Age-related Differences in SARS-CoV-2 Binding Factors: An Explanation for Reduced Susceptibility to Severe COVID-19 Among Children?

Overview

Journal Paediatr Respir Rev

Specialties Pediatrics
Pulmonary Medicine

Date 2022 Mar 1

PMID 35227628

Authors

Thomas Abrehart

Randy Suryadinata

Conor McCafferty

Jonathan Jacobson

Vera Ignjatovic

Phil Robinson

Nigel W Crawford

Paul Monagle

Kanta Subbarao

Catherine Satzke

Danielle Wurzel

Affiliations

Soon will be listed here.

Abstract

Context: In contrast with other respiratory viruses, children infected with SARS-CoV-2 are largely spared from severe COVID-19.

Objectives: To critically assess age-related differences in three host proteins involved in SARS-CoV-2 cellular entry: angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin.

Methods: We systematically searched Medline, Embase, and PubMed databases for relevant publications. Studies were eligible if they evaluated ACE2, TMPRSS2 or furin expression, methylation, or protein level in children.

Results: Sixteen papers were included. Age-dependent differences in membrane-bound and soluble ACE2 were shown in several studies, with ACE2 expression increasing with age. TMPRSS2 and furin are key proteases involved in SARS-CoV-2 spike protein cleavage. TMPRSS2 expression is increased by circulating androgens and is thus low in pre-pubertal children. Furin has not currently been well researched.

Limitations: High levels of study heterogeneity.

Conclusions: Low expression of key host proteins may partially explain the reduced incidence of severe COVID-19 among children, although further research is needed.

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