Genetics Insight for COVID-19 Susceptibility and Severity: A Review

Abstract

Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to a severe clinical course. The host genetic background influence on the susceptibility and outcome of multiples infectious diseases has been previously reported. Herein, we aimed to describe relevant identified genetic variants and those potentially related to the inter-individual variability of COVID-19 susceptibility and/or severity considering the physiopathological pathway of the disease TheHLA-A*25:01, -B*15:27,-B*46:01,-C*01:02, and-C*07:29alleles have been associated with COVID-19 susceptibility; whileHLA-A*02:02,-B*15:03, and-C*12:03have been identified as low-risk alleles. Variants in cytokine genes such asIL1B,IL1R1,IL1RN,IL6,IL17A,FCGR2A, andTNFcould be related to disease susceptibility and cytokine storm, and/or COVID-19 complications (e.g., venous thrombosis). Several variants inACE2andTMPRSS2affecting the expression of the receptors related to COVID-19 have been associated with the disease susceptibility and risk factors. Finally, two GWAS have identified theloci3p21.31 (LZTFL1,SLC6A20,CCR9,FYCO1,CXCR6, andXCR1) and 9q34.2 (ABO) with COVID-19 severity. Heterogeneous results in the association of genetic variants with COVID-19 susceptibility and severity were observed. The mechanism of identified risk-genes and studies in different populations are still warranted.