[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®).

The investigation of the dynamics of changes in neutralizing antibody titers against type 5 adenovirus in the context of vaccination against a new coronavirus infection.

This research focuses on analyzing the dynamics of neutralizing antibody (nAbs) titers against type 5 adenovirus (Ad5) in the adult population of Russia following vaccination against the novel coronavirus infection with recombinant adenovirus type-5 COVID-19 vaccine (CanSino Biologics, China). The impact of the Ad5 vector on nAb titers was investigated using 302 blood serum samples from individuals who received a single dose of the Ad5-nCoV vector vaccine. The research revealed that 33.8% of adults in Russia had pre-existing anti-Ad5 nAbs before the pandemic. Notably, 40% of vaccinated individuals did not exhibit an increase in nAbs titers upon receiving the Ad5-based vaccine. However, in the group with no or low titers of anti-Ad5 nAbs (1:10-1:40), a significant 8-16-fold increase in nAb titers to Ad5 was observed.

[Prognostic factors in patients with hematological malignancies and concomitant chronic hepatitis C].

The study evaluated the impact of HCV infection on the prognosis in patients with hematological malignancies. A total of 96 patients with anti-HCV antibodies were enrolled, with the age of 37.8 (3.0-81.0) years old, 39.6% had non-Hodgkin's lymphoma. Chronic hepatitis C (CHC) was diagnosed in 46.9% patients prior to malignancy development, in 38.5% patients simultaneously with malignancy, and in 14.6% patients during malignancy treatment. Clinical and biochemical signs of HCH were mild in most of the patients, minimal liver fibrosis (F0-1 by METAVIR system) was discovered in 47.3% patients, severe fibrosis or cirrhosis (F3-4) was diagnosed in 40% of participants. Only 20 (20.8%) of patients received antiviral therapy against HCV prior to enrollment. Regression analysis demonstrated that age >55 years old, late onset of antiviral therapy, and poor nutritional status were significant predictors of death from hematological malignancy. Survey conducted among physicians of hematological oncology hospitals in Saint-Petersburg revealed gaps in knowledge on presentation and risks of HCV infection, as well as on opportunities of modern antiviral therapy.

[Informativeness estimation for the main clinical and laboratory parameters in patients with severe COVID-19].

AIM: To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death. MATERIALS AND METHODS: A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately. RESULTS: Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74). CONCLUSION: Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

[Evaluation of the effectiveness of ARVI treatment regimen including etiotropic (enisamium iodide) and symptomatic treatment].

AIM: To assess the effectiveness of the use of the antiviral drug enisamium iodide in the complex treatment of acute respiratory viral infections (ARVI) caused by various pathogens in routine clinical practice. MATERIALS AND METHODS: А prospective randomized study included 134 patients who were treated in the epidemic season of influenza and ARVI in 20182019. All patients were examined for the presence of influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, rhinoviruses, adenoviruses in nasopharyngeal swabs by PCR. Patients of the main group received enisamium iodide along with symptomatic therapy, the control group received only symptomatic therapy. The primary parameter of the effectiveness of therapy was evaluated on the scale of the general severity of the manifestations of ARVI (Total Symptom Score TSS) from the 2nd to the 4th day and by the secondary criteria of effectiveness: assessment of the duration of ARVI, the severity of fever, the proportion of patients with normal body temperature, the duration of the main clinical symptoms of acute respiratory viral infections, the proportion of patients in whom complications requiring antibiotics were noted, the dynamics of interferon status on the 6th day. To conduct a statistical analysis, depending on the efficiency parameter, the ANCOVA method with a fixed group factor and an initial score on the TSS severity scale was used as covariates, a criterion for comparing quantitative indicators in two independent groups. RESULTS: According to the results of the analysis of the primary efficacy parameter, the median (interquartile range) of the average score on the scale of the general severity of ARVI manifestations in the main group was 4.33 (3.675.83), in the comparison group 6.00 (4.677.25; p0.001). The duration of systemic and local manifestations of acute respiratory viral infections was statistically significantly less in the main group (p=0.002 and p=0.019, respectively). Prescription of additional therapy was required in 2 (2.9%) patients of the main group (patients taking enisamium iodide), compared with 8 (11.9%) patients in the control group. Serum levels of interferon  and interferon  on the last day of treatment were statistically significantly higher in patients of the main group compared with the control group (p0.001). Treatment (excellent) was evaluated by 42 (62.7%) patients, while in the control group only 17 (25.8%) patients gave similar ratings. Both patients (p0.001) and doctors (p0.002) rated therapy tolerance better in the study group. CONCLUSION: The results confirmed the safety and effectiveness of enisamium iodide as a treatment for ARVI and influenza. The antiviral, interferonogenic and anti-inflammatory properties of the drug are involved in the formation of an antiviral response and reduce the risk of complications, which makes it possible to reduce the number of symptomatic agents used.

[The practice of using a domestic antiviral drug in the etiotropic therapy of acute respiratory viral infection].

AIM: Evaluation of efficacy, safety, tolerability, and determination of the optimal dose of riamilovir in patients diagnosed with acute respiratory viral infection (ARVI). MATERIALS AND METHODS: The study included 270 patients with uncomplicated ARVI of mild and moderate severity (with a laboratory-confirmed PCR method for the presence of ARVI antigens, absence of influenza virus antigens). Patients were included in the study after signing an informed consent. Patients were randomized into 3 groups in a 1:1:1 ratio of 90 patients in each group. Completed the study in accordance with the Protocol: 267 patients. The study involved patients diagnosed with ARVI. RESULTS: Confirmed the efficacy, safety and tolerability of the drug riamilovir. Adverse drug reactions associated, in the opinion of the doctor, with taking the drug and resulting in discontinuation of the drug, were not noted in this study. CONCLUSION: As a result of clinical study, the effectiveness of both ARVI treatment regimens with drug riamilovir has been shown. There were no differences in the effectiveness and safety of the proposed treatment regimens. Practical use of both treatment regimens is recommended. However, according to the authors, taking the drug 3 times a day is much more convenient for patients, improves the quality of life and adherence to therapy.

Co-morbidity of infectious and addictive diseases in St. Petersburg and the Leningrad Region, Russia.

The Russian health care system is organized around specific diseases, with relatively little focus on integration across specialties to address co-morbidities. This organizational structure presents new challenges in the context of the recent epidemics of injection drug use (IDU) and HIV. This paper uses existing and new data to examine the prevalence of reported new cases of drug dependence (heroin) and HIV over time as well as associations between drug dependence and alcoholism, hepatitis B and C, and tuberculosis in the City of St. Petersburg and the Leningrad region. We found a sharp rise in reported cases of IDU beginning in 1991 and continuing until 2002/2003, followed by a sharp rise in newly reported cases of HIV. These rises were followed by a drop in new cases of HIV and drug addiction in 2002/2003 and a drop in the proportion of HIV-positive individuals with IDU as a risk factor. Infection with hepatitis B and C were common, especially among injection drug users (38 and 85%, respectively), but also in alcoholics (7 and 14%). Tuberculosis was more common in alcoholics (53%) than in persons with alcoholism and drug dependence (10%), or with drug dependence alone (4%). Though these data have many limitations, they clearly demonstrate that drug dependence and/or alcoholism, HIV, hepatitis, and tuberculosis frequently co-occur in St. Petersburg and the Leningrad Region. Prevention and treatment services across medical specialties should be integrated to address the wide range of issues that are associated with these co-morbidities.

[The assessment of the course of an infectious process by the membrane status of the peripheral blood lymphocytes]. / Otsenka techeniia infektsionnogo protsessa po sostoianiiu membran limfotsitov perifericheskoi krovi.

Lipid peroxidation in lymphocyte membranes is studied in patients with acute viral hepatitis B and B + C and in chronic alcoholics with Flexner's dysentery and with uneventful premorbid history. The intensity of lipid peroxidation in lymphocytes was increased, corresponding to the severity and period of infection. The premorbid background and therapy influenced the lymphocyte membrane status, which can serve as an integral indicator of immunological reactivity of the organism.