*Statistically significant value for a difference between groups. Table 3. Clinical outcomes between groups O/B and groups A/AB = .02; Physique 2A), highest recorded value for fibrin D-dimer (= .05; Physique 2D), AST (= .02; Physique 2E), ALT (= SB 431542 .01; Physique 2F), and highest recorded value for serum creatinine (= .03; Physique 2H) were lower in O or B patients than in A or AB patients. Open in a separate window Figure 2. Box plots of clinical laboratory results and serum inflammatory biomarkers. required mechanical ventilation (= .02) and CRRT (= .004) and had a longer ICU stay (= .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of 1 1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n = 11) vs O or B (n = 14; .10 for all SB 431542 those cytokines). Collectively, our data indicate that critically ill COVID-19 patients with TNR blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms. Visual Abstract Open in a separate window Introduction Preliminary reports suggest a link between ABO blood groups and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contamination.1-3 Specifically, individuals with blood group O have been reported to be less susceptible to SARS-CoV-2 infection. Comparable associations were observed with SARS-CoV-1.4 In vitro, the anti-A antibody, found in individuals with blood group O or B, appears to antagonize the conversation between SARS-CoV-1 and the receptor for angiotensin converting enzyme 2 (ACE2), which is expressed by host target cells.5 Given that SARS-CoV-2 also binds to ACE2,6,7 it is reasonable to consider that blood groups may also be determinants of susceptibility to SARS-CoV-2 infection. Because a large proportion of individuals infected with SARS-CoV-2 remain asymptomatic, and hospital admission data are limited to patients with symptoms, populace screening would be necessary to accurately assess the relationship between blood group and susceptibility to SARS-CoV-2 contamination. Therefore, early preliminary data may have better reflected the relationship between ABO group and SARS-CoV-2 contamination severity, and the relationship between ABO blood group and COVID-19 severity has remained unresolved, despite more recent investigations.8,9 Multiorgan tropism of SARS-CoV-2 has recently been reported.10 This is consistent with multiple reports indicating that COVID-19 is a multisystem disease that includes renal11 and hepatic12 manifestations. If ABO blood groups play a role in determining disease severity, these differences would be expected to manifest within multiple organ systems10 and hold relevance for multiple resource-intensive treatments, such as mechanical ventilation and continuous renal replacement therapy (CRRT).13 Therefore, we conducted a retrospective analysis of a multicenter case series with a nested prospective substudy of inflammatory cytokines of critically ill COVID-19 patients. In addition, we acquired nationwide population ABO blood group distribution data. Our specific aims were to determine whether ABO blood group is associated with clinical indicators of COVID-19 severity (eg, mechanical ventilation, ventilator-free days, CRRT, length of rigorous care unit [ICU] stay, and mortality) and to determine whether ABO blood group is associated with differences in serum biomarkers of organ dysfunction. Further, given the role of the host immune response as a potential determinant of COVID-19 severity,11,14-21 we aimed to assess whether ABO blood type is related to the levels of serum inflammatory cytokines. We hypothesized that (1) that there would be a greater proportion of critically ill COVID-19 patients with blood group A or AB requiring mechanical ventilation and/or CRRT than those with blood group O or B, (2) clinical laboratory indices SB 431542 of multiorgan dysfunction would be elevated in patients with blood group A or AB compared with group O or B, and (3) serum inflammatory cytokines would be higher in SB 431542 critically ill COVID-19 patients with blood group A or AB compared with group O or B. Methods.