Abstract
Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection. In multivariate analysis, advanced age was an independent risk factor for death. Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. Aged individuals have a basal predisposition to over-react to infection, displaying an increased hyper-inflammatory cascade, that seems not to be fully physiologically controlled. NLRP3 inflammasome is over-activated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19. Strategies blocking inflammasome would deserve to be studied.
Highlights
Infection leads to activation of the inflammatory T helper 1 (Th1) cells and macrophages
Participate in the production of several pro-inflammatory cytokines, enter the pulmonary circulation and induce the so-called “cytokine storm” that lead to rapid, wide-spread damage of the pulmonary epithelium and alveolar cells, as well as other vital organs [2]
Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection
Summary
COVID-19: consider cytokine storm syndromes and immunosuppression. Interleukin-6 use in COVID-19 pneumonia related macrophage activation syndrome. Kidney disease is associated with inhospital death of patients with COVID-19. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-. The Journal of Heart and Lung Transplantation, in press [7]. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. Cytokines (IL-1 and IL-6) and Lung Inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-. NLRP3 inflammasome: molecular activation and regulation to therapeutics. The Roles of the NLRP3 Inflammasome in Neurodegenerative and Metabolic Diseases and in Relevant Advanced. Recent advances in the mechanisms of NLRP3 inflammasome activation and its Inhibitors. NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome.
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