Why do some people get so sick from COVID-19? Is it in their Neanderthal genes?

An article yesterday in Science Magazine by Jocelyn Kaiser highlights one of the most crucial questions on COVID-19 illness.  Why are there people who get horribly ill with COVID-19? In fact, COVID-19 seems to be almost a binary disease, with people becoming deathly ill or having a relatively mild or even no apparent illness. Most of us in the medical community felt there was something inherent in these individual’s ability to fight the virus that was behind this dichotomy.

Now, a Scottish study of more than 2,200 COVID-19 patients has identified many common genes linked to the most severe cases of COVID-19. Importantly, their findings suggest that existing drugs that alter these genetic pathways could be used to treat COVID-19 disease. 

The study, out of the University of Edinburgh, was part of a world-wide effort called the COVID-19 Host Genetics Initiative. The findings of their study, posted in a preprint on medRxiv, still requires validation by being published in a journal. 

Much like prior studies looking for associations between genetic markers and severe cases of COVID-19, the new study confirmed that certain regions of chromosome 3 are involved in the development of severe COVID-19 disease. Interestingly, however, 74% of the patients that were evaluated were so sick that they needed ventilators. This was a unique group that provided the ability to identify many genes important to protecting people from COVID-19. 

The chromosome 3 region appears to be important as it more than doubles an infected person’s odds of developing severe COVID-19. It was reported in Nature that this genetic area came from Neanderthals through breeding with humans tens of thousands of years ago. 

One of the potentially most significant findings is a gene called IFNAR2 that makes the receptor for interferon, a powerful anti-viral protein. A specific type of IFNAR2 gene found in 25% of Europeans increased the risk of severe COVID-19 by 30%. A more surprising finding indicated the importance of OAS genes, which make proteins that help break down viral RNA. This might impair the immune response to RNA viruses like SARS-CoV-2, allowing the virus to survive. 

The results from this work were different from a study in The New England Journal of Medicine (NEJM) which found respiratory failure in European COVID-19 patients was associated with the ABO gene (which determines a person’s blood type). The NEJM study did agree with the association with chromosome 3. Both studies support ongoing trials of interferons as drugs to treat COVID-19.

There were also a number of genes associated with severe COVID-19 that are identified as involved in lung inflammation that could underlie the bad pneumonias found in association with COVID-19.

This finding in this study does not explain the severe COVID-19 illness in African Americans since the chromosomal 3 regions are not present in these individuals. Other work needs to examine genetic factors that may be important for this group.