Lung Inflammasome Activation in SARS-CoV-2 Post-Mortem Biopsies

• Published in: International journal of molecular sciences 2022-10, Vol.23 (21), p.13033
• Main Authors: Baena Carstens, Lucas, Campos D'amico, Raissa, Fernandes de Moura, Karen, Morais de Castro, Eduardo, Centenaro, Flávia, Silva Barbosa, Giovanna, Vieira Cavalcante da Silva, Guilherme, Brenny, Isadora, Honório D'Agostini, Júlio César, Hlatchuk, Elisa Carolina, Pissette de Lima, Sabrina, Camargo Martins, Ana Paula, De Castro Deus, Marina, Konzen Klein, Carolline, Kubaski Benevides, Ana Paula, Nagashima, Seigo, Machado-Souza, Cleber, Pinho, Ricardo A, Pellegrino Baena, Cristina, de Noronha, Lúcia
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin-Converting Enzyme 2; Apoptosis; Autopsies; Autopsy; Bacterial infections; Biomarkers; Biopsy; Caspase 1 - metabolism; Cell death; Chronic illnesses; Coronaviruses; COVID-19; cytokine; Cytokines; Cytokines - metabolism; Dengue fever; Humans; IL-1β; immunohistochemistry; Infections; inflammasome; Inflammasomes; Inflammasomes - metabolism; Inflammatory diseases; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - metabolism; Interleukin 18; Lung - metabolism; Lungs; Monoclonal antibodies; NF-kappa B - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NOX4 protein; Oxidative stress; Pandemics; Pathogenesis; Population; Proteins; pulmonary tissue; Pyroptosis; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Staining; Statistical analysis; Statistical tests; TLR4 protein; Toll-like receptors; Tumor necrosis factor-α; Viral infections; Viruses
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232113033

The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease’s mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.