U ntil recently, the clinical course of coronavirus disease 2019 (COVID-19) in children has been reported to be largely mild. 1,2 Recently, it has become evident that a subset of children exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can become critically ill with a condition now referred to as multisystem inflammatory syndrome in children (MIS-C), characterized by systemic hyperinflammation with fever and multisystem organ dysfunction. 3 Gastrointestinal symptoms are increasingly recognized to be associated with the presentation of MIS-C, potentially confusing the diagnosis of MIS-C with other common, less toxic gastrointestinal infections and even inflammatory bowel disease. In the first published correspondence describing MIS-C in 8 patients from the United Kingdom, 100% presented with gastrointestinal (GI) symptoms. 4 Similarly, 6 of 10 patients from an Italian cohort had GI issues. 5 This is in contrast to adults, who most commonly present with respiratory symptoms and report GI symptoms in <10%-15% of cases. 6,7 We examined whether similar presentations and prevalence extended to our comparatively larger US cohort of 44 patients (<21 years old) with MIS-C.

Background and Aims A newly recognized multisystem inflammatory syndrome in children (MIS‐C) has had a paradigm‐shifting effect on the perception of severe acute respiratory syndrome, coronavirus‐2 (SARS‐CoV‐2) illness severity in children. We report the clinical and biochemical features of liver involvement, and the comorbidities that present with hepatitis, in a substantial cohort of patients. Approach and Results This is a retrospective cohort study of 44 patients with MIS‐C admitted at Morgan Stanley Children’s Hospital of New York‐Presbyterian during April and May 2020. We evaluated the number of patients who developed hepatitis and examined both demographics and inflammatory laboratory values to ascertain those that were at higher risk for liver involvement and more severe disease. Hepatitis was present in 19 subjects (43%) and was associated with more severe disease. Persons with hepatitis had significantly higher rates of shock at presentation (21.1% vs. 0%; P = 0.008), greater respiratory support requirement (42.1% vs. 12%; P = 0.005), and longer hospitalization times (median, 7 [interquartile range {IQR}, 5, 10] vs. 4 days [IQR, 3.5, 6.5]; P < 0.05). Patients with hepatitis also had significantly higher levels of ferritin (706.9 vs. 334.2 mg/mL; P < 0.01), interleukin‐6 (233.9 vs. 174.7 pg/mL; P < 0.05), troponin (83.0 vs. 28.5 ng/L; P < 0.05), and B‐type natriuretic peptide (7,424.5 vs. 3,209.5 pg/mL; P < 0.05). The single patient with liver failure also developed multiorgan failure requiring vasopressors, hemodialysis, and mechanical ventilation. All patients were discharged, though >50% had persistent hepatitis up to 1 month after discharge. Conclusions Hepatitis is common in children with MIS‐C and is associated with a more severe presentation and persistent elevation of liver function tests in many. Despite the positive outcomes reported here, close follow‐up is warranted given the limited knowledge of the long‐term impact of SARS‐CoV‐2 on the liver.

Background and Aims Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) associated acute liver injury (ALI) has been linked to poor outcomes in adults. Here we compare characteristics in children with elevated ALT (E‐ALT) in two distinct manifestations of the infection, multisystem inflammatory syndrome‐children (MIS‐C) and coronavirus disease 2019 (COVID‐19). Methods This is a retrospective study of patients ≤21 years of age with positive for SARS‐CoV‐2 PCR. E‐ALT was defined as alanine aminotransferase (ALT) > 40 U/L. Bivariate analysis and multivariable logistic regression were obtained to describe differences in children with and without E‐ALT in COVID‐19 and MIS‐C. Results E‐ALT was detected in 36% of the 291 patients; 31% with COVID‐19, and 51% with MIS‐C. E‐ALT in COVID‐19 was associated with obesity (P < .001), immunocompromised status (P = .04), and chronic liver disease (P = .01). In the regression models, E‐ALT in COVID‐19 was associated with higher c‐reactive protein (OR 1.08, P = .01) after adjusting for common independent predictors. Children with E‐ALT and MIS‐C were more often boys (P = .001), Hispanic (P = .04), or Black (P < .001). In MIS‐C, male gender (OR 5.3, P = .02) and Black race (OR 4.4, P = .04) were associated with increased odds of E‐ALT. Children with E‐ALT in both cohorts had significantly higher multiorgan dysfunction, longer hospitalization, and ICU stay. Children with MIS‐C had 2.3‐fold increased risk of E‐ALT compared to COVID‐19. No association was found between E‐ALT and mortality. Conclusion E‐ALT with SARS‐CoV‐2 presents as elevated transaminases without hepatic synthetic dysfunction. Patients with either manifestation of SARS‐CoV‐2 infection and E‐ALT experienced more severe disease.