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

Authors:

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

Details:

Paediatric Respiratory Reviews, Volume 44, 2022-12-31

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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.