Researchers from the Boston University School of Public Health in the United States say there is no evidence to support a correlation between ABO blood group and the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or the severity of coronavirus disease 2019 (COVID-19).

The team’s systematic review of studies assessing the correlation between the ABO blood group and COVID-19 risk found that the majority are of low quality and subject to major methodologic flaws.

Furthermore, the few higher-quality studies that do exist found no association between ABO blood type and COVID outcomes adds Eleanor Murray and colleagues.

A large proportion of COVID-19 research has focused on trying to identify markers of high-risk individuals, and one suspected risk indicator that has been repeatedly investigated is ABO blood type.

“Given the ease of measuring this biomarker, it is an appealing target for identifying high-risk individuals,” writes Murray and the team.

However, the researchers say they found no evidence to support the use of the ABO blood group as a marker for COVID risk or severity.

The team recommends that clinicians, public health officials, and science communicators advise patients and the general public to adhere to infection control measures, irrespective of their ABO blood group.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

Study: Systematic review of the association between ABO blood type and COVID-19 incidence and mortality. Image Credit: Schira / Shutterstock

The problems with “risk factor epidemiology”

The COVID-19 pandemic has placed an unprecedented burden on healthcare and public health systems globally.

In efforts to improve the response to the pandemic, researchers worldwide have been striving to identify potential biological characteristics that could serve as markers for SARS-CoV-2 infection and the risk and severity of COVID-19.

This so-called “risk factor epidemiology” is appealing since the ability to identify or predict which individuals may become ill, require hospitalization, or die could lead to more targeted public health measures and relieve the burden on overwhelmed systems.

“However, this research often fails to consider basic epidemiologic concepts to prevent bias in the design, selection, and analysis of observational data,” says Murray and colleagues.

Despite this, several high-profile studies have reported a positive association between blood group A and COVID-19 risk and a negative association between blood group O and COVID-19 risk.

This has led to the (incorrect) belief among some members of the public that individuals with blood type O are not at risk of SARS-CoV-2 infection and COVID-19.

“Importantly, several additional studies of ABO blood type and COVID risk have found no association between blood type and risk,” says Murray and colleagues. “This suggests that a deeper look is needed to understand whether a true relationship exists or whether the relationship should be attributed to bias.”

What did the researchers do?

The researchers used PubMed and Google to identify studies published before November 2020 that assessed the correlation between ABO blood group and COVID incidence, hospitalization, and mortality.

After reviewing the titles, extracts, and full text of each article, 24 epidemiologic studies (seven retrospective cohort studies, 13 case-control studies, two ecological studies, and three cross-sectional surveys) were selected for the final analysis.

Each of these studies was assessed using the ROBINS-I (Risk of Bias In Non-randomized Studies – of Interventions) tool to determine the risk of bias level in each article.

Nineteen studies reported a significant association

Overall, 19 (79%) of the 24 studies reported a significant association between at least one ABO blood group and at least one COVID-19 outcome.

Four (17%) studies found no such association, and one generated conflicting city-specific results.

Fifteen (63%) of the 24 studies reported improved outcomes such as no infection, decreased severity, or no death among Type O individuals, while 13 (54%) reported worse outcomes (infection, increased severity, death) among Type A individuals.

Only eight (33%) studies reported both improved outcomes for Type O individuals and worse outcomes for Type A individuals.

Most studies had an overall risk of bias

The researchers found that 12 of the 24 articles had an overall severe risk of bias, while 10 had a moderate overall risk, one a low overall risk and one a low risk of bias for the primary outcome but the moderate risk for all other outcomes.

Furthermore, the two studies with the most negligible bias reported no association between ABO blood type and primary COVID outcomes.

Overall, the researchers identified several common methodologic flaws in the data collection or analytical procedures that could reduce the validity and generalizability of the findings and lead to inaccurate or misleading conclusions.

Murray and colleagues identified seven potential sources of bias that may have generated spurious associations between ABO blood type and COVID risk or severity. These included confounding, selection bias, inappropriate selection of control group, missing data, inappropriate statistical analyses, insufficient sample size, and misclassification.

No evidence to support that COVID-19 risk can be determined by ABO blood group

The researchers say that overall, the review findings suggest that there is no actual relationship between ABO blood type and SARS-CoV-2 infection or COVID-19 severity or mortality.

“The evidence does not support the claim that COVID-19 risk is determined by ABO blood group,” they write.

“We urge clinicians, public health officials, and science communicators to council patients and the general public to take infection control precautions, regardless of their ABO blood group,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.