Spontaneous NLRP3 inflammasome-driven IL-1-β secretion is induced in severe COVID-19 patients and responds to anakinra treatment

SARS-CoV-2 infection may result in a severe pneumonia associated to elevation of blood inflammatory parameters, reminiscent of cytokine storm syndrome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients, however the mechanisms by which SARS-CoV2 virus trigger such an extensive inflammation remain unexplained. A pivotal cytokine driving inflammatory phenotypes is IL-1β, whose maturation and secretion is regulated by NLRP3 inflammasome. In the present report we provide a mechanistic explanation for the strong inflammatory manifestations associated to COVID-19 and further evidence that NLRP3 and IL-1β targeting could be an effective strategy in this disease. Whole blood samples were collected upon informed consent from 4 SARS-CoV2 infected patients with a positive nasopharyngeal swab and a clinical presentation including dyspnea associated with fever, systemic inflammation, rapidly worsening respiratory distress and marked lung abnormalities on chest computed tomography. Patients were treated with anakinra compound. Blood samples for RNA-seq analysis were collected before and 7 days after treatment.