Greater severity of covid-19 linked to DNA inherited from Neanderthals

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Modern humans left Africa about 65,000 years ago and along the way were fornicating with other older human species they found in their path in Europe and Asia, such as Neanderthals. Two Swedish scientists now argue that the genetic footprint of those prehistoric interactions explains the greater fragility of some current people to the new coronavirus. “The main genetic risk factor for suffering the severe form of covid-19 is inherited from Neanderthals,” the two researchers conclude, highly respected in their field. They are Svante Pebo, director of the Max Planck Institute for Evolutionary Anthropology, in Leipzig, Germany, and his colleague Hugo Zeberg.

Not everyone has this genetic variant of presumed Neanderthal origin and supposedly able to triple the risk of more severe covid. In Africa, where there were no Neanderthals, it barely appears. In some populations in The Americas, 4% of people have the suspicious variant. In Europe, 8%. In South Asia, the frequency reaches 30%, with a peak of 63% in Bangladesh. “Given the high frequency of the Neanderthal genetic variant in South Asia, it is striking that there is an excess of mortality in the UK precisely in people from South Asia, but not in other ethnic minorities,” Zeberg reflects. A preliminary study of 35,000 patients has detected a 19% higher covid mortality rate in these South Asian citizens compared to groups classified as “white”.

A human’s operating manual is written in his genes, which are sections of the long DNA chains called chromosomes. Each human cell has about 23,000 genes distributed in 23 pairs of chromosomes. Three weeks ago, a study of 1,600 patients from Spain and Italy showed a statistical association between a genetic variant of chromosome 3 and an increased risk of the most severe effects of covid-19. Two Swedish scientists now argue that this variant is of Neanderthal origin and, in particular, very similar to the remains of a Neanderthal woman who lived about 50,000 years ago in the Vindija cave in Croatia.

A pioneer in the recovery of ancient DNA and winner of the Princess of Asturias Prize, Svante Pebo led the international project to read the Neanderthal genome, a species extinct about 30,000 years ago.

After a week of intensive work in a secluded hut in Sweden, the results were published on 3 July in a repository of preliminary studies without an independent review. Their conclusions are controversial. “They start from a base that is not proven. There is still no one who knows exactly which genetic variants confer susceptibility or resistance to coronavirus,” says Carles Lalueza Fox, a geneticist at the Institute of Evolutionary Biology in Barcelona who collaborated with Pebo in the Neanderthal genome.

The study of 1,600 patients from Spain and Italy, in fact, found two genetic variants associated with a more severe covid: that of chromosome 3 (now classified as Neanderthal) and another on chromosome 9 that determines the blood group. The authors stated three weeks ago that people with blood group A have a 45% higher risk of severe covid than the population average. Another further analysis with more European patients, prepared by the international consortium COVID-19 Host Genetics Initiative, has not found this supposed link between the blood group and the severity of covid. “It seems that a signal associated with the severity of the covid on chromosome 3 is confirmed, while for the blood group you have to wait to see if it is confirmed,” explains Angel Carracedo, a geneticist at the University of Santiago de Compostela who co-directs another of these massive genetic tests — called GWAS – in 20,000 patients.

Geneticist Athletic Lao warns that these GWAS studies offer “many false positives”: alleged gene-disease relationships that fade when more samples are analyzed. It is usual to do these GWAS studies with hundreds of thousands of people, not with a few thousand as has been done so far with the covid, says Lao, of the National Center for Genomic Analysis (CNAG-CRG), in Barcelona. His colleague Simon Heath agrees: “We lack studies to draw some conclusions about genetic variants associated with susceptibility to covid.””We’re moving through dangerously sensational terrain,” says paleoanthropologist María Martinón Torres.

Most of the genetic information of a current person comes from those modern humans who left Africa, the cradle of humanity, tens of thousands of years ago, but between 1% and 4% of the Genome of Europeans is of Neanderthal origin. Geneticist Elos, Miss Laos recalls that these Neanderthal remnants have been associated with problems such as obesity and depression. Laos himself published a study a month ago linking some Neanderthal genetic sequences to an increased risk of attention deficit hyperactivity disorder (ADHD) in today’s people. “The tricky thing is not to find these results, but to interpret them. The fact that a Neanderthal genetic variant is more associated with covid, what does it mean from a Neanderthal point of view? Did it provide them with any protection from other diseases that were present at the time? We don’t know,” Lao acknowledges.

Paleoanthropologist María Martinón Torres also shows her skepticism of the new study. “I’m afraid of reductionist readings about what it means to have a certain mutation or not. They are often read as curses or predestinations,” says the expert, director of the National Research Center on Human Evolution (CENIEH). “We must avoid reductionist associations. One disease is, in the vast majority of cases, multifactorial,” the scientist stresses. Risk factors for dying from covid include old age, uncontrolled diabetes, severe asthma, poverty and being male, according to a study of 17 million people in the UK.

Martinón Torres believes that knowledge of possible genetic susceptibility to covid is so limited that “venturing into inferences about the past and Neanderthals is a little premature.” The researcher is blunt: “We are moving through very swampy and dangerously sensational terrain.” For The current pandemic, however, “it is clear that the genetic flow from Neanderthals has tragic consequences”.