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Review
. 2022 Feb 1;41(2):e36-e45.
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

Petra Zimmermann  1   2   3   4 , Nigel Curtis  3   4   5
Affiliations
Review

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

Petra Zimmermann et al. Pediatr Infect Dis J. .

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.

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Conflict of interest statement

Disclosures: The authors have no conflicts of interest to disclose.

Figures

FIGURE 1.
FIGURE 1.
Mechanisms proposed to contribute to the age-related difference in the severity of COVID-19.
See this image and copyright information in PMC

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