This study investigates the relationship between ABO blood group antigens and susceptibility to various infectious diseases, including the recent COVID-19 pandemic. The objective is to understand the genetic variations of blood types and their role in infectious disease susceptibility. The methodology involves a comprehensive review of existing literature, genomic studies, and statistical analysis of single nucleotide polymorphisms (SNPs) associated with blood types. The results indicate significant correlations between blood group antigens and susceptibility to bacterial, parasitic, and viral infections. Notably, blood group O is associated with a lower risk of severe malaria due to decreased rosetting, while blood group A shows a higher incidence of smallpox and Pseudomonas aeruginosa infections. The findings support the importance of early diagnosis and therapeutic development based on blood group genetic variations.