Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age

OBJECTIVE: Beginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DESIGN: We conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. RESULTS: Compared to propensity-score-matched children with other respiratory infections, children aged 1–10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74–2.69)) or total bilirubin (HR (CI) 3.02 (1.91–4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21–2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1–4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. CONCLUSION: These results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (~1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. WHAT IS ALREADY KNOWN ON THIS TOPIC: Clusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent. WHAT THIS STUDY ADDS: SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Despite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.