Interleukin-1 and the NLRP3 inflammasome in COVID-19: Pathogenetic and therapeutic implications
Nicola Potere,
Marco Giuseppe Del Buono,
Roberto Caricchio,
Paul C. Cremer,
Alessandra Vecchié,
Ettore Porreca,
Daniela Dalla Gasperina,
Francesco Dentali,
Antonio Abbate,
Aldo Bonaventura
Affiliations
Nicola Potere
Department of Medicine and Ageing Sciences and Department of Innovative Technologies in Medicine and Dentistry, G. D'Annunzio University, Chieti, Italy
Marco Giuseppe Del Buono
Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
Roberto Caricchio
UMass Chan Medical School, Worcester, MA, USA
Paul C. Cremer
Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA
Alessandra Vecchié
Medicina Generale 1, Medical Center, Ospedale di Circolo e Fondazione Macchi, Department of Internal Medicine, ASST Sette Laghi, Varese, Italy
Ettore Porreca
Department of Medicine and Ageing Sciences and Department of Innovative Technologies in Medicine and Dentistry, G. D'Annunzio University, Chieti, Italy
Daniela Dalla Gasperina
Department of Medicine and Surgery, University of Insubria, Varese, Italy
Francesco Dentali
Department of Medicine and Surgery, University of Insubria, Varese, Italy
Antonio Abbate
Robert M. Berne Cardiovascular Research Center and Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA
Aldo Bonaventura
Medicina Generale 1, Medical Center, Ospedale di Circolo e Fondazione Macchi, Department of Internal Medicine, ASST Sette Laghi, Varese, Italy; Corresponding author.
Summary: 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-1β (IL-1β) 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-1β in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19.
