Introduction: It is not clear which individual characteristics can determine susceptibility and intensity of symptoms, however, age, sex, ethnicity, hypertension and some haematological biomarkers, as D-dimer, thrombocytopenia and lymphopenia were associated with a worse outcome. Recently, it has been hypothesized that ABO blood groups can be related to susceptibility to the SARS-CoV-2 infection. Considering that the first studies reported A group as a risk factor and O group as a protection, some authors have been suggested that the anti-A antibodies, and not the blood group, could be responsible for the findings. Objectives: Based on these findings, this study analysed the association of SARS-CoV-2 infection with the presence (O and B blood groups type) or absence (A and AB blood groups type) of anti-A antibodies, considering the production of specific immunoglobulins (IgA, IgM and IgG) and neutralizing antibodies. Material and Methods: Retrospective study with 430 COVID-19 individuals (268 COVID-19 convalescent plasma donors-CCPD and 162 COVID-19 inpatients-CIP) from two Brazilian reference hospitals, confirmed by RT-PCR, and 2,212 healthy volunteer blood donors (VBD) as control group, that were evaluated and divided into two groups: with anti-A (O/B blood groups) and without anti-A group (A/AB blood groups). Immunoglobulins and neutralizing antibody titres were measured for CCPD and CID. Multivariate logistic regression and non-parametric tests were performed. Results: Although O blood group was the most frequent ABO group among VBD, A blood group was more frequent among COVID-19 individuals (CCPD 47.8%, CIP 43.2%, VBD 35.5%, p < 0.001). There was no statistical difference in blood groups distribution between CCPD and CIP (p=0.268). In our cohort, for each increased age year there was 6% more chance for COVID-19 (OR: 1.06; CI 95%: 1.05-1.06, p < 0.001), males showed 27% more chance for the disease (OR: 1.27; CI 95%: 1.02-1.59, p = 0.035) and O/B blood groups showed 38% less infection prevalence (OR: 0.62; CI 95%: 0.5-0.7, p < 0.001). Considering the fact that higher anti-A is usually described in O blood group, data from O versus B blood groups individuals were analysed and the former showed 34% less chance for COVID-19 (OR: 0.66; CI 95%: 0.46-0.95, p = 0.026). No difference regarding ABO group was found when COVID-19 inpatients of all blood types were analysed. Immunoglobulins A, M and G (IgA, IgM, and IgG) and neutralizing antibodies for SARS-CoV-2 were lower in COVID-19 individuals O/B blood groups (IgM p = 0.03, IgG p = 0.02, IgA p = 0.03). Discution: In our retrospective cohort, the COVID-19 individuals O/B blood groups (which produces anti-A) had 38% less chance to have a diagnosis of COVID-19 (p < 0.001) and the same groups showed lower titers of neutralizing antibodies, IgM, IgG and IgA. Groups O/B showed a protective factor against the SARS-CoV-2 infection, but it was not associated to COVID-19 inpatients (versus COVID-19 convalescent plasma donors) suggesting that blood type is not associated to SARS-CoV-2 infection severity. Conclusion: COVID-19 individuals from groups O/B showed lower titers of neutralizing antibodies, and IgM, IgG, and IgA lower levels.