Severe COVID-19 associated with Neanderthal inheritance?

News broke in 2010 about evidence from modern and ancient DNA samples that showed some anatomically modern humans who left Africa before 40 thousand years ago to have interbred with the Neanderthal occupants of Eurasia (see: Yes, it seems that they did …; May 2010). In 2011 it turned out that the same had happened when AMH migrants in Asia met with Denisovans (see: Snippets on human evolution; November 2011). The resulting human hybrids went on to spread their new genes as they populated East Asia, Australasia and the Americas. Genomes of thousands of living people from these continents all show varying proportions – but generally less than about 5% – of genetic contributions from one or the other and in some cases both. Some of the modern humans who remained in Africa also had a similar opportunity. A few Neanderthals did set foot in Africa sharing their genes with its original inhabitants, but those venturing far from their normal range had already interbred with early ‘out-of-Africa’ AMH migrants about 150 to 100 thousand years ago, as had  AMH returning from Eurasia around 20 ka ago. Five widespread groups of modern Africans (but not all) carry up to 0.3% of the Neanderthal genome. Moreover, the ancestors of some living Africans had also exchanged genes with as-yet unknown archaic humans (see also: Everyone now has their Inner Neanderthal; February 2020).

Personally, I reacted to the news with a sense of pride. Neanderthals were tough, survivors of several hundred thousand years of climatic extremes hunting fearsome prey, and they probably had an intellect as advanced as that of the AMH with whom they mingled. My little bit of Neanderthal has conferred several advantages including resistance to Eurasian pathogens, but also has its downside, such as a tendency to depression and excessive blood clotting. But an unedited paper released in advance of publication by the journal Nature suggests that my pride turns out to include an unwelcome element of hubris.

Early in the COVID-19 pandemic, genetic research on over 3000 individuals, whose symptoms were severe enough for them to be hospitalised – a high proportion of whom sadly died – revealed that there was more to their being prone to severe symptoms than age, co-morbidities, gender and ethnicity. A short segment (around 50,000 base pairs long) on the DNA of their chromosome-3 is significantly associated with severe COVID-19 outcomes. Svante Pääbo, the leader of the team than reconstructed the Neanderthal and Denisovan genomes and discovered their presence in living people, and his co-author, Hugo Zeberg, have linked this segment to a stretch in the Neanderthal genome (Zeberg, H. & Pääbo, S. 2020. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature, accelerated preview; DOI: 10.1038/s41586-020-2818-3). One gene included in the segment plays a role in the human immune response and another is linked to the way the coronavirus invades human cells, but how they influence health outcomes in COVID-19 victims is yet to be established. Sixteen percent of Europeans and 30% of South Asians carry the segment. If infected, they are at higher risk of severe outcomes than the rest of the population. That the relatively small segment still persists 40 ka after Neanderthals became extinct suggests that it has not always conferred high risk: probably because it once conferred significant advantages, perhaps by protecting against other, now extinct pathogens. A fitness benefit is passed on through natural selection

The pandemic has yet to run its course and genetic research, such as that by Zeberg and Pääbo, takes second place to that aiming at lessening the effects of the disease and developing vaccines that, hopefully, will wipe it out. The country-by-country statistics of COVID-19 morbidity and mortality are shaky, but an interesting feature may be emerging. Although there have been many cases in Africa, where health services are under developed, it seems that deaths as a proportion of infections are significantly lower there than in the more advanced countries. Hopefully that will continue, perhaps as a result of lower Neanderthal inheritance.

See also: Sample, I. 2020. Neanderthal genes increase risk of serious Covid-19, study claims. (The Guardian, 30 September 2020)