The course of disease in individuals infected with SARS-CoV-2 is hugely variable, ranging from asymptomatic infections to severe COVID-19 and death. The GenOMICC genome-wide association study, published in Nature, now identifies significant associations of severe disease with several genes involved in antiviral defence mechanisms or in host-driven inflammatory lung injury. These include a cluster of genes that encode antiviral restriction enzyme activators (OAS1, OAS2 and OAS3), TYK2, encoding a tyrosine kinase, the dipeptidyl peptidase gene DPP9 and the interferon receptor gene IFNAR2. Mendelian randomization revealed a causal link between severe disease, low expression of IFNAR2 and high expression of TYK2. Moreover, a transcriptome-wide association study showed the monocyte/macrophage chemotactic receptor CCR2 is associated with severe COVID-19. These findings indicate opportunities for the potential repurposing of existing drugs.
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Pairo-Castineira, E. et al. Genetic mechanisms of critical illness in Covid-19. Nature https://doi.org/10.1038/s41586-020-03065-y (2020)
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Flemming, A. Genetic clues for predisposition to severe disease. Nat Rev Immunol 21, 70 (2021). https://doi.org/10.1038/s41577-020-00495-7
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DOI: https://doi.org/10.1038/s41577-020-00495-7