期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20201707
关键词
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资金
- Fundacao de Amparo a Pesquisa do Estado de SAo Paulo (FAPESP) [2013/08216-2, 2019/11342-6, 2020/04964-8]
- Center for Research in Inflammatory Disease (CRID/FAPESP) [2013/08216-2]
- Conselho Nacional de Desenvolvimento Cientfico e Tecnologico (CNPq) [304775/2016-9]
- Instituto Nacional de Ciencia e Tecnologia de Vacinas (INCTV/CNPq)
- CoordenacAo de Aperfeicoamento de Pessoal de Nvel Superior (CAPES) [88887.507253/2020-00]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [20/04964-8] Funding Source: FAPESP
The active NLRP3 inflammasome in response to SARS-CoV-2 infection is associated with disease severity in COVID-19 patients, with higher levels of IL-18 and Casp1p20 correlating with poor clinical outcomes. These findings suggest that inflammasomes may serve as markers of disease severity and potential therapeutic targets for COVID-19.
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 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.
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