Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

Abstract

Host-specific genetics, such as epigenetic profiles and genetic variants, can contribute to the pathogenesis of infectious diseases. Strong associations have been previously identified in infections by human immunodeficiency virus (HIV), Plasmodium falciparum, norovirus, and influenza A virus. Despite the efforts to characterize the role of host genetics in severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2) infection, this comprehension remains incipient. Coronavirus disease 2019 (COVID-19) can evolve with a wide spectrum of manifestations, ranging from asymptomatic and mild cases to severe forms with acute respiratory distress syndrome, multi-organ complications, and even death. Classic clinical risk factors only partially explain this interindividual variability, suggesting that host genetics may contribute to the heterogeneity of courses. Robust evidence has revealed the multiple associations of genes (ABO, PPP1R15A, SLC6A20, IFNAR2, OAS, TYK2, CCR2, CCR5, TLR7, ApoE, TMPRSS2, HLA, ACE2, etc.) with the susceptibility and/or severity of SARS-CoV-2 infection. In addition, the genetics behind the established risk factors have been considered: at least four loci associated with COVID-19 severity (DPP9, FOXP4, SFTPD and MUC5B) have been previously linked to lung fibrosis, interstitial lung disease, lung carcinomas, and/or decreased lung function. In summary, identifying the host-specific genetic factors may improve our knowledge of risk groups for infection and severe outcomes, as well as the biological mechanisms of therapeutic relevance. Therefore, the present literature review aims to understand the genetics underlying the patterns of susceptibility and prognosis of COVID-19.