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Journal Article Review Ppublish 42 citations

PubMed: 34966142 DOI: 10.1097/INF.0000000000003413

Why Does the Severity of COVID-19 Differ With Age?: Understanding the Mechanisms Underlying the Age Gradient in Outcome Following SARS-CoV-2 Infection.

Pediatr Infect Dis J 41(2):e36-e45

Authors: Petra Zimmermann, Nigel Curtis

Affiliations

  • From the Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
  • Department of Paediatrics, Fribourg Hospital HFR, Fribourg, Switzerland.
  • Department of Paediatrics, The University of Melbourne, Parkville, Australia.
  • Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia.
  • Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia.

Abstract

Although there are many hypotheses for the age-related difference in the severity of COVID-19, differences in innate, adaptive and heterologous immunity, together with differences in endothelial and clotting function, are the most likely mechanisms underlying the marked age gradient. Children have a faster and stronger innate immune response to SARS-CoV-2, especially in the nasal mucosa, which rapidly controls the virus. In contrast, adults can have an overactive, dysregulated and less effective innate response that leads to uncontrolled pro-inflammatory cytokine production and tissue injury. More recent exposure to other viruses and routine vaccines in children might be associated with protective cross-reactive antibodies and T cells against SARS-CoV-2. There is less evidence to support other mechanisms that have been proposed to explain the age-related difference in outcome following SARS-CoV-2 infection, including pre-existing immunity from exposure to common circulating coronaviruses, differences in the distribution and expression of the entry receptors ACE2 and TMPRSS2, and difference in viral load.

MeSH

Infections, Communicable Diseases, Viruses, Immunity, Innate, Sars Virus, Covid-19, Sars-Cov-2

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