Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1β, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1β and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1β and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00011-022-01540-y.
Highlights
Coronavirus disease 2019 (COVID-19)—the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—is caused by a dysregulated hyperinflammatory response of the host during the late phase of immune response against SARS-CoV-2 [1, 2]
Progression towards severe and critical COVID-19 leading to multi-organ failure is mainly driven by increasing levels of pro-inflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), IL-18, granulocyte–macrophage colony-stimulating factor (GM-CSF), among others [4,5,6,7,8]
SARS-CoV-2 can induce the activation of the NLRP3 inflammasome that leads to the activation of several proinflammatory pathways
Summary
Coronavirus disease 2019 (COVID-19)—the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—is caused by a dysregulated hyperinflammatory response of the host during the late phase of immune response against SARS-CoV-2 [1, 2]. It is reasonable that the downregulation of NLRP3 inflammasome might blunt the inflammatory cascade elicited by SARS-CoV-2 infection, especially in high-risk patients (i.e., those with obesity, diabetes, cardiovascular or pulmonary diseases) This could depend by the fact that most of these patients have an IL‐1β-mediated inflammation related to their underlying conditions, further exacerbated by viral infection. Based on current, limited evidence, it might be hypothesized that colchicine should be administered (i) in very early phases of disease (when dexamethasone is contraindicated) or (ii) in patients with low-grade inflammation and on low-flow oxygen on top of glucocorticoids or (iii) as a long-term therapy (i.e. 1 to 3 months) after hyperinflammation has been controlled For the latter case, colchicine may be considered as a good choice for patients with persistently increased levels of pro-inflammatory cytokines and persisting symptoms (i.e. Long COVID patients), allowing to switch off inflammation without the long-term side effects of glucocorticoids. While considering hyperinflammation and the role of NLRP3 inflammasome/IL-1β axis in COVID-19, results from the SAVE-MORE (suPAR-guided Anakinra treatment for Validation of the risk and Early Management Of seveRE respiratory failure by COVID-19) trial showed a significant
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
