Differential platelet protein release profiles in community-acquired pneumonia and COVID-19.

INTRODUCTION: Platelets play a crucial role, amongst others, in the host response to infection through the release of proinflammatory and procoagulant proteins. Pneumonia represents a major disease burden, which has further increased since the onset of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine platelets' protein release profiles in hospitalised patients with non-COVID community-acquired pneumonia (CAP) or COVID-19. METHODS: Platelets from patients with CAP or COVID-19 and from control subjects were incubated with platelet receptor agonists stimulating either glycoprotein (GP)VI or protease-activated receptor 1 (PAR1), or medium (spontaneous release); nine platelet products were measured in supernatants. Platelet activation was also assessed by measuring P-selectin and active GPIIbIIIa surface expression by flow cytometry. RESULTS: We enrolled 32 patients with CAP, 104 patients with COVID-19 and 47 control subjects. Platelets from CAP patients spontaneously released less chemokines as compared to controls, which sharply contrasted with the platelets' release profile in COVID-19, which was characterised by enhanced release of chemokines, plasminogen activator inhibitor 1 (PAI-1) and CD40 ligand relative to both controls and CAP patients. These differences were partially maintained upon ex vivo stimulation of GPVI or PAR1. Enhanced GPVI-induced platelet release of P-selectin, CD40 ligand, PAI-1 and CCL5 was associated with an increased risk for the need of (non)invasive ventilation and/or mortality in COVID-19 patients. Platelet expression of P-selectin and GPIIbIIIa did not differ between groups. CONCLUSION: Platelet release profiles differ strongly between CAP and COVID-19 patients, wherein platelets from COVID-19 patients released more bioactive products, linking with an adverse clinical outcome.