Non-hepatitis A-E Acute Severe Hepatitis in Children During the SARS-CoV-2 Pandemic: An Ambispective Observational Study of Emerging Trends and Potential Etiologies

Introduction: Severe acute hepatitis of unknown origin in children has become a significant global concern during the SARS-CoV-2 pandemic. This study investigates the epidemiological, clinical, and laboratory characteristics of pediatric hepatitis cases, focusing on possible viral, immune- mediated, or environmental etiologies. Methods: An ambispective observational study was conducted at Minia University Hospital, Egypt, comparing pre-pandemic (March 2016–February 2020) and pandemic/post-pandemic (March 2020– March 2024) pediatric patients with probable acute severe hepatitis (ALT/AST >500 IU/L). Data were obtained from records and prospective follow-up, including serologic/molecular testing and inflammatory biomarkers. Logistic regression models, adjusted for confounders, were used to analyze predictors of adverse outcomes. Results: Among 2,928 children screened, 198 were included (82 pre-pandemic; 116 pandemic/postpandemic). During the pandemic/post-pandemic period, patients had longer hospital stays (median: 6.5 vs. 4.0 days, p<0.001), higher inflammatory markers (IL-6: 28.0% vs. 18.0%, p=0.04; CRP: 34.4% vs. 15.6%, p=0.01), and increased mortality (27.3% vs. 19.5%, p<0.05). SARS-CoV-2 was the predominant virus (52.6%). Elevated IL-6 (OR=3.2), CRP (OR=2.7), and hospital stays >7 days (OR=2.4) predicted adverse outcomes. Discussion: The data suggest that SARS-CoV-2 may contribute to the severity of pediatric hepatitis through immune dysregulation or co-infection with other pathogens. The observed increase in severe cases and systemic complications warrants attention to inflammatory biomarkers for prognosis and intervention planning. Conclusion: Pediatric acute severe hepatitis during the SARS-CoV-2 pandemic has exhibited heightened severity and mortality. Elevated IL-6 and CRP are valuable prognostic markers. Multidisciplinary strategies are essential to better understand this emerging condition and optimize management.