The major genetic risk factor for severe COVID-19 is inherited from Neanderthals.

Hugo Zeberg,Svante Pääbo

doi:10.1038/s41586-020-2818-3

Abstract

A recent genetic association study1 identified a gene cluster on chromosome3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.

Highlights

The genetic variants that are most associated with severe COVID19 on chromosome 3 (45,859,651–45,909,024) are all in high linkage disequilibrium (LD)—that is, they are all strongly associated with each other in the population (r2 > 0.98)—and span 49.4 thousand bases (Fig. 1b)
We found that the risk alleles of both of these variants are present in a homozygous form in the genome of the Vindija 33.19 Neanderthal, an approximately 50,000-year-old Neanderthal from Croatia in southern Europe[8]
Three of these variants occur in the Altai[9] and Chagyrskaya 810 Neanderthals, both of whom come from the Altai Mountains in southern Siberia and are around 120,000 and about 60,000 years old, respectively (Extended Data Table 1), whereas none of the variants occurs in the Denisovan genome[11]

Summary

Introduction

The genetic variants that are most associated with severe COVID19 on chromosome 3 (45,859,651–45,909,024 (hg19)) are all in high linkage disequilibrium (LD)—that is, they are all strongly associated with each other in the population (r2 > 0.98)—and span 49.4 thousand bases (kb) (Fig. 1b). The index variants of the two studies[1,2] are in high linkage disequilibrium (r2 > 0.98) in non-African populations (Extended Data Fig. 3). We found that the risk alleles of both of these variants are present in a homozygous form in the genome of the Vindija 33.19 Neanderthal, an approximately 50,000-year-old Neanderthal from Croatia in southern Europe[8].

Results

Conclusion