Colchicine is one of the oldest medicines with potent anti-inflammatory functions, widely used to treat rheumatic diseases such as gout, calcium pyrophosphate deposition disease (CPDD), and familial Mediterranean fever (FMF). The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is continuing to pose a healthcare scare. COVID-19 causes fever, fatigue, cold and cough, respiratory distress, and in some cases, death. New reports have shown colchicine, an antirheumatic drug, as a promising candidate agent for COVID-19 treatment.
Study: Colchicine Against SARS-CoV-2 Infection: What is the Evidence?. Image Credit: Sonis Photography/Shutterstock
A recent article, published in Rheumatology and Therapy, reviews the potent evidence of colchicine against the SARS-CoV-2 infection. It highlighted how colchicine’s mode of action plays a role in the COVID-19 pathophysiology and its pleiotropic effects on the neutrophils, inflammasome inhibition, and any effective viral activity. Importantly, the reviewers discussed the clinical studies where colchicine is used for the COVID-19 treatment.
Colchicine is an old drug, which with the recent understanding of its mechanism of action, pharmacology and safety, has been repurposed with new perspective treatments. In the past year, colchicine has been used as a potential therapeutic agent against SARS-CoV-2. With more experience gained in using this drug in COVID-19 treatment, there are, however, reports of contradictory results. Some exhibit encouraging data favoring its use against SARS-CoV-2, while some data supports its ineffectiveness.
This review looks at Colchicine’s pathophysiology, its effect on the immune response, and its viral activity. To this end, the reviewers adopted a searching strategy where they used Medline and Scopus to search for clinical studies that evaluated colchicine for COVID-19.
Colchicine and COVID-19
Colchicine is an old drug widely used in rheumatic diseases. It is a tricyclic lipid-soluble alkaloid extracted from the plant colchicum autumn crocus. It is an anti-inflammatory drug also used in some heart diseases such as pericarditis and myocardial infarction.
Colchicine’s mode of action involves tubulin disruption leading to downregulation of multiple inflammatory pathways and modulation of the innate immunity. As colchicine binds to tubulins, it blocks the assembly of microtubule polymerization. Because microtubules are key components of the cell cytoskeleton, their integrity helps maintain cell shape, intracellular trafficking, regulate ion channels, cell deviation, and mitosis, as well as modulate cytokine and chemokine. Colchicine, at low concentrations, arrests microtubule growth, and at high concentrations, it promotes microtubule depolymerization.
This association with microtubules interferes with neutrophil recruitment, inhibits inflammasome formation, and suppresses superoxide production. In addition to anti-inflammatory properties, colchicine also has cardioprotective effects.
The myocardial injury appears to be a major component of the COVID-19. When biologically treated with cytokine inhibitors, patients suffering from autoimmune rheumatic diseases (ARD) and contracted COVID-19 demonstrated mild clinical symptoms, less hospitalization, and less severe complications. On the other hand, patients with FMF or gouty arthritis who received colchicine for treatment did not suffer severe respiratory complications. They recovered well without additional treatments. A detailed look at the pathways in the above two cases reveals that it leads to IL-1 beta and IL-6 production in both cases.
The heterogeneous clinical manifestations and the laboratory abnormalities during the COVID-19 disease course result from an uncontrolled release of pro-inflammatory cytokines like IL-1b, IL-6, IL-18, TNFa, and chemokines.
Because of the large evidence demonstrating colchicine’s inhibitory effects on neutrophil activity, cytokine generation, inflammation, and thrombosis- all of which aids in the effective immune response against SARS-COV-2, it is rational to investigate its role as a potential anti-SARS-CoV-2 therapeutic agent.
Clinical colchicine studies in COVID-19
In different clinical trial studies, including double-blind, randomized, open-label randomized, placebo-controlled, cohort, case-control, cross-sectional, observational, and retrospective studies, the effectiveness of colchicine against SARS-CoV-2 infection was observed to improve both the outpatients and inpatients significantly. The beneficial outcomes ranged from improvement time to deterioration, D-dimer suppression, significant mortality benefit (84% vs. 64% survival), reduced oxygen therapy and hospitalizations, and low intubation rate.
In a large-sample study, the use of colchicine in patients testing positive for SARS-CoV-2 demonstrated lower rates of death or hospital admission than those in the placebo group (patients who did not use colchicine). In a similar study, it was observed that patients receiving colchicine had lower rates of intubation (47% vs. 87%) and mortality (47% vs. 80.8%) than those who did not.
Even when administered in combination therapy, the researchers have reported colchicine combination therapy reduced the hospital mortality rate compared to other therapeutic strategies.
COVID-19 patients with pneumonia, when administered corticosteroids plus colchicine, responded well and had better mortality rates than those who received only corticosteroids. Furthermore, in a randomized open-label multicenter clinical trial (in everyday clinical practice), colchicine was used as an early therapeutic intervention in patients infected with SARS-CoV-2 and over 60 years of age with at least one additional comorbidity. It is reported that in line with the aforementioned results, colchicine reduced acute lung injury and respiratory failure in experimental acute respiratory distress syndrome.
Most of the studies reported were indicative of a definite benefit of using colchicine in COVID-19 patients - decreased mortality, hospitalization, and mechanical ventilation.
To date finding therapeutic solutions for COVID-19 remains a huge challenge. The effectiveness against inflammation, safe pharmacokinetics, and ease of administration, make colchicine a promising drug to reduce the risk of severe COVID-19 disease. However, further well-designed studies with many patients are needed to answer this thesis, the reviewers concluded.