There was no association with blood type and either susceptibility to COVID-19 infection or disease severity in a large US cohort study.
Among 11,000 patients, blood type A was not associated with increased viral positivity (OR 0.97, 95% CI 0.93-1.01, P=0.11), hospitalisation (OR 0.89, 95% CI 0.80-0.99, P=0.03) or ICU admission (OR 0.84, 95% CI 0.69-1.02, P=0.08) compared to type O, and neither were there associations with worse outcomes among patients type B or AB, reported Dr Jeffrey Anderson, of the University of Utah School of Medicine in Salt Lake City, and colleagues.
There was no association with blood type and either susceptibility to COVID-19 infection or disease severity in a large cohort study, researchers said.
Because each set underwent nine comparisons, significance for individual comparisons was set at P=0.006, meaning none of these associations were significant, they said.
They noted conflicting research about blood types and COVID, with studies around the world finding links between the two – particularly, increased susceptibility in people with type A and/or decreased risk with type O – while others found no links.
"The smaller sample sizes and retrospective, observational nature of many prior studies, in addition to their striking heterogeneity of ABO associations with disease susceptibility and severity, could be due to chance variations, publication bias, differences in genetic background, geography and environment, and viral strains," they wrote.
Anderson's group examined data from Intermountain Healthcare, an integrated system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada. They looked at patients from 3 March to 2 November 2020 who were tested for SARS-CoV-2 and had a recorded blood type, comparing positive versus negative tests, hospitalised versus non-hospitalised patients and ICU versus non-ICU patients.
Of the 107,796 individuals tested for COVID-19, 11,468 patients tested positive.
Patients' mean age was 42, 77% were women, and most were white.
Among those who had COVID-19, hospitalisation and ICU admission was associated with male sex and age. They also found non-white race, defined as African American, American Indian/Alaskan Native, Native Hawaiian, or Pacific Islander was associated with viral positivity (13.9% vs 6.9%, respectively) and hospitalization (23.9% vs 11.3%) versus white race.
While Anderson and colleagues noted their sample was mostly white, with a minority contribution from other ethnicities, they added their results were similar when restricted to white race alone.
"Given the large and prospective nature of our study and its strongly null results, we believe that important associations of SARS-CoV-2 and COVID-19 with ABO groups are unlikely and will not be useful factors associated with disease susceptibility or severity on either an individual or population level for similar environments and ancestries."
Study details
Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population
Jeffrey L Anderson; Heidi T May; Stacey Knight; Tami L Bair; Joseph B Muhlestein; Kirk U Knowlton; Benjamin D Horne
Published in JAMA Network Open on 5 April 2021
Abstract
Introduction
The observed variability in susceptibility to SARS-CoV-2 and severity of the ensuing COVID-19 have raised intense interest in their environmental and genetic risk factors. An early report from China1 suggested that blood group A was associated with increased susceptibility and blood group O was associated with reduced susceptibility to SARS-CoV-2 infection. These reports motivated widespread interest in examining ABO blood groups as potential COVID-19 risk factors. Subsequent studies from Italy and Spain2 reported that blood group A was associated with an increased risk of severe COVID-19 and blood group O was associated with a reduced risk. In contrast, a large Danish study3 implicated disease susceptibility but not severity. However, observations from Boston, Massachussets,4 and New York, New York,5 did not confirm any specific associations between ABO blood group and disease. The controversy raised by these contrasting reports led to this case-control study.
Methods
Our objective in this case-control study was to independently test whether blood type is associated with SARS-CoV-2 susceptibility and COVID-19 severity. The study was approved by the Intermountain Medical Center institutional review board with a waiver of consent because the study represented no more than minimal privacy risk to individuals. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Intermountain Healthcare, a nonprofit, integrated health care system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada, generated a SARS-CoV-2 and COVID-19–specific electronic health records database. We searched this database for individuals who were tested for SARS-CoV-2 between March 3 and November 2, 2020, and had a recorded blood type. For individuals who underwent multiple tests, the first test with a positive result was chosen, otherwise the first test with a negative result was used. We compared positive vs negative test results, hospitalized vs nonhospitalized patients, and intensive care unit (ICU) vs non-ICU patients. Infectivity was determined by SARS-CoV-2–specific polymerase chain reaction testing of nasal swabs or saliva samples. Analysis of variance assessed associations across ABO groups. Odds ratios (ORs) between ABO groups were assessed by logistic regression adjusted for age, sex, and Rh factor. P values were 2-sided, and statistical significance was set at P < .167 for each of the 3 primary comparisons. Statistical significance was set at P = .006 for assessment of ORs because each set underwent 9 comparisons. Data were analyzed from November 20, 2020, to February 26, 2021.
Results
A total of 107 ,796 individuals (mean [SD] age, 42.0 [17.8] years; 82 875 [76.9%] women) who had been tested for SARS-CoV-2 infection were included in the study. Further demographic characteristics of the studied population and ABO blood group associations are shown in Table 1. Among individuals with COVID-19, hospitalization was associated with male sex (1165 men [50.1%] hospitalized vs 1871 men [20.5%] not hospitalized) and age (mean [SD] age among hospitalized patients, 57.0 [18.1] years vs 41.4 [14.9] years among nonhospitalized individuals). Admission to an ICU was also associated with male sex (426 men [61.8%] admitted to ICUs vs 725 men [44.8%] not admitted) and age (mean [SD] age among patients admitted to ICUs, 60.7 [158] years vs 55.4 [18.8] years in patients not admitted). Non-White race, which included African American, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, Asian, and unknown or declined to answer, was associated with viral positivity (1592 individuals [13.9%] with positive results vs 6610 individuals [6.9%] with negative results) and hospitalization (556 patients [23.9%] hospitalized vs 1036 individuals [11.3%] not hospitalized). Blood type was not associated with disease susceptibility or severity, including viral positivity, hospitalization, or ICU admission (Table 1). Compared with type O blood, type A was not associated with increased viral positivity (OR, 0.97 [95% CI, 0.93-1.01]; P = .11), hospitalization (OR, 0.89 [95% CI, 0.80-0.99]; P = .03), or ICU admission (OR, 0.84 [95% CI, 0.69-1.02]; P = .08) (Table 2). Similarly, types B and AB were not associated with worse outcomes than type O. Analyses restricted to White race produced similar results (Table 2).
Discussion
With contrasting reports from China,1 Europe,2,3 Boston,4 New York,5 and elsewhere,6 we embarked on a large, prospective case-control study that included more than 11 000 individuals who were newly infected with SARS-CoV-2, and we found no ABO associations with either disease susceptibility or severity. The smaller sample sizes and retrospective, observational nature of many prior studies, in addition to their striking heterogeneity of ABO associations with disease susceptibility and severity, could be due to chance variations, publication bias, differences in genetic background, geography and environment, and viral strains. The ABO gene is highly polymorphic, and ABO blood groups are distributed differently across ancestries and geographies. Differing disease susceptibilities could be due to natural antibodies or prothrombotic effects with nongroup O.6 The Utah population is dominated by Northern European ancestry, with a minority contribution of Hispanic/Latinx and other ethnicities. However, our results are similar among individuals of White race alone.
Given the large and prospective nature of our study and its strongly null results, we believe that important associations of SARS-CoV-2 and COVID-19 with ABO groups are unlikely and will not be useful factors associated with disease susceptibility or severity on either an individual or population level for similar environments and ancestries. Additional studies, closely controlled for genetics, geography, and viral strain, are required before accepting blood group as a determinant of predisposition to or severity of COVID-19.
JAMA Network Open study (Open access)
See also MedicalBrief archives:
Blood type link to COVID-19 susceptibility and severity — Danish & Canadian studies