Indigenous Arabs have an intermediate frequency of a Neanderthal-derived COVID-19 risk haplotype compared with other world populations.

SARS-CoV-2 has been identified as the cause of an ongoing pandemic (COVID-19) that has infected more than 25 m individuals and caused more than 1 m deaths worldwide (WHO). The highly variable clinical course despite a relatively stable viral genome strongly implicates host factors, including genetics. Mendelian large effect variants have recently been identified although these likely account for a very small number of cases.1 On the other hand, the contribution of several common variants has been demonstrated,2 particularly one locus on chr3 which was identified in the first major GWAS on genetic predisposition to severe COVID19.3 Interestingly, a very recent study has convincingly shown that the risk haplotype in the chr3 locus was introgressed into modern humans from Neanderthal.4 The distribution of this risk haplotype was estimated for a wide range of human populations although Middle Eastern Arabs were missing.4 Here, we calculate the distribution of the risk haplotype in Arabia and discuss that in the context of the overall Neanderthal ancestry in the local population. Representative samples from the major indigenous tribes in Arabia were chosen for analysis with informed consent and genotyped as described in detail elsewhere (Mineta et al, 2020).5 We first confirmed by Haploview that the 13 SNPs that constitute the risk haplotype are in complete LD in indigenous Arabs using previously published WGS data. We then tested the frequency of rs13078854 in 953 samples representing the 28 major indigenous tribes in Arabia. The overall risk allele frequency was 8.6% with 135 heterozygotes and 14 homozygotes (of note, homozygotes had only been documented among South Asians [~10%] and 1 individual in Colombia). As shown in Figure 1, the distribution was largely similar between the different regions.