Abstract: Background: ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association. Methods: Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed. Results: We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p = .036), and number of symptoms of PCS (p = .017) were noted in group O. Concerning biomarkers, PCS + and PCS- showed no differences in A, B, and AB groups. In contrast, group O PCS + patients had significantly lower albumin-to-globulin ratio and higher lymphocyte count, fibrinogen, CRP levels, and higher percentages of 3 composite indices, than PCS- subjects. Group O showed a 6-fold increased risk of PCS, compared to non-O (adjusted OR = 6.25 [95%CI, 1.6-23]; p = .007). Conclusions: Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

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