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

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Pediatr Infect Dis J


. 2021 Dec 28.
doi: 10.1097/INF.0000000000003413. Online ahead of print.
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 , Nigel Curtis



Affiliations

• PMID: 34966142
• DOI: 10.1097/INF.0000000000003413

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.