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

Thomas Abrehart; Randy Suryadinata; Conor McCafferty; Jonathan Jacobson; Vera Ignjatovic; Phil Robinson; Nigel W Crawford; Paul Monagle; Kanta Subbarao; Catherine Satzke; Danielle Wurzel

doi:10.1016/j.prrv.2022.01.008

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

Paediatr Respir Rev. 2022 Dec:44:61-69. doi: 10.1016/j.prrv.2022.01.008. Epub 2022 Feb 8.

Authors

Affiliations

¹ Department of Paediatrics, the University of Melbourne, Parkville, Australia. Electronic address: tabrehart@student.unimelb.edu.au.
² Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
³ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Haematology, Murdoch Children's Research Institute, Melbourne, Australia.
⁴ Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁵ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
⁶ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
⁷ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Haematology, Murdoch Children's Research Institute, Melbourne, Australia; Department of Haematology, Royal Children's Hospital, Parkville, Australia; Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia.
⁸ WHO Collaborating Centre for Reference and Research on Influenza, the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁹ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
¹⁰ Department of Paediatrics, the University of Melbourne, Parkville, Australia; Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia; Infection and Immunity, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Melbourne School of Population and Global Health, the University of Melbourne, Melbourne, Victoria, Australia.

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.

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

Publication types

Systematic Review
Review

MeSH terms

COVID-19*
Child
Humans
Peptidyl-Dipeptidase A / metabolism
SARS-CoV-2* / metabolism
Spike Glycoprotein, Coronavirus / metabolism

Substances

spike protein, SARS-CoV-2
Peptidyl-Dipeptidase A
Spike Glycoprotein, Coronavirus