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Blood Group Locus Contributes to COVID-19 Severity Risk, GWAS Finds

NEW YORK – An international team has tracked down variants in two parts of the genome – one of them containing the ABO blood group locus – that appear to coincide with severe cases of COVID-19 that involve respiratory failure.

"Further exploration of current findings, both as to their usefulness in clinical risk profiling of patients with COVID-19 and toward a mechanistic understanding of the underlying pathophysiology, is warranted," co-corresponding author Andre Franke, a researcher at Kiel University in Germany and a member of the COVID-19 Host Genetics Initiative, and his colleagues wrote in a study published in the New England Journal of Medicine on Wednesday.

For the study, the researchers conducted a genome-wide association study and meta-analysis encompassing thousands of COVID-19 patients treated at hospitals in Italy, Spain, Norway, and Germany. These included 1,980 individuals with PCR-confirmed SARS-CoV-2 infections who experienced respiratory failure as well as seemingly healthy control individuals from the same populations. The analyses used array-based genotyping profiles based on nearly 8.6 million SNPs.

"At the peak of the epidemic in Italy and Spain in early 2020, we performed a genome-wide association study in an attempt to delineate host genetic factors contributing to severe COVID-19 with respiratory failure," the authors explained. "The relatively low disease burden of COVID-19 in Norway and Germany allowed for a complementary team to be set up, whereby genotyping and analysis could occur in parallel with the rapid recruitment of patients in the heavily affected Italian and Spanish epicenters."

Using this approach, they narrowed in on severe COVID-19-related variants in around half a dozen genes at a chromosome 3 locus known as 3p21.31, along with a signal stemming from a chromosome 9 site containing the ABO blood group locus. 

The same chromosome 3 locus turned up in a preliminary analysis of data collected by the COVID-19 Host Genetics Consortium alone, the authors noted, though that team's analyses relied on genetic data from individuals with both mild and severe COVID-19 infections. From these and other findings, they explained, "it seems reasonable to conclude that the chromosome 3p21.31 locus is involved in COVID-19 susceptibility per se, with a possible enrichment in patients with severe disease."

The apparent ties between the ABO blood group locus COVID-19 severity also tracks with some prior phenotype-based reports, including a preprint from a team in China in March that suggested blood type O might protect against SARS-CoV-2 infections to some extent, while type A blood may correspond to enhanced COVID-19 risk.

"Non-genetic studies that were reported as preprints have previously implicated the involvement of ABO blood groups in COVID-19 susceptibility, and ABO blood groups have also been implicated in susceptibility to SARS-CoV-1 infection," the authors explained. "Our genetic data confirm that blood group O is associated with a risk of acquiring COVID-19 that was lower than that in non-O blood groups, whereas blood group A was associated with a higher risk than non-A blood groups."

In a blog post today, National Institutes of Health Director Francis Collins referenced a preprint version of the NEJM study that was posted to MedRxiv in early June, noting that the results "completed in two months under very difficult clinical conditions, clearly warrant further study to understand the implications more fully."

"The hope is that these and other findings yet to come will point the way to a more thorough understanding of the biology of COVID-19," Collins wrote, adding that "a genetic test and a person's blood type might provide useful tools for identifying those who may be at greater risk of serious illness."

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