ABSTRACT
Background: Thrombotic events are frequent and life-threating complications of COVID-19, but are also observed in patients with bacterial sepsis. Disseminated thrombosis may occur despite strict anticoagulation, suggesting that platelets play a direct, but yet undefined role. Several studies demonstrate altered platelet function in COVID-19, but the impact of platelets in COVID-19 and sepsis remains poorly understood. Aim(s): Platelet phenotype and function were comprehensively assessed in over 100 patients with either COVID-19 (non-ECMO, all-ICU, n = 23), bacterial infection without sepsis (SOFA-score < 2;n = 29), or sepsis/septic shock (SOFA-score >=2;n = 49) at multiple time points during the disease. Method(s): Patients were recruited at the local University Hospital (Ethical vote 94/19). Platelet phenotype and function were studied using flow cytometry (lumino-) aggregometry and whole-mount transmission electron-microscopy. Thrombus formation was investigated using a collagen-and tissue factor-coated flow chamber model at arterial shear rate (1000s-1). Thrombi were imaged by confocal microscopy. Result(s): Upon stimulation with ADP or CRP-XL platelets of infection patients without sepsis showed reduced PAC-1 binding and CD62P exposition. In sepsis patients reactivity was even more impaired and highly associated with disease severity (mean normalized geo-MFI PAC-1 infection: 0.56 vs sepsis: 0.25, p < 0.01;ROC-AUC: 0.76, p < 0.001). Intriguingly, platelets of COVID-19 patients were more responsive towards stimulation compared to comparably-ill ICU patients with sepsis. This relative hyper-reactivity was reflected by increased clot-formation in the flow chamber, compared to sepsis patients (mean surface coverage: 36% vs. 19%, p < 0.05). Thrombi of COVID-19 patients were platelet-rich with little fibrin, in contrast to healthy donors or sepsis patients showing increased amount of fibrin and less platelets. Subtherapeutic doses of GPIIb/IIIa blockers eptifibatide or tirofiban, which had minor effect in control blood, sufficiently prevented thrombus formation in COVID-19 samples under arterial flow. Conclusion(s): Our findings provide evidence that low dose GPIIb/ IIIa blockade might act as a powerful therapeutic tool in COVID-19 patients.