. 2022 Dec:44:61-69.

doi: 10.1016/j.prrv.2022.01.008. Epub 2022 Feb 8.

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

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.

PMID: 35227628
PMCID: PMC8823960
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?

Thomas Abrehart et al. Paediatr Respir Rev. 2022 Dec.

. 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.

PMID: 35227628
PMCID: PMC8823960
DOI: 10.1016/j.prrv.2022.01.008

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.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Schematic representation of the host cell receptors and proteases involved in SARS-CoV-2 cellular entry via the membrane-fusion pathway, as originally published in Oz et al. .

**Fig. 2**
PRISMA flow chart of article identification, retrieval, and inclusion.

See this image and copyright information in PMC

References

1. WHO Coronavirus (COVID-19) Dashboard: World Health Organisation; 2021 [cited 12 September 2021]. Available from: https://covid19.who.int/.
1. Zimmermann P., Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J. 2020;39(5):355–368. - PMC - PubMed
1. Castagnoli R., Votto M., Licari A., Brambilla I., Bruno R., Perlini S., et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: A systematic review. JAMA Pediatr. 2020;174(9):882–889. - PubMed
1. Viner R.M., Mytton O.T., Bonell C., Melendez-Torres G.J., Ward J., Hudson L., et al. Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: A systematic review and meta-analysis. JAMA Pediatr. 2021;175(2):143–156. - PMC - PubMed
1. Tregoning J.S., Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev. 2010;23(1):74–98. - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources