A hyperinflammatory response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection crucially worsens clinical evolution of coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) triggers the activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Enhanced inflammasome activity has been associated with increased disease severity and poor prognosis. Evidence suggests that inflammasome activation and interleukin-1 beta (IL-1 beta) release aggravate pulmonary injury and induce hypercoagulability, favoring progression to respiratory failure and widespread thrombosis eventually leading to multiorgan failure and death. Observational studies with the IL-1 blockers anakinra and canakinumab provided promising results. In the SAVE-MORE trial, early treatment with anakinra significantly shortened hospital stay and improved survival in patients with moderate-to-severe COVID-19. In this review, we summarize current evidence supporting the pathogenetic role of the NLRP3 inflammasome and IL-1 beta in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19. Copyright (C) 2022 The Authors. Published by Elsevier B.V.

Interleukin-1 and the NLRP3 inflammasome in COVID-19: Pathogenetic and therapeutic implications: IL-1 and NLRP3 inflammasome in COVID-19

Dalla Gasperina D.;Dentali F.;
2022-01-01

Abstract

A hyperinflammatory response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection crucially worsens clinical evolution of coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) triggers the activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Enhanced inflammasome activity has been associated with increased disease severity and poor prognosis. Evidence suggests that inflammasome activation and interleukin-1 beta (IL-1 beta) release aggravate pulmonary injury and induce hypercoagulability, favoring progression to respiratory failure and widespread thrombosis eventually leading to multiorgan failure and death. Observational studies with the IL-1 blockers anakinra and canakinumab provided promising results. In the SAVE-MORE trial, early treatment with anakinra significantly shortened hospital stay and improved survival in patients with moderate-to-severe COVID-19. In this review, we summarize current evidence supporting the pathogenetic role of the NLRP3 inflammasome and IL-1 beta in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19. Copyright (C) 2022 The Authors. Published by Elsevier B.V.
2022
2022
Anakinra; C-reactive protein; COVID-19; Canakinumab; Colchicine; IL-18; IL-1β; NLRP3 inflammasome; SARS-CoV-2
Potere, N.; Del Buono, M. G.; Caricchio, R.; Cremer, P. C.; Vecchie, A.; Porreca, E.; Dalla Gasperina, D.; Dentali, F.; Abbate, A.; Bonaventura, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2143834
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