COVID-19 genetic risk and Neanderthals: A case study highlighting the importance of scrutinizing diversity

Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. The first published study reported a 1bp insertion rs11385942 on chromosome 3 (1) and subsequent studies single nucleotide variants (SNVs) such as rs35044562, rs67959919 (2) and rs13078854 (3), all highly correlated with each other. Zeberg and Pääbo (4) subsequently traced them back to Neanderthal origin. They found that a 49.4 kb genomic region including the risk allele of rs35044562 is inherited from Neanderthals of Vindija in Croatia. Here we add a differently focused evaluation of this major genetic risk factor to these recent analyses. We show that (i) COVID-19-related genetic factors of three previously assessed Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic.