Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia

Taus F, Salvagno G, Canè S, Fava C, Mazzaferri F, Carrara E, Petrova V, Barouni RM, Dima F, Dalbeni A, Romano S, Poli G, Benati M, De Nitto S, Mansueto G, Iezzi M, Tacconelli E, Lippi G, Bronte V, Minuz P.

Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2975-2989. doi: 10.1161/ATVBAHA.120.315175., 12/2020.

Objective: Pulmonary  thrombosis is observed in severe acute respiratory syndrome coronavirus  2 pneumonia. Aim was to investigate whether subpopulations of platelets  were programmed to procoagulant and inflammatory activities in  coronavirus disease 2019 (COVID-19) patients with pneumonia, without  comorbidities predisposing to thromboembolism. Approach and Results:  Overall, 37 patients and 28 healthy subjects were studied.  Platelet-leukocyte aggregates, platelet-derived microvesicles, the  expression of P-selectin, and active fibrinogen receptor on platelets  were quantified by flow cytometry. The profile of 45 cytokines,  chemokines, and growth factors released by platelets was defined by  immunoassay. The contribution of platelets to coagulation factor  activity was selectively measured. Numerous platelet-monocyte (mean±SE,  67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001)  were detected in patients. Resting patient platelets had similar levels  of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets  (8.7±1.5%), which was not further increased by collagen activation on  patient platelets (12.4±2.5%, P=nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001  versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4,  IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines  (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors  (VEGF [vascular endothelial growth factor]-A/D) were released in  significantly larger amounts upon stimulation of COVID-19 platelets.  Platelets contributed to increased fibrinogen, VWF (von Willebrand  factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s,  n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation.

Conclusions: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

Keywords: blood platelets; inflammation; interferons; monocytes; thrombosis.