Colchicine and COVID-19: A Look Backward and a Look Ahead
Main Article Content
Abstract
Colchicine, a tricyclic alkaloid derived from Colchicum autumnale, is well known for its anti-inflammatory properties, and has been used to treat conditions such as gout, familial Mediterranean fever, and pericarditis. Colchicine's inhibition of the NLRP-3 inflammasome and reduction of key pro-inflammatory cytokines has been considered potentially beneficial in managing COVID-19. While early anecdotal reports and small-scale studies suggest potential benefits, including reduced hospital stay and oxygen requirements, larger randomized controlled trials (RCT) have largely failed to demonstrate significant improvement in mortality, the need for mechanical ventilation, or ICU admissions. Meta-analyses of RCT data corroborate these findings, showing no substantial benefit of colchicine in treating COVID-19. In non-hospitalized patients, the data also suggests limited efficacy, with some studies indicating potential benefit in specific subgroups, though these findings have not been consistently replicated. Colchicine for the treatment of cardiac injury in individuals infected with COVID-19 has also been an area of interest; despite early work suggesting benefit, subsequent RCTs have not shown clear benefit in this subgroup of patients. Overall, despite its promising mechanism of action, the evidence does not support the use of colchicine as standard treatment for COVID-19, either in hospitalized or community-based settings, or with evidence of cardiac injury. This review highlights the need for further research to better understand the potential role of colchicine – looking back as well as a look ahead – in the management of COVID-19.
Article Details
How to Cite
RABBANI, Amir B. et al.
Colchicine and COVID-19: A Look Backward and a Look Ahead.
Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5835>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v12i9.5835.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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10. Bonaventura A, Vecchie A, Dagna L, Tangianu F, Abbate A, Dentali F. Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation. Inflamm Res. 2022;71:293-307.
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31. Singh AK, Vidyadhari A, Singh H, Haider K, Kumar A, Sharma M. Role of colchicine in the management of COVID-19 patients: A meta-analysis of cohort and randomized controlled trials. Clin Epidemiol Glob Health. 2022;16:101097.
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35. Della-Torre E, Ramirez GA, Dagna L, Tresoldi M. Colchicine treatment in community healthcare setting to prevent severe COVID-19. Ann Rheum Dis. 2022;81:e198.
36. Elshiwy K, Amin GEE, Farres MN, Samir R, Allam MF. The role of colchicine in the management of COVID-19: a Meta-analysis. BMC Pulm Med. 2024;24:190.
37. Tardif JC, Bouabdallaoui N, L'Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021;9:924-932.
38. Barco S, Schreiber K. COVID-19: ACT trials for colchicine and antithrombotic therapies. Lancet Respir Med. 2022;10:1106-1108.
39. Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022;10:1169-1177.
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42. Hernandez-Rodriguez J, Duran-Sanclemente J, Prieto-Gonzalez S, et al. FRAGILE-COLCOVID19: A Clinical Trial Based on Early Administration of an Oral Combination of Colchicine and Prednisone in Elderly Patients with COVID-19 in Geriatric Facilities. Clin Drug Investig. 2022;42:949-964.
43. Rabbani AB, Parikh RV, Rafique AM. Colchicine for the Treatment of Myocardial Injury in Patients With Coronavirus Disease 2019 (COVID-19)-An Old Drug With New Life? JAMA Netw Open. 2020;3:e2013556.
44. Lala A, Johnson KW, Januzzi JL, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection. J Am Coll Cardiol. 2020;76:533-546.
45. Giustino G, Croft LB, Stefanini GG, et al. Characterization of Myocardial Injury in Patients With COVID-19. J Am Coll Cardiol. 2020;76:2043-2055.
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47. Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020;14:247-250.
48. Bieber S, Kraechan A, Hellmuth JC, et al. Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury. Infection. 2021;49:491-500.
49. Labbe V, Ederhy S, Lapidus N, et al. Characterization and outcomes of acute myocardial injury in COVID-19 intensive care patients. Infection. 2021;49:563-566.
50. Prasitlumkum N, Chokesuwattanaskul R, Thongprayoon C, Bathini T, Vallabhajosyula S, Cheungpasitporn W. Incidence of Myocardial Injury in COVID-19-Infected Patients: A Systematic Review and Meta-Analysis. Diseases. 2020;8.
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54. Deftereos SG, Siasos G, Giannopoulos G, et al. The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design. Hellenic J Cardiol. 2020;61:42-45.
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2. Schlesinger N, Firestein BL, Brunetti L. Colchicine in COVID-19: an Old Drug, New Use. Curr Pharmacol Rep. 2020;6:137-145.
3. Leung YY, Yao Hui LL, Kraus VB. Colchicine--Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45:341-50.
4. Surma S, Basiak M, Romanczyk M, Filipiak KJ, Okopien B. Colchicine - From rheumatology to the new kid on the block: Coronary syndromes and COVID-19. Cardiol J. 2023;30:297-311.
5. Slobodnick A, Shah B, Pillinger MH, Krasnokutsky S. Colchicine: old and new. Am J Med. 2015;128:461-70.
6. Guo ZY, Tang YQ, Zhang ZB, Liu J, Zhuang YX, Li T. COVID-19: from immune response to clinical intervention. Precis Clin Med. 2024;7:pbae015.
7. Soy M, Keser G, Atagunduz P, Tabak F, Atagunduz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020; 39:2085-2094.
8. Papadopoulos C, Patoulias D, Teperikidis E, et al. Colchicine as a Potential Therapeutic Agent Against Cardiovascular Complications of COVID-19: an Exploratory Review. SN Compr Clin Med. 2020;2:1419-1429.
9. Amaral NB, Rodrigues TS, Giannini MC, et al. Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients. Inflamm Res. 2023;72:895-899.
10. Bonaventura A, Vecchie A, Dagna L, Tangianu F, Abbate A, Dentali F. Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation. Inflamm Res. 2022;71:293-307.
11. Xu H, Akinyemi IA, Chitre SA, et al. SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway. Virology. 2022;568: 13-22.
12. Kamel NA, Ismail NSM, Yahia IS, Aboshanab KM. Potential Role of Colchicine in Combating COVID-19 Cytokine Storm and Its Ability to Inhibit Protease Enzyme of SARS-CoV-2 as Conferred by Molecular Docking Analysis. Medicina (Kaunas). 2021;58.
13. Vrachatis DA, Papathanasiou KA, Giotaki SG, et al. Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine. J Clin Med. 2021;10.
14. Andreu JM, Timasheff SN. Tubulin bound to colchicine forms polymers different from microtubules. Proc Natl Acad Sci U S A. 1982;79: 6753-6.
15. Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest. 1995;96:994-1002.
16. Hegazy A, Soltane R, Alasiri A, et al. Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle. BMC Complement Med Ther. 2024;24:49.
17. Richter M, Boldescu V, Graf D, et al. Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents. ChemMedChem. 2019;14:469-483.
18. Biswas K, Das Sarma J. Effect of microtubule disruption on neuronal spread and replication of demyelinating and nondemyelinating strains of mouse hepatitis virus in vitro. J Virol. 2014;88: 3043-7.
19. Lu N, Yang Y, Liu H, et al. Inhibition of respiratory syncytial virus replication and suppression of RSV-induced airway inflammation in neonatal rats by colchicine. 3 Biotech. 2019;9:392.
20. de Haan CA, Rottier PJ. Molecular interactions in the assembly of coronaviruses. Adv Virus Res. 2005;64:165-230.
21. Li G, Hilgenfeld R, Whitley R, De Clercq E. Therapeutic strategies for COVID-19: progress and lessons learned. Nat Rev Drug Discov. 2023;22: 449-475.
22. Lopes MI, Bonjorno LP, Giannini MC, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD Open. 2021;7.
23. Brunetti L, Diawara O, Tsai A, et al. Colchicine to Weather the Cytokine Storm in Hospitalized Patients with COVID-19. J Clin Med. 2020;9.
24. Gaitan-Duarte HG, Alvarez-Moreno C, Rincon-Rodriguez CJ, et al. Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial. EClinicalMedicine. 2022;43:101242.
25. Sunil Naik K, Andhalkar N, Pendse S. Effect of colchicine and aspirin given together in patients with moderate COVID-19. Contemp Clin Trials Commun. 2023;32:101070.
26. Group RC. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Respir Med. 2021;9:1419-1426.
27. Danjuma MI, Sayed R, Aboughalia M, et al. Does colchicine reduce mortality in patients with COVID-19 clinical syndrome? An umbrella review of published meta-analyses. Heliyon. 2023;9:e20155.
28. Nawangsih EN, Kusmala YY, Rakhmat II, et al. Colchicine and mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression. Int Immunopharmacol. 2021;96:107723.
29. Hariyanto TI, Halim DA, Jodhinata C, Yanto TA, Kurniawan A. Colchicine treatment can improve outcomes of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Clin Exp Pharmacol Physiol. 2021;48:823-830.
30. Salah HM, Mehta JL. Meta-analysis of the Effect of Colchicine on Mortality and Mechanical Ventilation in COVID-19. Am J Cardiol. 2021;145: 170-172.
31. Singh AK, Vidyadhari A, Singh H, Haider K, Kumar A, Sharma M. Role of colchicine in the management of COVID-19 patients: A meta-analysis of cohort and randomized controlled trials. Clin Epidemiol Glob Health. 2022;16:101097.
32. Lien CH, Lee MD, Weng SL, et al. Repurposing Colchicine in Treating Patients with COVID-19: A Systematic Review and Meta-Analysis. Life (Basel). 2021;11.
33. Zein A, Raffaello WM. Effect of colchicine on mortality in patients with COVID-19 - A systematic review and meta-analysis. Diabetes Metab Syndr. 2022;16:102395.
34. Toro-Huamanchumo CJ, Benites-Meza JK, Mamani-Garcia CS, et al. Efficacy of Colchicine in the Treatment of COVID-19 Patients: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11.
35. Della-Torre E, Ramirez GA, Dagna L, Tresoldi M. Colchicine treatment in community healthcare setting to prevent severe COVID-19. Ann Rheum Dis. 2022;81:e198.
36. Elshiwy K, Amin GEE, Farres MN, Samir R, Allam MF. The role of colchicine in the management of COVID-19: a Meta-analysis. BMC Pulm Med. 2024;24:190.
37. Tardif JC, Bouabdallaoui N, L'Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021;9:924-932.
38. Barco S, Schreiber K. COVID-19: ACT trials for colchicine and antithrombotic therapies. Lancet Respir Med. 2022;10:1106-1108.
39. Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022;10:1169-1177.
40. Dorward J, Yu LM, Hayward G, et al. Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial. Br J Gen Pract. 2022;72:e446-e455.
41. Hejazi S, Jahani Z, Elyasi S, Salarbashi D, Kabiri M. The Efficacy of Colchicine as an Adjunct Therapy in Non-hospitalized COVID-19 Patients: A Randomized Placebo-Controlled Trial. Recent Adv Antiinfect Drug Discov. 2024;19:254-263.
42. Hernandez-Rodriguez J, Duran-Sanclemente J, Prieto-Gonzalez S, et al. FRAGILE-COLCOVID19: A Clinical Trial Based on Early Administration of an Oral Combination of Colchicine and Prednisone in Elderly Patients with COVID-19 in Geriatric Facilities. Clin Drug Investig. 2022;42:949-964.
43. Rabbani AB, Parikh RV, Rafique AM. Colchicine for the Treatment of Myocardial Injury in Patients With Coronavirus Disease 2019 (COVID-19)-An Old Drug With New Life? JAMA Netw Open. 2020;3:e2013556.
44. Lala A, Johnson KW, Januzzi JL, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection. J Am Coll Cardiol. 2020;76:533-546.
45. Giustino G, Croft LB, Stefanini GG, et al. Characterization of Myocardial Injury in Patients With COVID-19. J Am Coll Cardiol. 2020;76:2043-2055.
46. Fu L, Li XY, Fei J, et al. Myocardial Injury at Early Stage and Its Association With the Risk of Death in COVID-19 Patients: A Hospital-Based Retrospective Cohort Study. Front Cardiovasc Med. 2020;7:590688.
47. Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020;14:247-250.
48. Bieber S, Kraechan A, Hellmuth JC, et al. Left and right ventricular dysfunction in patients with COVID-19-associated myocardial injury. Infection. 2021;49:491-500.
49. Labbe V, Ederhy S, Lapidus N, et al. Characterization and outcomes of acute myocardial injury in COVID-19 intensive care patients. Infection. 2021;49:563-566.
50. Prasitlumkum N, Chokesuwattanaskul R, Thongprayoon C, Bathini T, Vallabhajosyula S, Cheungpasitporn W. Incidence of Myocardial Injury in COVID-19-Infected Patients: A Systematic Review and Meta-Analysis. Diseases. 2020;8.
51. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5:802-810.
52. Deng YW, Tsuei YW. Acute Myocardial Infarction in Anaphylactic Shock After an Ant Bite: Case Report. J Acute Med. 2020;10:156-160.
53. Yang C, Liu F, Liu W, et al. Myocardial injury and risk factors for mortality in patients with COVID-19 pneumonia. Int J Cardiol. 2021;326:230-236.
54. Deftereos SG, Siasos G, Giannopoulos G, et al. The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design. Hellenic J Cardiol. 2020;61:42-45.
55. Rabbani A, Rafique A, Wang X, et al. Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With Coronavirus Disease-19. Front Cardiovasc Med. 2022;9:876718.
56. Mastrocola R, Aragno M, Alloatti G, Collino M, Penna C, Pagliaro P. Metaflammation: Tissue-Specific Alterations of the NLRP3 Inflammasome Platform in Metabolic Syndrome. Curr Med Chem. 2018;25:1294-1310.
57. Schleh MW, Caslin HL, Garcia JN, et al. Metaflammation in obesity and its therapeutic targeting. Sci Transl Med. 2023;15:eadf9382.
58. Sanchis-Gomar F, Lavie CJ, Mehra MR, Henry BM, Lippi G. Obesity and Outcomes in COVID-19: When an Epidemic and Pandemic Collide. Mayo Clin Proc. 2020;95:1445-1453.
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