Coronavirus and genetics: a study by Humanitas University

Why are male individuals more easily infected by SARS-CoV-2 and with more severe symptoms? Why are there important differences in the amount of infections in Italy, China and other countries? Do genetic factors increase the risk of contracting the infection and the severity of the clinical course of COVID-19 disease? A group of researchers from Humanitas University tried to answer these questions to identify the reasons for the unique characteristics of the epidemic in Italy.

The team led by Prof. Stefano Duga, Professor of Molecular Biology, and with the contribution of professors Rosanna Asselta, Elvezia Maria Paraboschi and Alberto Mantovani (Professor Emeritus Humanitas University and Scientific Director Humanitas Research Hospital), analysed two proteins that are crucial for the entry of the virus into our cells: the angiotensin 2 converting enzyme (encoded by the ACE2 gene) and the transmembrane serine protease 2 (encoded by the TMPRSS2 gene). Both genes are good candidates for mediating the different clinical manifestations that are observed in males and females and in different populations.

The study focused on data already existing in the literature, using the huge databases available online with sequences of large portions of the genome of over 150,000 people. Prof. Duga’s group also has information about 4 thousand Italian subjects. The researchers searched for differences in the frequency of genetic variants and in the expression level of the ACE2 and TMPRSS2 genes. Prof. Duga’s team proved that there are important differences in genetic variants between the Italian and Chinese populations. In particular, there is a variant, called p.Val160Met, and two combinations of variants (haplotypes) of TMPRSS2 that show the most striking differences. One of these haplotypes is almost absent in the Chinese population while it can be found largely in the Italian population.

The researchers’ hypothesis is that some variants, which are more frequent in the Italian population, are responsible for a greater production of TMPRSS2, which favours the internalization of the virus. The Italians could therefore have characteristics that facilitate the entry of SARS-CoV-2 into our cells. But there is more than that. The TMPRSS2 gene is regulated by androgens and this could explain why males are more susceptible to the infection. The genetic variants are present in both men and women, but sex hormones could push a greater production of the protein.

What does this result suggest? Humanitas researchers believe it shows that the existence of genetic differences may affect the different course of SARS-CoV-2 infection from person to person. It is good to keep in mind that these studies are conducted so far on the general population, not on COVID-19 patients. This means that the results of the study only provide the basis for future insights. Further studies will be needed to confirm the role of these two genes in the spread and effects of the disease. In this view, Prof. Duga’s group has launched, in collaboration with the University of Milano Bicocca and the University of Milan, a project, named GENIUS (for GENetics agaInst coronavirUS) that will analyse the entire human genome searching for genetic variants that can predispose or protect from SARS-CoV-2 infection.

This is a starting point. The aim of this work is to provide genetic information that can be used to identify the individuals who are at higher risk of severe complications, particularly among frail patients, i.e. the elderly and patients with comorbidities.