A STUDY OF ABO BLOOD GROUP AND ANTICOVID ANTIBODY TITER IN SYMPTOMATIC COVID-19 DISEASE

COVID-19, an emerging infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first identified in December 2019 when several cases of pneumonia of unknown etiology were noted in Wuhan city, Hubei province, Central China. The cases were initially reported in patients who worked or lived around the local Huanan Seafood wholesale market starting December 8, 2019. The disease spread rapidly, infecting more than 12,000 people in China and 82 confirmed cases worldwide by January 2020, prompting WHO to declare the SARS-CoV-2 outbreak as a Public Health Emergency of International Concern on January 30, 2020.[16] Subsequently, it was declared a pandemic in March 2020 by WHO. Globally, as of December 23, 2022, there have been 651 million confirmed cases of COVID-19, including 6.6 million deaths reported to WHO, with a total of 130 million vaccine doses administered as of December 21, 2022.[1]

India experienced one of the highest COVID-19 infection rates globally, with over 25 million confirmed cases and an escalating death toll. The first case was identified on January 30, 2020, in Kerala in a student who had returned from Wuhan, China. Since March 2020, there has been a significant upsurge in the spread of infection.[16] The coronavirus outbreak caused a major public catastrophe and evolved into a global concern. The virus can spread from person to person and was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) due to its characteristic appearance in electron microscopy.[14] Humoral immunity, especially neutralizing antibodies, are thought to play a vital role in acquiring protection against SARS-CoV-2 infection. Studies have shown that the receptor binding domain of the viral spike protein is a highly targeted site in COVID-19 patients. Some experimental models indicate that adaptive transfer of neutralizing monoclonal antibodies reduces mortality and viral burden. However, in severe cases, it has been observed that antibodies may trigger immunopathogenic events and demonstrate higher antibody titers compared to mild symptomatic patients.[4]The incidence of previous infections including SARS-CoV in 2002-2003 and MERS-CoV in 2012 demonstrated that transmission from animal to human and person-to-person transmission are possible with novel coronaviruses.[15]

The ABO blood group system, discovered in 1900, has been extensively studied for its role in various diseases. Humans have four different types of ABO blood groups—A, B, AB, and O—based on agglutination patterns. A and B antigens are present on red blood cells, while corresponding antibodies are absent in the sera. These antigens are expressed on the surface of RBCs, and the human ABO gene, weighing 18 kilobases and consisting of 7 coding exons, is located on chromosome 9. The genes for A and B encode A and B transferases due to amino acid substitution caused by nucleotides. O genes are not active as they do not produce functional enzymes. Many studies have found that ABO blood group plays an important role in various diseases such as cardiovascular, oncological, and some infectious and non-infectious diseases.[2] Only a few studies have examined the relationship between SARS-CoV-2 and blood groups. Studies have shown that individuals with blood group A are more susceptible to COVID-19, while blood group O appears protective.[3]However, there are insufficient studies on blood groups and antibody titers in different clinical categories of COVID-19 disease, which prompted the present investigation.

The study included 70 COVID-19 positive patients with ages ranging from 19 to 72 years and a median age of 41 years. Male patients comprised 65.7% (n=46) of the study population compared to 34.3% (n=24) female patients.

Distribution of ABO Blood Groups and Disease Severity

Blood group B was the most common (45.7%, n=32), followed by blood group O (25.7%, n=18), blood group A (24.3%, n=17), and blood group AB was least common (4.3%, n=3). Among the total COVID-19 patients, 45.7% (n=32) had moderate disease, 40% (n=28) had mild disease, and 14.3% (n=10) had severe disease (Table 1). The severity of disease was most common in blood group O patients (27.8%, n=5), followed by blood group A (23.5%, n=4) and blood group B (4%, n=1). Notably, blood group AB patients presented only with mild and moderate disease without any severe cases (Table 2, Fisher's Exact Test = 7.694, p=0.243).

Clinical Presentation

The most common symptom among patients was cough (40%, n=28), followed by headache (34.29%, n=24), dyspnea and sputum production (31.43%, n=22 each). The least common presentation was anosmia (12.86%, n=9). In severe disease, cough with sputum production (n=9) was the most common symptom, followed by dyspnea and myalgia (n=8 each), while only 2 patients presented with fever (Table 3).

TABLE 1: Distribution of COVID-19 patients according to ABO blood group and severity

Fisher's Exact Test = 7.694, p = 0.243

TABLE 2: Age distribution and disease severity

Fisher's Exact Test = 22.574, p = 0.000

TABLE 3: Clinical symptoms and disease severity

TABLE 4: Anti-COVID antibody distribution by blood group and disease severity

Anti-COVID Antibody Distribution

Among all COVID-19 patients, 50% (n=35) tested positive for anti-COVID antibodies while the other 50% (n=35) tested negative. Anti-COVID antibodies were present in significant titers in 50% of both male and female patients (p=0.05). Among patients with blood group A, 58.8% (10 of 17) had antibodies present, followed by 55.6% (10 of 18) with blood group O, 43.8% (14 of 32) with blood group B, and 33.3% with blood group AB (Table 4, Fisher's Exact Test = 1.544, p=0.706).

Correlation between Severity and Antibody Response

All patients with severe disease (100%, n=10) showed anti-COVID antibodies, while 65.6% (n=21) of moderate cases and only 14.3% (n=4) of mild cases had detectable antibodies (Table 4). Patients who tested positive for anti-COVID antibodies presented more frequently with fever, fatigue, dyspnea, headache, and diarrhea compared to those who tested negative for antibodies, and these differences were statistically significant (p<0.05).

The present hospital-based cross-sectional study included 70 patients who tested positive for COVID-19 by RT-PCR or Rapid Antigen Test and attended follow-up after 6 months. The median age was 41 years (range 19-72 years), which was comparable to other studies, though Harapan et al.[16]reported a slightly higher median age of 49 years. Male predominance was observed in our study (65.7%), contrasting with the study by Harapan et al.[16] which reported 62.1% female patients. Blood group B was most common (45.7%) in our study, while AB was least common (4.3%), which differs from population-based cohort studies^(2,3) that reported blood group O as most prevalent. In our study, moderate disease was most common (45.7%), followed by mild (40%) and severe disease (14.3%). Severe disease was predominantly found in blood group O patients (27.8%) (Table 1), which aligns with findings by Dal MS et al.[24]who reported severe COVID-19 in 40.82% of O blood group patients and mild disease predominantly in AB positive patients.

The association between O blood group and severe disease despite lower susceptibility suggests complex immunological mechanisms that warrant further investigation.

Regarding antibody response, 50% of our study participants showed anti-COVID antibodies at 6 months follow-up, considerably lower than the 85.6% reported by Harapan et al.[16] in RT-PCR positive patients. This discrepancy may reflect variations in timing of antibody testing, disease severity distribution, or individual immune response variability. Blood group B patients showed maximum antibody positivity (31.43%), while AB blood group showed least positivity (Table 4). Importantly, all severe COVID-19 patients (100%) demonstrated anti-COVID antibodies, compared to 65.6% of moderate cases and only 14.3% of mild cases, suggesting a strong correlation between disease severity and antibody response. This finding is consistent with observations by Gozalbo-Rovira et al.[4]who noted higher antibody titers in severe cases, though they did not find this association statistically significant. The clinical presentation in our study revealed cough as the most common symptom (40%), and patients with detectable antibodies more frequently presented with fever, fatigue, dyspnea, headache, and diarrhea (p<0.05), indicating that symptomatic severity correlates with robust antibody production.

Several mechanisms have been proposed to explain ABO blood group associations with COVID-19 outcomes.[17]The receptor-binding domain of SARS-CoV-2 spike protein may share sequence similarity with ancient lectin family known to bind blood group antigens. Anti-A antibodies present in non-A blood groups could potentially block viral attachment to ACE2 receptors, providing protective effects. Additionally, differences in blood group antigen expression can influence host susceptibility to various pathogens through mechanisms involving lectin binding, toxin neutralization, and evasion of host clearance mechanisms.[22,23]These immunological variations may explain why blood group O individuals, despite having lower susceptibility to infection, experience greater disease severity when infected.

This study demonstrates that ABO blood group may influence COVID-19 severity and immune response. Blood group B was most prevalent among symptomatic COVID-19 patients, while blood group O patients exhibited maximum disease severity despite decreased overall susceptibility to infection. Fifty percent of COVID-19 patients demonstrated detectable anti-COVID antibodies at 6 months post-infection. Blood group B patients showed maximum antibody positivity, while AB blood group showed least antibody response. A strong correlation was observed between disease severity and antibody presence, with all severe cases demonstrating antibody positivity compared to only 14.3% of mild cases. These findings suggest that ABO blood group could be one of several factors influencing COVID-19 clinical outcomes and immune response. Further multicentric studies with larger sample sizes are warranted to validate these findings and elucidate the underlying immunological mechanisms.

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