At the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, a potential link between ABO blood type and susceptibility to the disease was reported. The evidence supporting this link is strengthening as the volume and quality of research expand. Recently, interest has shifted from merely examining susceptibility to exploring the severity of the disease and the immune response characteristics of patients in relation to their blood groups. Objective: to investigate the immunological reactivity and reactive response of peripheral blood neutrophilic granulocytes in patients with COVID-19 patients based on their blood group. Materials and methods. This prospective study included 198 patients with COVID-19-associated pneumonia of mild, moderate, and severe degrees. The cohort comprised 50.51% (100) men and 49.49% (98) women, with an average age of 54.18 ± 7.25 years (range: 18 to 80 years). The distribution of blood groups according to the ABO system was as follows: 0 (I) - 37.37% (74 patients), A (II) - 37.37% (74 patients), B (III) - 18.18% (36 patients), and AB (IV) - 7.07% (14 patients). The immunological reactivity and reactive response of neutrophilic granulocytes were assessed through the analysis of 14 integral leukocyte indices, including the leukocyte shift index, the ratio of the absolute number of leukocytes to the erythrocyte sedimentation rate (ESR), the lymphocyte-granulocyte index, the lymphocyte index, the index of immunological resistance, and reactivity, among others. Results. In moderate and severe coronavirus infection, the indices of cellular and total immune reactivity and resistance are significantly lower compared to mild coronavirus infection: 1.35-3.08 times (p≤0.042-0.001) for resistance, 2.02-3.87 times (p<0.001) for reactivity, respectively, showing the highest activity among them in the owners of blood group 0 (I), with significantly lower values for A (Ⅱ), B (Ⅲ) and AB (Ⅳ) group variants by 3.94-19.10%. Whereas, with increasing severity of the disease, the reactive response of neutrophilic granulocytes, on the contrary, increases significantly compared to the mild degree: in moderate disease by 43.79-87.62% (p≤0.018-0.005), in severe disease by 1.62-2.11 times (p≤0.012-0.001), with the highest average value in AB (Ⅳ) blood group owners – by 46.69-68.44% (p≤0.017-0.005). Conclusions. The highest index of immunological reactivity is observed in individuals with blood group AB (IV) experiencing a mild clinical course of the disease. Conversely, the lowest index of immunological reactivity is found in patients with blood group A (II) who have a moderate clinical course. Additionally, the reactive response of neutrophilic granulocytes significantly increases in patients with a severe clinical course, with the highest average value recorded in those with blood group AB (IV).