Age-related differences in SARS-CoV-2 binding factors: An explanation for reduced susceptibility to severe COVID-19 among children? - 07/12/22

Doi : 10.1016/j.prrv.2022.01.008

Thomas Abrehart ^a,^⁎ , Randy Suryadinata ^b,^c, Conor McCafferty ^a,^d, Jonathan Jacobson ^c,^h, Vera Ignjatovic ^a,^d, Phil Robinson ^a,^b,^c, Nigel W. Crawford ^a,^c, Paul Monagle ^a,^d,^e,^f, Kanta Subbarao ^g,^h, Catherine Satzke ^a,^c,^h,^{^{1
These authors contributed equally.}}, Danielle Wurzel ^a,^b,^c,^i,^{^{1
These authors contributed equally.}}
^a Department of Paediatrics, the University of Melbourne, Parkville, Australia
^b Department of Respiratory Medicine, Royal Children’s Hospital, Melbourne, Victoria, Australia
^c Infection and Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia
^d Haematology, Murdoch Children’s Research Institute, Melbourne, Australia
^e Department of Haematology, Royal Children’s Hospital, Parkville, Australia
^f Kids Cancer Centre, Sydney Children’s Hospital, Randwick, Australia
^g WHO Collaborating Centre for Reference and Research on Influenza, the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
^h Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
ⁱ Melbourne School of Population and Global Health, the University of Melbourne, Melbourne, Victoria, Australia

^⁎Corresponding authors at: Department of Paediatrics, the University of Melbourne Grattan Street, Parkville, Victoria 3052, Australia.Department of Paediatricsthe University of Melbourne Grattan StreetParkvilleVictoria3052Australia

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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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Keywords : COVID-19, SARS-CoV-2, ACE2, TMPRSS2, Furin, Paediatric

Plan

Introduction

Materials and methods

Results

Discussion

ACE2 expression levels

ACE2 gene methylation

Soluble ACE2

TMPRSS2 and the role of circulating androgens

Other receptors and future direction

Conclusion

Educational Aims

Directions for future research

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Vol 44

P. 61-69 - décembre 2022 Retour au numéro

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Age-related differences in SARS-CoV-2 binding factors: An explanation for reduced susceptibility to severe COVID-19 among children? - 07/12/22

Abstract

Context

Objectives

Methods

Results

Limitations

Conclusions

Plan

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