Role of the Inflammasome Pathway According to the Expression of Proteins and Genetic Polymorphisms in COVID-19 Patient
et al., International Journal of Molecular Sciences, doi:10.3390/ijms26209993, Oct 2025
Post-mortem study of 42 deceased COVID-19 patients in Brazil identifying molecular differences between the first and second pandemic waves that suggest potential therapeutic targets. Patients from the second wave showed significantly increased lung tissue expression of inflammasome-related proteins, most robustly Interleukin-18 (IL-18), as well as TLR-4 and NLRP3. Specific genetic polymorphisms in NFKB1 and NOX4 were linked to higher protein expression in the more severe second wave cases, suggesting these pathways may be valuable targets for future therapies.
dos Santos et al., 14 Oct 2025, retrospective, Brazil, peer-reviewed, 11 authors, study period June 2020 - May 2021.
Contact: cleber.souza@pelepequenoprincipe.org.br, cleberius@gmail.com.
Role of the Inflammasome Pathway According to the Expression of Proteins and Genetic Polymorphisms in COVID-19 Patients
International Journal of Molecular Sciences, doi:10.3390/ijms26209993
COVID-19 severity is frequently linked to exacerbated inflammation, with the inflammasome pathway playing a key role in activating inflammatory interleukins. This observational post-mortem study evaluated the expression of inflammasome-associated molecules in patients who died from COVID-19 during the second wave. Minimally invasive autopsies were performed on patients from the first (n = 24) and second (n = 18) waves. Lung tissue samples underwent immunohistochemical staining for ACE-2, TLR-4, NF-κB, TNF-α, NOX4, NLRP3, ASC, CASPASE-1, IL-1β, IL-18, GSDMD, and CASPASE-9. Additionally, genetic polymorphisms within inflammasome-related genes were assessed via real-time polymerase chain reaction. Lung tissue expressions of TLR-4, NLRP3, and IL-18 were significantly higher in patients from the second wave compared to those from the first, with expression levels of 26.3 versus 12.1, 13.9 versus 6.4, and 25.6 versus 3.8, respectively. The A allele at rs4648090 of NFKB1 and the T allele at rs317155 of NOX4 were associated with increased corresponding protein expression by factors of 5.1 and 8.9, respectively. Notably, IL-18 demonstrated substantial immunological relevance, correlating strongly with elevated expression linked to these genetic variants in second wave cases. These findings suggest that the inflammasome pathway harbors biologically meaningful molecules implicated in severe COVID-19, meriting further investigation for their potential as diagnostic or therapeutic targets.
Conflicts of Interest: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Abbreviations The following abbreviations are used in this manuscript:
ACE2 Angiotensin-converting enzyme
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