Inflammasome activation in COVID-19 patients

Rodrigues, T. S.; Sa, K. S.; Ishimoto, A. Y.; Becerra, A.; Oliveira, S.; Almeida, L.; Goncalves, A. V.; Perucello, D. B.; Andrade, W. A.; Castro, R.; Veras, F. P.; Toller-Kawahisa, J. E.; Nascimento, D. C.; de Lima, M. H.; Silva, C. M.; Caetite, D. B.; Martins, R. B.; Castro, I. A.; Pontelli, M. C.; de Barros, F. C.; do Amaral, N. B.; Giannini, M. C.; Bonjorno, L. P.; Lopes, M. I. F.; Benatti, M. N.; Santana, R. C.; Vilar, F. C.; Auxiliadora-Martins, M.; Luppino-Assad, R.; de Almeida, S. C.; de Oliveira, F. R.; Batah, S. S.; Siyuan, L.; Cunha, T. M.; Alves-Filho, J. C.; Cunha,

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-1{beta} and IL-18. Although the participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease is unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and it is active in COVID-19, influencing the clinical outcome of the disease. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of post-mortem 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 the inflammasome is key in the pathophysiology of the disease, indicating this platform as a marker of disease severity and a potential therapeutic target for COVID-19.