Colchicine reduces lung injury in experimental acute respiratory distress syndrome

Dupuis, Jocelyn; Sirois, Martin G.; Rhéaume, Éric; Nguyen, Quang Trinh; Clavet-Lanthier, Marie-Élaine; Brand, Geneviève; Mihalache-Avram, Téodora; Théberge-Julien, Gabriel; Charpentier, Daniel; Rhainds, David; Neagoe, Paul‐Eduard; Tardif, Jean‐Claude

doi:10.1371/journal.pone.0242318

Cited by 32 publications

(26 citation statements)

References 31 publications

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“…Colchicine has previously been shown to reduce acute lung injury in an experimental model of acute respiratory distress syndrome. 14 The risk of viral inflammatory pneumonitis might therefore be lowered by colchicine in patients with COVID-19. In contrast, there was no evidence of an increased risk of bacterial pneumonia in COLCORONA.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19

Tardif

Bouabdallaoui

L’Allier

et al. 2021

Preprint

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BackgroundEvidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.MethodsWe performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.ResultsA total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).ConclusionAmong non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

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Section: Discussionmentioning

confidence: 99%

“…11-13 In an experimental model of acute respiratory distress syndrome, colchicine was shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment. 14…”

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confidence: 99%

Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19

Tardif

Bouabdallaoui

L’Allier

et al. 2021

Preprint

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“…The drug, which is well-known for its immunomodulatory properties in severe auto-inflammatory diseases [ 6 ], has been recently shown to modulate the release of circulating cytokines such as IL-6 [ 8 , 9 ]. In addition, colchicine reduces lung injury in experimental acute respiratory distress syndrome (ARDS) [ 13 ]. Finally, colchicine may be an effective treatment for inflammation-induced thrombosis [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study

et al. 2021

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Objectives Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival. Methods This retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups. Results Amongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients. Conclusion In this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients.

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“…Colchicine has been recommended as potential therapy for complications of COVID-19, as an IL-1 inhibitor. 72 Other drugs include a recombinant humanized anti-IL6 receptor antibody called sarilumab, a recombinant human mouse chimeric monoclonal antibody called siltuximab, and an IL-1 blocker called anakinra. 73 , 74 Anakinra, an anti-rheumatic drug, was studied in the trial setting to inhibit pathological effects of IL-1 alpha and IL-1 beta.…”

Section: Drugs Targeting the Cytokine Stormmentioning

confidence: 99%

Cytokine Storm of COVID-19 and its Impact on Patients with and without Chronic Liver Disease

Premkumar¹,

Kedarisetty²

2021

Journal of Clinical and Translational Hepatology

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The coronavirus pandemic has resulted in increased rates of hepatic decompensation, morbidity and mortality in patients suffering from existing liver disease, and deranged liver biochemistries in those without liver disease. In patients with cirrhosis with coronavirus disease 2019 (COV-ID-19), new onset organ failures manifesting as acute-onchronic liver failure have also been reported. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) also directly binds to enterocytes and cholangiocytes via the angiotensin converting enzyme receptor 2, although the lung remains the portal of entry. Superadded with the COVID-19 related bystander hepatitis, a systemic inflammatory response is noted due to unregulated macrophage activation syndrome and cytokine storm. However, the exact definition and diagnostic criteria of the 'cytokine storm' in COVID-19 are yet unclear. In addition, inflammatory markers like C-reactive protein, ferritin, D-dimer and procalcitonin are frequently elevated. This in turn leads to disease progression, activation of the coagulation cascade, vascular microthrombi and immune-mediated injury in different organ systems. Deranged liver chemistries are also noted due to the cytokine storm, and synergistic hypoxic or ischemic liver injury, drug-induced liver injury, and use of hepatotoxic antiviral agents all contribute to deranged liver chemistry. Control of an unregulated cytokine storm at an early stage may avert disease morbidity and mortality. Several immunomodulator drugs and repurposed immunosuppressive agents have been used in COVID-19 with varying degrees of success.

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Colchicine reduces lung injury in experimental acute respiratory distress syndrome

Cited by 32 publications

References 31 publications

Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19

Efficacy of Colchicine in Non-Hospitalized Patients with COVID-19

Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study

Cytokine Storm of COVID-19 and its Impact on Patients with and without Chronic Liver Disease

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