Common genetic variation in humans impacts in vitro susceptibility to SARS-CoV-2 infection

The world is in the midst of an ongoing pandemic caused by the novel and highly contagious SARS-CoV-2. There is marked inter-individual variability in the tissues affected as well as the severity of response to SARS-CoV-2. It is unclear why some otherwise healthy individuals experience profound clinical complications to SARS-CoV-2 and others do not. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants also impact vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR-engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single nucleotide polymorphism (rs4702), common in the population at large, and located in the 39UTR of the protease FURIN, impacts alveolar and neuron infection by SARS-CoV-2 in vitro. Thus, we provide a proof-of-principle finding that common genetic variation can impact viral infection, and so potentially contribute to clinical heterogeneity in SARS-CoV-2. Ongoing genetic studies will help to better identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs that might treat disease.