The hidden role of NLRP3 inflammasome in diabesity-related COVID-19
exacerbations: lessons for drug repurposing
Abstract
COVID-19, the illness caused by SARS-CoV-2, has a wide-ranging clinical
spectrum that, in the worst-case scenario, involves a rapid progression
to severe acute respiratory syndrome and even death. Epidemiological
data show that “diabesity”, the association of obesity and diabetes,
is among the main risk factors associated with high morbidity and
mortality. The increased susceptibility to SARS-CoV-2 infection
documented in diabesity argues for initial defects in defense
mechanisms, most likely due to an elevated systemic metabolic
inflammation (“metaflammation”). The NLRP3 inflammasome is a master
regulator of metaflammation and has a pivotal role in the
pathophysiology of diabesity. Here we discuss the most recent findings
suggesting contribution of NLRP3 inflammasome to the increase in
complications in COVID-19 patients with diabesity. We also review
current pharmacological strategies for COVID-19, focusing on treatments
whose efficacy could be due, at least in part, to interference with the
activation of the NLRP3 inflammasome.