Host genetic factors determining COVID-19 susceptibility and severity

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.