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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Exp+Med 2021 ; 218 (3): ä Nephropedia Template TP
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Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients #MMPMID33231615
Rodrigues TS; de Sa KSG; Ishimoto AY; Becerra A; Oliveira S; Almeida L; Goncalves AV; Perucello DB; Andrade WA; Castro R; Veras FP; Toller-Kawahisa JE; Nascimento DC; de Lima MHF; Silva CMS; Caetite DB; Martins RB; Castro IA; Pontelli MC; de Barros FC; do Amaral NB; Giannini MC; Bonjorno LP; Lopes MIF; Santana RC; Vilar FC; Auxiliadora-Martins M; Luppino-Assad R; de Almeida SCL; de Oliveira FR; Batah SS; Siyuan L; Benatti MN; Cunha TM; Alves-Filho JC; Cunha FQ; Cunha LD; Frantz FG; Kohlsdorf T; Fabro AT; Arruda E; de Oliveira RDR; Louzada-Junior P; Zamboni DS
J Exp Med 2021[Mar]; 218 (3): ä PMID33231615show ga
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-1beta, 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.