Identification of human genetic variants modulating the course of COVID-19 infection with importance in other viral infections

Lana Salihefendić; Ivana Čeko; Larisa Bešić; Naida Mulahuseinović; Selma Durgut; Dino Pećar; Lejla Prnjavorac; Enis Kandić; Neven Meseldžić; Tamer Bego; Besim Prnjavorac; Damir Marjanović; Rijad Konjhodžić; Adna Ašić

doi:10.3389/fgene.2023.1240245

Identification of human genetic variants modulating the course of COVID-19 infection with importance in other viral infections

Front Genet. 2023 Aug 29:14:1240245. doi: 10.3389/fgene.2023.1240245. eCollection 2023.

Authors

Lana Salihefendić^{1

2}, Ivana Čeko^{1

2}, Larisa Bešić², Naida Mulahuseinović¹, Selma Durgut¹, Dino Pećar¹, Lejla Prnjavorac³, Enis Kandić¹, Neven Meseldžić⁴, Tamer Bego⁴, Besim Prnjavorac³, Damir Marjanović^{2

5}, Rijad Konjhodžić^{1

2}, Adna Ašić²

Affiliations

¹ ALEA Genetic Center, Sarajevo, Bosnia and Herzegovina.
² Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.
³ General Hospital Tešanj, Tešanj, Bosnia and Herzegovina.
⁴ Department of Pharmaceutical Biochemistry and Laboratory Diagnostics, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
⁵ Institute for Anthropological Research, University of Zagreb, Zagreb, Croatia.

Abstract

Introduction: COVID-19 has been a major focus of scientific research since early 2020. Due to its 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. Methods: We, therefore, performed next-generation sequencing of coding and regulatory regions of 16 human genes, involved in maintenance of the immune system or encoding 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 clinical conditions of different severity ("mild," "moderate," and "severe"). Results: We confirmed that the male sex and older age are risk factors for severe clinical picture and 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 modifiers of the infection severity. Our results include variants reported for the first time as potentially associated with COVID-19, but further research and larger patient cohorts are required to confirm their effect. Discussion: Such studies, focused on candidate genes and/or variants, have a potential to answer the questions regarding the effect of human genetic makeup on the expected infection outcome. In addition, loci we identified here were previously reported to have clinical significance in other diseases and viral infections, thus confirming a general, broader significance of COVID-19-related research results following the end of the pandemic period.

Keywords: ACE2; COVID-19; IRF7; SARS-CoV-2; TMPRSS2; host genetics.

Grants and funding

This research is a part of the project titled “Personalized approach to COVID-19 infection through analysis of molecular genetic predisposition of the patients for a differential immune response,” that is co-financed by the Ministry of Science, Education, and Youth of the Sarajevo Canton (decision no. 11/05-34-12880-8/20). The authors would like to thank the International Burch University in Sarajevo for providing institutional support in covering a part of the article publication fee.