Low-Grade Inflammation in Long COVID Syndrome Sustains a Persistent Platelet Activation Associated With Lung Impairment

• Published in: JACC. Basic to translational science Vol. 10; no. 1; pp. 20 - 39
• Main Authors: Brambilla, Marta, Fumoso, Federica, Conti, Maria, Becchetti, Alessia, Bozzi, Silvia, Mencarini, Tatiana, Agostoni, Piergiuseppe, Mancini, Maria E., Cosentino, Nicola, Bonomi, Alice, Nallio, Kevin, Galotta, Arianna, Pengo, Martino, Tortorici, Elena, Bosco, Miriam, Cernigliaro, Franco, Pinna, Chistian, Andreini, Daniele, Camera, Marina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2025; Elsevier
• Subjects: antiplatelet drugs; Cardiovascular; inflammation; long COVID; Original Research - Clinical; platelet-leukocyte aggregates; tissue factor; CRP; RT; IL; tissue factor; PLA; PMA; DLNO; DM; HAA; MV; HS; PGA; VA; WB; FU; CT; TF; antiplatelet drugs; DLCO; Vcap; inflammation; long COVID; platelet-leukocyte aggregates; platelet-monocyte aggregates; microvesicle; room temperature; C-reactive protein; nitric oxide lung diffusion; V cap; capillary volume; whole blood; follow-up; platelet-granulocyte aggregates; membrane diffusion; interleukin; computed tomography; DL CO; alveolar volume; healthy subject; DL NO; high attenuation area; carbon monoxide lung diffusion
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2024.09.007

[Display omitted] •Long COVID patients, compared to COVID-recovered asymptomatic subjects, present a platelet activation phenotype characterized mainly by a high number of circulating platelet-leukocyte aggregates.•The number of platelet-leukocyte aggregates is significantly associated with residual lung damage that sustains the most frequently referred symptoms, such as dyspnea, chest pain, fatigue at rest and after exertion.•Low-grade inflammation, sustained mainly by CRP but also by IL-6, is present in long COVID patients and correlates with the degree of platelet activation.•In ex vivo mixing experiments, plasma of long COVID patients mixed with plasma-depleted blood of healthy subjects reproduces the platelet activation observed in vivo through a mechanism that is blunted by Fcγ-receptor inhibitor and tocilizumab, highlighting the role of CRP and IL-6, and also by antiplatelet drugs. In the present study, we provide evidence on the potential mechanisms involved in the residual pulmonary impairment described in long COVID syndrome. Data highlight that lung damage is significantly associated with a proinflammatory platelet phenotype, characterized mainly by the formation of platelet-leukocyte aggregates. In ex vivo experiments, long COVID plasma reproduces the platelet activation observed in vivo and highlights low-grade inflammation as a potential underpinning mechanism, exploiting a synergistic activity between C-reactive protein and subthreshold concentrations of interleukin-6. The platelet-activated phenotype is blunted by anti-inflammatory and antiplatelet drugs, suggesting a potential therapeutic option in this clinical setting.