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Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study

https://doi.org/10.18087/cardio.2021.2.n1560

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Abstract

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.
Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.
Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].
Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).
The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.
Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

About the Authors

V. Yu. Mareev
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Chief Researcher Medical Research and Education Center of Moscow State University M.V. Lomonosova, Moscow, Russia



Ya. A. Orlova
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Department of Age-Associated Diseases Medical Research Center of Moscow State University M.V. Lomonosova



A. G. Plisyk
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Senior Researcher



E. P. Pavlikova
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Deputy Director Clinical Work, Chief Physician Medical Research and Education Center of Moscow State University M.V. Lomonosova



Z. A. Akopyan
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Deputy Director of the Moscow State University



S. T. Matskeplishvili
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia
Russian Federation

Deputy Director for Research, Cardiologist Medical Research and Education Center of Moscow State University M.V. Lomonosova



P. S. Malakhov
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia
Russian Federation

Head of the Department of Anesthesiology and Resuscitation, ISRC, Moscow State University named after M.V. Lomonosov



T. N. Krasnova
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

and about Head of the Department of Internal Diseases FFM Medical Research and Educational Center of Moscow State University M.V. Lomonosova



E. M. Seredenina
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Department of Therapy, Senior Researcher



A. V. Potapenko
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Admissions Department, Senior Researcher



M. A. Agapov
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Surgery department



D. A. Asratyan
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia
Russian Federation

Head of the Department of Traumatology, Associate Professor



L. I. Dyachuk
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of Cardiology departmеnt



L. M. Samokhodskaya
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Laboratory Diagnostics Department Medical Research and Education Center of Moscow State University M.V. Lomonosova



Е. А. Mershina
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head Department of X-ray diagnostics, CT and MRI, radiologist Medical Scientific and Educational Center of Moscow State University M.V. Lomonosova



V. E. Sinitsyn
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Head of the Department of Radiation Diagnostics Medical Research and Educational Center of Moscow State University M.V. Lomonosova



P. V. Pakhomov
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

CLINICAL ORDINATOR



E. A. Zhdanova
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

specialist in internal medicine of the specialized care department of the moscow state university



Yu. V. Mareev
National Medical Research Centre for Therapy and Preventive Medicine, Moscow, Russia Robertson Centre for Biostatistics, Glasgow, Great Britain
Russian Federation

Senior Researcher



Yu. L. Begrambekova
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Leading Researcher Medical Research and Education Center of Moscow State University M.V. Lomonosova



А. А. Kamalov
Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia
Russian Federation

Director Medical Research and Educational Center of Moscow State University M.V. Lomonosova



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Supplementary files

1. Boxplot plots with the dynamics of SHOCS-COVID, NEWS2, SP02, CRP, lymphocytes / CRP ratios
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Mareev V.Yu., Orlova Y.A., Plisyk A.G., Pavlikova E.P., Akopyan Z.A., Matskeplishvili S.T., Malakhov P.S., Krasnova T.N., Seredenina E.M., Potapenko A.V., Agapov M.A., Asratyan D.A., Dyachuk L.I., Samokhodskaya L.M., Mershina Е.А., Sinitsyn V.E., Pakhomov P.V., Zhdanova E.A., Mareev Yu.V., Begrambekova Yu.L., Kamalov А.А. Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study. Kardiologiia. 2021;61(2):15-27. https://doi.org/10.18087/cardio.2021.2.n1560

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ISSN 0022-9040 (Print)
ISSN 2412-5660 (Online)