Pyroptosis in the lung and spleen of patients died from COVID-19

Abstract

The purpose of this study was to investigate the expression of pyroptosis-related factors (NLRP3, IL-18, NF-κB, HMGB-1, and GSDMD) in patients who died of COVID-19. The expression levels of NLRP3, IL-18, NF-κB, HMGB-1, and GSDMD in lung and spleen tissues of the COVID-19 group and the control group were detected by tissue immunofluorescence. The control group includes lung tissues and spleen tissues of two patients who died unexpectedly without SARS-CoV-2 infection, and the COVID-19 group includes the lung and spleen tissues of three patients who died of SARS-CoV-2 virus infection. The positive rates of NF-κB, NLRP3, IL-18, and GSDMD in the lung tissues from the control group and COVID-19 group were 9.8% vs 73.4% ( p = 0.000), 5.5% vs 63.6% ( p = 0.000), 24.4% vs 76.2% ( p = 0.000), and 17.5% and 46.8% ( p = 0.000) respectively. The positive rates of NF-κB, NLRP3, IL-18, HMGB-1, and GSDMD in the spleen tissues from the control group and COVID-19 group were 20.6% vs 71.2% ( p = 0.000), 18.9% vs 72.0% ( p = 0.000), 15.2% vs 64.8% ( p = 0.000), 27.6% vs 69.2% ( p = 0.000), and 23% and 48.8% ( p = 0.000), respectively. The positive rates of SARS-CoV-2 spike protein in the CD68 positive cells of the lung and spleen in the control group and COVID-19 group were 2.5% vs 56.8% ( p = 0.000); 3.0% vs 64.9% ( p = 0.000) respectively. The rates of NF-κB positive nuclei in the control group and COVID-19 group were 13.4% vs 51.4% ( p = 0.000) in the lung and 38.2% vs 59.3% ( p = 0.000) in the spleen. The rates of HMGB-1 positive cytoplasm in the control and the COVID-19 group were 19.7% vs 50.3% ( p = 0.000) in the lung and 12.3% vs 45.2% ( p = 0.000) in the spleen. The targets of SARS-CoV-2 are the lung and spleen, where increased macrophages could be involved in the up-regulation of pyroptosis-related inflammatory factors such as NF-κB, HMGB-1, NLRP3, IL-18, and GSDMD.

The Emerging Role of Photobiomodulation in COVID-19 Therapy Part II

“…Cytoplasmic releases from cell bursts include inflammatory factors (IL-1β, IL-18, and HMGB-1) and NLRP3 inflammasomes. These tissue factors are present in lung inflammation observed in acute COVID-19 92 and ARDS 93 patients. So, in this sense, even though they are not considered immune cells, mitochondria perform important immune functions at the subcellular level.…”

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

“…Multiple lines of evidence support a critical role of inflammasomes in COVID-19 and – likely - its autoimmune complications ( 12 , 13 , 22 , 29 , 39 , 181 , 228 – 232 ) (for a review, see ( 39 )). The lung and spleen tissue obtained from patients who died from COVID-19 exhibited higher densities of cells expressing NLRP3, IL-18, NF-κB and gasdermin D, and even HMGB-1, than age-matched controls who had died unexpectedly, but free of SARS-CoV-2-infection ( 13 , 233 ). This observation indicates that the cells were already in the primed stage.…”

“…In addition, enhanced plasma levels of pyroptosis markers were detected in COVID-19 patients, and the levels of caspase -1 and IL-18 in serum correlated with the degree of COVID-19 severity ( 12 , 22 , 29 , 220 , 221 ), particularly in elderly patients ( 234 ). Neutrophils, macrophages and PBMCs from SARS-CoV-2-infected patients also exhibited active AIM2 or NLRP3 inflammasomes and enhanced expression of ASC-speck protein, caspase 1 or gasdermin-D ( 12 , 13 , 22 , 29 , 199 , 221 , 233 ). Correspondingly, specific inhibition of the NLRP3 inflammasome suppressed immune overactivation and alleviated COVID-19-like pathology in mice ( 235 ).…”