Neanderthal Gene Variants Both Increase, Decrease Risk of Severe COVID-19

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In October 2020, researchers at Karolinska Institutet and Max Planck Institute showed that a specific gene variant inherited from Neanderthals makes it 3x more likely for modern-day humans to develop severe COVID-19 when infected with the virus.

Now, in a new study, those same researchers show Neandertals also contributed a protective gene variant that reduces the risk of needing intensive care for COVID-19 by 20 percent.

“They have given us variants that we can both curse and thank them for," said study co-author Hugo Zeberg, researcher at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropology.

Zeberg and Svante Pääbo’s most recent research builds on work done by the Genetics of Mortality in Critical Care consortium in the UK. In December 2020, based on the genome sequences of 2,244 people who developed severe COVID-19, the consortium pinpointed genetic regions on four chromosomes that impact how individuals respond to SARS-CoV-2.

In their PNAS article, the researchers show that one of those four regions carries a variant that is almost identical to those found in three Neanderthals—a 50,000-year-old Neanderthal from Croatia, a 70,000-year-old from Southern Siberia and a 120,000-year-old from the same region.

The variant is located on chromosome 12 and reduces the risk that an individual will require intensive care after infection by about 22%. In contrast, the earlier study indicated a region on chromosome 3—inherited from 60,000-year-old ancestors in Southern Europe—carries up to a 3x higher risk of mechanical ventilation.

The genes in chromosome 12, called OAS, regulate the activity of an enzyme that breaks down viral genomes—and the Neandertal variant of the enzyme seems to do this more efficiently, thereby reducing the risk of severe illness due to SARS-CoV-2 infection.

Zeberg and Pääbo also examined the frequency of the Neanderthal-like genetic variants. Using genomic data from thousands of human skeletons of varying ages, the researchers found that the variant increased in frequency after the last Ice Age, then increased again during the past millennium. As a result, today it occurs in about half of people living outside Africa and in around 30% of people in Japan. In contrast, the major risk variant identified in the previous study is almost completely absent in Japan.

"The rise in the frequency of this protective Neanderthal variant suggests that it may have been beneficial also in the past, maybe during other disease outbreaks caused by RNA viruses," said Pääbo.

Photo: New research has found that a group of genes that reduces the risk of developing severe COVID-19 by around 20% is inherited from Neanderthals. Credit: Bjorn Oberg, Karolinska Institutet