Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals

Pillar 2
Host-Pathogen Interactions

People who have COVID-19 can show a wide variety of symptoms ranging from nothing to very severe and even lethal outcomes. Previous research has shown that a genetic haplotype on chromosome 3, which became part of the modern human genome through ancient mating with Neanderthals, is a strong risk factor for severe presentation of SARS-CoV-2 infections. In this work published in eLife, by an international team of scientists that included Pillar 2 Deputy Arinjay Banerjee, Virologist and Principal Scientist at the Vaccine and Infectious Disease Organization (VIDO) in Saskatoon, Saskatchewan, this chromosomal region was further analyzed to reveal regulatory elements and their target genes. The team used population genetics, functional genomics, and experimental assays to determine which of over 600 variants were strong functional candidates for driving a genetic predisposition to severe COVID-19. Four strong candidates were identified in this fashion and were further evaluated in cell reporter assays with and without SARS-CoV-2 infection. It is likely that these variants modulate two critical chemokine receptor genes, CCR1 and CCR5. This work is an excellent example of the value of studying the interaction between host genomics and COVID-19 outcomes, and how it can reveal risk factors and critical biological pathways connected to the severity of the disease.

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