Study Links Blood Groups to Severe COVID-19 Risk Through Protein Analysis

A team of researchers working across King's College London and the Medical University of Vienna has identified a biological mechanism that may explain why some people fall severely ill with COVID-19 while others recover with minimal symptoms. The answer, they found, lies partly in blood type—and in a handful of proteins that either amplify or dampen the body's vulnerability to the worst forms of the disease.

The study, published in PLOS Genetics, screened more than 3,000 proteins using genetic data from large population studies. From that vast catalog, the researchers isolated fourteen proteins with causal links to COVID-19 severity: six that increased risk and eight that appeared protective. The work represents a shift in how scientists think about the disease. Rather than asking which proteins are simply associated with severe illness, the researchers used genetic tools to establish which ones actually drive the outcome—a distinction that matters enormously when designing treatments.

The most striking finding concerns the ABO enzyme, the protein that determines a person's blood group. The enzyme showed a causal connection to both hospitalization and the need for respiratory support or death. This aligns with earlier observations that people with blood group A appear overrepresented among those hospitalized with COVID-19, suggesting the blood type itself may be a risk factor worth investigating further. The discovery opens a door: if blood group influences severity through this enzyme, then targeting the enzyme's effects might offer a new angle for intervention.

Alish Palmos, one of the study's lead authors, described the work as a first step toward identifying drug targets. The researchers were careful to use a genetic approach that could establish causation rather than mere correlation, avoiding the confounding effects of environment or lifestyle. By grouping people according to their genetic propensity for different blood protein levels, they could trace a clearer line from protein to disease outcome. Vincent Millischer, from Vienna, emphasized that this method allows researchers to understand the underlying mechanisms at play—knowledge essential for developing or repurposing existing drugs.

The analysis revealed another layer of complexity: the proteins linked to hospitalization differed somewhat from those linked to respiratory support or death, suggesting that different biological mechanisms may govern these two stages of severe disease. Three adhesion molecules—proteins that mediate interaction between immune cells and blood vessel walls—emerged as protective factors. This finding supports a growing body of research suggesting that late-stage COVID-19 involves damage to the blood vessel lining itself, not just the lungs.

Christopher Hubel, another researcher on the team, noted that the ABO enzyme's connection to both hospitalization and respiratory support needs represents a concrete target for future work. Rather than treating COVID-19 as a single disease with a single mechanism, the research suggests multiple biological pathways are at work, each potentially amenable to different interventions. The fourteen proteins identified in this study now represent possible candidates for drug development—molecules that, if modulated correctly, might prevent the cascade toward severe illness. For patients and clinicians, the implications are significant: a clearer understanding of why blood type matters could eventually translate into more precise, protein-targeted therapies that reduce hospitalization and death.