Participation of Single-Nucleotide Variants in <i>IFNAR1</i> and <i>IFNAR2</i> in the Immune Response against SARS-CoV-2 Infection: A Systematic Review.

Abstract

Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). <i>IFNAR2</i> and <i>IFNAR1</i> genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the <i>IFNAR</i> genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe <i>IFNAR1</i> and <i>IFNAR2</i> variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on <i>IFNAR1</i> and <i>IFNAR2</i> studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in <i>IFNAR1</i> and <i>IFNAR2</i> could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.