A genetic variant protective against severe COVID-19 is inherited from Neandertals

Abstract

It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by SARS-CoV-2 is inherited from Neandertals. Thanks to new genetic association studies additional risk factors are now being discovered. Using data from a recent genomewide associations from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region associated with requiring intensive care is inherited from Neandertals. It encodes proteins that activate enzymes that are important during infections with RNA viruses. As compared to the previously described Neandertal risk haplotype, this Neandertal haplotype is protective against severe COVID-19, is of more moderate effect, and is found at substantial frequencies in all regions of the world outside Africa. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.05.327197; this version posted October 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Main text Neandertals and Denisovans are archaic hominin groups that became extinct about 40,000 years ago (Higham et al. 2014). They have a biological impact on human physiology today through genetic contributions to modern human populations that occurred during the last tens of thousands of years of their existence (e.g., Simonti et al. 2016, Dannemann and Kelso 2017). Several of these contributions affect genes involved in the immune system (e.g., Laurent et al. 2011, Quach et al. 2016). In particular, variants at several loci containing genes involved in innate immunity come from Neandertals and Denisovans, for example toll-like receptor gene variants which decrease the susceptibility to Helicobacter pylori infections and increase the risk for allergies (Dannemann et al. 2016). Recently, it was shown that a region on chromosome 3 harbors the major genetic risk locus for becoming critically ill upon infection with the novel coronavirus SARS-CoV-2 (Ellinghaus et al. 2020) and that the haplotype that confers the risk was contributed by Neandertals to modern humans (Zeberg and Pääbo 2020). This haplotype reaches carrier frequencies of up to ~65% in South Asia whereas it is almost absent in East Asia and occurs at ~16% in Europe. …