Identification of COVID-19-Associated Hepatitis in Children as an Emerging Complication in the Wake of SARS-CoV-2 Infections: Ambispective Observational Study.

Background: Although the pediatric population has largely remained free of severe COVID-19 symptoms, in some cases, SARS-CoV-2 infection has been associated with complications such as multiple inflammatory syndrome in children (MIS-C). We identified another a unique form of hepatitis occurring subsequent to asymptomatic SARS-CoV-2 infection, designated by us as COVID-19-associated hepatitis in children (CAH-C), in a subset of children who presented with hepatitis. Objective: Our study describes the clinical presentations, temporal association, and viral parameters of the CAH-C cases and compares them to those of MIS-C cases or other known forms of hepatitis in children. Methods: In an ambispective (retrospective and follow-up) observational study, records from April to July 2021 were reviewed for all children aged ≤14 years who were previously healthy and presented with a sudden onset of hepatitis, elevated transaminases, and nonobstructive jaundice. After performing all routine tests, those lacking marked inflammatory responses and without evidence of (1) other known causes of acute hepatitis or previous underlying liver disease and (2) multisystem involvement were classified as having CAH-C. Their characteristics were compared to those of children with MIS-C or other known forms of hepatitis. Results: Among the 5539 children tested for SARS-CoV-2, a total of 475 (8.6%) tested positive and 47 (0.8%) presented with hepatitis. Among the 47 children with hepatitis, 37 (79%) had features of CAH-C: having symptoms of hepatitis only, without protracted illness (mean length of stay 5 d), and an uneventful recovery following supportive treatment. In contrast, the remaining 10 (21%) had features of MIS-C-associated hepatitis: multiple system involvement; protracted illness (mean length of stay 8 d); and requiring admission to critical care, with a mortality rate of 30% (3/10). Conclusions: Our data suggest that CAH-C might be one of the new clinical complications associated with the emergence of newer variants of concern of SARS-CoV-2, which often result in changing presentations. Our findings should facilitate its early identification and thorough workup and aid its differentiation from other emerging syndromes in children, which would help initiate appropriate measures, enable better resource prioritization, and thus limit adversities.