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One of the most urgent needs worldwide is to vaccinate against SARS-CoV-2 as many people as possible. We evaluated humoral response to Comirnaty vaccine in Thalassemia Major patients (TM). We measured SARS-CoV-2-specific antibodies against Spike protein in 57 TM patients and 58 healthy blood donors (HBD). TM and HBD subjects revealed a homogeneous serological response to the Comirnaty (Mean ± SD; TM = 1917,21 ± 1384,49; HBD = 2039,81 ± 1064,44; p = 0,5884). No statistically significant differences were observed among two groups. Interestingly, we observed in 73.3% of asplenic patients Ab-S titres above 800 BAU, whereas only in 26% of non splenectomized patients showed Ab-S titres above 800 BAU). This differences were statistically significant p 0.039. Further measurement on other Ab types was needed for better understanding humoral response to Comirnaty.