Colchicine to Weather the Cytokine Storm in Hospitalized Patients with COVID-19

Abstract

The repurposing of colchicine for the treatment of COVID-19 was suggested based in its immunomodulatory, anti-inflammatory, and anti-viral properties. We performed a single-center propensity score matched cohort study, including all consecutive COVID-19 patients admitted to a community hospital between 1 March 2020 and 30 May 2020. Patients were stratified according to the receipt of colchicine. The primary endpoint was defined as in-hospital death within 28-days follow-up. Secondary endpoints included favorable change in the Ordinal Scale for Clinical Improvement on days 14 and 28 versus baseline, proportion of patients not requiring supplemental oxygen on days 14 and 28, and proportion of patients discharged by day 28. In total data for 303 PCR positive COVID-19 patients were extracted and 66 patients were included in the 1:1 matched cohort study. At the end of the 28 day follow-up, patients receiving colchicine were approximately five times more likely to be discharged (odds ratio, 5.0; 95% confidence interval, 1.25–20.1; p = 0.023) and when comparing mortality, there were 3 deaths (9.1%) in patients receiving colchicine versus 11 deaths (33.3%) in the groups receiving standard of care (odds ratio, 0.20; 95% confidence interval, 0.05–0.80; p = 0.023). These observations warrant further investigation in large controlled clinical trials.

Impact of colchicine on mortality in patients with COVID-19: A meta-analysis

“…A total of 112 articles were screened, 106 were excluded since they did not meet inclusion criteria ( Figure 1 ). A total of six studies, four published after peer-review 7 , 9 , 10 , 11 and two pre-prints 12 , 13 including 881 patients with confirmed COVID-19 were evaluated, 406 of whom were treated with colchicine in addition to standard-of-care ( Table ). To address one study 12 that reported no events in both arms, a value of 0.5 was added to the respective cells.…”

A systematic review of the infectious complications of colchicine and the use of colchicine to treat infections

“…The retrospective study by Brunetti et al. [17] was able to demonstrate significant differences in mortality and length of stay in hospital. The GRECCO-19 trial was the first published randomized-controlled trial and found colchicine reduced the time to clinical deterioration but there was no difference in high-sensitivity cardiac troponin or C-reactive protein levels.…”

“… Brunetti et al. [17] COVID-19 Retrospective cohort N=66 (33 colchicine, 33 control) Median age 63, 65% males Study length 28 days 73% of patients in colchicine cohort received a loading dose of 1.2mg and maintenance dose of 0.6mg twice daily. Standard of care Patients were more likely to be discharged by day 28 compared to standard therapy (OR 5.0, 95% CI, 1.25-20.1, P<0.05).…”

“…A retrospective observational study by Brunetti et al. [17] compared COVID-19 patients given colchicine (1.2mg daily) to standard of care. The primary endpoint was in-hospital death within 28 days of follow up.…”

Genetic determinants of COVID-19 drug efficacy revealed by genome-wide CRISPR screens

“…Colchicine is an immunomodulatory agent used to suppress inflammation in gout, and more recently shown to greatly reduce cardiovascular events and death in chronic coronary disease 23 . Multiple studies showed colchicine significantly lowered death rate in COVID-19 patients 1–3 . Mechanistically, colchicine destabilizes microtubule and damages mitotic spindles, thereby ceasing the proliferation of immune cells and alleviating COVID-19 symptoms.…”