How our cellular identity shapes our response to viral invaders
When COVID-19 swept across the globe, it left behind a trail of puzzling questions. Why did some healthy individuals succumb to severe illness while others experienced barely a sniffle? Why did some families experience devastating losses while others emerged relatively unscathed? As scientists raced to understand the virus's behavior, one unexpected factor emerged from the data: our blood type might be playing a crucial role in this biological drama.
The connection between blood groups and disease susceptibility isn't entirely new to medicine. Before COVID-19, researchers had noted links between ABO blood types and vulnerability to various pathogens, including norovirus and cholera.
The coronavirus pandemic brought this relationship into sharp focus, triggering a scientific investigation that would span continents and involve hundreds of thousands of patients. What researchers discovered reveals fascinating insights about the hidden defenses within our bodies and how the most microscopic details of our biology can determine our response to a global threat.
To understand the connection between blood types and COVID-19, we first need to understand what makes our blood types different. The ABO blood group system, discovered by Karl Landsteiner in 1901, classifies our blood based on the presence or absence of specific sugar molecules called antigens on the surface of red blood cells and other cells throughout our body.
Has A antigens
Produces anti-B antibodies
Has B antigens
Produces anti-A antibodies
Has both A and B antigens
Produces neither antibody
Has neither antigen
Produces both anti-A and anti-B antibodies
These antigens aren't just limited to our blood cells—they're expressed throughout our bodies, including in the respiratory and digestive tracts, precisely where pathogens like SARS-CoV-2 enter our systems.
These biological differences create unique landscapes that viruses must navigate to establish infection. As one researcher noted, "Blood groups are receptors for toxins and microorganisms, where they can facilitate colonization, adherence, transduction, and cellular uptake of microorganisms" 9 .
Early in the pandemic, patterns began emerging from the data. Multiple studies suggested that people with blood type O might have some protection against SARS-CoV-2 infection, while those with type A appeared more vulnerable. A meta-analysis of 31,100 patients found that blood group A patients were at higher risk of COVID infection, while those with blood group O were at lower risk of both disease and severe outcomes 9 . Another study suggested that patients with blood type A or AB appeared to show greater disease severity than patients with blood group O or B 1 .
| Study Reference | Sample Size | Key Finding | Limitations |
|---|---|---|---|
| Stowell et al. (2023) 2 | Laboratory study | SARS-CoV-2 preferentially infects blood group A cells | Laboratory setting may not reflect real-world complexity |
| Michigan Health System (2024) 3 | 9,416 patients | No association between blood type and severe outcomes across variants | Retrospective design |
| Ethiopian Hospital (2025) 1 | 570 patients | No relationship between ABO type and COVID-19 severity/mortality | Single-center study |
| Saudi Arabia Study (2024) 7 | 2,302 patients | No significant correlation with susceptibility or mortality | Cross-sectional design |
But the research picture wasn't entirely clear. Different studies yielded conflicting results, with some finding no significant association at all. A 2024 study of 9,416 COVID-19 encounters found no statistically significant difference in severe outcomes between blood types during the Alpha, Delta, and Omicron waves 3 . Similarly, a 2025 study from Ethiopia concluded: "We found no relationship between ABO blood group differences and COVID-19 severity, and mortality" 1 .
This scientific disagreement highlighted the complexity of the relationship and suggested that blood type might be just one piece in a much larger puzzle of COVID-19 risk factors.
Interactive chart would display here showing relative risk percentages for each blood type
For years, the blood type-COVID connection remained statistical—researchers could see patterns in the data but didn't understand the biological mechanism. Then, in 2023, a team of researchers from Harvard Medical School and Brigham and Women's Hospital published a breakthrough study in the journal Blood that would change everything 2 .
Led by Dr. Sean R. Stowell, the team designed elegant laboratory experiments to test whether SARS-CoV-2 actually showed preference for different blood types at a cellular level. "Until now, however, no study had identified a 'smoking gun'—a mechanism that might explain this apparent risk imbalance," noted the researchers 2 .
They obtained blood group A and blood group O cells for comparison.
These cells were exposed to the SARS-CoV-2 virus, including both the original strain and the Omicron variant.
They added a protein that inhibited SARS-CoV-2 from recognizing blood group antigens to test if this would reduce infection rates.
As a control, they used a different protein that didn't block the recognition of blood group antigens.
They measured and compared infection rates between the different conditions.
The findings were striking. The researchers discovered that the part of the SARS-CoV-2 spike protein that's key to enabling the virus to invade cells displays a distinct affinity for blood group A cells. Correspondingly, the virus showed a "preferential ability to infect blood group A cells" compared with blood group O cells 2 .
| Experimental Condition | Effect on Blood Group A Cells | Effect on Blood Group O Cells |
|---|---|---|
| Normal viral exposure | Higher infection rate | Lower infection rate |
| With blocking protein | Reduced infection preference | No significant effect |
| With control protein | No reduction in infection | No significant effect |
| Omicron variant exposure | Stronger infection preference | Lower infection rate |
When they added a protein that inhibited the virus from recognizing blood group antigens, it blocked the virus's preference for infecting blood group A cells but had no effect on blood group O cells. The control protein that didn't block antigen recognition had no infection-inhibiting effects on either A or O cells.
Perhaps most intriguingly, the Omicron strain of SARS-CoV-2 demonstrated an even stronger preference for infecting blood group A cells than the original virus 2 .
The relationship between blood types and COVID-19 may extend beyond initial infection to include how our immune systems respond over time. A 2021 study followed recovered COVID-19 patients for up to 10 months after infection and discovered intriguing differences in their immune memory based on blood type 5 .
Researchers found that O-blood group individuals maintained persistent specific immune responses against SARS-CoV-2, while non-O group individuals lost cellular immune responses over time and needed longer to clear the virus 5 . This suggests that blood type O might confer not only initial protection but also more durable immunity.
| Immune Parameter | Blood Group O | Non-O Blood Groups |
|---|---|---|
| Initial infection risk | Potentially lower | Potentially higher |
| Specific CD4+ T-cell response | Sustained against multiple viral proteins | Diminished over time |
| Viral clearance time | Faster | Longer |
| Natural antibody protection | Anti-A and Anti-B antibodies present | Limited to missing natural antibodies |
Another proposed mechanism involves the natural antibodies that come with our blood type. Type O individuals naturally have both anti-A and anti-B antibodies, and research suggests these may provide additional defense. "The association between blood group O and protection from COVID-19 and severe disease is mainly due to the higher titers of the naturally occurring IgG anti-A and anti-B antibodies," noted one review 9 .
A study from Bangladesh further supported this, finding that higher natural anti-A and anti-B antibody titers may offer protection against symptomatic COVID-19 infections 6 .
Understanding the science behind blood types and COVID-19 requires sophisticated tools and methods. Here are some of the key components of the researcher's toolkit that have enabled these discoveries:
(Enzyme-Linked Immunosorbent Assay) - This technique allows researchers to measure and quantify natural anti-carbohydrate antibodies (including anti-A and anti-B) in plasma samples. It was used in the Bangladesh study to demonstrate different antibody titers between symptomatic and asymptomatic patients 6 .
A powerful technology for counting and analyzing cells. It was employed in immune response studies to determine absolute numbers of lymphocytes and T-cell subsets in COVID-19 patients 5 .
(Pep-S, Pep-M, Pep-N) - These are collections of protein fragments derived from different parts of the virus (Spike, Membrane, and Nucleocapsid proteins). Researchers use them to stimulate immune cells and measure the response to specific viral components 5 .
Specialized proteins that can block the virus from recognizing blood group antigens. These were crucial in the 2023 mechanism study to demonstrate the virus's preference for blood group A cells 2 .
While the connection between blood type and COVID-19 reveals fascinating insights into human biology, it's crucial to maintain perspective. As Dr. Stowell emphasized, "Among a group of several thousand people, some studies suggest that those with blood group A may be 20% more likely to be infected after exposure to SARS-CoV-2 compared with those who have blood group O. But people with blood group O can still contract the virus and may transmit it to others" 2 .
He further noted that "factors such as age and chronic conditions like heart disease rank higher than blood type in determining individuals' risk for severe SARS-CoV-2 infection" 2 . Regardless of blood type, vaccination remains our most powerful tool against serious COVID-19 outcomes.
The story of blood types and COVID-19 serves as a powerful reminder of the incredible complexity of human biology and how our unique genetic makeup creates different landscapes for pathogens to navigate. As research continues, this understanding may lead to more personalized approaches to disease prevention and treatment—not just for COVID-19, but for future infectious challenges we have yet to face.
As one comprehensive review aptly stated, "Humans and infectious microorganisms co-evolve, in a constant arms race of genetic and evolutionary wits" . In this ongoing battle, understanding the subtle advantages and vulnerabilities written into our biological blueprint may be key to maintaining the upper hand.