The Russian Health Ministry has provided Version 4 (27/03/2020) interim recommendations for the treatment of COVID-19, which includes their intended dosage and timeline of use.

NOTE* This excerpt has been translated. Please see the official recommendation in Russian here:

TREATMENT OF CORONAVIRUS INFECTION
Monitoring is required as part of medical care the patient’s condition to detect signs of deterioration in his clinical condition. Patients infected with SARS-CoV-2 should receive supporting pathogenetic and symptomatic therapy.

Treatment of comorbid diseases, conditions and complications
carried out in accordance with clinical recommendations, standards of care for these diseases, conditions and complications.

These guidelines provide only the main significant features of medical care this group of patients with comorbid diseases, conditions and complications based on the results of the analysis of treatment of patients with other coronavirus infections.

Etiotropic treatment

Etiotropic treatment in adults:
Analysis of literature data on the clinical experience of patient management with SARS associated with SARS-CoV and MERSCoV coronaviruses, it is possible to isolate several etiotropic drugs that recommended to use in combination. These include lopinavir + ritonavir, chloroquine, hydroxychloroquine, drugs interferons. Among the drugs that are at the clinical stage trials in patients with COVID-19, umifenovir can also be noted, remdesivir, favipiravir.
According to published data, these drugs 16 Version 4 (03/27/2020) today can also be used in the treatment of patients with COVID-19.

However, currently available information about the results of treatment using these drugs do not allow an unambiguous conclusion about their efficiency / inefficiency, and therefore their use is permissible for in accordance with the established procedure, if the potential benefit to the patient will exceed the risk of their use. The combined drug lopinavir + ritonavir is used to treatment of HIV infection and is an inhibitor of the protease of the virus. IN studies have shown that it is also able to suppress activity coronavirus proteases. This drug has found its use in the treatment of MERS-CoV infections are still used today to treat infections, caused by the new coronavirus SARS-CoV-2.

Currently in China randomized controlled trial initiated
efficacy and safety of lopinavir + ritonavir in patients with
COVID-19.

Interferon beta-1b (IFN-β1b) has antiproliferative,
antiviral and immunomodulatory activity. In current
clinical trials of MERS-CoV IFN-β1b infection used in
combination with lopinavir + ritonavir.

Previously conducted in vitro studies have shown that it exhibits maximum activity in comparison with other variants of interferons (IFN-α1a, IFN-α1b and IFNβ1a). Due to the ability to stimulate the synthesis of anti-inflammatory cytokine IFN-β1b drugs may have a positive
pathogenetic effect.

Although in a randomized a controlled study in which 199 patients participated lopinavir / ritonavir has not shown statistically significant efficacy for compared with standard therapy, this combination remains in clinical recommendations of many countries.

In contrast, the parenteral use of IFN-α in severe acute
respiratory infection (SARI) may be associated with a risk of developing ARDS due to increased expression of pro-inflammatory factors.

Recombinant interferon alfa-2b (IFN-α2b) as a solution for
intranasal administration has immunomodulatory, anti-inflammatory and antiviral effects. Mechanism of action based on preventing the replication of viruses entering the body through the airways.

Chloroquine is a drug for the treatment of malaria and some
other protozoal infections. In addition, due to anti-inflammatory and immunosuppressive effect, it has found its application in the treatment of patients with systemic connective tissue diseases such as rheumatoid arthritis and lupus erythematosus.

The mechanism of action of chloroquine against some viral infections is not fully understood in published data there are several options for its effects on COVID-19, which prevent the penetration of the virus into the cell and its replication.

Hydroxychloroquine is similar in structure and mechanism of action to chloroquine due to anti-inflammatory and immunosuppressive properties it also found its use in the treatment of malaria and some systemic diseases of connective tissue and is also seen in as a treatment for COVID-19 infection.

Compared to chloroquine, hydroxychloroquine probably has less cytotoxicity and more pronounced antiviral effect. In small clinical studies have shown that the combination of azithromycin with hydroxychloroquine enhances the antiviral effect of the latter.

Before prescribing chloroquine and hydroxychloroquine, as well as during taking these drugs should pay special attention to the result of the ECG, in particular, the value of QT.

Chloroquine and hydroxychloroquine possess cardiotoxicity, and their administration may be accompanied by development, for example, long QT syndrome. Questions about the purpose of these drugs in case of altered ECG and further therapy in case of treatment
ECG changes are resolved strictly individually, in close collaboration with cardiologists.

To control cardiotoxicity of hydroxychloroquine, azithromycin is
instrumental, and clinical monitoring is necessary, in
including the QT interval, in the following groups of patients with increased
risk:

  1. men over 55,
  2. women over 65,
  3. persons of any age with a history of cardiovascular
    diseases.

An ECG is prescribed before treatment, control is carried out 1 in 5 days. The duration of the corrected QT interval is estimated by Bazett formula, it should not exceed 480 ms. Upon reaching threshold value on the recommendation of a cardiologist individually beta-blockers are prescribed (bisoprolol, carvedilol, nebivolol, metoprolol).

When complaints of arrhythmia, a feeling of palpitations, pain and heart discomfort, episodes of weakness and dizziness, syncopal conditions are assigned an extraordinary ECG.

For patients not at high risk cardiotoxicity, clinical monitoring is carried out.

When ECG is assigned to complaints. The list of possible medications for etiotropic therapy COVID-19 is given in Appendix 2.

Recommended treatment regimens depending on the severity of the disease are given in

Appendix 3. Given the lack of objective evidence the effectiveness of the above drugs with COVID-19, the appointment of treatment must necessarily be accompanied by receipt voluntary informed consent of the patient (or his legal representative).
According to WHO recommendations, it is possible to prescribe drugs with the estimated etiotropic efficacy of off-label (i.e. application with medical purpose does not comply with medical instructions application), while their use must comply with ethical

WHO recommended standards and based on Federal Law of November 21, 2011 No. 323-ФЗ “On the Basics of Protection
Health of Citizens in the Russian Federation ”, Federal Law of 12
April 2010, No. 61-FZ “On the circulation of medicines”,
National standard of the Russian Federation GOST R ISO 14155-2014
Good Clinical Practice, Order of the Ministry
Healthcare of the Russian Federation of April 1, 2016 No. 200n “About
Approval of Good Clinical Practice “(registered
The Ministry of Justice of the Russian Federation on August 23, 2016,

See the official Russian Health Ministry’s interim recommendations:
https://static-3.rosminzdrav.ru/system/attachments/attaches/000/049/877/original/COVID19_recomend_v4.pdf

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