ABO Blood Groups are not Associated With COVID-19 Disease Incidence and Severity When Correcting for Ethnicity Differences in Blood Type

Bryce E. Pasko, MD; Diana Abbott, PhD; Gregary T. Bocsi, DO; Nicole L. Draper, MD

Disclosures

Am J Clin Pathol. 2022;158(2):249-253. 

In This Article

Abstract and Introduction

Abstract

Objectives: To determine if blood type is a risk factor for coronavirus disease 2019 (COVID-19) disease incidence and severity after correcting for ethnicity differences between novel infections and known ABO blood type frequency differences.

Methods: We performed a retrospective analysis on all severe acute respiratory system coronavirus 2 (SARS-CoV-2) infections and disease severity across two major testing sites in Colorado. We evaluated all individuals with a SARS-CoV-2 nucleic acid test (NAT) and a known blood type between March 1, 2020, and June 1, 2020. We then created a prediction algorithm based on the corrected blood types by ethnicity using data from the Colorado Department of Health and established blood types by ethnicity. We applied this prediction algorithm to all patients in our sample.

Results: Of 8,676 patients, 485 (5.6%) had a positive SARS-CoV-2 NAT test and 8,191 (94.4%) had a negative test. All patients had ABO blood types that mirrored the expected blood type distribution within the state of Colorado (P = .15, χ2 statistic = 5.31). No differences in expected blood groups were present between ethnicity-adjusted SARS-CoV-2–negative and SARS-CoV-2–positive patients (χ2 = 3.416313, P = .332).

Conclusions: Blood type is not associated with COVID-19 disease incidence or severity after correcting for ethnicity differences in expected blood type frequencies.

Introduction

The severe acute respiratory system coronavirus 2 (SARS-CoV-2) is responsible for the 2019 coronavirus disease (COVID-19) causing a worldwide pandemic, leading to staggering numbers of life lost and morbidity around the globe.[1] Thus, it is imperative to understand key risk factors associated with disease contraction and progression. Several risk factors have been associated with COVID-19 disease severity, such as age, diabetes, cardiovascular disease, and pulmonary disease. Other reported risk factors are less well understood but could play a major role in COVID-19 severity, such as blood type.[2–9]

Studies both before and after peer review have demonstrated that individuals with group A blood type are at a higher risk for contracting SARS-CoV-2 and for disease progression requiring hospital admission, intensive care unit (ICU) stays, and ultimately death, whereas people with group O blood type are relatively protected from SARS-CoV-2 infection and sequela.[2–4,6] Multiple theories attempt to explain why individuals with differing ABO blood groups could have different disease courses and disease severity with COVID-19. It is important to highlight that none of these prior studies have examined the relationship of blood type when accounting for ethnicity and known differences in blood types based on ethnicity.

The most popular theory for an ABO association with COVID-19 relies on the angiotensin-converting enzyme 2 receptor, the proposed mechanism of cellular entry by SARS-CoV-2, being more prominent in individuals with group A blood type than those with group O blood type.[6] This would imply that individuals with group A blood type would have a higher number of binding sites for SARS-CoV-2 attachment and cellular entry than group O individuals. However, conflicting data show no association with blood type and COVID-19 disease severity.[5]

Disease associations with blood type are not a new phenomenon and have been associated with increased risks of numerous diseases and infections with organisms based on cellular biochemistry and antigen-binding sites; for instance, blood groups A and B confer higher risk for contracting Plasmodium falciparum, or Helicobacter pylori infections have a strong association with blood group O.[10] So, biologic plausibility exists. However, one major concern for our group when examining the data from prior studies is the lack of ethnicity correlation with expected blood types as a possible confounding variable. This was addressed briefly by Latz et al,[5] who encouraged additional ethnicity specific analysis.

Ethnicity is a very important consideration when studying biologic markers of SARS-CoV-2 infection and disease severity for two reasons: (1) there are disproportionate numbers of Latinos and Blacks who are infected with SARS-CoV-2 compared with Whites,[11] and (2) expected blood type prevalence is different across different ethnic groups, which can bias the data used for analysis if the researchers are not controlling for ethnicity blood group variables. None of the other studies account for these differences in blood type across different ethnicities Table 1. Therefore, given the implications of the associations with ABO blood groups and COVID-19 disease incidence and severity, we sought to examine whether these associations would still be present after controlling for ethnicity differences in ABO blood type.

We set out to accomplish this by using the data from major COVID-19 testing centers in Colorado, the University of Colorado Hospital and Children's Hospital Colorado. We selected a time period with high state reporting of demographics data and prior to the COVID-19 vaccinations and vaccine studies. We analyzed COVID-19 data, expected distributions of blood type by ethnicity, and ethnicity and SARS-CoV-2 infection data from the Colorado Department of Health.

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