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• W3132053018 abstract "Due to the significant healthcare and economic burdens of the coronavirus disease 2019 (COVID-19) and the lack of effective treatment, repurposing of existing medications based on plausible mechanism of action have been used. Colchicine, an anti-inflammatory medication, has been proposed as a possible treatment option for COVID-19. Colchicine exerts its anti-inflammatory effects via inhibition of neutrophil chemotaxis, adhesion, and mobilization; suppression of superoxide production; and reduction of tumor necrosis factor (TNF)-α generation and activity.1Schlesinger N Firestein BL Brunetti L. Colchicine in COVID-19: an old drug, new use.Curr Pharmacol Rep. 2020; 6: 137-145Crossref PubMed Scopus (75) Google Scholar Additionally, it is proposed that colchicine may have some antiviral properties through inhibition of microtubule polymerization and regulation of production of antioxidative factor.1Schlesinger N Firestein BL Brunetti L. Colchicine in COVID-19: an old drug, new use.Curr Pharmacol Rep. 2020; 6: 137-145Crossref PubMed Scopus (75) Google Scholar, 2Jackman RW Rhoads MG Cornwell E Kandarian SC. Microtubule-mediated NF-kappaB activation in the TNF-alpha signaling pathway.Exp Cell Res. 2009; 315: 3242-3249Crossref PubMed Scopus (58) Google Scholar, 3Richter M Boldescu V Graf D Streicher F Dimoglo A Bartenschlager R Klein CD. Synthesis, biological evaluation, and molecular docking of combretastatin and colchicine derivatives and their hCE1-activated prodrugs as antiviral agents.ChemMedChem. 2019; 14: 469-483Crossref PubMed Scopus (35) Google Scholar Early reports suggested possible benefits for colchicine in patients with COVID-19.4Deftereos SG Giannopoulos G Vrachatis DA Siasos GD Giotaki SG Gargalianos P Metallidis S Sianos G Baltagiannis S Panagopoulos P Dolianitis K Randou E Syrigos K Kotanidou A Koulouris NG Milionis H Sipsas N Gogos C Tsoukalas G Olympios CD Tsagalou E Migdalis I Gerakari S Angelidis C Alexopoulos D Davlouros P Hahalis G Kanonidis I Katritsis D Kolettis T Manolis AS Michalis L Naka KK Pyrgakis VN Toutouzas KP Triposkiadis F Tsioufis K Vavouranakis E Martinèz-Dolz L Reimers B Stefanini GG Cleman M Goudevenos J Tsiodras S Tousoulis D Iliodromitis E Mehran R Dangas G Stefanadis C. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial.JAMA Netw Open. 2020; 3e2013136Crossref PubMed Scopus (308) Google Scholar Further, a recent meta-analysis showed mortality benefit associated with the use of colchicine in patients with COVID-19.5Vrachatis DA Giannopoulos GV Giotaki SG Raisakis K Kossyvakis C Iliodromitis KE Reimers B Tousoulis D Cleman M Stefanadis C Lansky A Deftereos SG. Impact of colchicine on mortality in patients with COVID-19. A meta-analysis.Hellenic J Cardiol. 2021 Jan 6; ([published online ahead of print])Crossref PubMed Scopus (26) Google Scholar However, since then, more observational studies were published, and the results of the Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA; NCT04322682), the largest clinical trial to date investigating the use of colchicine in non-hospitalized patients with COVID-19 infection, were reported. In this report, we sought to examine the association between colchicine use and severity of COVID-19 infection in the light of the recent evidence. We searched PubMed and MedRxiv (preprint repository) databases to look for relevant articles using (colchicine and COVID-19) on January 29, 2021. We also searched the bibliographies of relevant articles. Inclusion criteria were: (1) Clinical trial, cohort studies, and case-control studies; (2) Studies included patients with confirmed COVID-19 infection who received colchicine and were compared to patients with confirmed COVID-19 infection who did not receive colchicine; (3) Desired outcomes were reported in the study. No language or time restriction were applied. The desired outcomes were all-cause mortality and mechanical ventilation. The Review Manager software (version 5.4.1, The Cochrane Collaboration) was used for all statistical analyses. Mantel–Haenszel risk ratios and 95% confidence intervals (CIs) were calculated. A random-effects modeling approach was used. Cochran's Q and I2 index were used for heterogeneity estimation. We considered an I2 index <25% to be low, an I2 index between 25% and 80% be moderate, and an I2 index >80% be high. Sensitivity analysis was done by excluding the studies that were published as preprints. Due to the low number of the included studies (<10), small-study bias was not examined as our analysis was underpowered to detect such bias. The initial databases query resulted in 132 potential studies. After careful evaluation, only 7 studies met the inclusion criteria.4Deftereos SG Giannopoulos G Vrachatis DA Siasos GD Giotaki SG Gargalianos P Metallidis S Sianos G Baltagiannis S Panagopoulos P Dolianitis K Randou E Syrigos K Kotanidou A Koulouris NG Milionis H Sipsas N Gogos C Tsoukalas G Olympios CD Tsagalou E Migdalis I Gerakari S Angelidis C Alexopoulos D Davlouros P Hahalis G Kanonidis I Katritsis D Kolettis T Manolis AS Michalis L Naka KK Pyrgakis VN Toutouzas KP Triposkiadis F Tsioufis K Vavouranakis E Martinèz-Dolz L Reimers B Stefanini GG Cleman M Goudevenos J Tsiodras S Tousoulis D Iliodromitis E Mehran R Dangas G Stefanadis C. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial.JAMA Netw Open. 2020; 3e2013136Crossref PubMed Scopus (308) Google Scholar,6Scarsi M Piantoni S Colombo E Airó P Richini D Miclini M Bertasi V Bianchi M Bottone D Civelli P Cotelli M-S Damiolini E Galbassini G Gatta D Ghirardelli M-L Magri R Malamani P Mendeni M Molinari S Morotti A Salada L Turla M Vender A Tincani A Brucato A Franceschini F Furloni R Andreoli L Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome.Ann Rheum Dis. 2020; 79: 1286-1289Crossref PubMed Scopus (121) Google Scholar, 7Sandhu T Tieng A Chilimuri S Franchin G. A case control study to evaluate the impact of colchicine on patients admitted to the hospital with moderate to severe COVID-19 infection.Can J Infect Dis Med Microbiol. 2020; 20208865954Crossref PubMed Scopus (47) Google Scholar, 8Lopes MI Bonjorno LP Giannini MC Amaral NB Benatti MN Rezek UC Filho LLE Sousa BA Almeida SC Luppino-Assad R Veras FP Schneider A Rodrigues TS Leiria LO Cunha LD Alves-Filho JC Cunha TM Arruda E Miranda CH Pazin-Filho A Martins MA Borges MC Fonseca BA Bollela VR Del-Ben CM Cunha FQ Zamboni DS Santana RC Vilar FC Louzada-Junior P Oliveira RD. Beneficial effects of colchicine for moderate to severe COVID-19: an interim analysis of a randomized, double-blinded, placebo controlled clinical trial.medRxiv. 2020; (2020.08.06.20169573)Google Scholar, 9Mahale N Rajhans P Godavarthy P Narasimhan VL Oak G Marreddy S Bedekar A Dhundi U Pawar HS Akole P Pawar B Bhurke B Chavan S Prayag P Purandare B Dalvi P Telbhare V Marudwar P Diwane D Shahane M Prayag A Gugale S Bhor S Jog S. A retrospective observational study of hypoxic COVID-19 patients treated with immunomodulatory drugs in a Tertiary Care Hospital.Indian J Crit Care Med. 2020; 24: 1020-1027Crossref PubMed Scopus (14) Google Scholar, 10Brunetti L Diawara O Tsai A Firestein BL Nahass RG Poiani G Schlesinger N. Colchicine to weather the cytokine storm in hospitalized patients with COVID-19.J Clin Med. 2020; 9: 2961Crossref Scopus (53) Google Scholar, 11Tardif J-C Bouabdallaoui N L'Allier PL Gaudet D Shah B Pillinger MH Lopez-Sendon J da Luz P Verret L Audet S Dupuis J Denault A Pelletier M Tessier PA Samson S Fortin D Tardif J-D Busseuil D Goulet E Lacoste C Dubois A Joshi AY Waters DD Hsue P Lepor NE Lesage F Sainturet N Roy-Clavel E Bassevitch Z Orfanos A Grégoire JC Busque L Lavallée C Hétu P-O Paquette J-S Levesque S Cossette M Nozza A Chabot-Blanchet M Dubé M-P Guertin M-C Boivin G Efficacy of colchicine in non-hospitalized patients with COVID-19.medRxiv. 2021; (2021.01.26.21250494)Google Scholar Review of the bibliographies of relevant articles showed one study available on another database (Research Square) that met our inclusion criteria.12Pinzón MA AD Betancur JF Holguín H Arias CA Muñoz BJ Amarillo M Llano JF Montoya P Clinical outcome of patients with COVID-19 pneumonia treated with corticosteroids and colchicine in Colombia.Res Sqaure. 2020; Google Scholar Therefore, a total of 8 studies were included with a total of 5,259 patients with COVID-19 infection. About 48.3% of patients in these studies received colchicine. In the mortality analysis, 8 studies were included. Mortality among patients who received colchicine was 3.2%, whereas mortality among those who did not receive colchicine was 8.3%, with a statistically significant difference (RR 0.62; CI [0.48, 0.81]; I2 = 22%; Figure 1). In the risk of mechanical ventilation analysis, only 5 studied reported this outcome. About 2.4% of the patients who received colchicine required mechanical ventilation, whereas 6.7% of those who did not receive colchicine required mechanical ventilation. However, this difference did not reach statistical significance (RR 0.75; CI [0.45, 1.25]; I2 = 57%; Figure 2). Sensitivity analysis for both analyses yielded consistent results.Figure 2Forest plot examining the association between colchicine use and risk of mechanical ventilation requirement in patients with COVID-19 infection. CI = confidence interval; M-H = Mantel-Haenszel.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The results of the present analysis show possible mortality benefits associated with the use of colchicine in patients with COVID-19 infection. Although patients who received colchicine tended to have lower risk of mechanical ventilation, the difference between the 2 groups did not reach a statistically significant difference. There are some limitations of our meta-analysis. First, most of the included studies were observational studies. Second, individual studies had different inclusion criteria and different follow-up periods. Third, there was moderate heterogeneity in the mechanical ventilation analysis. Larger clinical trials are needed to confirm our findings. In this context, several ongoing clinical trials may provide additional information on the safety and efficacy of colchicine in patients with COVID-19 (e.g., NCT04472611, NCT04539873, NCT04667780, and NCT04510038). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper." @default.
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• W3132053018 title "Meta-analysis of the Effect of Colchicine on Mortality and Mechanical Ventilation in COVID-19" @default.
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