COVID-19Research Paper|Volume 12, Issue 11|pp 10087—10098

ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy

Rosanna Asselta^1,², Elvezia Maria Paraboschi^1,², Alberto Mantovani^1,^2,³, Stefano Duga^1,²

¹Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan 20090, Italy
²Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan 20089, Italy
³The William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK

* Equal contribution

Received: April 16, 2020Accepted: May 25, 2020Published: June 5, 2020

Copyright © 2020 Asselta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 one of the highest numbers of SARS-CoV-2-related deaths and one of the highest mortality rates. 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 COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection.

Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians. Moreover, we looked into gene expression databases to check for sex-unbalanced expression.

While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts.