Susceptibility of ABO blood group to COVID-19 infections: clinico-hematological, radiological, and complications analysis

Abstract In the wake of the COVID-19 pandemic, research indicates that the COVID-19 disease susceptibility varies among individuals depending on their ABO blood groups. Researchers globally commenced investigating potential methods to stratify cases according to prognosis depending on several clinical parameters. Since there is evidence of a link between ABO blood groups and disease susceptibility, it could be argued that there is a link between blood groups and disease manifestation and progression. The current study investigates whether clinical manifestation, laboratory, and imaging findings vary among ABO blood groups of hospitalized confirmed COVID-19 patients. This retrospective cohort study was conducted between March 1, 2020 and March 31, 2021 in King Faisal Specialist Hospital and Research Centre Riyadh and Jeddah, Saudi Arabia. Demographic information, clinical information, laboratory findings, and imaging investigations were extracted from the data warehouse for all confirmed COVID-19 patients. A total of 285 admitted patients were included in the study. Of these, 81 (28.4%) were blood group A, 43 (15.1%) were blood group B, 11 (3.9%) were blood group AB, and 150 (52.6%) were blood group O. This was almost consistent with the distribution of blood groups among the Saudi Arabia community. The majority of the study participants (79.6% [n = 227]) were asymptomatic. The upper respiratory tract infection (P = .014) and shortness of breath showed statistically significant differences between the ABO blood group (P = .009). Moreover, the incidence of the symptoms was highly observed in blood group O followed by A then B except for pharyngeal exudate observed in blood group A. The one-way ANOVA test indicated that among the studied hematological parameters, glucose (P = .004), absolute lymphocyte count (P = .001), and IgA (P = .036) showed statistically significant differences between the means of the ABO blood group. The differences in both X-ray and computed tomography scan findings were statistically nonsignificant among the ABO age group. Only 86 (30.3%) patients were admitted to an intensive care unit, and the majority of them were blood groups O 28.7% (n = 43) and A 37.0% (n = 30). However, the differences in complications’ outcomes were statistically nonsignificant among the ABO age group. ABO blood groups among hospitalized COVID-19 patients are not associated with clinical, hematological, radiological, and complications abnormality.


Introduction
In December 2019, the new coronavirus illness COVID-19, caused by the severe acute respiratory syndrome coronavirus-2, was discovered in Wuhan, China. COVID-19 infection quickly became a worldwide pandemic, impacting nearly all nations and posing a public health threat. [1] There is much evidence that blood antigens have a role in COVID-19 etiology. [2] Blood group antigens are known to affect the innate immune system's responses and allow pathogen absorption and signal transduction. [3][4][5] For instance, the risk of hepatitis B virus infection was considerably lower in those with blood type O, according to Mohammadali et al. [2] Elnady et al observed that rotavirus gastroenteritis was more common in blood type A people and considerably less common in blood type B people. [6] Another research by Degarege et al found that those with blood group A, malaria had a greater risk of anemia than people with non-A phenotypic. [7] Murugananthan et al discovered that individuals with the AB blood group had a 2.5-fold increased chance of having dengue hemorrhagic fever than those with any other blood type. [8] Due to specific underlying biological characteristics, blood type O has been linked to a decreased risk of diseases such as diabetes, atherosclerosis, heart disease, and some infections. [9][10][11][12] It is debatable if these associations lead to clinically worse results in various blood types. A systematic review meta-analysis has recently shown that the COVID-19 infection rate was more likely to be observed in persons with blood group A > O > B > AB; also, the study indicated substantial variation between observation research that showed a correlation between ABO blood group and COVID-19. [13] . Nevertheless, no significant differences were found in several other observational investigations. [14][15][16] Because severe acute respiratory syndrome coronavirus-2 is a novel virus, it is still unknown if ABO blood groups influence an individual's susceptibility or severity of illness. Accordingly, the current study aims at investigating whether clinical manifestation, laboratory evaluation, and imaging findings vary among ABO blood groups of hospitalized confirmed COVID-19 patients; this will add to the growing body of evidence suggesting blood group may play a role in COVID-19.

Study design and study population
The current research is a retrospective cohort analysis of hospitalized confirmed COVID-19 patients in King Faisal Specialist Hospital and Research Centre (KFSH&RC) Riyadh and Jeddah, Saudi Arabia. It included all confirmed COVID-19 patients with complete investigation admitted to the hospital between the March 1, 2020 and the March 31, 2021.

Data collection
Medical records were obtained from the data warehouse for all confirmed COVID-19 patients diagnosed according to the WHO guideline with a positive result for nasal and pharyngeal swab specimens analyzed by real-time reverse transcriptase-polymerase chain reaction assay. Extracted data included demographic information, clinical information, laboratory findings, and imaging investigations. All radiological images were analyzed and diagnosed by three radiologists, each with 3 to 4 years of experience in reporting various chest X-ray and computed tomography (CT) examinations. All hematological and radiologic examinations were conducted at day fourth of infection.

Statistical analysis
The data analysis was made using the Statistical Packages for Social Sciences (SPSS) version 24 (IBM Corp, Armonk, NY). Descriptive statistics of frequency and percentage and mean and standard deviation were performed for categorical and continuous variables, respectively. The chi-square test was used to examine differences in the prevalence of different categorical variables. The one-way ANOVA test was applied to investigate the differences between the ABO blood group means. A Pvalue < .05 was considered statistically significant.

Results
A total of 60,000 patients were admitted to the KFSH&RC and diagnosed with COVID-19 infection between the March 1, 2020 and the March 31, 2021. Altogether 285 patients were included in this study due to the missing clinical information and/or laboratory and imaging investigation. Of these cases, 81 (28.4%) were blood group A, 43 (15.1%) were blood group B, 11 (3.9%) were blood group AB, and 150 (52.6%) were blood group O. Majority of patients (71.2%) were of age group 25-64 years and 104 (36.5%) were of blood group O. Also, 50.9% (n = 145) participants were females, and 49.1% (n = 140) were males. The nationality of the study participants showed statistically significant differences between the ABO blood group at P < .05 as most participants were Saudi (81.1%). Based on body mass index, 38.2% (n = 109) and 33.7% (n = 96) of the study participants were of overweight and obese status, respectively. Only 3.5% (n = 10) of the study participants were pregnant women. Of the study participants, only 8.8% (n = 25) were smokers, and the smoking status of the study participants showed statistically significant differences between the ABO blood group at P < .05. Most of the smokers, 7.0% (n = 20), belong to blood group O (Table 1).
There was a statistically significant difference in the incidence of upper respiratory tract infection (P = .014) and shortness of Kabrah et al. Medicine (2021) 100:52 Medicine breath among participants with different ABO blood groups (P = .009). About 79.6% (n = 227) of the study participants were asymptomatic (as seen in Table 2), and the remaining 20.4% (n = 58) showed varying degrees of symptoms. The clinical symptoms were more likely to be observed in participants with O, A, and B blood groups, respectively, except for pharyngeal exudate that was more likely to be observed in cases with blood group A. Haemoptysis, jaundice, abnormal auscultation of the lung and hepatomegaly were reported only in patients with O blood groups.
The relationship between the results of radiological imaging of patients and their corresponding blood type is shown in Table 4. Although the analysis showed no statistically significant relationship between the blood group of the patient and the radiology outcomes, there were some observational differences. Out of all patients, 29.8% (n = 85) of cases had abnormalities in the radiological chest finding. Of those, 64.7% (n = 55) experienced bilateral lung abnormality. The most common Xray findings among cases were infiltration and consolidation infiltrate. The blood types O and A were determined to have the highest abnormal chest X-ray outcome with a total percentage of O (31.3%) and A (30.9%).
There were no statistically significant relationships after comparing the findings of CT scans among patients with their blood groups, as seen in Table 4. There were abnormal CT chest findings in 8.8% (n = 55) of all cases. About 38.2% (n = 21) of the patients with abnormal chest CT scans had bilateral lung abnormalities. The most common imaging features seen in CT scan findings were fibrosis, bud appearance, and ground-glass opacity. The highest abnormal chest CT scan with a total percentage of O (8.7%) and A (7.4%) suggested a strong correlation between these two blood groups and the severity of COVID-19 infection (Table 4). However, the differences in both X-ray and CT scan findings were statistically nonsignificant among the ABO age group (Table 4). Table 5 indicated that only 86 (30.3%) patients were admitted to an intensive care unit, and most of them were blood groups O (28.7% [n = 43]) and A (37.0% [n = 30]). Additionally, 54.6% (n = 47) of them received mechanical ventilation (MV), and their blood groups were O > A > B > AB. Only one patient (blood group A) received extracorporeal membrane oxygenation due to low oxygen levels. Additionally, results showed that two cases developed coma and their blood groups were B and O. Also, encephalitis and seizure were produced in four patients with blood groups O and A. Death was reported in blood groups O and A. Results presented that most complications were highly reported in group O then A, followed by group B and AB. This indicated that patients with blood group O have more difficulties than other groups; moreover, blood group AB has fewer complications. However, the differences in complications outcomes were statistically nonsignificant among the ABO age group (Table 5).

Discussion
Since Karl Landsteiner discovered the ABO blood type system in 1901, researchers have been looking for a link between the ABO blood group system and numerous illnesses. [17] The relationship between the ABO blood type and various illnesses, including bacterial and viral infections, has been thoroughly investigated. [18][19][20][21] The ABO blood group is now widely associated with various illnesses. [22] Several recent investigations of COVID-19 infection in China and the United States have found a link      between ABO blood types and infection severity and death. These investigations found that people with blood group A are more likely to get COVID-19 infection, whereas those with blood group O are less likely to contract COVID-19 infection. The severity of the illness may also be influenced by blood type. Individuals with blood type A had a lower risk of COVID-19 infection than those with other blood types. [13,23,24] The current findings indicated that blood group O was the most prevalent blood group (52.6%) among the study participants, followed by A (28.4%), B (15.1%), and AB (3.9%). This was almost consistent with the distribution of blood groups among the Saudi Arabia community: blood group O (52%), A (26%), B (18%), and AB (4%). [25] The results also showed that the upper respiratory tract infection and shortness of breath showed statistically significant differences between the ABO blood group (P = .014 and P = .009 retrospectively). Moreover, all symptoms were observed highly in blood group O followed by A then B except for pharyngeal exudate observed in blood group A. In addition, hemoptysis, jaundice, abnormal auscultation of the lung, and hepatomegaly were only reported in O blood groups. According to Wu Y et al 2020 and Komal et al 2021, COVID-19-infected people with blood types O and AB had a different clinical spectrum of signs and symptoms, with participants with the AB blood group having a slightly higher probability of fever and sore throat and a lower chance of losing their sense of taste and smell. [19,26] The study indicated that among the studied hematological parameters, glucose (P = .004), absolute lymphocyte count (P = .001), and IgA (P = .036) showed statistically significant differences between the means of the ABO blood group. The findings of Kazancioglu et al 2020 revealed that eosinophils, lymphocytes, and platelet-to-lymphocyte ratio were the most critical factors in distinguishing COVID-19 patients from healthy controls. [27] Sun et al found fewer eosinophils and lymphocytes, as well as a greater platelet-to-lymphocyte ratio, in COVID-19 patients compared to controls. [28] Results showed that 29.8% (n = 85) and 8.8% (n = 55) of the study participants experienced abnormal chest findings using Xray and CT scans, respectively. The most common results were infiltration and consolidation infiltrate. The blood types O and A were determined to have the highest abnormal chest outcome. In comparison to patients with other blood groups, Mansour et al 2021 discovered a significant association between patients with blood group A and a more severe pneumonic process in their noncontrast high-resolution CT chest with a comparatively higher severity score. [29] Also, the findings indicated that only 86 (30.3%) patients were admitted to an intensive care unit, and the majority of them were blood groups O (28.7%, n = 43) and A (37.0%, n = 30). In the blood group analysis of the intensive care unit (ICU) COVID-19 patients, Yaylacı et al 2020 found that the distribution of patients' blood group was O > B > A > AB (15.6%, 15.1%, 14.8%, 9.5%, respectively). [30] Additionally, it is observed that 54.6% (n = 47) of admitted patients into the ICU received MV, and their blood groups were O > A > B > AB. Only one patient (blood group A) received extracorporeal membrane oxygenation due to low oxygen levels. Results showed that two cases developed coma and their blood groups were B and O. Also, encephalitis and seizure were produced in four patients with blood groups O and A. Death was reported in blood groups O and A. Results presented that most complications were highly reported in group O then A, followed by group B and AB. This indicated that patients with blood group O have more difficulties than other groups; moreover, blood group AB has fewer complications.
The multicenter retrospective research of Hoiland et al aimed at investigating if ABO blood types are linked to various severities of COVID-19 among ICU admitted patients and found that The differences between means were tested by using the independent sample t-test. A P-value of less than .05 was considered statistically significant. df = degree of freedom, ESR = erythrocyte sedimentation rate, INR = international normalized ratios, IgE = Immunoglobulin E, LD = lactate dehydrogenase, SD = standard deviation.  Kumar et al. [32] Non-O classes had a slightly higher infection prevalence, according to Zietz et al. When compared to type O, the risk of intubation was lower for type A and higher for types of AB and B. In contrast, the mortality risk was higher for type AB and lower for types A and B. Having a Rh-negative blood type protects an individual from all three consequences. [33] The current study has several limitations that warrant consideration, such as primarily single-center, retrospective nature, small sample size, and no information about the strain of coronavirus. Future research will aim to address these limitations and unresolved questions.

Conclusion
The present study reported the susceptibility of the ABO blood group to COVID-19 infections. The clinical, laboratory, imaging findings, and symptoms variation were investigated. All symptoms were observed highly in blood group O except for pharyngeal exudate observed in blood group A. The findings in the current study may have a clinical recommendation that individuals with blood group O might need to particularly strengthen their immunity and personal protection to reduce the chances of getting COVID-19 infection. The overall symptoms trends of hospitalized COVID-19 patients belonging to different blood groups varied nonsignificantly. Larger scale replication research with comprehensive information should be encouraged to pursue and needed to verify the current outcomes.