- An international group of geneticists has compared DNA of patients hospitalized for severe COVID-19 infection with that of healthy volunteers and found six gene clusters that may provide insight into the wide range of responses to the virus.
- Results showed that patients with Type A blood appeared to have a greater susceptibility for severe infection, while those with Type O blood may have some protection.
- The study lent credibility to an earlier study out of China that showed the same possible effect for individuals with differing blood types, and scientists are calling for further study to clarify and confirm the potential impact of biodiversity on response to infection.
A number of characteristics have been associated with a greater chance of developing a more serious symptomatic infection with COVID-19, among them older age, male gender and co-morbidity with diabetes, heart and lung disease or other serious underlying conditions.1 Now, researchers have drawn a potential link to blood type, suggesting that having Type O blood may provide some protection, while those with Type A blood may face a worse outcome.2
A collaborative group of international researchers from Germany, Italy, Norway, and Spain set out to determine whether genetic factors might help explain why COVID-19 infections elicit such a dramatic variation in responses among different people, ranging from mild or asymptomatic infection to life-threatening, multi-organ failure and death. They recruited 1,980 hospitalized patients with varying degrees of respiratory failure and confirmed COVID-19 infection from hospitals in pandemic epicenters of Italy and Spain. An additional 2,381 control subjects included randomly selected blood donors, healthy volunteers and outpatients in Italy and healthy blood donors in Spain. Following quality control exclusions, the final genotyped cohort included 835 patients and 1,255 control participants from Italy and 775 patients and 950 control participants from Spain.3
Genome Analysis Searches for Answers to Variations in COVID-19 Severity
The data were analyzed in a “genome-wide association study,” which involves sorting the genetic map to see if there are DNA variations common to the sickest patients.4 Analysis of the data indicated that variations in six genetic locations might reflect both an individual’s susceptibility to SARS-CoV-2 (the virus that causes COVID-19) and the risk of developing a more severe case, although the authors stressed that further study is needed.
One of the genetic clusters identified contains the gene that controls for a person’s blood type, and the study analysis suggested that blood type might in fact play a role. In reporting the results of this study, the authors write, ”In the meta-analysis corrected for age and sex, we found a higher risk among persons with blood group A than among patients with other blood groups (odds ratio, 1.45; 95 percent CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect for blood group O as compared with the other blood groups (odds ratio, 0.65; 95 percent CI, 0.53 to 0.79; P=1.06×10−5).”5
The locus that houses the gene for determination of blood type also contains DNA coding involved in triggering strong immune responses such as the cytokine storms associated with severe COVID-19 complications and death.6
Earlier Study Showed Similar Results About COVID-19 Links to Blood Type
This result appears to confirm an earlier report out of Shenzhen, China, that reached the same conclusion but was greeted with some skepticism at the time. That study compared the blood group distribution of 2,173 patients hospitalized with COVID-19 to that of 3,694 individuals in the general population. Preliminary results revealed a significantly higher proportion of hospitalized patients had blood type A compared to the general population (38 percent vs 31 percent, respectively). Conversely, the proportion of hospitalized patients with blood Type O was significantly lower than was found in the general population (25 percent vs 34 percent).
The authors concluded, ““People with blood group A have a significantly higher risk for acquiring COVID-19, compared with non-A blood groups, whereas blood group O has a significantly lower risk for the infection, compared with non-O blood groups.”7 Of note, the patient population in that study was limited to patients hospitalized with serious COVID-19 infection, so conclusions don’t reflect overall risk for infection.
Conceding that the results of the Chinese study were preliminary and had not been peer reviewed, Dr. William A. Petri, Jr. of the University of Virginia said, “It is biologically plausible that different blood groups might vary in their susceptibility to COVID-19.” Explaining how that could be, he said it has to do with the way proteins on the surface of the virus bind to the different sugars on surface cells, and those sugars are different for different blood types.
People with Type A blood have an extra sugar on the surface of the cells that is not present in Type O blood.
Blood Type Has Been Associated with Infectious Disease Susceptibility in Earlier Studies
The idea that blood type could have an impact on susceptibility or severity of an infectious disease is not without precedent. According to Dr. David Valle, director of the Institute of Genetic Medicine at Johns Hopkins University, blood type has been associated with susceptibility to other infectious diseases such as cholera, recurrent urinary tract infections from E. coli, and H. pylori, which can cause ulcers and stomach cancers.8 The phenomenon also has been observed in response to such infections as Norwalk virus, hepatitis B and severe acute respiratory syndrome (SARS).9
Blood type is determined by the antibody-producing antigens residing on the surface of the blood cells. In the case of SARS, it has been suggested that anti-A antibodies (found in the plasma of Type O but not in Type A blood10) may inhibit the virus, a mechanism that theoretically could be important in SARS-CoV-2 as well.11
Diversity and Influence of Human Blood Types is a New Science
It has only been a just over 100 years since trial and error with blood transfusions began to give way to understanding that human blood is not all the same. The science of blood typing is still relatively young: the Rh factor was only identified in 1939.12
Given the relatively small size of the study and other possible explanations for the results, researchers say it is still too soon to establish that blood type per se is directly responsible for differences in susceptibility. Their hope is that these type of studies provide more information about how biodiversity might affect different responses to infectious diseases and how to manage patient risk and design therapies to treat COVID-19.13
1 Caizheng Y, et al. Clinical Characteristics, Associated Factors, and Predicting COVID-19 Mortality Risk: A Retrospective Study in Wuhan, China. American Journal of Preventive Medicine May 27, 2020.
2 Ellinghaus D. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. New England Journal of Medicine June 17, 2020.
4 Fox M. European Study Links Genes, Blood Type With Risk Of Severe Coronavirus Infection. CNN June 18, 2020.
5 See Footnote 2.
6 Smith C. Study Says Blood Type May Determine The Severity Of Coronavirus Cases. BGR June 7, 2020.
7 Cohut M. Is Blood Type Linked To COVID-19 Risk? Medical News Today Mar. 20, 2020.
8 Marchione M. Study Ties Blood Type To COVID-19 Risk; O May Help, A Hurt. ABC News June 18, 2020.
9 Gonzales M. COVID-19 Study In China: Blood Type O Are More Resistant, Type A Are More Susceptible To Infection. MSN Mar. 18, 2020.
10 Estes C. What The Relationship Between Blood Type And Coronavirus Susceptibility Means For Future Treatments. Forbes Mar. 20, 2020.
11 Why COVID-19 Kills Some People And Spares Others. Here’s What Scientists Are Finding. Live Science May 5, 2020.
12 Raines K. Blood Transfusion Trial and Errors Through the Ages. The Vaccine Reaction Sept. 13, 2017.
13 See Footnote 10.