Type O and Rh-Negative Blood Type Protective Against COVID-19

Close up photo of female scientist holding a laboratory pipette and a blood sample tube for covid-19 in laboratory. She is wearing a protective suit, laboratory glasses, surgical mask and surgical gloves. Selective focus on tube. Shot with a full frame mirrorless camera.
Investigators determined whether ABO and Rh blood groups were associated with risk for SARS-CoV-2 infection and severe COVID-19 illness.

Patients with type O and rhesus negative (Rh-) blood groups may have a lower risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) illness, according to a study published in the Annals of Internal Medicine.

Investigators conducted a population-based, retrospective cohort study of 225,556 patients who had their ABO blood group assessed between January 2007 and December 2019, and subsequently tested for SARS-CoV-2 between January 15 and June 30, 2020. The mean age was 53.8 years and 29% were men. Common comorbidities included preexisting cardiac disease (13-15%), chronic kidney disease (11%), anemia (21%), cancer (27-29%), dementia or frailty (33-38%), diabetes mellitus (21%), asthma (18-21%), and chronic hypertension (39-41%).

The study’s primary outcome was SARS-CoV-2 infection. The secondary outcome was severe COVID-19 illness or death. Adjusted relative risks (aRRs) and absolute risk differences (ARDs) were adjusted for demographic characteristics and comorbidities. For the primary outcome, analyses were further stratified by patients aged younger than 70 years vs 70 years or older.

The O- blood group had a 2.1% chance of getting SARS-CoV-2 infection (95% CI, 1.8-2.3%), the lowest unadjusted probability of all blood groups. The aRR for SARS-CoV-2 infection in the O blood group was 0.88 (95% CI, 0.84-0.92) vs all other blood groups, and the ARD was -3.9 per 1,000 (95% CI, -5.4 to -2.5). Comparatively, the highest unadjusted probability of SARS-CoV-2 infection was in the B+ blood group (4.2%; 95% CI, 4.0-4.5%). Results also indicated the aRR for SARS-CoV-2 infection was higher in patients with AB blood type compared with type A.

Rh- status seemed protective against SARS-CoV-2 infection with an aRR of 0.79 (95% CI, 0.73-0.85) and an ARD of -6.8 per 1,000 (95% CI, -8.9 to -4.7). The O- blood group also seemed protective, with an aRR of 0.74 (95% CI, 0.66-0.83) and an ARD of -8.2 per 1,000 (95% CI, -10.8 to -5.3). The relative protective effects of O, Rh-, and O- blood groups were greatest in patients younger than age 70.

Secondary outcome results indicated that type O blood group had an aRR of 0.87 (95% CI, 0.78-0.97) for severe COVID-19 illness and death versus all other blood groups and Rh- status had an aRR of 0.82 (95% CI, 0.68–0.96) compared to Rh+ status. The O- blood group did not appear protective against severe COVID-19 illness and death (aRR, 0.84; 95% CI, 0.64-1.07) compared with other blood groups.

“Studies of the accuracy of serologic tests for anti-SARS-CoV-2 immunoglobulins may assess whether there is variation in antibody titers by ABO and Rh status,” the authors noted. “Furthermore, among ongoing clinical trials of immunotherapy using convalescent plasma or of SARS-CoV-2 vaccines, the interaction between participant blood groups and therapeutic efficacy could be measured.”

Investigators also suggested further research on how ABO status may moderate venous thromboembolism occurrence, a known complication of COVID-19, since blood group O patients have been associated with a decreased risk of venous thromboembolism in prior research.


Ray JG, Schull MJ, Vermuelen MJ, Park A. Association between ABO and Rh blood groups and SARS-CoV-2 infection or severe COVID-19 illness. Ann Intern Med. Published online November 24, 2020. doi:10.7326/M20-4511