Host genetic factors determining COVID-19 susceptibility and severity

Abstract

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic to severe courses of COVID-19 with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI and pre-existing comorbidities. Ethnicity is also relevant to COVID-19 susceptibility and severity. Host genetic predisposition to COVID-19 is now increasingly recognized and whole genome and candidate gene association studies regarding COVID-19 susceptibility have been performed. Several common and rare variants in genes related to inflammation or immune responses have been identified. We summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID-19 and disease severity. We discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine, and drug repurposing.

Keywords: COVID-19; Candidate genes; Host genetics; Immunity; Susceptibility.

Fig. 1

Host genetic variants and/or genes associated with SARS-CoV-2 infection and COVID-19 severity. Cell with representation of GWAS and candidate genes; in addition, boxes represent genes with respective variants which were associated with SARS-CoV-2 infection and COVID-19 severity. Genes which were associated in GWAS are represented in green, genes from candidate gene association studies in orange. SLC6A20, solute carrier family 6 member 20; LZTFL1, leucine zipper transcription factor like 1; CCR9, CC motif chemokine receptor 9; FYCO1, fyve and coiled-coil domain-containing protein 1; CXCR6, C-X motif chemokine receptor 6; XCR1, X-C motif chemokine receptor 1; ABO, ABO gene; IFNAR2, interferon alpha and beta receptor subunit 2; OAS3, 2′−5′-oligoadenylate synthetase 3; DPP9, dipeptidyl peptidase 9; TYK2, tyrosine kinase 2; HLA-G, human leukocyte antigen-G; HLA-DPB1, human leukocyte antigen-DPB1; CCHCR1, coiled-coil alpha-helical rod protein 1; ACE2, angiotensin-converting enzyme 2; ACE1, angiotensin-converting enzyme 1; TMPRSS2, transmembrane protease serine 2; MX1, myxoma resistance 1; TLR7, toll like receptor 7; HLA, human leukocyte antigen; KLRC2, killer cell lectin like receptor C2; MUC5B, mucin 5B; FOXP4 Forkhead Box P4 (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article).