Our understanding of the epidemiology and clinical manifestations of SARS-CoV-2 infection in children continues to grow at a rapid pace, though at each pass there are new wrinkles that raise even more questions. For example, in recent weeks, we’ve learned about pediatric multisystem inflammatory syndrome, which has raised numerous inquiries about its prevalence, epidemiology, and potential therapy. Another wrinkle is provided in the case report by Feld et al (10.1542/peds.2020-1056) that describes three febrile infants ≤60 days old who tested positive for SARS-CoV-2. None of the infants had the frequently described symptoms of cough or respiratory distress, and one infant had no identifiable exposure to a SARS-CoV-2 infected individual. There are other case reports that similarly report fever as the only presenting symptom of SARS-CoV-2 infection in a young infant.

So what questions are raised with this new wrinkle? One question is the prevalence of SARS-CoV-2 infection among febrile infants ≤60 days old. While this will certainly depend on local disease prevalence, we are acquiring the data to answer this question through the common practice that all febrile infants who are being hospitalized have a test for SARS-CoV-2. However, as testing capacity increases, it may be prudent to test all febrile infants, regardless of disposition, to determine the true prevalence of infection. In addition to facilitating appropriate isolation and contact tracing, this universal testing strategy would also allow us to assess the risk concomitant serious bacterial infection among infants with SARS-CoV-2 infection. There is extensive literature on the risk of serious bacterial infection among febrile infants with other respiratory viruses (respiratory syncytial virus, influenza, rhinovirus). Determining the risk of concomitant serious bacterial infection in the presence of SARS-CoV-2 would be useful for risk stratification of these infants. If febrile infants with SARS-CoV-2 infection had a negligible risk of serious bacterial infection, these infants could be discharged home from the emergency department, reducing not only iatrogenic risks for the infant and family but also decreasing the risks to healthcare providers and other families by avoiding an admission. Testing all febrile infants would also allow for collection of more robust longitudinal data, to facilitate the evaluation of outcomes of infants ≤60 days old with SARS-CoV-2 infection.

Once again, each new wrinkle raises more questions than answers, but as we answer more and more of these questions, we gain an increasingly better hold on this novel infection.