clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2021-99-3-165-171clinmed-209Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESВозможности и перспективы применения колхицина в комплексной терапии у пациентов с COVID-19Possi bilities and perspectives of colchicine application in complex therapy in patients with COVID-19https://orcid.org/0000-0003-3501-2354ЛебедевП. А.LebedevP. A.

Самара

Samara

https://orcid.org/0000-0001-6665-1533ГаранинА. А.GaraninA. A.

Андрей Александрович Гаранин - канд. мед. наук, ассистент кафедры пропедевтической терапии

Самара

Andrey A. Garanin - MD, PhD, assistant

Samara

sameagle@yandex.ruhttps://orcid.org/0000-0001-7021-4061ПаранинаЕ. В.ParaninaE. V.

443095, Самара

Samara

https://orcid.org/0000-0002-9040-9576ЧернышевА. В.ChernyshevA. V.

443095, Самара

443095, Samara

ДулинП. А.DulinP. A.

107392, Москва

107392, Moscow

ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава РоссииРоссияSamara State Medical University of the Ministry of Health of the Russian FederationRussian FederationГБУЗ «Самарская областная клиническая больница им. В.Д. Середавина»РоссияSamara Regional Clinical Hospital named after Seredavin V.D.Russian FederationФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» (Московский филиал) Минобороны РоссииРоссияMilitary Medical Academy named after Kirov S.M. (Moscow Branch) of the Ministry of Defense of the RussiaRussian Federation202115092021993165171Copyright © Лебедев П.А., Гаранин А.А., Паранина Е.В., Чернышев А.В., Дулин П.А., 20212021Лебедев П.А., Гаранин А.А., Паранина Е.В., Чернышев А.В., Дулин П.А.Lebedev P.A., Garanin A.A., Paranina E.V., Chernyshev A.V., Dulin P.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/209

Новая коронавирусная инфекция, приобретя характер пандемии, в огромной степени увеличивает интерес к поиску новых фармакологических препаратов, имеющих противовирусные и противовоспалительные свойства. Колхицин, использующийся в медицине на протяжении столетий, известный в основном как противоподагрическое средство, весьма неожиданно стал рассматриваться в качестве препарата, способного повлиять на кумулятивную конечную точку у амбулаторных пациентов, включающую смерть и потребность в госпитализации, по результатам недавнего достаточно крупного хорошо спланированного рандомизированного контролируемого исследования. В статье приводятся данные о механизме действия колхицина, который состоит в блокаде многобелкового олигомерного комплекса, отвечающего за активацию воспалительного ответа (инфламмасомы) у пациентов с COVID-19 и подагрой. Особую привлекательность перспективам использования перорального колхицина при COVID-19 придают сведения о том, что его спектр противовоспалительной активности может объяснять вазопротекторные эффекты у пациентов с ИБС, перенесших острый инфаркт, в исследовании COLCOT. Хорошая переносимость препарата, отсутствие тяжелых нежелательных реакций, простой режим дозирования, небольшая стоимость колхицина, отсутствие существенного межлекарственного взаимодействия являются дополнительными преимуществами. Авторы статьи считают, что приведенная информация вполне достаточна для планирования исследования эффективности колхицина как элемента комплексной терапии у госпитализированных пациентов с COVID-19 в сочетании с острым коронарным синдромом, в том числе с потребностью в чрескожном коронарном вмешательстве. Ранняя противовоспалительная терапия у пациентов с COVID-19 до сих пор не является рекомендованной, несмотря на то, что приходит понимание ее необходимости. И в этой ситуации колхицин может быть полезен.

The new coronavirus infection, which has become a pandemic, is greatly increasing interest in the search for new pharmacological drugs with antiviral and anti-infl ammatory properties. Colchicine, which has been used in medicine for centuries and has been mainly known as arthrifuge, has come to be unexpectedly considered as a drug aff ecting the cumulative endpoint in outpatients, including death and hospitalization requirement in a recent large, well-planned, randomized controlled trial. The article provides data on the pharmacodynamics of the drug, which consists in blockade of infl ammasome activation in patients with COVID-19, and an eff ective impact on the mechanisms of “cytokine storm” — a predictor of acute respiratory distress syndrome and sepsis as a major cause of multi-organ lesions and death. The information that its spectrum of anti-infl ammatory activity may explain the vasoprotective eff ects in patients with coronary heart disease (CHD) who underwent acute infarction in the COLCOT study, is particularly attractive from the point of view of the perspectives for the oral colchicine application in COVID-19. High tolerability of the drug, the absence of severe adverse reactions, simple dosing regimen, low cost of colchicine, the absence of signifi cant drug interactions are additional advantages. The authors of this article believe that this information is suffi cient for planning a study of the eff ectiveness of colchicine as an element of complex therapy in hospitalized patients with COVID-19 in combination with acute coronary syndrome, including the need for percutaneous coronary intervention. Early anti-infl ammatory therapy in patients with COVID-19 is still not recommended, despi te th e fact t h at there comes an understanding of its necessity. And in this situation, colchicine has the potential to challenge.

колхицинCOVID-19противовоспалительная активностьпрофилактика осложненийcolchicineCOVID-19anti-infl ammatory activityprevention of complicationsReferencesDalbeth N., Lauterio T.J., Wolfe H.R. Mechanism of Action of Colchicine in the Treatment of Gout. Clin. Ther. 2014;36(10):1465–79. DOI: https://doi.org/10.1016/j.clinthera.2014.07.017Dalbeth N., Lauterio T.J., Wolfe H.R. Mechanism of Action of Colchicine in the Treatment of Gout. Clin. Ther. 2014;36(10):1465–79. DOI: https://doi.org/10.1016/j.clinthera.2014.07.017Nidorf S.M., Eikelboom J.W., Budgeon C.A. et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J. Am. Coll. Cardiol. 2013;61(4):404–410. DOI: http://doi.org/10.1016/j.jacc.2012.10.027Nidorf S.M., Eikelboom J.W., Budgeon C.A. et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J. Am. Coll. Cardiol. 2013;61(4):404–410. DOI: http://doi.org/10.1016/j.jacc.2012.10.027Tardif J.C., Kouz S., Waters D.D. et al. Effi cacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N. Engl. J. Med. 2019;381(26):2497–2505. DOI: http://doi.org/10.1056/NEJMoa1912388Tardif J.C., Kouz S., Waters D.D. et al. Effi cacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N. Engl. J. Med. 2019;381(26):2497–2505. DOI: http://doi.org/10.1056/NEJMoa1912388Katsanos A.H., Palaiodimou L., Price C. et al. Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis. Eur. J. Neurol. 2020;27(6):1035–1038. DOI: http://doi.org/10.1111/ene.14198Katsanos A.H., Palaiodimou L., Price C. et al. Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis. Eur. J. Neurol. 2020;27(6):1035–1038. DOI: http://doi.org/10.1111/ene.14198Shah B., Pillinger M., Zhong H., Cronstein B. Eff ects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI Randomized Trial. Circ. Cardiovasc. Inter. 2020;13(4):e008717. DOI: http://doi.org/10.1161/CIRCINTERVENTIONS.119.008717Shah B., Pillinger M., Zhong H., Cronstein B. Eff ects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI Randomized Trial. Circ. Cardiovasc. Inter. 2020;13(4):e008717. DOI: http://doi.org/10.1161/CIRCINTERVENTIONS.119.008717Stewart S., Yang K. C., Atkins K. et al. Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials Arthritis Res. Therapy. 2020;22(1):28. DOI: https://doi.org/10.1186/s13075-020-2120-7Stewart S., Yang K. C., Atkins K. et al. Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials Arthritis Res. Therapy. 2020;22(1):28. DOI: https://doi.org/10.1186/s13075-020-2120-7Nishiga M., Wang D. W., Han Y. et al. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat. Rev. Cardiol. 2020;17(9):543–558. DOI: http://doi.org/10.1038/s41569-020-0413-9Nishiga M., Wang D. W., Han Y. et al. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat. Rev. Cardiol. 2020;17(9):543–558. DOI: http://doi.org/10.1038/s41569-020-0413-9Richardson S., Hirsch J.S., Narasimhan M. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052–2059. DOI: https://doi.org/10.1001/jama.2020.6775Richardson S., Hirsch J.S., Narasimhan M. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052–2059. DOI: https://doi.org/10.1001/jama.2020.6775Grasselli G., Zangrillo A., Zanella A. et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323(16):1574–1581. DOI: https://doi.org/10.1001/jama.2020.53942020Grasselli G., Zangrillo A., Zanella A. et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323(16):1574–1581. DOI: https://doi.org/10.1001/jama.2020.53942020Zhou F., Ting Y., Ronghui D. et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62. Published Online March 9, 2020. https://doi.org/10.1016/S0140-6736(20)30566-3Zhou F., Ting Y., Ronghui D. et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62. Published Online March 9, 2020. https://doi.org/10.1016/S0140-6736(20)30566-3Schaller T., Hirschbühl K., Burkhardt K. et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518–2520. DOI: https://doi.org/10.1001/jama.2020.8907Schaller T., Hirschbühl K., Burkhardt K. et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518–2520. DOI: https://doi.org/10.1001/jama.2020.8907Shang J., Du L., Han N. et al. Severe acute respiratory syndrome coronavirus 2 for physicians: Molecular characteristics and host immunity (Review). Mol. Med. Rep. 2021;23(4):1. DOI: https://doi.org/10.3892/mmr.2021.11901.Shang J., Du L., Han N. et al. Severe acute respiratory syndrome coronavirus 2 for physicians: Molecular characteristics and host immunity (Review). Mol. Med. Rep. 2021;23(4):1. DOI: https://doi.org/10.3892/mmr.2021.11901.Мареев В.Ю., Орлова Я.А., Павликова Е.П. и др. Упреждающая противовоспалительная и антикоагулянтная терапия в лечении продвинутых стадий новой коронавирусной инфекции (COVID-19). Разбор клинических случаев и дизайн иссле дования: колхицин против руксолитиниба и секукинумаба в от крытом проспективном рандомизируемом исследовании у пациентов с COVID-19 (КОЛОРИТ). Кардиология. 2020;60(9): 4–21.Mareev V.Yu., Orlova Ya.A., Pavlikova E.P., etc. Preventive anti-infl ammatory and anticoagulant therapy in the treatment of advanced stages of new coronavirus infection (COVID-19). Clinical case analysis and study design: colchicine versus ruxolitinib and secukinumab in an open, prospective, randomized trial in patients with COVID-19 (COLORIT). Kardiologiya. 2020;60(9):4–21. (in Russian). https://doi.org/10.18087/cardio.2020.9.n1338Thakur V., Ratho R.K., Kumar P. et al. Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations. J. Clin. Med. 2021;10(3):446. DOI: DOI: https://doi.org/10.3390/jcm10030446Thakur V., Ratho R.K., Kumar P. et al. Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations. J. Clin. Med. 2021;10(3):446. DOI: DOI: https://doi.org/10.3390/jcm10030446Bellosta R., Luzzani L., Natalini G. et al. Acute limb ischemia in patients with COVID-19 pneumonia. J. Vasc. Surg. 2020;72(6):1864–1872. DOI: https://doi.org/10.1016/j.jvs.2020.04.483Bellosta R., Luzzani L., Natalini G. et al. Acute limb ischemia in patients with COVID-19 pneumonia. J. Vasc. Surg. 2020;72(6):1864–1872. DOI: https://doi.org/10.1016/j.jvs.2020.04.483Deng Q., Hu B., Zhang Y. et al. Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China. Int. J. Cardiol. 2020;311:116–121. DOI: https://doi.org/10.1016/j.ijcard.2020.03.087Deng Q., Hu B., Zhang Y. et al. Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China. Int. J. Cardiol. 2020;311:116–121. DOI: https://doi.org/10.1016/j.ijcard.2020.03.087Martos L., Oto J., Fernández-Pardo Á. et al. Increase of Neutrophil Activation Markers in Venous Thrombosis-Contribution of Circulating Activated Protein C. Int. J. Mol. Sci. 2020;21(16):5651. DOI: https://doi.org/10.3390/ijms21165651Martos L., Oto J., Fernández-Pardo Á. et al. Increase of Neutrophil Activation Markers in Venous Thrombosis-Contribution of Circulating Activated Protein C. Int. J. Mol. Sci. 2020;21(16):5651. DOI: https://doi.org/10.3390/ijms21165651Временные методические рекомендации. Профилактика, диагностика и лечение новой коронавирусной инфекции COVID-19. Версия 10 (08.02.2021 г.) утвержденная МЗ РФ.Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection COVID-19. Version 10 (08.02.2021) approved by the Ministry of Health of the Russian Federation. (in Russian). DOI: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/054/804/original/Chen I.Y., Moriyama M., Chang M.F., Ichinohe T. Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Infl ammasome. Front. Microbiol. 2019;10:50. DOI: https://doi.org/10.3389/fmicb.2019.00050Chen I.Y., Moriyama M., Chang M.F., Ichinohe T. Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Infl ammasome. Front. Microbiol. 2019;10:50. DOI: https://doi.org/10.3389/fmicb.2019.00050Rodrigues T.S., de Sá K.S.G., Ishimoto A.Y. et al. Infl ammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J. Exp. Med. 2021;218(3):e20201707. DOI: https://doi.org/10.1084/jem.20201707Rodrigues T.S., de Sá K.S.G., Ishimoto A.Y. et al. Infl ammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J. Exp. Med. 2021;218(3):e20201707. DOI: https://doi.org/10.1084/jem.20201707Dupuis J., Sirois M.G., Rhéaume E. et al. Colchicine reduces lung injury in experimental acute respiratory distress syndrome. PLoS ONE. 2020;15(12):e0242318. DOI: https://doi.org/10.1371/journal.pone.0242318Dupuis J., Sirois M.G., Rhéaume E. et al. Colchicine reduces lung injury in experimental acute respiratory distress syndrome. PLoS ONE. 2020;15(12):e0242318. DOI: https://doi.org/10.1371/journal.pone.0242318Papadopoulos 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;4:1–11. DOI: https://doi.org/10.1007/s42399-020-00421-xPapadopoulos 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;4:1–11. DOI: https://doi.org/10.1007/s42399-020-00421-xTardif J.-C., Bouabdallaoui N., L’Allier P. et al. Effi cacy of Colchicine in Non-Hospitalized Patients with COVID-19. MedRxiv preprint this version posted January 27, 2021. DOI: https://doi.org/10.1101/2021.01.26.21250494Tardif J.-C., Bouabdallaoui N., L’Allier P. et al. Effi cacy of Colchicine in Non-Hospitalized Patients with COVID-19. MedRxiv preprint this version posted January 27, 2021. DOI: https://doi.org/10.1101/2021.01.26.21250494Salah H.M., Mehta J.L. Meta-analysis of the Eff ect of Colchicine on Mortality and Mechanical Ventilation in COVID-19. Am. J. Cardiol. 2021;145:170–172. DOI: https://doi.org/10.1016/j.amjcard.2021.02.005Salah H.M., Mehta J.L. Meta-analysis of the Eff ect of Colchicine on Mortality and Mechanical Ventilation in COVID-19. Am. J. Cardiol. 2021;145:170–172. DOI: https://doi.org/10.1016/j.amjcard.2021.02.005Deftereos S.G., Giannopoulos G., Vrachatis D.A. et al. Eff ect of Colchicine vs Standard Care on Cardiac and Infl ammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw. Open. 2020;3(6):e2013136. DOI: https://doi.org/10.1001/jamanetworkopen.2020.13136Deftereos S.G., Giannopoulos G., Vrachatis D.A. et al. Eff ect of Colchicine vs Standard Care on Cardiac and Infl ammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw. Open. 2020;3(6):e2013136. DOI: https://doi.org/10.1001/jamanetworkopen.2020.13136The ECLA PHRI COLCOVID Trial. Eff ects of Colchicine on Moderate/ High-risk Hospitalized COVID-19 Patients. (COLCOVID). https://clinicaltrials.gov/ct2/show/NCT04328480The ECLA PHRI COLCOVID Trial. Eff ects of Colchicine on Moderate/ High-risk Hospitalized COVID-19 Patients. (COLCOVID). https://clinicaltrials.gov/ct2/show/NCT04328480Kaul S., Gupta M., Bandyopadhyay D. et al. Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes. Am. J. Cardiovasc. Drugs. 2020:1–14. DOI: https://doi.org/10.1007/s40256-020-00459-1Kaul S., Gupta M., Bandyopadhyay D. et al. Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes. Am. J. Cardiovasc. Drugs. 2020:1–14. DOI: https://doi.org/10.1007/s40256-020-00459-1

The authors declare that there are no conflicts of interest present.