Why are some asymptomatic and others in the ICU with severe #COVID19 ?

Here we provide updated pre-print evidence that a form of a protein derived from Neanderthals protects against #COVID19 susceptibility and severity.


Using #MendelianRandomization to test if 931 circulating proteins influence COVID19 , we found the that increased OAS1 levels protect against susceptibility and severity.

Eg. OR = 0.54; P = 7E-8 in 4,336 cases of death or ventilation compared to 623,902 controls

Digging deeper, we found that protection seems to be afforded by an isoform of OAS1 which was introduced into the European population by Neanderthals.

Due to a splicing variant that leads to a more active form OAS1 isoform that degrades viral RNA.

This isoform is present in sub-Saharan Africans, but was lost when modern day Europeans migrated out of Africa. When Europeans mated with Neanderthals, the variant was then re-introduced into the European population, where it underwent positive selection.

Next, measuring OAS1 levels in patients with #COVID19 during the course of their infection, we found that individuals with higher OAS1 levels in a non-infected state had lower odds of susceptibility and severe #COVID19

Providing, two separate lines of evidence implicating OAS1
These data provide an example of why Neanderthal ancestry matters in COVID19 outcomes.

A great collaboration led by Sirui Zhou @GBL_Unit @TomokoNakanish1 @forgetta Hugo Zeberg Daniel Kaufmann, and others

What can be done with this knowledge?

Medications already exist that seem to increase OAS1 levels. These should be prioritized for testing in randomized controlled trials.

This is pre-print evidence, so should be read with caution and several other important limitations are listed in the paper.
You can follow @BrentRichards19.
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