Colchicine Counteracting Inflammation in COVID-19 Pneumonia
Status:
Recruiting
Trial end date:
2020-12-21
Target enrollment:
Participant gender:
Summary
Cytokines and chemokines are thought to play an important role in immunity and
immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum
levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to
individuals with mild disease or healthy controls, similar to patients with SARS or MERS .
The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and
increased NLR in infected patients are correlated with the severity of the disease and
adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19
pathogenesis. Importantly, previous studies showed that viroporin E, a component of
SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the
NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome
activation . The mechanisms are unclear.
Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean
Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome,
thereby reducing the release of IL-1b and an array of other interleukins, including IL-6,
that are formed in response to danger signals. Recently, colchicine has been successfully
used in two cases of life-threatening post-transplant capillary leak syndrome. These patients
had required mechanically ventilation for weeks and hemodialysis, before receiving
colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
Phase:
Phase 2
Details
Lead Sponsor:
Azienda Ospedaliero-Universitaria di Parma Lucio Manenti