Mathematical model of SARS-Cov-2 propagation versus ACE2 fits COVID-19 lethality across age and sex and predicts that of SARS, supporting possible therapy

Ugo Bastolla

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Received date: 30th September 2020

The fatality rate of Covid-19 escalates with age and is larger in men than women. I show that these variations correlate strongly with the level of the viral receptor protein ACE2 in rat lungs, which is consistent with the still limited and apparently contradictory data on human ACE2. Surprisingly, lower levels of the receptor correlate with higher fatality. However, a previous mathematical model predicts that the speed of viral progression in the organism has a maximum and then declines with the receptor level. Moreover, many manifestations of severe CoViD-19, such as severe lung injury, exacerbated inflammatory response and thrombotic problems may derive from increased Angiotensin II (Ang-II) level that results from degradation of ACE2 by the virus.
I present here a mathematical model based on the influence of ACE2 on viral propagation and disease severity. The model fits Covid-19 fatality rate across age and sex with high accuracy (r^2>0.9) under the hypothesis that SARS-CoV-2 infections are in the dynamical regimes in which increased receptor slows down viral propagation. Moreover, rescaling the model parameters by the ratio of the binding rates of the spike proteins of SARS-CoV and SARS-CoV-2 allows predicting the fatality rate of SARS-CoV across age and sex, thus linking the molecular and epidemiological levels.
The presented model opposes the fear that angiotensin receptor blockers (ARB), suggested as a therapy against the most adverse effects of CoViD-19, may favour viral propagation, and suggests that Ang-II and ACE2 are candidate prognostic factors for detecting population that needs stronger protection.

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This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.

Scientific Reports

Nature Research, Springer Nature