Association analyses within the chr12q24.13 region for COVID-19 hospitalization in patients of European and African ancestries. a, Genomic region and association results (ORs) for 79 genotyped or confidently imputed (r2 > 0.8) markers associated (logistic regression, P < 0.05) with hospitalized compared to nonhospitalized (mild) COVID-19 in patients of European (blue dots) or African (red dots) ancestries. The COVID-19 susceptibility GWAS lead SNP (rs10774671) is included, although it is not significantly associated in patients of African ancestry (P = 0.079). A blue highlight indicates the OAS1 region with markers significantly associated in both ancestries. b, LD (r2) plots of the region in COVID-19 patients of European and African ancestries. Darker shading in the plots indicates stronger correlations between markers. c, Single-marker and haplotype association analyses in patients with hospitalized compared to nonhospitalized COVID-19 performed with logistic regression and omnibus haplotype tests, respectively, controlling for sex, age, squared mean-centered age and 20 principal components. The GGGT haplotype comprised of ancestral alleles of the corresponding markers is shared with the Neandertal lineage of archaic humans and is protective from hospitalized COVID-19 in COVNET patients of European and African ancestries. Regional LD plots (r2, 14-kb region) are shown for the OAS1 region associated with protection from hospitalized COVID-19. Credit: Nature Genetics (2022). DOI: 10.1038/s41588-022-01113-z

Researchers from the National Cancer Institute, part of the National Institutes of Health, and their collaborators have discovered that people of European and African ancestries who were hospitalized for COVID-19 are more likely to carry a particular combination of genetic variants in a gene known as OAS1 than patients with mild disease who were not hospitalized. People with this combination of genetic variants also remain positive for SARS-CoV-2 infection longer. However, interferon treatment may reduce the severity of COVID-19 in people with these genetic factors. Interferons are a type of protein that can help the body's immune system fight infection and other diseases, such as cancer.

The study appears in Nature Genetics.

These findings build on previous studies that have suggested that , such as genetic variants affecting OAS antiviral proteins that facilitate the detection and breakdown of the SARS-CoV-2 virus, may influence the risk of SARS-CoV-2 infection.

The NCI researchers and their collaborators found that treatment of cells with an decreased the viral load of SARS-CoV-2. The researchers also analyzed data from a clinical trial in which patients with COVID-19 who were not hospitalized were treated with the recombinant interferon pegIFN-λ1 and found that treatment improved viral clearance in all patients; those with the OAS1 risk variants benefitted the most. The results suggest that interferon treatment may improve COVID-19 outcomes and specifically in patients with certain OAS1 genetic variants who have impaired ability to clear infection.

More information: A. Rouf Banday et al, Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries, Nature Genetics (2022). DOI: 10.1038/s41588-022-01113-z

Journal information: Nature Genetics

Provided by National Institutes of Health