The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients

Frontiers in Immunology

Immunology

Juana Maria Sanz¹  Alessandra Violi²  Francesco Di Virgilio²  Anna Lisa Giuliani²  Valentina Vultaggio-Poma²  Stefano Pizzicotti³  Sara Ghisellini³  Andrea Amico³  Marco Libanore⁴  Angelina Passaro⁵  Alberto Papi⁵ 

[1] Department of Chemical, Pharmaceutic and Agricultural Sciences, University of Ferrara, Ferrara, Italy;Department of Medical Sciences, University of Ferrara, Ferrara, Italy;Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy;Infectious Diseases Unit, St. Anna Hospital, Ferrara, Italy;Laboratory of Clinical Pathology, St. Anna Hospital, Ferrara, Italy;

关键词: COVID-19;    shed P2X7R;    shed NLRP3;    disease progression;    circulating markers;   

DOI  :  10.3389/fimmu.2023.1182454

 received in 2023-03-08, accepted in 2023-04-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis. The P2X7 receptor (P2X7R), a plasma membrane ATP-gated ion channel, is a main activator of the NLRP3 inflammasome, of the ensuing release of inflammatory cytokines and of cell death by pyroptosis. The P2X7R has been implicated in COVID-19-dependent hyperinflammation and in the associated multiorgan damage. Shed P2X7R (sP2X7R) and shed NLRP3 (sNLRP3) have been detected in plasma and other body fluids, especially during infection and inflammation.MethodsBlood samples from 96 patients with confirmed SARS-CoV-2 infection with various degrees of disease severity were tested at the time of diagnosis at hospital admission. Standard haematological parameters and IL-6, IL-10, IL-1β, sP2X7R and sNLRP3 levels were measured, compared to reference values, statistically validated, and correlated to clinical outcome. ResultsMost COVID-19 patients included in this study had lymphopenia, eosinopenia, neutrophilia, increased inflammatory and coagulation indexes, and augmented sNLRP3, IL-6 and IL-10 levels. Blood concentration of sP2X7R was also increased, and significantly positively correlated with lymphopenia, procalcitonin (PCT), IL-10, and alanine transaminase (ALT). Patients with increased sP2X7R levels at diagnosis also showed fever and respiratory symptoms, were more often transferred to Pneumology division, required mechanical ventilation, and had a higher likelihood to die during hospitalization. ConclusionBlood sP2X7R was elevated in the early phases of COVID-19 and predicted an adverse clinical outcome. It is suggested that sP2X7R might be a useful marker of disease progression.

【 授权许可】

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Copyright © 2023 Vultaggio-Poma, Sanz, Amico, Violi, Ghisellini, Pizzicotti, Passaro, Papi, Libanore, Di Virgilio and Giuliani