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ACE2 and TMPRSS2 Variants and Expression as Candidates to Sex and Country Differences in COVID-19 Severity in Italy

27 Pages Posted: 1 Apr 2020

See all articles by Rosanna Asselta

Rosanna Asselta

Humanitas University - Department of Biomedical Sciences

Elvezia Maria Paraboschi

Humanitas University - Department of Biomedical Sciences

Alberto Mantovani

Humanitas University - Department of Biomedical Sciences

Stefano Duga

Humanitas University - Department of Biomedical Sciences; Humanitas University - Clinical and Research Center

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Abstract

Background: As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has the highest rate of SARS-CoV-2 infection, the highest number of deaths, and the highest mortality rate among large countries. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of the peculiar severity of COVID-19 among Italians, by looking at expression levels and variants in ACE2 and TMPRSS2 genes, which are crucial for viral infection.

Methods: Exome and SNP array data from a large Italian cohort representative of the country’s population were used to compare the burden of rare variants and the frequency of polymorphisms with European and East Asian populations. Moreover, we looked into gene expression databases to check for sex-unbalanced expression.

Findings: While we found no significant evidence that ACE2 is associated with disease severity/sex bias in the Italian population, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients.

Interpretation:Our analysis suggests a role for TMPRSS2 variants and expression levels in modulating COVID-19 severity, a hypothesis that fosters a rapid experimental validation on large cohorts of patients with different clinical manifestations.

Funding Statement: Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). A generous contribution of the Dolce&Gabbana Fashion Firm is gratefully acknowledged.

Declaration of Interests: The authors stated that there was no conflict of interest to disclose.

Keywords: SARS-CoV-2; COVID-19; ACE2; TMPRSS2; genetic variants; Italian population

Suggested Citation

Asselta, Rosanna and Paraboschi, Elvezia Maria and Mantovani, Alberto and Duga, Stefano, ACE2 and TMPRSS2 Variants and Expression as Candidates to Sex and Country Differences in COVID-19 Severity in Italy (3/21/2020). Available at SSRN: https://ssrn.com/abstract=3559608 or http://dx.doi.org/10.2139/ssrn.3559608

Rosanna Asselta

Humanitas University - Department of Biomedical Sciences

Milan
Italy

Elvezia Maria Paraboschi

Humanitas University - Department of Biomedical Sciences

Milan
Italy

Alberto Mantovani

Humanitas University - Department of Biomedical Sciences ( email )

Milan
Italy

Stefano Duga (Contact Author)

Humanitas University - Department of Biomedical Sciences ( email )

Milan
Italy

Humanitas University - Clinical and Research Center ( email )

Italy

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