key: cord-1021809-1a5ajw7b
authors: Nauffal, Victor; Achanta, Aditya; Goldhaber, Samuel Z.; Piazza, Gregory
title: Association of ABO blood group type with cardiovascular events in COVID-19
date: 2021-01-15
journal: J Thromb Thrombolysis
DOI: 10.1007/s11239-020-02364-5
sha: b849d03a63b46396670ce3ae265b7fd18ff5a470
doc_id: 1021809
cord_uid: 1a5ajw7b

Cardiovascular complications have been reported in patients with COVID-19. We sought to examine the association of ABO blood group type with cardiovascular complications in COVID-19. We examined 409 individuals enrolled in the COVID-19 Registry to Assess Frequency, Management, and Outcomes of Arterial and Venous Thromboembolic Complications (CORONA-VTE) who had ABO blood group data available. Multiple logistic regression was used to assess the association of ABO blood group types with three primary outcomes: major adverse cardiovascular events (MACE), major arterial and venous thrombosis and all-cause mortality. 201, 121, 61 and 26 individuals had blood group O, A, B and AB, respectively. In multivariable analysis, blood group A was associated with a 2.5-fold higher odds of MACE than blood group O (OR 2.47[1.18–5.18]). There was an effect suggesting a 2-fold higher odds of major thrombotic events in blood group A vs. O that did not reach statistical significance (OR 2.15 [0.89–5.20]). No association between blood group type and all-cause mortality was found. Compared with the other blood group types, blood group A was associated with an increased odds of MACE(OR(A/non−A) 2.18[1.11–4.29]), while blood group O was associated with lower odds of MACE(OR(O/non−O) 0.50[0.26–0.97]). In conclusion, blood group A was associated with an increased odds of MACE, whereas blood group O was associated with a reduction in the odds of MACE in patients with COVID-19. These findings may inform risk stratification of COVID-19 patients for cardiovascular complications. Additional studies are needed to validate our findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11239-020-02364-5.

Patients with coronavirus disease 2019 (COVID-19) are at risk of cardiovascular complications [1] . There are conflicting reports in the literature on the association of ABO blood group type with both the susceptibility to COVID-19 and the severity of the ensuing illness [2, 3] . We sought to examine the association of blood group type with cardiovascular complications in COVID-19.

We analyzed a retrospective observational cohort study using data abstracted through the electronic health record within the Mass General Brigham health network. From March 13 to April 3, 2020 

In this cohort, 201 (49.1%), 121 (29.6%), 61 (14.9%) and 26 (6.4%) were blood group O, A, B and AB, respectively (Supplemental Material- Table 1 ). Individuals with history of cerebrovascular events, cigarette smokers and non-Hispanic Whites were more prevalent in blood group A vs. O (Supplemental Material- Table 1 ). Hypertension was less common in blood group B vs. O (Supplemental Material- Table 1 ). The unadjusted incidence proportion of 30-day MACE, major arterial and venous thrombotic events and all-cause mortality was highest for blood groups A and AB and lowest for blood groups O and B (Fig. 1a) . In multivariable analysis, blood group A was associated with a 2.5fold higher odds of MACE than blood group O (OR 2.47, [1.18-5.18 ]; p-value = 0.02). There was an effect suggesting a twofold higher odds of major thrombotic events in blood group A vs. O that did not reach statistical significance (OR 2.15, [0.89-5.20]; p-value = 0.09). There was no association between blood group type and all-cause mortality (Fig. 1b) . Table 2 ). Fig. 1 a 30-day unadjusted incidence proportions of major adverse cardiovascular events, major thrombotic events and all-cause mortality per ABO blood group type (N represents absolute number of events). b Forest plot of multivariable association of ABO blood group type with thirty-day major adverse cardiovascular events, major thrombotic events and all-cause mortality. The multivariable model is adjusted for age, race, sex, cigarette smoking status, body mass index, rhesus antigen status, established atherosclerotic cardiovascular disease, heart failure, atrial fibrillation, chronic therapeutic anticoagulation, chronic antiplatelet therapy and statin therapy

We found that blood group A is associated with an increased odds of MACE, whereas blood group O was associated with a reduction in the odds of MACE in patients with COVID-19. A recent genome wide association study found the ABO locus to be associated with respiratory failure in COVID-19 [2] . Furthermore, the authors found blood group A to be associated with increased risk of respiratory failure while blood group O was protective [2] . Our study expands these findings and suggests an association between blood group type and cardiovascular complications in COVID-19. The biological mechanism behind the role of ABO blood groups in COVID-19 remains elusive. Natural anti-glycan ABO antibodies have been shown to inhibit SARS-CoV1 spike protein-angiotensin converting enzyme 2 mediated cellular entry [4, 5] . Furthermore, non-O blood groups have been shown to be associated with increased arterial and venous thrombotic events possibly mediated by increased levels of von Willebrand factor and factor VIII in non-O blood groups [6] .

This study has several limitations. Blood group type was available in a subset of patients who overall had more comorbidities (Supplemental Material- Table 3 ). Thus, we cannot exclude selection bias. Additionally, our sample size was relatively small, which limited the ability to examine the individual components of the composite outcomes and the effect of Rhesus antigen status on outcomes. Our findings suggest an association between ABO blood group types and cardiovascular complications in COVID-19, but no causal relationship should be assumed. Larger studies with longer follow-up are needed to validate our findings.

Funding This study was funded, in part, by a research grant from Janssen.

Code availability Available on request.

Conflict of interest Dr. Piazza hasreceived research grant support from EKOS, a BTG International Group company,Bayer, the Bristol Myers Squibb/Pfizer Alliance, Portola, and Janssen andconsulting fees from Amgen, Pfizer, Boston Scientific Corporation, Agile, andThrombolex. Dr. Goldhaber has received research support from Boehring-erIngelheim, Boston Scientific EKOS Division, BMS/Pfizer, Portola, and Janssen,and the NHLBI. He has receivedconsulting fees from Boehringer Ingelheim, Bayer, and Agile. Dr. Nauffal andMr. Achanta have no conflicts to disclose.

Ethical approval Approved by the Institutional Review Board of Mass GeneralBrigham.

Registry of arterial and venous thromboembolic complications in patients with COVID-19

Genomewide association study of severe Covid-19 with respiratory failure

Blood type and outcomes in patients with COVID-19

Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2

Inhibition of the interaction between the SARS-CoV spike protein and its cellular receptor by anti-histo-blood group antibodies

ABO blood group and risk of thromboembolic and arterial disease: a study of 1.5 Million blood donors