Elevated liver enzymes and bilirubin following SARS-CoV-2 infection in children under 10

Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. We performed a retrospective cohort study on a nation-wide database of patient electronic health records (EHRs) in the US. The study population comprise 796,369 children between the ages of 1-10 years including 245,675 who had contracted COVID-19 during March 11, 2020 - March 11, 2022 and 550,694 who contracted non-COVID other respiratory infection (ORI) during the same timeframe. Compared to children infected with other respiratory infections, children infected with COVID-19 infection were at significantly increased risk for elevated AST or ALT (hazard ratio or HR: 2.52, 95% confidence interval or CI: 2.03-3.12) and total bilirubin (HR: 3.35, 95% CI: 2.16-5.18). These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients. Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by grants AG057557, AG061388, AG062272, AG076649 from the National Institute on Aging, grant R01AA029831 from the National Institute on Alcohol Abuse and Alcoholism, grant UG1DA049435 from the National Institute on Drug Abuse, and grant 1UL1TR002548-01 from the Clinical and Translational Science Collaborative of Cleveland ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. 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