Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics

Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):24620-24626. doi: 10.1073/pnas.2012358117. Epub 2020 Sep 3.

Abstract

The reduced development of COVID-19 for children compared to adults provides some tantalizing clues on the pathogenesis and transmissibility of this pandemic virus. First, ACE2, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, is reduced in the respiratory tract in children. Second, coronavirus associated with common colds in children may offer some protection, due to cross-reactive humoral immunity and T cell immunity between common coronaviruses and SARS-CoV-2. Third, T helper 2 immune responses are protective in children. Fourth, surprisingly, eosinophilia, associated with T helper 2, may be protective. Fifth, children generally produce lower levels of inflammatory cytokines. Finally, the influence of the downturn in the global economy, the impact of living in quarters among families who are the most at risk, and factors including the openings of some schools, are considered. Those most disadvantaged socioeconomically may suffer disproportionately with COVID-19.

Keywords: ACE2; COVID-19; SARS-CoV-2; children.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / metabolism*
  • COVID-19
  • Child
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Respiratory Mucosa / metabolism*
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / virology
  • SARS-CoV-2
  • Th2 Cells / physiology

Substances

  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2