COVID and Blood Type: Does Group Matter?

Researchers have explored many factors influencing COVID-19 susceptibility and severity, including preexisting conditions, age, and genetics. One area of study is whether blood type affects infection risk or severe outcomes.

Some studies suggest certain blood groups may be linked to a slightly higher or lower likelihood of contracting the virus or developing severe symptoms, but the exact mechanisms remain under investigation.

ABO Group Variation

Blood type has been a focus of COVID-19 research, with multiple studies examining whether certain ABO groups influence susceptibility or severity. Early in the pandemic, observational studies suggested individuals with type A blood had a higher likelihood of contracting SARS-CoV-2, while those with type O had a lower risk. A 2020 study in The New England Journal of Medicine analyzed genetic data from COVID-19 patients in Italy and Spain, finding that individuals with type A blood had a 45% higher risk of severe symptoms, while those with type O had a 35% lower risk.

A 2021 meta-analysis in Transfusion Medicine Reviews examined data from multiple countries and found a consistent trend of reduced infection rates among type O individuals. One hypothesis is that natural anti-A and anti-B antibodies in type O blood may interfere with viral adhesion, reducing infection efficiency. Conversely, type A individuals lack anti-A antibodies, potentially allowing for easier viral binding. However, these associations do not imply absolute protection or susceptibility, as many other factors influence disease progression.

Geographic and demographic variations further complicate the relationship between blood type and COVID-19 outcomes. Early studies in China and Denmark reported a higher prevalence of blood type A among hospitalized patients, while research from the U.S. and Brazil yielded mixed results. Differences in study design, sample sizes, and population genetics make direct comparisons challenging.

Rhesus Factor And Infection

Beyond ABO blood groups, the Rhesus (Rh) factor has also been examined for its potential role in COVID-19 susceptibility and severity. The Rh factor, determined by the presence or absence of the RhD antigen, classifies individuals as Rh-positive or Rh-negative.

A 2021 study in Annals of Hematology suggested Rh-negative individuals might have a slightly lower likelihood of testing positive for SARS-CoV-2. This analysis of hospital records from multiple countries found that Rh-negative patients were underrepresented among COVID-19 cases. However, the effect size was small, and confounding factors like genetic variability and healthcare access could not be ruled out.

Subsequent research has sought to clarify this trend. A study in Turkey, published in Transfusion and Apheresis Science, examined over 2,000 COVID-19 patients and found no significant difference in infection rates based on Rh status. Similarly, a meta-analysis from North America and Europe found only minimal variation in disease susceptibility. While some datasets hinted at a marginal protective effect for Rh-negative individuals, the results were inconsistent across regions, suggesting any association is weak and influenced by additional factors.

Potential mechanisms behind a connection between Rh factor and COVID-19 remain speculative. Some researchers propose that structural differences in red blood cell membranes could affect viral attachment or circulation dynamics. Others suggest Rh-negative individuals might have a slightly different inflammatory response due to genetic variations linked to the RhD gene locus. However, no definitive molecular pathways have been identified.

Possible Mechanisms In Viral Entry

Blood type may influence COVID-19 susceptibility through interactions between SARS-CoV-2 and host cells. ABO antigens, present on red blood cells and epithelial cells, could affect viral adhesion. Since SARS-CoV-2 enters cells through the ACE2 receptor, differences in ABO expression might alter infection efficiency.

Another factor is the presence of naturally occurring anti-A and anti-B antibodies in type O and B individuals. A 2021 study in Blood Advances showed that plasma from type O individuals was more effective at blocking SARS-CoV-2 binding to ACE2-expressing cells in vitro compared to type A plasma. This suggests preexisting antibodies might partially inhibit infection, though real-world protection remains uncertain.

Glycosylation patterns on the viral spike protein may also affect susceptibility. The spike protein, which facilitates viral entry, can be modified by host-derived glycan structures, potentially influencing its interaction with different ABO blood groups. Some researchers hypothesize these modifications could enhance or weaken viral binding affinity, though experimental validation is needed.

Genetic Factors In Host Susceptibility

Genetic factors beyond blood type also influence COVID-19 susceptibility. Large-scale genomic studies have identified markers linked to increased risk, particularly in regions associated with immune regulation, inflammation, and viral entry pathways.

One significant finding is a genetic segment on chromosome 3 associated with severe respiratory failure. A 2020 genome-wide association study (GWAS) in Nature found that individuals carrying this risk haplotype were up to twice as likely to require hospitalization. This variant, inherited from Neanderthals, is more common in people of European and South Asian descent.

Variations in genes coding for viral entry proteins have also been implicated. Differences in the ACE2 receptor gene may affect how efficiently SARS-CoV-2 binds and replicates. Some ACE2 variants could lead to structural changes in the receptor, influencing susceptibility. Similarly, polymorphisms in the TMPRSS2 gene, which encodes a protease that primes the viral spike protein for cell entry, may contribute to disease severity.

Observations From Large Populations

Epidemiological studies have analyzed data from diverse populations to determine whether blood type correlates with infection rates, hospitalization risk, or mortality. While some trends have emerged, results vary significantly across studies.

A large-scale study by 23andMe analyzed data from over 750,000 participants and found that individuals with type O blood were about 10-15% less likely to contract SARS-CoV-2. A study in PLOS Genetics observed similar trends, suggesting a modest protective effect for type O blood. However, the overall impact of blood type was small compared to factors like age, comorbidities, and viral variants.

Regional differences complicate conclusions. Studies in China and Europe reported a higher prevalence of type A blood among severe COVID-19 cases, while research from the U.S. and South America yielded mixed results. A study by the New York-Presbyterian Hospital system found no significant association between blood type and hospitalization rates. These discrepancies highlight the complexity of genetic and environmental interactions in disease susceptibility.

Laboratory Insights On Immunological Responses

Laboratory studies have explored how blood type might influence immune responses to SARS-CoV-2, focusing on ABO antigens and preexisting antibodies.

One hypothesis is that individuals with type O blood, who naturally produce anti-A and anti-B antibodies, may mount a more rapid immune response. In contrast, individuals with type A blood, who lack anti-A antibodies, may have a delayed initial reaction, allowing the virus to establish a stronger foothold. Experimental studies using blood plasma have shown that type O plasma exhibits higher neutralization potential against SARS-CoV-2 in vitro, though real-world implications remain uncertain.

Another area of interest is complement activation, a key component of the immune response. Some studies suggest ABO-related glycosylation patterns may influence complement activity, affecting how efficiently the body responds to SARS-CoV-2. Research has also examined whether ABO blood group differences contribute to variations in inflammatory markers like cytokine levels, which play a role in severe COVID-19 cases. While these findings are intriguing, more research is needed to determine their clinical significance.