ABO blood group and COVID-19 severity: Associations with endothelial and adipocyte activation in critically ill patients.

Background: ABO blood group has been implicated both in susceptibility to, and severity of, SARS-CoV-2 infection. The aim of this study was to explore a potential association between ABO blood group and severity of COVID-19 infection in critically ill patients and the following biological mechanisms: inflammatory cytokines, endothelial injury, and adipokines.

Methods: We conducted a retrospective study of 128 critically ill COVID-19 patients admitted to Vancouver General Hospital from March 2020-March 2021. Outcomes including 28-day mortality, need for mechanical ventilation and length of intensive care unit (ICU) stay were compared between patients with A & AB blood type vs. B & O blood type. Likewise, serum inflammatory markers, markers of endothelial activation, and adipokines were compared.

Results: The association between ABO and severity of disease was confirmed. Patients with A&AB blood group had more frequent ventilation requirements compared to patients with blood group B&O (N(%): 35 (71%) vs 41 (52%), p = 0.041), higher total ICU mortality (14 (29%) vs 9 (11%), p = 0.018), longer median ICU stay (days, median [interquartile range]: 10 [6-19], vs 7 [3-14], p = 0.016) and longer median hospital stay (26 [14-36] vs. 17 [10-30] p = 0.034). No association was found between ABO blood group and serum inflammatory cytokines or their receptors [IL-6, IL-1b, IL-10, TNF, sIL-6R, sgp130] measured within the first 10 days of ICU stay. No association was found between ABO and plasma markers of endothelial injury [Thrombomodulin, ADAMTS13, sP-Selectin, Factor IX, Protein C, Protein S, vWF]. Among the plasma adipokines, there were no differences between lipocalin-2, PAI-1 or resistin. Notably, however, median adipsin was higher in patients with A&AB blood group compared to O&B (16.3 [4.2-38.5] x106 pg/mL vs. 9.61 [3.0-20.8] x 106 pg/mL, p = 0.048).

Conclusions: This retrospective single-center study confirms an association between A and AB blood type with more severe COVID-19. While an underlying mechanism was not identified, the finding of higher adipsin levels in patients with type A/AB blood warrants further investigation in larger prospective studies.