Formation and activity of NLRP3 inflammasome and histopathological changes in the lung of corpses with COVID-19

Abstract

COVID-19 is a contagious disease that attacks many organs but the lungs are the main organs affected. The inflammasome activation results in the exacerbation of inflammatory response in infectious disease. The aim of this study is to investigate the formation and activity of the NLRP3 inflammasome complex and the histopathological changes caused by the coronavirus in the lung of deceased persons with COVID-19. In total, 10 corpses; 5 corpses with no history of any infectious diseases and COVID-19 and 5 corpses with the cause of death of COVID-19 were included in this study. Lung tissue samples were harvested during autopsy under safe conditions. Fresh tissues in each group were used to measure the genes expression and proteins level of NLRP3, ASC, Caspase-1, IL-1β, IL-6 and TNF-α and a routine hematoxylin and eosin staining was performed for histological assessment. Data are represented as the means ± SD. Statistical significance difference was accepted at a p-value less than 5%. The NLRP3, ASC, Caspase-1, IL-1β, IL-6 and TNF-α genes expression and proteins level were elevated in the lung of the COVID-19 group in comparison with the control group. Histological findings presented the increasing number of polymorphonuclear leukocytes, macrophages and also pulmonary fibrosis in the lungs of corpses with the cause of death of COVID-19. High expression of NLRP3 inflammasome components and its relation with the pathophysiology of the coronavirus-infected lung suggested that targeting the NLRP3 inflammasome could be helpful in achieving a more effective treatment in patients with COVID-19.

Breaking Bad: Inflammasome Activation by Respiratory Viruses

“…It has been proposed that inflammasome hyperactivation and the excessive production of inflammatory cytokines, known as a cytokine storm, may be linked to acute respiratory distress syndrome (ARDS) resulting from SARS-CoV-2 infection [52,[57][58][59][60]. Studies suggest that the magnitude of inflammasome activation directly correlates with COVID-19 outcomes [14,[60][61][62][63][64][65][66][67]. For example, elevated levels of IL-1β [14], Casp1p20 [14], IL-1RA, IL-18, and lactate dehydrogenase (LDH) [62] were detected in severe COVID-19 patients' plasma.…”

Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model

“…Studies on SARS-CoV-2-mediated cytokine induction also report positive regulation of these markers [ 17 , 18 , 19 ], and the association of the nfκbiab marker to activate the “cytokine storm” [ 33 , 34 , 35 ]. Additionally, we decided study these markers due to their involvement with the inflammasome process, which is considered to be the central role of inflammation in COVID-19 cases [ 36 , 37 , 38 , 39 ].…”

The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view

“…The lung inflammation caused by SARS-CoV-2 leads to diffuse alveolar damage, alveolar–capillary barrier dysfunction, edema, alveolar exudate containing neutrophils and macrophages, reduced surfactant synthesis because of loss of type II alveolar epithelial cells (type II pneumocytes), fibrin deposition and microthrombi, formation of hyaline membranes, thickening, and congestion of alveolar septa filled with lymphomonocytic infiltrate and fibroblasts, intra-alveolar epithelial debris due to hyperplastic pneumocytes desquamation, and interstitial fibrosis [ 55 , 79 ]. These histopathological modifications of the lungs result in diminished gas exchange, which causes hypoxemia [ 55 ].…”