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This systematic review and meta-analysis of almost 4,000 febrile infants ≤ 90 days old diagnosed with COVID-19 indicated that these patients have a low prevalence of invasive bacterial infection (IBI), especially the subgroup >28 days old.

Hot Topic! Does febrile infant + positive COVID-19 test = low risk for serious bacterial illness?
Febrile neonates are a high-risk population with an alarmingly high prevalence of bacterial infection (10-20%) and invasive bacterial infection, such as meningitis or bacteremia (2-4%).1,2 Previous studies have demonstrated that febrile neonates with positive viral studies are less likely to have a serious bacterial infection.3 However, much of the data on febrile infants were collected before the COVID-19 pandemic, and the American Academy of Pediatrics Febrile Infant Guidelines do not include viral testing in their algorithms. The significance of a positive COVID-19 test during the workup and management of febrile infants is unclear, though we covered a small study from 2021 that suggests a lower risk of IBI. The goal of this study was to determine the prevalence of IBI among febrile infants with COVID-19.

This was a systematic review and meta-analysis that included 3,943 febrile infants ≤ 90 days old with a positive COVID-19 test who also had blood and/or CSF cultures. The pooled prevalence of IBI (defined as bacteria identified in the blood or CSF via culture or PCR) was 0.14% (95%CI 0.02% to 0.27%). The weighted prevalence of bacteremia was 0.10% (95%CI 0.00% to 0.20%); weighted prevalence of meningitis was 0.06% (95%CI 0.00% to 0.15%), and the weighted prevalence of UTI was 0.76% (95%CI 0.50% to 1.03%; 3,975 urine cultures included in the secondary outcome analysis).

Importantly, the prevalence of IBI was lower for patients older than 28 days. Infants who were 29–60 days old had an overall IBI prevalence of 0.11% (95%CI 0.0% to 0.24%) compared to 0.56% (95%CI 0.0% to 1.27%) for patients 0-21 days old and 0.53% (95%CI 0.0% to 1.22%) for patients 22–28 days old.

These data are promising and suggest that infants with COVID-19 are at low risk of IBI. However, the study had several limitations. In particular, there was a lack of information on the prevalence of COVID-19 in the general population during the study periods. Normally, increased COVID-19 in the general population should be associated with decreased odds of IBI. Nevertheless, when COVID-19 infection is particularly widespread, a positive COVID-19 result could simply represent an incidental positive and may not affect the post-test probability of IBI.

How will this change my practice?
COVID-19 is here to stay. Febrile infants will continue to test positive for COVID-19 as we navigate the endemic stage of COVID-19. This study is reassuring that febrile infants diagnosed with COVID-19, especially those > 28 days old, appear to be at relatively low risk of IBI. The authors postulate that febrile infants older than 28 days who test positive for COVID-19 can possibly be managed without blood tests, although they still recommend evaluating for UTI in all patients. For now, I will continue to follow the AAP Febrile Infant Guidelines as well as my institutional protocols. However, this study does make me feel better about discharging well-appearing, febrile infants > 28 days old with COVID-19 after I obtain blood cultures, a bland urinalysis, and normal inflammatory makers.

Prevalence of invasive bacterial infection in febrile infants ≤90 days with a COVID-19 positive test: a systematic review and meta-analysis. Emerg Med J. Published online December 6, 2023. doi:10.1136/emermed-2023-213483

Works Cited

  1. Greenhow TL, Hung YY, Herz AM. Changing epidemiology of bacteremia in infants aged 1 week to 3 months. Pediatrics 2012;129:e590–6.
  2. Schwartz S, Raveh D, Toker O, et al. A week-by-week analysis of the low-risk criteria for serious bacterial infection in febrile neonates. Arch Dis Child 2009;94:287–92.
  3. Mahajan P, Browne LR, Levine DA, et al. Risk of bacterial coinfections in febrile infants 60 days old and younger with documented viral infections. J Pediatr 2018;203:86–91