[Results of a randomized double-blind multicenter clinical trial of the efficacy and safety of riamilovir in the treatment of COVID-19].

AIM: To evaluate the efficacy and safety of riamilovir in the treatment of COVID-19 in adults. MATERIALS AND METHODS: The study included 180 patients with a laboratory-confirmed diagnosis of COVID-19 which fully meet the criteria for inclusion, non-inclusion and exclusion, signed a voluntary informed consent to participate in a clinical trial. RESULTS: The efficacy, good tolerability and safety of the drug riamilovir in the treatment of COVID-19 have been established. CONCLUSION: As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for therapeutic use in patients with COVID-19 according to the 1250 mg/day scheme (250 mg capsules 5 times per day) for 10 days was established. The drug riamilovir in a daily dose of 1250 mg for 10 days does not differ in safety from placebo.

[Results of a randomized double-blind multicenter clinical trial of the efficacy and safety of the drug riamilovir for the prevention of COVID-19].

AIM: Evaluation of the efficacy and safety of riamilovir as a drug for the prevention of coronavirus infection (COVID-19) in adults who have constant contact with COVID-19 patients as a result of living together. MATERIALS AND METHODS: The study included 750 adult participants living with patients with confirmed polymerase chain reaction method COVID-19, who had a negative polymerase chain reaction result for the SARS-CoV-2 virus at the initial level, met the criteria for inclusion, non-inclusion and exclusion, and signed a voluntary informed consent to participate in a clinical trial. RESULTS: The efficacy, good tolerability and safety of the drug riamilovir for the prevention of COVID-19 infection among people who have come into contact with COVID-19 patients in a family focus of infection have been established. CONCLUSION: As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for the prevention of COVID-19 infection was established. It was shown that the relative risk of disease in the group taking riamilovir for prophylaxis was 88.96% lower than in the control group. Based on the results of a clinical trial, in October 2023 Ministry of Health of the Russian Federation approved the inclusion of a new indication (prophylaxis of COVID-19 infection) in the instructions for the medical use of the drug riamilovir (trade name - Triazavirin®).

General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

[Clinical efficiency and safety of riamilovir under various dosage regimens for treatment of acute respiratory viral infections in adults].

AIM: To evaluate the clinical efficacy and safety of antiviral drug riamilovir in patients with acute respiratory viral infections (ARVI) of non-coronavirus (SARS-CoV-2) etiology with different dosing regimens. MATERIALS AND METHODS: The study included 150 patients with ARVI aged 18-27 years (50 patients received riamilovir in the regimen of 250 mg 3 times a day for 5 days, 50 patients received riamilovir in the off label regimen of 250 mg 5 times a day for 5 days, 50 patients received only pathogenetic treatment). RESULTS: The use of riamilovir in both treatment regimens led to a reduction in the duration of inpatient treatment. The shortest periods of hospitalization were noted in patients who received the study drug at higher daily dosages. The use of riamilovir reduced the duration and severity of general infectious manifestations of the disease, while the shortest total duration of fever and a number of respiratory tract syndromes was registered among people who received riamilovir in the regimen of 1250 mg per day for 5 days, no adverse events were registered, additionally, 100% elimination of ARVI pathogens was noted in 1250 mg per day group. CONCLUSION: Riamilovir has shown clinical efficacy and a good safety profile in in both treatment regimens. The dosage regimen of 1250 mg per day led to more significant clinical effects and to 100% elimination of ARVI pathogens in the study group by the 6th day of hospitalization.

[The experience in treatment of dengue fever using antiviral drug riamilovir in the Republic of Guinea (case report)].

Dengue fever is classified as one of the most common viral diseases with a transmission mechanism implemented through arthropod vectors. The expansion of of the Aedes aegypti mosquito is leading to a significant increase in the number of cases of dengue fever in more than 100 countries, highlighting the importance of developing and implementing specific prevention and treatment measures. Etiotropic drugs with proven efficacy against the pathogen are not registered, and the use of the vaccine is approved only among seropositive individuals. In this regard, pathogenetic treatment remains the main therapeutic strategy, however, work on the synthesis of antiviral drugs is being actively carried out. Due to the unique functions of non-structural proteins NS3 and NS5 in the viral replication cycle, they have become the main targets for studying the antiviral activity of a number of chemotherapy drugs. Of these proteins, due to the most conserved structure, the NS5 protein is a promising target for inhibition, however, success in obtaining a clinical effect using a number of available antiviral drugs has not been reached. This study describes the positive experience of using the nucleoside analogue riamilovir in the treatment of a patient with dengue fever in the Republic of Guinea.

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.

[Analysis of fatal outcomes of meningococcal infection in adults].

Clinical characteristics and pathomorphological manifestations in 69 patients aged 18 to 86 years with a fatal outcome of the disease were examined in order to analyze the causes of severe course and high mortality of generalized forms meningococcal infection. It was found that the main clinical form was meningococcemia (90%), in the majority in combination with meningitis (52%). The fulminant course in 77% of patients with meningococcal sepsis manifested itself as a sudden onset, rapid development of typical symptoms. Hemorrhagic exanthema was detected on the first day of meningococcemia. The leading complications and critical conditions were infectious-toxic shock, disseminated intravascular coagulation and acute adrenal insufficiency (Waterhouse-Friederiksen syndrome). The severe course of meningitis (in 10%) led to the development of cerebral coma, the morphological substrate of which was edema - swelling of the brain.

[Efficacy and safety of bulevirtide in patients with chronic hepatitis D and compensated cirrhosis].

AIM: To study the efficacy and safety of bulevirtide, the HBV and HDV entry inhibitor. MATERIALS AND METHODS: Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha-2a (PEG-IFN). RESULTS: Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients. Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%). Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events. CONCLUSION: Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.

[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.

[Possibilities of endovenous laser obliteration of subcutaneous veins with tumescence by cold saline solution]. / Vozmozhnosti éndovenoznoi lazernoi obliteratsii podkozhnykh ven s tumestsentsiei okhlazhdennym fiziologicheskim rastvorom.

AIM: The purpose of the present study was to assess the possibility of carrying out endovenous laser obliteration (EVLO) with radial light guides on a laser device operating at a wavelength of 1470 nm, using for tumescence only cold normal saline solution without additional sedation or narcosis in patients with allergy to local anaesthetics. PATIENTS AND METHODS: Our prospective non-comparative single-centre study consecutively included 37 patients who from November 2014 to June 2019 underwent a total of 41 isolated EVLO procedures without simultaneous miniphlebectomy or sclerotherapy of tributaries. Given the previous history of allergy to amide-group local anaesthetics and/or multiple allergic reactions to other agents, these patients received as anaesthesia and tumescence exclusively normal saline solution cooled to a temperature of +3-6ºC, without addition of local anaesthetics or any other therapeutic agents, with neither sedation nor narcosis. RESULTS: The great saphenous vein was subjected to coagulation in 33 (80.5%) cases, the anterior accessory saphenous vein in 5 (12.2%), and the small saphenous vein in 3 (7.3%) cases. The median of the mean diameter of the veins at 3 cm from the saphenofemoral or saphenopopliteal junction amounted to 10 mm (1st quartile 8.2; 3rd quartile 11). The median of the mean length of the coagulated vein - 45 cm (1st quartile 22; 3rd quartile 51), the median of the average amount of the administered normal saline solution - 300 ml (1st quartile 200; 3rd quartile 450), the median of the average amount of normal saline per 1 centimetre of the venous length - 8.7 ml (1st quartile 7.5; 3rd quartile 10). All patients without exception tolerated the intervention. The process of laser obliteration was not discontinued due to pronounced perioperative pain syndrome in any case. All patients after the procedure answered the question 'Would you repeat a similar intervention if the need arises?' in the affirmative. All the 41 (100 %) veins subjected to coagulation were obliterated at early terms of follow up, with no ultrasonographic evidence of recanalization. CONCLUSION: The obtained findings suggest a possibility of performing EVLO in patients with an allergy-burdened history in relation to local anaesthetics using for tumescence exclusively normal saline solution chilled to a temperature of +3-6ºC, with no additional sedation or narcosis. Such an approach makes it possible, on the one hand, not to change the organization of outpatient phlebological care and on the other hand to refuse from involving anaesthesiological support. Besides, it is absolutely safe in relation to the risk for the development of allergic reactions.

Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia.

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

[ZIKA FEVER: CLINICAL, EPIDEMIOLOGICAL, LABORATORY, AND DIAGNOSTIC ASPECTS].

The authors overview data on the prevalence of Zika fever with reference to biological properties of the causative agent, epidemiological process, pathogenesis, and clinical symptoms of the disease. Special attention is given to the identification of the virus in pregnant women, microcephaly in the babies born by Zika-infected women, algorithm of laboratory diagnostics, and measures needed to prevent and control mosquitoes that spread viruses.

[Zika virus infection: clinical and diagnostic aspects and organization of preventive measures].

The article presents modem data about Zika virus outbreak, the biological characteristics of the pathogen, vectors, the nature of the epidemic process, pathogenesis and diagnosis of infection. This infection has a high potential for epidemic spread because vectors are widely represented in the fauna of many climatic and geographic zones. It presents information on the main clinical manifestations of the disease. Particular attention is paid to the problem of congenital maiformations of the nervous system (microcephaly and others) detected in infants born to women infected with Zika virus. The basis of therapy in this disease constitute a pathogenic agent. The'package of, measures for the prevention of disease caused by Zika virus, including early identification and treatment of patients, as well as measures for the destruction of the virus vectors.

[Evacuation of contagious patients in the modern system of medical support].

Evacuation of contagious patients in the modern system. of medical support. The main problematic issues of organizing and conducting the evacuation of contagious patients are defined. A peculiarity of evacuation and healthcare delivery to contagious patients is the need for permanent complex of sanitary and anti-epidemic (preventive) measures aimed at preventing the spread of infectious diseases. Set out fundamental approaches to triage of infectious patients at different stages of medical evacuation, defined sorting group. The attention is focused on the clinical-and-syndrome principle infectious pathology diagnostics. The experience of the medical evacuation of infectious diseases in Afghanistan is analysed. The necessity of protecting the accompanying medical staff is showed. The possibilities, the benefits and how to use for the isolation of infectious patients and the evacuation of mobile autonomous units - the transport of insulating boxes are studied.

[Organisation of medical care to military personnel with viral hepatitis. A during the local armed conflicts].

Organisation of medical care to military personnel with viral hepatitis A during the local armed conflicts. The article provides an analysis of medical care organisation system to patients with viral hepatitis A during conducting counterterror operations on the North Caucasus (1994-1996 and 1999-2002). The authors provided information on the main problems of medical support in modern local armed conflicts and shortcomings of organization of medical care to patients with viral hepatitis A in the following conditions: multistage, discrepancy between calculation of forces and facilities and character of military conditions, shortcoming of staff structure of medicalfacilities, inappropriate level ofproficiency ofphysicians of infectious profile and absence of regulations, concerning the use for equipment of infectious hospitals. 'Possible -ways for resolving these problems are showed.

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

Chemokine Receptors CXCR3 and CCR6 and Their Ligands in the Liver and Blood of Patients with Chronic Hepatitis C.

We performed a comprehensive analysis of CCR6 and CXCR3 chemokine receptors and their ligands CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, and CXCL11/ITAC in the liver and blood of patients with chronic hepatitis C at different stages of the disease. TaqMan PCR was used to determine mRNA gene expression of chemokines and their receptors in liver specimens, xMAP multiplex analysis was performed to estimate the concentration of chemokines in blood plasma, and fl ow cytofluorometry was used to evaluate CCR6 and CXCR3 expression on peripheral blood lymphocyte populations. In the liver of patients with hepatitis C, mRNA expression of CXCL10, CCR6, and CXCR3 genes increases with fibrosis progression in the liver tissue. In the plasma, concentrations of all studied chemokines increased depending on the stage of liver fibrosis, CCR6 and CXCR3 expression was changed in various lymphocyte populations. Thus, chemokines are involved in the immunopathogenesis and fibrogenesis in chronic viral hepatitis C. The results suggest using these chemokines in the diagnosis and prognosis of the disease.

[Effectiveness and safety of antiviral therapy of military personnel suffering from chronic hepatitis C].

In order to evaluate effectiveness and safety of antiviral therapy schemes examined and treated 191 patients with chronic bepatitis C were assigned standard interferon and ribavirin, pegslated interferon and ribavirin, the total duration of the course coput 24-48 weeks. Based on clinical and laboratory parameters evaluated the safety of antiviral therapy. Formation of sustainable viral response, depending on the genotype observed, was given at 58,9-70%.of patients. In case of insufficient. antiviral therapy was prescribed a second course that will improve the effectiveness of treatment to 90-95%. Correction of adverse events was held lower dosages of interferon and/or ribavirin.

[Meningococcal disease: early clinical diagnosis and emergency care].

Late diagnosis of meningococcal disease leads to high mortality. Early diagnosis of its generalized forms plays a crucial role in the pre-hospital phase and mainly based on the clinical picture of the disease. In most cases, pre-hospital typical mistake is late diagnosis of meningococcal disease: We propose an algorithm of early diagnosis of generalized forms of the disease in order to reduce the number of diagnostic errors. Proper and timely diagnosis will enable the physician pre-hospital fully implement measures to provide emergency and urgent care in generalized meningococcal infection, leading to. a more.favourable course and a significant improvement in the outcomes of the disease in the course of further hospital treatment.

[EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.