The COVID-19 pandemic caused by SARS-CoV-2 infection has resulted in significant morbidity and mortality, primarily due to lung damage and acute respiratory distress syndrome. While remdesivir has shown efficacy, there's a need for additional effective treatments. Colchicine, an anti-inflammatory agent with known effects on inhibiting interleukin-18, IL-1β, and IL-6 (key players in cytokine storms associated with severe COVID-19), has been explored as a potential treatment. Colchicine's ability to inhibit neutrophil chemotaxis and its anti-inflammatory actions, mediated potentially through microtubule polymerization inhibition, make it a candidate for managing COVID-19 inflammation. This study aimed to assess the safety and efficacy of colchicine in improving clinical outcomes in hospitalized COVID-19 patients, leveraging its known anti-inflammatory properties and potential to modulate the inflammatory response characteristic of severe COVID-19.

Existing literature on colchicine's use in various inflammatory diseases (gout, familial Mediterranean fever, Behcet's disease, pericarditis, acute coronary syndrome) established its anti-inflammatory profile and acceptable safety. Some studies suggested a potential role for colchicine in COVID-19 due to its ability to modulate inflammatory pathways implicated in the disease's severity. However, prior to this study, the evidence regarding colchicine's effectiveness in COVID-19 treatment was inconclusive and varied across different study designs and treatment regimens. Some studies reported positive effects on clinical outcomes, while others found no significant benefit or even potential negative effects. The existing literature highlighted the need for a robust, well-designed clinical trial to definitively evaluate colchicine's efficacy and safety in hospitalized COVID-19 patients.

This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted between February and May 2021 at Ibn Sina Hospital in Iran. 110 adult patients (≥18 years) with PCR-confirmed or CT-scan-diagnosed COVID-19 were included. Patients with renal or hepatic impairment, colchicine hypersensitivity, pregnancy, or breastfeeding were excluded. Patients were randomly assigned (1:1) using a permuted block randomization method to receive either colchicine (2mg loading dose followed by 0.5mg twice daily for 7 days) or a matching placebo. Both groups received standard COVID-19 treatment, including remdesivir and interferon beta-1b, along with other supportive care as per national guidelines. An eight-point ordinal scale assessed clinical status on days 7 and 14. A score of 1 or 2 indicated clinical recovery. Secondary outcomes included ICU admission, ICU days, intubation rate, and 28-day mortality. Safety outcomes monitored adverse drug reactions (ADRs), particularly gastrointestinal effects. Statistical analysis included the Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney U test, Pearson's chi-square test, Fisher's exact test, Kendall's tau-b, logistic regression, and Kaplan-Meier survival analysis. A sample size of at least 50 patients per group was estimated based on a previous study's findings on colchicine's effect on mortality.

106 patients were analyzed (57 female, 49 male, mean age 54.62). Baseline characteristics were similar between groups, except for vomiting (p=0.04). At day 7, 58.8% of the control group and 63.6% of the colchicine group showed clinical response (p=0.61). At day 14, 82.4% of the control group and 87.3% of the colchicine group responded (p=0.48). There were no significant differences between groups in 28-day mortality (p=0.99), ICU admission (p=0.59), or hospital length of stay (p=0.06). Logistic regression showed higher body mass index and high-dose corticosteroids were associated with lower recovery rates (p=0.033, 0.015, respectively). Nausea and diarrhea were significantly more frequent in the colchicine group (p=0.006, p<0.001, respectively). One patient discontinued colchicine due to severe diarrhea.

This study demonstrates that adding colchicine to standard COVID-19 treatment did not improve clinical outcomes in hospitalized patients. The lack of significant benefit contrasts with some prior studies, possibly due to differences in study design, colchicine dosing regimens, concomitant treatments, and patient populations. The higher incidence of gastrointestinal side effects with colchicine raises safety concerns. The observed association of higher body mass index and high-dose corticosteroids with lower recovery rates highlights the impact of these factors on COVID-19 outcomes. The study’s findings support the conclusion that short-term adjunctive colchicine therapy does not offer clinical advantages for hospitalized COVID-19 patients.

This randomized controlled trial provides evidence that colchicine does not improve clinical outcomes in hospitalized COVID-19 patients when given as adjunctive therapy for a short duration. The increased risk of gastrointestinal side effects further limits its clinical utility in this setting. Future research should focus on exploring alternative dosing regimens or investigating colchicine's role in specific COVID-19 patient subgroups or disease stages.

The study's limitations include its single-center design, the absence of inflammatory cytokine level measurements, and the fact that PCR testing wasn't performed on all patients. The majority of patients had baseline ordinal scores of 3 and 4, which might have limited the ability to detect a treatment effect. The relatively short duration of colchicine administration may also have influenced the results.