Prevalence of invasive bacterial infection in febrile infants ≤90 days with a COVID-19 positive test: a systematic review and meta-analysis

Abstract

Background: Febrile infants with an infection by influenza or enterovirus are at low risk of invasive bacterial infection (IBI). Objective: To determine the prevalence of IBI among febrile infants ≤90 days old with a positive COVID-19 test. Methods: MEDLINE, Embase, Cochrane Central Register databases, Web of Science, ClinicalTrials.gov and grey literature were searched for articles published from February 2020 to May 2023. Inclusion criteria: researches reporting on infants ≤90 days of age with fever and a positive test for SARS-CoV-2 (antigen test/PCR). Case reports with <3 patients, articles written in a language other than English, French or Spanish, editorials and other narrative studies were excluded. Preferred Reposting Items for Systematic Reviews and Meta-analysis guidelines were followed, and the National Institutes of Health Quality Assessment Tool was used to assess study quality. The main outcome was the prevalence of IBI (a pathogen bacterium identified in blood and/or cerebrospinal fluid (CSF)). Forest plots of prevalence estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random effects model. A fixed continuity correction of 0.01 was added when a study had zero events. Results: From the 1023 studies and 3 databases provided by the literature search, 33 were included in the meta-analysis, reporting 3943 febrile infants with a COVID-19 positive test and blood or CSF culture obtained. The pooled prevalence of IBI was 0.14% (95% CI, 0.02% to 0.27%). By age, the prevalence of IBI was 0.56% (95% CI, 0.0% to 1.27%) in those 0-21 days old, 0.53% (95% CI, 0.0% to 1.22%) in those 22-28 days old and 0.11% (95% CI, 0.0% to 0.24%) in those 29-60 days old. Conclusion: COVID-19-positive febrile infants ≤90 days old are at low risk of IBI, especially infants >28 days old, suggesting this subgroup of patients can be managed without blood tests. Prospero registration number: CRD42022356507.