COVID-19 Induces Greater NLRP3 Inflammasome Activation in Obese Patients than Other Chronic Illnesses: A Case–Control Study

TL;DR

Obese patients with COVID-19 show stronger NLRP3 inflammasome activation compared to obese patients with other chronic diseases.

Contribution

This study compares NLRP3 inflammasome activation in obese patients with critical COVID-19 versus non-COVID-19 causes.

Findings

Obese patients with critical COVID-19 showed higher ASC and CASP-1 expression compared to non-COVID-19 obese patients.

Non-COVID-19 obese patients had elevated IL-6, IL-18, CASP-9, and HIF levels.

NLRP3 inflammasome activation in COVID-19 may lead to caspase-1-mediated pyroptosis, while non-COVID-19 obesity may involve caspase-9-mediated necroptosis.

Abstract

Obesity has been identified as an independent risk factor for severe COVID-19 unfavorable outcomes. Several factors, such as increased ACE2 receptor expression and chronic inflammation, can contribute to this relationship, yet the activation of the NLRP3 inflammasome pathway is also a key element. Our primary goal was to determine whether chronic NLRP3 inflammasome activation in people with obesity is different in critical COVID-19 and in critical chronic conditions. A retrospective analysis was conducted using clinical data and post-mortem lung tissue samples from 14 COVID-19 patients with obesity (group A) and 9 patients with obesity who died from non-COVID-19 causes (group B). Immunohistochemical analysis assessed twelve markers related to the NLRP3 inflammasome pathway. Group A showed a significantly higher expression of ASC (p = 0.0387) and CASP-1 (p = 0.0142). No significant differences were found for IL-8, TNF-α, NF-kB, NLRP3, IL-1β, and gasdermin-D. Group B had higher levels of IL-6 (p < 0.0001), IL-18 (p = 0.002), CASP-9 (p < 0.0001), and HIF (p = 0.0327). We concluded that COVID-19 activates the NLRP3 inflammasome pathway, possibly leading to pyroptotic cell death mediated by caspase-1. In contrast, people with obesity without COVID-19, despite exhibiting some markers of the NLRP3 inflammasome, are more likely to experience necroptosis mediated by caspase-9.

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