Background: Blood groups' antigens, represent polymorphic traits inherited among populations, their expression differences, can increase or decrease the host susceptibility to infections. We aimed here to correlate the relation between the different blood groups and hosts' susceptibility towards COVID-19 infection. Methods: 355 samples, were analyzed for SARS-CoV-2 and blood groups typing. The candidates were then divided according to their results into; 210 positive-PCR (viral persistent, clearance and ICU admitted), and 145 negative-PCR contacts and then results were compared. Results: The highest frequency in control and viral clearance group was O-phenotype, followed by Aphenotype and the least was AB-phenotype. The highest frequency in the viral persistent group, was A-group, showed followed by B-group and the least was O-group. Lastly in ICU group, A-group was the highest frequency, followed by O-group and the least was Bgroup. Using Chi-square method, a statistically significant result was observed (p-value= 0.034). Conclusions: The blood group-O was the protective phenotype, controversy to the O-group, A-group was the risky phenotype, also AB-group was risky, as it showed the lowest frequency in both control and viral clearance group. Interestingly, the B-group was the least group susceptible to have bad prognosis and be admitted to the ICU. This can be a safety guideline for classifying healthcare workers, according to their ABO, to work with suspected cases with COVID-19 and also may help in developing specific anti-histo-blood group antibodies as an effective co-therapy for COVID-19.

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