This study compared whole genome sequences from over 7,000 patients critically ill with COVID-19 with the genomes of more than 48,000 matched controls (that is, similar individuals in the general population were matched to each patient). The authors identified 23 gene variants that predispose to critical COVID-19, including 16 variants that had not previously been reported. Notable among these variants were genes linked to interferon responses (IFNA10, PLSCR1, IL10RB), leukocyte differentiation (BCL11A) and myeloid cell recruitment and function (SELE, ICAM5, CD209). The study also provides the first genetic evidence to support a causal role for coagulation and platelet activation in critical COVID-19, with F8 and PDGFRL identified as risk variants. Overall, the data strengthen the idea that a failure to control viral replication and dysregulation of the inflammatory and coagulation responses are key mechanisms that drive the development of severe COVID-19.
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Kousathanas, A. et al. Whole genome sequencing reveals host factors underlying critical Covid-19. Nature https://doi.org/10.1038/s41586-022-04576-6 (2022)
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Bordon, Y. A new set of genes linked to critical COVID-19. Nat Rev Immunol 22, 208 (2022). https://doi.org/10.1038/s41577-022-00709-0
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DOI: https://doi.org/10.1038/s41577-022-00709-0
