# Role of the Inflammasome Pathway According to the Expression of Proteins and Genetic Polymorphisms in COVID-19 Patients

## TL;DR

This study explores how the inflammasome pathway contributes to severe COVID-19 by analyzing protein expression and genetic variations in patients who died during the second wave.

## Contribution

The study identifies specific proteins and genetic polymorphisms in the inflammasome pathway associated with severe COVID-19 outcomes.

## Key findings

- Lung tissue expressions of TLR-4, NLRP3, and IL-18 were significantly higher in second wave patients.
- Genetic variants in NFKB1 and NOX4 were linked to increased protein expression in severe cases.
- IL-18 showed strong immunological relevance tied to genetic variations in second wave cases.

## Abstract

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.