Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection

Clin Immunol. 2022 Dec:245:109138. doi: 10.1016/j.clim.2022.109138. Epub 2022 Sep 30.

Abstract

Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8+ T cells playing a key role. Moreover, investigation of superantigen-mediated T-cell activation by the SARS-CoV-2 spike protein in pediatric severe acute hepatitis is needed in the context of the proposed mechanism of multisystem inflammatory syndrome in children (MIS-C). We investigated the immunological characteristics of a Japanese pediatric patient with severe acute hepatitis post SARS-CoV-2 infection. The patient demonstrated autoimmune hepatitis-like liver histology with CD8+ lymphocyte-predominant infiltration. There was Th1-type immune skewing, including remarkable peripheral CD8+ T-cell activation and a skewed T cell receptor repertoire. We also found elevated plasma levels of the anti-SARS-CoV-2 spike-specific IgG antibody, and the titer peaked after treatment, as seen with MIS-C. These findings support that immunological activation involving SARS-CoV-2 spike protein plays a crucial role in a pediatric patient with acute severe hepatitis post SARS-CoV-2 infection.

Keywords: Autoimmune hepatitis; COVID-19; Cytokine; Multisystem inflammatory syndrome in children; Superantigens; T-cell receptor.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • COVID-19*
  • Child
  • Hepatitis*
  • Humans
  • SARS-CoV-2

Substances

  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related