ABSTRACT
Background and objectives: Coronavirus disease 2019 (COVID-19) is a pandemic caused by SARS-CoV-2 virus that has taken a toll on people all over the world. Previous studies have demonstration association of ABO blood groups with increased susceptibility to various conditions such as infection with Helicobacter pylori, Hepatitis B virus and Norwalk virus and even SARS-CoV-1. In this cross-sectional study, we investigated the association between ABO blood groups and COVID-19 in a tertiary care hospital in western Uttar Pradesh, India.
Methods: The study included data from 500 SARS-CoV-2-positive patients who were referred to the hospital. Diagnosis of COVID-19 was made using RT-PCR. Data including demographic information, comorbidities, ABO blood group, Rh factor, clinical severity as well as the need for assisted ventilation, ICU admission and plasma therapy were collected from patients’ medical records.  The Pearson’s correlation, chi square and Fischer exact tests were used to analyze data at significance of 0.05.
Results:  Frequency of COVID-19 was highest in blood group B (34.8%) and lowest in blood group AB (11.2%). Furthermore, patients with blood group A had significantly more severe form of COVID-19 when compared to patients with other blood groups. The frequency of ICU admission, assisted ventilation and plasma therapy was significantly higher in patients with blood group A than in patients with other blood groups.
Conclusion: Our results suggest that patients with blood group A are at higher risk of developing severe COVID-19 infection that may require assisted ventilation and ICU admission. Hence, these patients might require more vigilant surveillance and aggressive treatment measures. Further studies are required to validate these findings.
Keywords: ABO blood groups, COVID-19, Disease Susceptibility, SARS-CoV-2
 
INTRODUCTION
It has been a year since the World Health Organization announced coronavirus disease 19 (COVID-19) a worldwide pandemic (1). So far, there have been 221 million confirmed cases and 4.5 million deaths due to COVID-19 as of September 5th 2021 (2). Various institutions across the globe have been successful in production of potent vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, but the RNA virus keeps mutating and is capable of re-infecting individuals (3,4). It has strained the healthcare system and testing resources, making it difficult to identify and prioritize individuals who are at greater risk of infection. Several factors and comorbidities including sex, age, hypertension, diabetes, cardiovascular and respiratory diseases are associated with COVID-19 mortality and morbidity (5,6)
Previous studies have identified the association between ABO blood groups and a number of infections, including Helicobacter pylori (7), Hepatitis B virus (8), Norwalk virus (9), Plasmodium falciparum (10) and Neisseria gonorrhoeae (11). This is due to the ABO gene polymorphisms. It has been also shown that individuals with blood group may be less susceptible to SARS-CoV-1 infection. Given that SARS-CoV-1 and SARS-CoV-2 share the same functional receptor, angiotensin-converting enzyme 2 receptor (ACE2) (13,14), it can be assumed that blood groups may also determine susceptibility to SARS-CoV-2 infection. Recent studies have demonstrated an association between blood groups and COVID-19. It has been found that the prevalence of COVID19 is slightly higher among non-O blood groups (15-19). It has been also reported that the Rh negative phenotype is associated with lower risk of severe COVID-19 (20). In this cross-sectional study, we evaluated association between ABO blood groups and COVID-19.
 
MATERIALS AND METHODS
The study included data from 500 SARS-CoV-2-positive patients who were referred to a tertiary hospital affiliated to the Government Institute of Medical Sciences, Greater Noida, India. Diagnosis of COVID-19 was made using RT-PCR. Data including demographic information, underlying comorbidities, ABO blood type, Rh factor and clinical severity were collected from patients’ medical records (21). Other information including the need for ICU admission, assisted ventilation, plasma therapy and disease outcome were also collected.
Continuous variables were expressed as mean ± standard deviation and categorical variables were expressed in proportions. The collected data were further stratified into groups on the basis of presence or absence of comorbidities. Data analysis was done in SPSS 15 using the Pearson’s correlation, Chi square and Fischer exact tests. All analyses were carried out at significance of 0.05.
 
RESULTS
Most patients were male (70.8%) and in the 21-30 years age range. The mean age of the patients was 41.99 ±15.76 years. Male patients presented with significantly more severe form of COVID-19 compared to females (p<0.004)(Table 1). According to the results, frequency of COVID-19 was highest in blood group B (34.8%) and lowest in blood group AB (11.2%). Furthermore, patients with blood group A had significantly more severe form of COVID-19 when compared to patients with other blood groups (Table 1). The data were further stratified based on the presence of comorbidities. The results showed that patients of type A blood group had a more severe form of COVID-19. 
Table 1. The association of ABO blood groups with clinical severity

 
The frequency of ICU admission, assisted ventilation and plasma therapy was significantly higher in patients with blood type A than in patients with other blood types (Table 2).
Table 2. Frequency of ICU admission, assisted ventilation and plasma therapy in patients with different blood groups

 
 
 
No correlation was found between Rh factor and severity of COVID-19, ICU admission, assisted ventilation and plasma therapy (Table 3). Out of 500 patients, 495 recovered and only five deaths were recorded. The outcome of disease had no significant association with the ABO blood group and Rh factor.
 
 
Table 3. Association of disease severity with the Rh factor

 
Frequency of comorbidities was also studied in relation to ABO blood groups. Based on the results, asthma was significantly more common among patients with blood group AB (Table 4).
 
Table 4. Association of comorbidities with the ABO blood groups

CAD: Coronary artery disease; TB: Tuberculosis; COPD: Chronic obstructive pulmonary disorder.
 
 
DISCUSSION
In this study, we investigated association of COVID-19 incidence and severity with blood groups in 500 patients admitted to a hospital in India. The results showed that male patients outnumbered female patients and had more severe form of the disease. These findings are in line with findings of two previous studies (16, 22). The reason for lower frequency and severity of COVID-19 in females is not clear, but the female sex hormones might be responsible for the altered immune response. It was demonstrated that male mice were more prone to SARS-CoV-1 infection than female mice. Ovariectomized female mice also had increased mortality rates. It was claimed that the estrogen receptor signaling might have protective against SARS-CoV-1 infection (23).
Advanced age is a known risk factor for COVID-19 (5,6), which was also confirmed in our study. Patients with advanced age and comorbidities had more severe symptoms. Besides gender and age, the ABO blood groups may be used as a suitable indicator of COVID-19 risk and severity. In the present study, COVID-19 was significantly more severe in patients with blood group A than in patients with other blood groups. In agreement with our results, in a study conducted by Zhao et al. on 2173 confirmed COVID-19 cases from three hospitals in China, the risk of severe COVID-19 was higher in patients with type A blood than in patients with non-A type blood (15). Similar results were obtained from another study in China (16) and a study in Canada (17). Blood type A was significantly associated with the need for ICU admission, assisted ventilation and plasma therapy, which is consistent with findings of Hoiland et al. (17). However, Zietz et al. reported a lower risk of intubation amongst patients with blood type A and a higher risk among patients with types AB and B compared to those with blood type O (16). Other studies also concluded that the blood type O was associated with decreased risk of COVID-19, which is inconsistent with our findings.
Comorbidities such as diabetes, hypertension and cardiovascular disease are known risk factors for COVID-19, which can alter the clinical presentation of the disease (5,6). We divided the patients into different groups based on the presence of comorbidities. The results showed that type A blood group was associated with more severe COVID-19 presentations even in the absence of comorbidities. This further highlights the association between blood type A and COVID-19 severity. A previous study reported that the presence of anti-A antibodies in patients with non-A blood groups could antagonize the interaction between the virus and ACE2 (12). Given that ACE2 acts as the receptor for both SARS-CoV-1 and SARS-CoV-2 (13,14), it is expected to observe a more severe form of COVID-19 in patients with blood type A. The Rh factor had no association with the clinical presentation of COVID-19, the need for ICU admission and assisted ventilation. Inconsistent with this finding, a study reported that the risk of severe COVID-19 was lower in Rh-negative patients (20). Similarly, Zietz found that Rh-negative patients required less ICU admission.
A limitation of our study was the relatively small sample size. Also, the relationship between asymptomatic COVID-19 patients and ABO blood groups could not be evaluated. It is recommended to conduct future studies with a case-control design and a larger sample size in order to remove any unmeasured confounding factor such as lead time bias.
 
CONCLUSION
Our results indicate that there is a link between the ABO blood groups and COVID-19 susceptibility. Specifically, patients with blood group A are at higher risk of developing severe COVID-19, which may require assisted ventilation and ICU admission. Hence, these patients might require more vigilant surveillance and aggressive treatment measures.
 
ACKNOWLEDGMENTS
None.
 
DECLARATIONS
Funding
The authors received no financial support for the research, authorship and/or publication of this article.
 
Ethics approvals and consent to participate
Ethics approval was taken from the local authorities.
 
Conflicts of interest
The authors declare that there is no conflict of interest.