Uncoupled GPIIb/IIIa activation and α-granule release in COVID-19. Characteristics of healthy control participants (ctrl), patients with infection (inf), sepsis, or COVID-19 are displayed on hospital/ICU admission day (t1) and days 4 to 7 (t2). Whole blood was preincubated with ADP (5 μM) (A-C) or CRP-XL (0.01 μg/mL) (D-G) for 5 minutes. Panels A, B, and D-F show GPIIb/IIIa activation, and panels C and G show CD62P exposition measured flow cytometrically. (E) CRP-XL–induced GPIIb/IIIa activation vs SOFA score, red area indicates patients fulfilling Sepsis 3 criteria. (F) Receiver operating characteristic curve analysis of GPIIb/IIIa activation between patients with infection and patients with sepsis at t1 upon CRP-XL stimulation. (H-J) Quadrant analysis of CD62P− and PAC-1+ events upon ADP (I) or CRP-XL (J) stimulation. (K-L) Automated clustering analysis of patients with sepsis (n = 9) and patients with COVID-19 (n = 9) upon CRP-XL stimulation. Representative curves are shown in panels A, H, and K. All graphs show median ± IQR except panels I and J that display mean ± 95% CI. Differences were analyzed using the Kruskal-Wallis test (B-J) or Kolmogorov-Smirnov test (L). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001. AUC, area under the curve; CRP-XL, collagen-related peptide cross-linked.
