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

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 (<i>p</i> = 0.0387) and CASP-1 (<i>p</i> = 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 (<i>p</i> < 0.0001), IL-18 (<i>p</i> = 0.002), CASP-9 (<i>p</i> < 0.0001), and HIF (<i>p</i> = 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.