ArticleCritical care (London, England)2022
Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology.
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Article in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
6.6field-weighted citation impact, top 2% of its field
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58 citing papers in PubMed, 80 citations in OpenAlex.
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Gasdermin D-Mediated Release of IL-33 Results in Fetal Brain Developmental Abnormalities During Maternal Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gasdermin D-dependent neutrophil pyroptosis exacerbates Coxsackievirus A6-induced neuroinflammation through NET formation.Journal of neuroinflammation · 2026Article
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Article
- TRIM30a coordinates neutrophil-macrophage crosstalk to resolve inflammation and drive osseointegration via suppressing NETosis/cGAS-STING axis.Materials today. Bio · 2026Article
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Convergent hub pathways targeted by IAV, SARS-CoV-2, and RSV in type II alveolar epithelial cells: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Neutrophil Inflammasome Activation and Pyroptosis Induced by a Metalloproteinase via HIF-1α and Gasdermin D Pathways.Journal of innate immunity · 2026Article
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Disulfiram as an anti-inflammatory agent: mechanisms, nano-delivery strategies, and applications in non-oncologic diseases.RSC advances · 2025Review
- Pyroptosis in Respiratory Virus Infections: A Narrative Review of Mechanisms, Pathophysiology, and Potential Therapeutic Interventions.Microorganisms · 2025Review
- Investigation of the effect of serum gasdermin d levels on clinical course and mortality in patients with covid-19.BMC infectious diseases · 2025Observational
- Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation.eLife · 2025Article
- The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D.Virologica Sinica · 2025Article
- NETosis: A key player in autoimmunity, COVID-19, and long COVID.Journal of translational autoimmunity · 2025Review
- A novel inflammatory biomarker in assessing disease activity in ulcerative colitis: gasdermin D.BMC gastroenterology · 2025Article
- Gasdermin D: A New Inflammatory Biomarker in Assessing Clinical Disease Activity in Crohn's Disease.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
46 authors at 2 institutions in 1 country.
Camila Meirelles S Silva *Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Carlos Wagner S Wanderley *Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Flavio Protasio VerasCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Augusto Velozo GonçalvesCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Mikhael Haruo Fernandes LimaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Juliana Escher Toller-KawahisaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Giovanni Freitas GomesCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Daniele Carvalho NascimentoCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Valter V Silva MonteiroCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Isadora Marques PaivaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Cícero José Luíz Ramos AlmeidaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Diego Brito CaetitéCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Juliana Costa SilvaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Maria Isabel Fernandes LopesDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Letícia Pastorelli BonjornoDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Marcela Cavichioli GianniniDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Natalia Brasil AmaralDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Maíra Nilson BenattiDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rodrigo Carvalho SantanaDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Luis Eduardo Alves DamascenoCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Bruna Manuella Souza SilvaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Ayda Henriques SchneiderCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Icaro Maia Santos CastroCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Juan Carlo Santos SilvaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Amanda Pereira VasconcelosCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Tiago Tomazini GonçalvesCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Sabrina Setembre BatahDepartment of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Tamara Silva RodriguesCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Victor Ferreira CostaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Marjorie Cornejo PontelliDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ronaldo B MartinsDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Timna Varela MartinsCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Danillo Lucas Alves EspósitoDepartment of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Guilherme Cesar Martelossi CebinelliCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Benedito Antônio Lopes da FonsecaDepartment of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Luiz Osório Silveira LeiriaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Larissa Dias CunhaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Eurico ArrudaDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Helder I NakaiaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Alexandre Todorovic FabroDepartment of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Rene D R OliveiraDivisions of Clinical Immunology, Emergency, Infectious Diseases, and Intensive Care Unit, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Dario S ZamboniCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Paulo Louzada-JuniorCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Thiago Mattar CunhaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
José Carlos Farias Alves-FilhoCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
Fernando Queiroz CunhaCenter for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil. fdqcunha@fmrp.usp.br.ORCID 0000-0003-4755-1670
Universidade de São Paulo · BRUniversidade de Ribeirão Preto · BR
Funding
São Paulo Research Foundation (FAPESP) 2013/08216-2
Abstract
backgroundThe release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear.
objectivesWe aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19.
methodsWe performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection.
resultsWe found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage.
conclusionThese results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.
Indexed as
COVID-19 Drug TreatmentExtracellular TrapsAnimalsDisulfiramMiceNeutrophilsSARS-CoV-2DisulfiramCOVID-19Innate immunityNETsNeutrophilOrgan damage
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