Reply to: Severe Hepatitis in Children Likely Caused by HAdV-41 Following SARS-CoV-2 (original) (raw)

To the editor:

We thank Mohammed et al for their interest in our paper “Long COVID-19 liver manifestation in children” (1) and for raising the hypothesis that severe hepatis in children is caused by HAdV-41 following SARS-CoV-2 infection. The authors’ speculated pathogenesis is that SARS-CoV-2 infection may cause mitochondrial permeability transition pore (mPTP) induction. Later a virus, possibly HAdV-41, may elicit an antibody response in genetically susceptible individuals, which causes immune-mediated hepatitis.

Since January 2022 there have been increasing reports of acute hepatitis in children worldwide. Kelgeri et al reported 44 children with acute hepatitis in the UK in which 90% were positive for adenovirus (2), and SARS-CoV-2 antibody tests were not performed. A report from the United States showed similar findings (3). However, a recent study (Mohammad S, et al, abstract in AASLD annual meeting (4)) which investigated hepatitis cases in 26 centers around the world found multiple different viruses and adenovirus was identified in 17% of patients. Serologic evidence of SARS-CoV-2 was not collected. In our study, we included patients that had evidence of a past COVID-19 infection and no other apparent etiology. One of them was positive for adenovirus in whole blood; however, liver histology and antibody staining were not typical for an adenovirus triggered hepatitis.

As the outbreak of hepatitis cases corresponded with a surge of SARS-CoV-2 infection with the omicron variant, it is possible that the infection predisposes to a virus-triggered hepatitis either due to mPTP induction or other mechanisms. Further studies are needed to establish these correlations and pathogenesis.

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