“Biggest risk factor for getting severely ill with COVID-19 comes from Neandertals”

“Biggest risk factor for getting severely ill with COVID-19 comes from Neandertals”

Svante Pääbo is Director, Max Planck Institute for Evolutionary Anthropology, Leipzig and Adjunct Professor, Okinawa Institute of Science and Technology, Japan.

Prof Pääbo is the lead author of studies titled The major genetic risk factor for severe COVID-19 is inherited from Neanderthals in Nature and A genomic region associated with protection against severe COVID-19 is inherited from Neandertals in PNAS.

A well-known scholar in evolutionary anthropology, Prof Pääbo has more than 340 published articles and scores of book chapters on the subject to his credit.

He is also on the editorial board of several scientific publications including Cell.

In an interaction, Svante Pääbo explains the importance of the Neandertal factor in the severity of COVID-19. Edited excerpts: 

To what extent do Neandertal-inherited genetic variants impact human immunity?

We know of some cases where that is the case. For example, there are variant genes for receptors on immune cells that come from Neandertals and increase the risk for allergies.

The current pandemic has yielded two striking examples: Neandertal variants on chromosome 3 that at least double the risk to become severely ill if infected with SARS-CoV-2, and other gene variants on chromosome 12 that reduce the risk by about 20%.

Which are the genes on chromosome number 12 locus possibly contributing to protection from severe illness?

The genes there are called OAS1-3 and they activate an enzyme in the cell that degrades double-stranded RNA which is formed when the virus replicates in the cell. The Neandertal version makes a more active form of the protein that activates this enzyme.

In what ways does this haplotype work with other pathogens of viral or bacterial origin?

That haplotype is protective also against other RNA viruses, for example, SARS-CoV-1 and the West Nile virus.

Despite having more Neandertal gene variants, the severe form of the disease and associated mortality rates are found to be higher among the East Asian populations compared to the people of Africa who have practically no Neandertal genes. Why is it so?

First of all, one should stress that other factors are more important than these genetic factors, like the age structure of the population and socioeconomic and cultural factors.

Nevertheless, it is interesting that the biggest risk factor for getting severely ill upon infection with SARS-CoV-2 comes from Neandertals and that is absent in East Asia and in Africa, and has a carrier rate of up to 60% in South Asia. It may influence outcomes in these regions as one factor among many.

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