“…13,17,18,21 The E-ALT mechanism in SARS-CoV-2 is not fully understood, but under investigation are an effect of viral lesions in hepatic/cholangiocyte cells, inflammatory damage, hypoxic/shock-related circulatory compromise, endothelial dysfunction, microthrombi formation, and drug toxicity. [22][23][24] The direct viral cytopathic effect in the pathophysiology of E-ALT via the cell receptors for angiotensin-converting enzyme II and transmembrane protease serine 2, invoked in the transmission of SARS-CoV-2, is supported by the demonstration of SARS-CoV-2 in the liver parenchyma in patients with higher liver enzyme elevation. 25 As previously reported, children with E-ALT in the COVID-19 cohort more frequently carried an underlying medical condition such as immunocompromised state (including malignancy), or CLD, significantly contrasting with those with E-ALT in MIS-C. 3,4,26 In our study, although children with MIS-C had >2× higher odds of any degree of elevation in ALT levels compared to children with COVID-19 (51% vs 31%), severe elevation, defined as ALT >200 U/L was observed at a higher frequency in children with COVID-19 (8% vs 4%) (Figure 1).…”