The effect of etiotropic therapy on the formation of immune disorders in patients with COVID-19

The course of a new coronavirus infection is associated with immune system disorders during the acute stage of the desease. Administration of effective etiotropic drugs contributes to early elimination of the virus. At the same time, risks of post-COVID immune system disorders are minimized. The aim of the study was to investigate features of the immune response formation against the background of etiotropic therapy in patients who underwent COVID-19. Material and methods. An observational retrospective comparative study was conducted. The study involved patients with COVID-19 3 months after treatment with etiotropic drugs (riamilovir or umifenovir). The study involved 87 patients (52 women and 35 men) with varying degrees of COVID-19 severity. In accordance with the study design, participants were divided into 2 groups: the first group - 41 patients (received riamilovir during the acute period of the disease);the second group - 46 patients (received umifenovir in the acute period of the disease). Statistical processing of the results was carried out using the Statistica 8.0 software package. Extensive indicators, median (Me) and interquarter range Q25-Q75 were calculated. Statistical significance between the indicators of independent samples was assessed by Mann-Whitney nonparametric test and Chi-square test. P-values below 0.05 were considered statistically significant. Results and discussion. Analysis of clinical and laboratory data showed that after suffering COVID-19, not all indicators of the immune system in patients who had had COVID-19 recovered to control values. However, it is noted that in patients of the main group, which using riamilovir, compared to the comparison group was less likely to be diagnosed with chronic systemic syndrome, inflammation, dysregulation of the cellular link of immunity in the early post-COVID period.Copyright © Eco-Vector, 2022.

Triazavirin-A Novel Effective Antiviral Drug.

This review outlines the data of numerous studies relating to the broad-spectrum antiviral drug Triazavirin that was launched on the Russian pharmaceutical market in 2014 as an anti-influenza drug (the international non-patented name is Riamilovir). The range of antiviral activity of Triazavirin has been significantly expanded during recent years; in particular, it has been shown that Triazavirin exhibits activity against tick-borne encephalitis, Rift Valley fever, West Nile fever, and other infections of viral etiology. This drug has been approved for treatment of influenza and acute respiratory infections by the Russian Ministry of Health on the basis of comprehensive clinical trials involving over 450 patients. Triazavirin was found to be a highly effective and well-tolerated drug, allowing its over-the-counter sale. The recently published data on the use of Triazavirin in clinical practice for the treatment of patients with COVID-19 are discussed, with special attention paid to potential biological targets for this drug.

The effect of etiotropic therapy on the formation of immune disorders in patients with COVID-19

The course of a new coronavirus infection is associated with immune system disorders during the acute stage of the desease. Administration of effective etiotropiс drugs contributes to early elimination of the virus. At the same time, risks of post-COVID immune system disorders are minimized. The aim of the study was to investigate features of the immune response formation against the background of etiotropic therapy in patients who underwent COVID-19. Material and methods. An observational retrospective comparative study was conducted. The study involved patients with COVID-19 3 months after treatment with etiotropic drugs (riamilovir or umifenovir). The study involved 87 patients (52 women and 35 men) with varying degrees of COVID-19 severity. In accordance with the study design, participants were divided into 2 groups: the first group – 41 patients (received riamilovir during the acute period of the disease);the second group – 46 patients (received umifenovir in the acute period of the disease). Statistical processing of the results was carried out using the Statistica 8.0 software package. Extensive indicators, median (Me) and interquarter range Q25–Q75 were calculated. Statistical significance between the indicators of independent samples was assessed by Mann–Whitney nonparametric test and Chi-square test. P-values below 0.05 were considered statistically significant. Results and discussion. Analysis of clinical and laboratory data showed that after suffering COVID-19, not all indicators of the immune system in patients who had had COVID-19 recovered to control values. However, it is noted that in patients of the main group, which using riamilovir, compared to the comparison group was less likely to be diagnosed with chronic systemic syndrome, inflammation, dysregulation of the cellular link of immunity in the early post-COVID period. © Eco-Vector, 2022.

Prospects of using the nucleoside analogue riamilovir in patients with SARS-CoV-2 infection.

AIM: To evaluate clinical efficacy of nucleoside analogues in therapy of moderate COVID-19 in in-patients. MATERIALS AND METHODS: Retrospective processing of 108 completed clinical cases with moderate novel coronavirus disease was carried out for the period 2020-2021. The duration of the disease at the time of admission did not exceed three days. Experimental group consisted of 53 patients who, in addition to standard therapy, were prescribed "off-label" riamilovir at a daily dosage of 1250 mg for 5 days by the decision of the medical commission. Comparison group included 55 patients who received a combination of umifenovir and ribavirin as antiviral therapy for 5 days. The duration of the main clinical manifestations of the disease, the indicators of clinical and biochemical blood tests, results of the SARS-CoV-2 virus RNA study using the nucleic acid amplification method (NAAT diagnostics). RESULTS: Significantly faster achievement of clinical improvement in the group of patients treated with riamilovir was shown, as well as faster sanitation from SARS-CoV-2 virus based on the results of etiological testing. CONCLUSION: The use of riamilovir for the treatment of patients with moderate novel coronavirus infection (COVID-19) resulted in a significant reduction of general infectious syndromes and respiratory symptoms. Patients from the experimental group significantly faster achieved clinical recovery and sanitation from the pathogen according to the results of NAAT diagnostics.

The efficacy of triazavirin (riamilovir)-based treatment for coronavirus disease 2019 (COVID-19) in clinical trials and preliminary practical experiences.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has plagued the human population as 2019 turned into 2020, when first cases were confirmed to be infected with the pathogen in Wuhan City, the largest mega-city and capital of Hubei Province in Central China. Since this time, many pharmacotherapeutic modalities were suggested and used to treat the patients suffering from COVID-19. Triazavirin (TZV; riamilovir) is a synthetic non-toxic broad-spectrum antiviral drug belonging into an azolotriazine class. Several hypotheses and suggestions based on the knowledge about morphology, structure of virion, genome, replication cycle and functions of particular proteins within SARS-CoV-2 as well as in silico analyzes were published aiming to employ TZV for the treatment of COVID-19. Results and conclusions from a well-known randomized controlled trial registered under the Registration No. ChiCTR2000030001, which was carried out in China in 2020, indicated not only the anti-SARS-CoV-2 efficacy of given aza analogue of guanine but also some limitations of these outcomes in the context of their general interpretability and applicability. Thus, a primary aim of this review article was to provide more complex view on pharmacotherapeutic interventions based on TZV against COVID-19/SARS-CoV-2. The focus was on relevant results and conclusions from clinical trials as well as practical experiences with given antiviral agent considering not only real benefits of chosen therapeutic strategies but also several obstacles connected with them.

Antiplatelet Activity of Riamilovir under Conditions of Lipopolysaccharide Intoxication.

We studied the effect of antiviral agent riamilovir on ADP-induced platelet aggregation in the absence and presence of LPS. Unlike acetylsalicylic acid (reference drug), riamilovir did not exhibit antiplatelet effect in vitro. However, it markedly suppressed platelet reactivity in LPS-treated blood samples and was 2.2-fold superior to acetylsalicylic acid in terms of IC50 value. In in vivo experiments, riamilovir under conditions of hypercytokinemia blocked platelet aggregation in rats by 64%.

Study of Riamilovir Activity Against SARS-CoV-2 Infection In Syrian Hamsters

The activity of the antimetabolic drug Riamilovir (TriazavirinR) was studied on a model of SARS-CoV-2 infection on Syrian hamsters. Infectious process was caused by the intranasal administration of the virus accumulated in the Vero-B culture with a concentration of 4.25×104 TCID50, in a volume of 26 μl/hamster. The effects of the drug at a dose of 20 mg/kg intraperitoneally daily in the midst of the infectious process were traced to accelerate the clearance of the virus in the lungs, prevent body weight loss and the severity of pulmonary edema, as well as preserve the mass of the spleen. The protective effects of Riamilovir on the structure of the lungs and brain are shown, it is suggested that the drug has the ability to penetrate the blood-brain barrier. It was concluded that Riamilovir has antiviral activity against SARS-CoV-2.

[Experience of the preventive use of the drug Riamilovir in the foci of coronavirus infection (COVID-19)].

AIM: The assessment of the effectiveness, safety and tolerance of the drug Riamilovir for emergency drug prevention in the foci of a new coronavirus infection (COVID-19). MATERIALS AND METHODS: The trial included 113 persons aged 18 years and older who had level 1 contacts with patients with a new coronavirus infection (COVID-19), who had not previously been ill, with negative PCR results for COVID-19. RESULTS: The high effectiveness, safety and good tolerance of the preventive use of the drug Riamilovir for the period of 20 days of taking a prophylactic dose of 1 capsule (250 mg) per day in the foci of COVID-19 has been established. CONCLUSION: The effectiveness and safety of the preventive use of the drug Riamilovir allow to recommend it for emergency drug prophylaxis in contact persons in the foci of a new coronavirus infection (COVID-19).

[Evaluation of the effectiveness of Riamilovir in the complex therapy of patients with COVID-19].

AIM: In this study we evaluated the effects of Riamilovir on SARS-CoV-2 viral shedding and on admission duration in patients with moderate COVID-19. MATERIALS AND METHODS: We have used data from 69 health records of patients with moderate severe PCR confirmed SARS-CoV-2 infection. Control group included 34 patients treated with off-label riamilovir 1250 mg per day for 5 days (250 mg 5 times a day), comparison groups 35 patients, who received ribavirin and umifenovir 800 mg a day for 5 days. The antiviral therapy was administered within 72 hours from the onset of the disease. The primary endpoints were elimination of virus in oropharyngeal and nasopharyngeal swabs on 7 day of admission and discharge from the hospital by 14 day. RESULTS: Patients assigned to riamilovir had significantly shorter time to clinical improvement as well as increased PCR negative rate by day 7. CONCLUSION: Yearly administration of riamilovir as opposed to the umifenovir and ribavirin in therapy of moderate SARS-CoV-2 infection was associated with significant shorter time to clinical improvement by 14 day of hospitalization. PCR negative rate by 7 days of hospitalization is significantly more likely in riamilovir group.