Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients
Tamara S Rodrigues, Keyla S G de Sá, Adriene Y Ishimoto, Amanda Becerra, Samuel Oliveira, Leticia Almeida, Augusto V Gonçalves, Debora B Perucello, Warrison A Andrade, Ricardo Castro, Flavio P Veras, Juliana E Toller-Kawahisa, Daniele C Nascimento, Mikhael H F de Lima, Camila M S Silva, Diego B Caetite, Ronaldo B Martins, Italo A Castro, Marjorie C Pontelli, Fabio C de Barros, Natália B do Amaral, Marcela C Giannini, Letícia P Bonjorno, Maria Isabel F Lopes, Rodrigo C Santana, Fernando C Vilar, Maria Auxiliadora-Martins, Rodrigo Luppino-Assad, Sergio C L de Almeida, Fabiola R de Oliveira, Sabrina S Batah, Li Siyuan, Maira N Benatti, Thiago M Cunha, José C Alves-Filho, Fernando Q Cunha, Larissa D Cunha, Fabiani G Frantz, Tiana Kohlsdorf, Alexandre T Fabro, Eurico Arruda, Renê D R de Oliveira, Paulo Louzada-Junior, Dario S Zamboni, Tamara S Rodrigues, Keyla S G de Sá, Adriene Y Ishimoto, Amanda Becerra, Samuel Oliveira, Leticia Almeida, Augusto V Gonçalves, Debora B Perucello, Warrison A Andrade, Ricardo Castro, Flavio P Veras, Juliana E Toller-Kawahisa, Daniele C Nascimento, Mikhael H F de Lima, Camila M S Silva, Diego B Caetite, Ronaldo B Martins, Italo A Castro, Marjorie C Pontelli, Fabio C de Barros, Natália B do Amaral, Marcela C Giannini, Letícia P Bonjorno, Maria Isabel F Lopes, Rodrigo C Santana, Fernando C Vilar, Maria Auxiliadora-Martins, Rodrigo Luppino-Assad, Sergio C L de Almeida, Fabiola R de Oliveira, Sabrina S Batah, Li Siyuan, Maira N Benatti, Thiago M Cunha, José C Alves-Filho, Fernando Q Cunha, Larissa D Cunha, Fabiani G Frantz, Tiana Kohlsdorf, Alexandre T Fabro, Eurico Arruda, Renê D R de Oliveira, Paulo Louzada-Junior, 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.
Conflict of interest statement
Disclosures: The authors declare no competing interests exist.
© 2020 Rodrigues et al.
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References
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