ABSTRACT
Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid-19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid-19-associated severe pneumonia. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Receptors, Purinergic P2X7/drug effects , Respiratory Distress Syndrome/drug therapy , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Cytokine Release Syndrome/virology , Humans , Macrophages/pathology , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Receptors, Purinergic P2X7/metabolism , Respiratory Distress Syndrome/virology , SARS-CoV-2 , T-Lymphocytes/pathology , COVID-19 Drug TreatmentABSTRACT
Coronavirus disease 2019 (COVID-19) pathogenesis remains under investigation. Growing evidence indicates the establishment of a hyperinflammatory response, characterized by sustained production of cytokines, such as IL-1ß. The release and maturation of this cytokine are dependent on the activation of a catalytic multiprotein complex, known as "inflammasome". The most investigated is the NLRP3 inflammasome, which can be activated by various stimuli, such as the recognition of extracellular ATP by the P2X7 receptor. Based on the recent literature, we present evidence that supports the idea that the P2X7R/NLRP3 axis may be involved in the immune dysregulation caused by the SARS-CoV-2 infection.