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HIV Risk Reduced in Carriers of Allele Linked to Severe COVID-19


NEW YORK – A new study by a single investigator has uncovered apparent genetic overlap between increased risk of severe COVID-19 and reduced risk of HIV infection.

"This shows how a genetic variant can be both good and bad news: Bad news if a person contracts COVID-19, good news because it offers protection against getting infected with HIV," Hugo Zeberg, an investigator at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institute and the author of the study, scheduled to appear in the Proceedings of the National Academy of Sciences this week, said in a statement.

Zeberg noted that a site on chromosome 3 associated with SARS-CoV-2 severity, identified through large efforts such as the COVID-19 Host Genetics Initiative, contains a cluster of chemokine receptor genes, including a coreceptor that HIV-1 uses to enter human cells. Consequently, he reasoned that shifts in the expression of these genes, mediated by risk variants, may impact vulnerability to both viral conditions.

Using data from the FinnGen, UK Biobank, and Michigan Genomics Initiative biobanks, Zeberg performed a meta-analysis looking at COVID-19-related risk on chromosome 3 in the context of chemokine receptor gene expression and HIV prevalence in 591 individuals of European ancestry with HIV and 667,215 unaffected control individuals.

The findings suggested that HIV risk is roughly 27 percent lower in individuals carrying a SARS-CoV-2-related risk allele associated with decreased expression of CCR5, which HIV uses to infiltrate white blood cells. The allele, which coincided with lower-than-usual expression of the CCR5 protein product and other chemokine receptors, falls in a stretch of sequence previously linked to Neanderthal introgression.

"The association described here highlights that gene flow from Neanderthals was a double-edged sword," Zeberg concluded. "Whereas this genetic variant has had tragic consequences during the last [two years] of the COVID-19 pandemic, it appears to have offered considerable protection against HIV during the last [40 years]. Its role in past and future pandemics remains to be seen."

Based on the prevalence of the variant, which appeared to have increased in frequency over the past 10,000 to 20,000 years, Zeberg said he suspects that alterations at the chromosome 3 site arose in response to viruses or conditions that began plaguing human populations long before HIV was identified.

"Now we know that this risk variant for COVID-19 provides protection against HIV," he suggested. "But it was probably protection against yet another disease that increased its frequency after the last Ice Age."

Though the identity of that condition, or conditions, remains to be identified, Zeberg noted that there are documented diseases stretching back to the time frame when the allele became more common. Smallpox-causing variola virus appears to have arisen more than 10,000 years ago, for example. Likewise, such variants may influence immune responses to still other conditions, he suggested, adding that the COVID-19 risk allele in question is found with particular frequency in parts of the world with endemic cholera cases.

Even so, he cautioned that he "can only speculate about the pathogen that exerted the genuine selective pressure on this allele."