Black Death genetic variant also protects against COVID-19

A genetic variant understood to have protected people against the Black Death, has been shown to also be protective against severe COVID-19, a study has found.

Previous research has shown individuals with a particular allele of the ERAP2 gene were up to half as likely to die from bacteria Yersinia pestis infection, which caused the Black Death pandemic in North Africa, Europe and Asia from 1346 to 1353 (see BioNews 1164). Although it proved helpful in the Middle Ages, it is now hypothesised that carrying this allele makes individuals more likely to develop autoimmune diseases, including Crohn's disease. Now, researchers from the UK have shown that carrying the allele also corresponds to an eight percent decreased likelihood of severe infection with COVID-19 resulting in admission to critical care.

'Although we don't know the exact mechanism influencing disease risk, carriers of alleles that provide more protection against respiratory disease seem to have an increased risk of autoimmune disease. It is potentially a great example of a phenomenon termed 'balancing selection' – where the same allele has different effect on different diseases,' said Dr Fergus Hamilton, the study's lead co-author and Wellcome GW4 clinical doctoral fellow at North Bristol NHS Trust.

Previous studies had identified the allele by examining the genomes from the bones of corpses of people who had died before and after the Black Death period. Since the Black Death affected people of reproductive age, genes associated with surviving it were more strongly represented in the following generations and explained the change in the genetic distribution of these particular alleles before and after this period.

Researchers for this latest study, published in the American Journal of Human Genetics, performed Mendelian randomisation on genomes contained within three genetic databases: UK BioBank, FinnGen and GenOMICC. Carrying that same allele was found to still carry a protective effect against respiratory infections, including being associated with a protective effect against severe COVID-19 infection that resulted in critical care admission.

No association was found between having the allele and the likelihood of sepsis, which was surprising to researchers as sepsis is thought to have been responsible for many deaths from the Black Death. The association between carrying the allele and having Crohn's disease was confirmed, as was a link between carrying the allele and lower parental longevity, which authors proposed was linked to risk of autoimmune disease.