Identification of Human Genetic Variants Modulating the Course of Covid-19 Infection

Abstract

COVID-19, caused by the SARS-CoV-2 virus, has been a major focus of scientific research since late 2019 and early 2020. Due to its enormous societal, economic, and clinical impact worldwide, research efforts aimed, among other questions, to address the effect of host genetics in susceptibility and severity of COVID-19. In this research, we performed next-generation sequencing of coding and regulatory regions of 16 selected human genes, involved in the maintenance of the immune system or encoding the receptors for viral entry into the host cells, in a subset of 60 COVID-19 patients from the General Hospital Tešanj, Bosnia and Herzegovina, classified into three groups of patients with clinical conditions of different severity (“mild”, “moderate”, and “severe” clinical groups). In accordance with previous studies, we found out that the male sex and older age are risk factors for severe clinical picture. We identified 13 variants on seven genes (CD55, IL1B, IL4, IRF7, DDX58, TMPRSS2, and ACE2) with potential functional significance, either as genetic markers of modulated susceptibility to SARS-CoV-2 infection or as modifiers of the course of infection in terms of predicted symptom severity. Our results include variants reported for the first time as potentially associated with COVID-19. Future studies on larger patient cohorts, focused on candidate genes and/or candidate genetic variants, have a potential to answer a range of open questions regarding the effect of host (human) genetic makeup on the expected outcome of COVID-19.