Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients
Tamara Silva Rodrigues, Keyla Santos Guedes de Sá, Adriene Y. Ishimoto, Amanda Becerra, Samuel Oliveira, Letícia de Almeida, Augusto V. Gonçalves, Debora B. Perucello, Warrison A. Andrade, Ricardo Cardoso Castro, Flávio P. Veras, Juliana E. Toller-Kawahisa, Daniele C. Nascimento, Mikhael Haruo Fernandes de Lima, Camila M. Silva, Diego B. Caetité, Ronaldo B. Martins, Ítalo A. Castro, Marjorie Cornejo Pontelli, Fábio Cury de Barros, Natália B. do Amaral, Marcela C Giannini, Letícia Pastorelli Bonjorno, Maria Isabel Fernandes Lopes, Rodrigo de Carvalho Santana, Fernando Crivelenti Vilar, Maria Auxiliadora‐Martins, Rodrigo Luppino Assad, Sérgio C. L. Almeida, Fabíola Reis de Oliveira, Sabrina Setembre Batah, Li Siyuan, Maíra Nilson Benatti, Thiago M. Cunha, José C. Alves‐Filho, Fernando Q. Cunha, Larissa D. Cunha, Fabiani Gai Frantz, Tiana Kohlsdorf, Alexandre Todorovic Fabro, Eurico Arruda, Renê Donizeti Ribeiro de Oliveira, Paulo Louzada‐Júnior, Dario S. Zamboni
Abstract
Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.