Distinct Mitochondria-Mediated T-Cell Apoptosis Responses in Children and Adults With Coronavirus Disease 2019

J Infect Dis. 2021 Oct 28;224(8):1333-1344. doi: 10.1093/infdis/jiab400.

Abstract

Background: Lymphopenia is a key feature for adult patients with coronavirus disease 2019 (COVID-19), although it is rarely observed in children. The underlying mechanism remains unclear.

Methods: Immunohistochemical and flow cytometric analyses were used to compare the apoptotic rate of T cells from COVID-19 adults and children and apoptotic responses of adult and child T cells to COVID-19 pooled plasma. Biological properties of caspases and reactive oxygen species were assessed in T cells treated by COVID-19 pooled plasma.

Results: Mitochondria apoptosis of peripheral T cells were identified in COVID-19 adult patient samples but not in the children. Furthermore, increased tumor necrosis factor-α and interleukin-6 in COVID-19 plasma induced mitochondria apoptosis and caused deoxyribonucleic acid damage by elevating reactive oxygen species levels of the adult T cells. However, the child T cells showed tolerance to mitochondrial apoptosis due to mitochondria autophagy. Activation of autophagy could decrease apoptotic sensitivity of the adult T cells to plasma from COVID-19 patients.

Conclusions: Our results indicated that the mitochondrial apoptosis pathway was activated in T cells of COVID-19 adult patients specifically, which may shed light on the pathophysiological difference between adults and children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).

Keywords: COVID-19; adult; children; lymphopenia; mitochondria apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Apoptosis / immunology
  • Autophagy
  • COVID-19 / blood
  • COVID-19 / complications*
  • COVID-19 / immunology
  • COVID-19 / virology
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Lymphopenia / blood*
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Lymphopenia / virology
  • Male
  • Middle Aged
  • Mitochondria / immunology
  • Mitochondria / pathology
  • Reactive Oxygen Species / metabolism
  • SARS-CoV-2 / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*

Substances

  • Reactive Oxygen Species