Role for Blood Type in COVID-19 Gains Support, Drives Questions

Evidence is accumulating to suggest a role for blood type in differences in susceptibility to COVID-19 infection and in severity of the disease once it is contracted.

Two genetic studies and 2 nongenetic studies have reached similar conclusions—that blood type O is associated with a lower risk of acquiring COVID-19 than non-O blood types and that blood type A is associated with a higher risk than non-A blood types. A parallel finding appears to hold for disease severity.

The most recent study, published online June 17 in the New England Journal of Medicine was a genomewide association study that included 1,980 people undergoing treatment for severe COVID-19 and respiratory failure at 7 medical centers in Italy and Spain. The team analyzed genome data for more than 8.5 million single-nucleotide polymorphisms (SNPs) and compared them with SNPs in more than 1200 healthy blood donors from the same population groups.

Researchers, led by David Ellinghaus, MD, of the Institute of Clinical Molecular Biology in Germany, found that participants with blood type A had a higher risk for acquiring COVID-19 with respiratory failure than other blood types (OR = 1.45; 95% CI, 1.2-1.75, P = 1.48 × 10^-4). The researchers also observed a protective effect in blood group O vs. other blood groups (OR = 0.65; 95% CI, 0.53-0.79, P = 1.06 × 10^-5). Both associations and effect directions were consistent in the separate Spanish and Italian case–control analyses. The authors found no significant difference in blood-group distribution between patients receiving supplemental oxygen only and those receiving mechanical ventilation of any kind.

The second set of data on the role of genetics in COVID-19 comes from preliminary, unpublished data generated by the genetic testing company 23andMe. The company has an ongoing genetic study of COVID-19 and based on information from 750,000 current participants reports that O blood type appears to be protective against the virus vs all other blood types (OR = 0.86; P < .0001) and that individuals with blood type O are between 9-18% less likely than individuals with other blood types to have tested positive for COVID-19. Patients with type O blood also were less likely to be hospitalized with COVID-19 (OR = 0.81; P = .05).

The findings held after adjustment for age, sex, body mass index, ethnicity, and co-morbidities.

Data on blood type and the preliminary genetic findings appear to support 2 obervational studies from China published in preprint on MedRxiv, one in late March, the other in mid-April. Authors of the latter found that the effect of blood type is not explained by the risk factors considered: age, sex, hypertension, diabetes mellitus, overweight status, and chronic cardiovascular and lung disorders.

Commentary on the studies and their findings recommends caution in interpretation and

Explanation for the findings is only speculative at this time and commentary from infectious disease specialists and other experts recommends caution in interpretation. Authors of the NEJM study conclude by saying: "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."