Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients

J Exp Med. 2021 Mar 1;218(3):e20201707. doi: 10.1084/jem.20201707.

Tamara S Rodrigues ¹, Keyla S G de Sá ¹, Adriene Y Ishimoto ¹, Amanda Becerra ¹, Samuel Oliveira ¹, Leticia Almeida ¹ ², Augusto V Gonçalves ¹, Debora B Perucello ¹, Warrison A Andrade ¹, Ricardo Castro ³, Flavio P Veras ⁴, Juliana E Toller-Kawahisa ⁴, Daniele C Nascimento ⁴, Mikhael H F de Lima ⁴, Camila M S Silva ⁴, Diego B Caetite ⁴, Ronaldo B Martins ¹, Italo A Castro ¹, Marjorie C Pontelli ¹, Fabio C de Barros ⁵ ⁶, Natália B do Amaral ⁷, Marcela C Giannini ⁷, Letícia P Bonjorno ⁷, Maria Isabel F Lopes ⁷, Rodrigo C Santana ⁷, Fernando C Vilar ⁷, Maria Auxiliadora-Martins ⁸, Rodrigo Luppino-Assad ⁷, Sergio C L de Almeida ⁷, Fabiola R de Oliveira ⁷, Sabrina S Batah ⁹, Li Siyuan ⁹, Maira N Benatti ⁹, Thiago M Cunha ² ⁴, José C Alves-Filho ² ⁴, Fernando Q Cunha ² ⁴, Larissa D Cunha ¹, Fabiani G Frantz ³, Tiana Kohlsdorf ⁵, Alexandre T Fabro ⁹, Eurico Arruda ¹, Renê D R de Oliveira ⁷, Paulo Louzada-Junior ⁷, Dario S Zamboni ¹ ²

Affiliations

1 Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
2 Center of Research in Inflammatory Diseases, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
3 Departamento de Análises Clínicas, Toxicológicas e Bromatologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
4 Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
5 Departamento de Biologia, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
6 Departamento de Ecologia e Biologia Evolutiva, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil.
7 Divisão de Imunologia Clinica, Emergência, Doenças Infecciosas e Unidade de Terapia Intensiva, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
8 Divisão de Medicina Intensiva, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
9 Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.

PMID: 33231615 DOI: 10.1084/jem.20201707

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.