The differential expression of the ACE2 receptor across ages and gender explains the differential lethality of SARS-Cov-2 and suggests possible therapy
Year: 2020
Type: article
Abstract: The fatality rate of SARS-Cov-2 escalates with age and is larger in men than \nwomen. I show that these variations are strongly correlated with the levels of the \nACE2 protein in the lungs but surprisingly, despite ACE2 is the viral receptor, \nhigher levels lead to lower fatality. This behaviour is consistent with a previous \nmathematical model that predicts that the speed of viral progression in the organism has a maximum and then declines with the receptor level. SARS-Cov-2 degrades \nACE2 and thus worsens lung injury, causes vasoconstriction, thrombotic problems, \nand exacerbated inflammatory response. I developed a mathematical model based \non the influence of ACE2 on viral propagation and on the negative effects of its \ndegradation. The model fits SARS-CoV-2 fatality rate across age and gender with \nhigh accuracy (r \n2 ≈ 0.9). Rescaling the model parameters with the binding rates \nof the spike proteins of SARS-CoV and SARS-CoV-2 allows predicting the fatality rate of SARS-CoV across age and gender, in particular its higher severity for \nyoung patients, thus linking the molecular and epidemiological levels. These results \nsupport the suggestion that drugs that enhance the expression of ACE2, such as \nACE inhibitors and angiotensin receptor blockers, constitute a promising therapy \nagainst the most adverse effects of CoViD-19. Furthermore, ACE2 is a candidate \nprognostic factor for detecting population that needs stronger protection.
Author: Ugo Bastolla
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3017120305