Neanderthal-derived proteins can reduce the weight of COVID-19

In the news – Researchers from the Lady Davis Institute (LDI) at the Jewish General Hospital found that increased levels of OAS1 protein are associated with reduced mortality and less severe diseases that require ventilation in patients with COVID-19. The use of drugs that increase OAS1 levels can be investigated to try to improve these outcomes. The findings were published today in Nature Medicine.

“Our analysis shows evidence that OAS1 has a protective effect against the sensitivity and severity of COVID-19,” explains Dr. Brent Richards, senior researcher at LDI’s Center for Clinical Epidemiology and professor of medicine, human genetics, epidemiology, and biostatistics at McGill University. “This is a very exciting development in the race to identify potential therapies to treat patients because there are already preclinical therapies in place that enhance OAS1 and that could be investigated for their effect against SARS-CoV-2 infection.”

It is understandable that a lot of effort is invested in the development of vaccines. However, given that hundreds of millions of people are already infected worldwide, it is important not to neglect the search for specific disease therapies, as few such therapies have been identified. Moreover, given the prevalence of vaccine variability in the community and the uncertainty of how long a vaccine will prove protective, COVID-19 is likely to be a global problem for years to come. Therefore, the need for therapeutic treatments will continue.

Researchers in the laboratory of others. Richards investigated proteins that can be found in peripheral blood as a potential target. The challenge was to determine which proteins play a causal role in disease progression, as their level may be affected by COVID-19 itself or other confusing factors. Recent advances in proteomic technology — that is, the ability to isolate and measure hundreds of circulating proteins at once — combined with genetic analysis by Mendel randomization (MR) allow for the delicate unraveling of proteins that affected the harmful outcomes of COVID-19, rather than vice versa.

From the genetic determinants of 931 circulating protein, dr. Sirui Zhou, a postdoctoral fellow at LDI and the first author in the paper, found that the increase in OAS1 levels was associated with reduced COVID-19 death or ventilation, hospitalization and susceptibility to up to 14,134 COVID-19 cases and 1.2 million controls. The results were consistent in multiple sensitivity analyzes. They continued to measure OAS1 levels in 504 patients with different COVID-19 outcomes from Biobanque Québec COVID-19 and found that increased OAS1 levels in postinfectious patients were associated with protection against very severe COVID-19, hospitalization, and susceptibility.

“The protective effect was especially great,” says Dr. Zhou, “such that we have noticed a 50% reduction in the chance of very serious COVID-19 by increasing the standard deviation in OAS1 circulation levels. Interestingly, for non-African peoples, this protective effect is probably inherited from a Neanderthal-derived form of OAS1 called p46.”

This form of OAS1 probably appeared in humans of European descent by crossing with Neanderthals tens of thousands of years ago. Evolutionary pressure has slowly increased the prevalence of this form of OAS1, so that it can now be detected in more than thirty percent of people of European descent. It is likely that the protein form served as protection against earlier pandemics.

Because drug development, even in an accelerated pandemic research environment, takes time, it is particularly exciting that molecules that can increase OAS1 activity are currently in preclinical preparation for possible use in clinical trials.

“Our recommendation is that those drugs that trigger increased OAS1 levels be further studied for their impact on COVID-19 outcomes so that we can better treat infected patients,” said Dr. Richards.


Neanderthal OAS1 isoform protects individuals of European origin from sensitivity and severity COVID-19, Sirui Zhou et al, Nature Medicine, doi: https: // /10.1038 /s41591-021-01281-1