[The effect of etiopathogenetic therapy of COVID-19 on the severity of the disease: results of a multicenter double-blind placebo-controlled randomized trial].

AIM: The search for etiopathogenetic agents to prevent the development of severe and extremely severe COVID-19 remains relevant. A placebo-controlled randomized clinical trial was conducted to evaluate the efficacy and safety of the antibody-based biological drug (Raphamin). MATERIALS AND METHODS: 785 outpatients 18-75 y.o. with laboratory confirmed mild COVID-19 were included within 24 hours from the disease onset. 771 patients were randomized to the group Raphamin (n=382) and the Placebo group (n=389). The study drug/placebo was prescribed for 5 days. The rate of progression to a more severe degree of COVID-19 by day 28 as well as the time to sustained clinical recovery and the frequency of hospitalization were evaluated. Safety was assessed taking into account adverse events, vital signs and laboratory parameters. RESULTS: The number of cases of progression to a more severe degree of COVID-19 in participants receiving Raphamin was 59 (15.5%) [52 (14.6%)] versus placebo - 89 (22.9%) [85 (23.7%)], ITT and [PP] analysis data are presented. The odds ratio between groups was OR=0.6157 [OR=0.5494], 95% confidence interval 0.4276-0.8866 [0.3750-0.8048], which meant a reduction in the chance of progression to a more severe degree by 38.4% [45.1%] or 1.48 [1.62] times; p=0.0088 [p=0.0019]. The time to sustained recovery in the Raphamin group was 4.5±2.4 [4.6±2.4] days, versus placebo - 5.8±4.7 [6.0±4.8] days; p=0.0025 [p=0.0036]. No adverse events with a certain relationship were registered. CONCLUSION: Raphamin reduces the risk of progression to a more severe degree of the COVID-19 and significantly shortens the duration of clinical symptoms.

[Non-specific prevention of COVID-19 during vaccination against a new coronavirus infection: results of a multicenter, double-blind, placebo-controlled, randomized clinical trial].

BACKGROUND: A multicenter, double-blind, placebo-controlled, randomized clinical trial (RCT) of the phase III efficacy and safety of Ergoferon® for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection was conducted (permission of the Ministry of Health of the Russian Federation №559 dated 22.09.2021; ClinicalTrials.gov Identifier: NCT05069649). AIM: To evaluate the efficacy and safety of the use of Ergoferon for the non-specific prevention of COVID-19 during vaccination against a new coronavirus infection. MATERIALS AND METHODS: From October 2021 to April 2022, 1,057 patients aged 18 to 92 years who received component I of the "Gam-COVID-Vac" vaccine were included. After screening, 1,050 patients were randomized into 2 groups: 526 people received Ergoferon according to the prophylactic scheme - 1 tablet per administration 2 times a day for 3 weeks, the drug is not allowed during the meal and should be kept in the mouth without swallowing, until completely dissolved; 524 patients received a placebo according to the Ergoferon® scheme. The total duration of participation in the study was 5 weeks + 3 days. The primary endpoint is the number of RT-PCR - confirmed cases of SARS-CoV-2 infection, regardless of the presence of symptoms during participation in the study. An additional criterion of effectiveness is the proportion of those hospitalized with COVID-19. The safety assessment included consideration of the presence and nature of adverse events (AEs), their severity, relationship with the drug intake, and outcome. Statistical data processing was carried out using SAS 9.4 with the calculation of the exact Fisher test, χ2 test, Cochrane-Mantel-Hensel test, Wilcoxon test and other parameters. RESULTS: The ITT (Intention-to-treat) and PP [Per Protocol] efficacy analysis included data from 1,050 [970] patients: 526 [489] people - Ergoferon® group and 524 [481] people - Placebo group. The primary endpoint - the number of laboratory-confirmed cases of SARS-CoV-2 infections was 3 times less compared to placebo - 7 (1.43%) vs 22 (4.57%), respectively (p=0.0046; [p=0.0041]). Taking Ergoferon® reduces the risk of SARS-CoV-2 infection by more than 3 times in vaccinated patients during 5 weeks of the vaccination and post-vaccination periods (p=0.0046 [p=0.0041]). Of the COVID-19 patients in the Ergoferon® group (1.33%) nobody was hospitalized. According to the Post hoc analysis, Ergoferon® reduces the risk of COVID-19 disease by 4 times in the period between the components I and II of the "Gam-COVID-Vac" vaccine (p=0.0066 [p=0.006]). The frequency of AEs in both groups did not differ. There were no registered AEs associated with the drug with a reliable degree. There was a high level of patient compliance and good tolerability. CONCLUSION: Ergoferon is an effective and safe drug for the prevention of COVID-19 in people vaccinated against a new coronavirus infection.

[Analysis of the dental care for the contagious patients in the in-patient units]. / Analiz sostoyaniya stomatologicheskoi pomoshchi infektsionnym bol'nym v usloviyakh statsionara.

OBJECTIVE: The aim of the study is to assess the status of dental care for contagious patients in hospitals using the example of the Volga Federal District. MATERIALS AND METHODS: The resource allocation of dental care for contagious patients in 313 hospitals of 14 subjects of the Volga Federal District was investigated. RESULTS: It was found that in 86.1% of multidisciplinary hospitals of the Volga Federal District, where infectious beds and dental offices are present, dental care for patients with infectious diseases accompanied by lesions of the oral mucosa is not provided. The bed capacity of 92.9% of infectious hospitals in the Volga Federal District is less than 400 beds, which does not allow to deploy dental offices on their basis. CONCLUSION: An important condition for improving the quality of medical care to patients of infectious hospitals and infectious diseases departments of multidisciplinary hospitals is the availability of dental offices and dental doctors, which will ensure timely diagnosis, treatment and prevention of lesions of the oral mucosa in diseases of infectious genesis.

[Pharmacoepidemiological research of COVID-19 in the Russian Federation EGIDA-2020].

AIM: An analysis of coronavirus infection in Russia and evaluation of different AVT regimens effectiveness. MATERIALS AND METHODS: The study involved a retrospective analysis of 1082 patient records with laboratory-confirmed COVID-19 in 17 regions of Russia. The number of men and women was equal, mean age 48.718.1 (median 50). Patients with moderate COVID-19 (85%) versus mild COVID-19 (15%) were characterized by higher age (median 54 vs 21 years; p0.001), higher body mass index (27.8 vs 23.4; p0.001), prevalence of chronic diseases (75.3% vs 8.5%; p0.001), including circulatory system diseases (37.8%). Moderate COVID-19 characterized higher intoxication (10.86.1 vs 4.22.7 days; p0.001) and catarrhal symptoms duration (10.25.4 vs 6.14.1 days; p0.001). RESULTS: During hospitalization 92% of the patients received AVT, 77% antibiotics, and 16% corticosteroids. Umifenovir therapy resulted in a significant reduction of intoxication (8.75.5 vs 11.75.5 days; p0.001) and catarrhal symptoms duration (8.85.1 vs 12.04.9 days; p0.001) compared to the group without AVT. The usage of INF reduced intoxication symptoms compared with the group without AVT (8.97.5 vs 11.75.5; p0.05). Therapy with hydroxychloroquine, imidazolylethanamide pentandioic acid, and lopinavir + ritonavir combination did not affect the course of COVID-19. Most of adverse reactions were related to antibiotics. CONCLUSION: Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients.

[Oral health as a factor of primary prevention of postinfectious complications]. / Zdorov'e organov rta kak faktor pervichnoi profilaktiki postinfektsionnykh oslozhnenii.

OBJECTIVE: The purpose of the study is to substantiate the need and importance of early diagnosis and treatment of oral lesions in infectious diseases (ID) by dentists. MATERIAL AND METHODS: A retrospective analysis of the provision of dental care in multi-specialty hospitals to 780 patients with infectious pathology: herpetic infections (HI) - 320 people (41.03%); ARVI - 160 people (20.51%); acute enteric infections (AEI) - 300 people (38.46%). The diagnosis of the disease was established by infectious diseases doctors. The etiology of ID was confirmed using PCR and IFA. RESULTS: The prevalence of caries is 98.5%, the CPEs index is 10.26±0.04. In 84.1% of patient's oral hygiene was unsatisfactory. In the acute period of ID in HI, ARVI and AEI oral mucosa (OM) lesions were detected in 75.89% of cases: stomatitis (81.75%), gingivitis (69.76%), glossitis (35.98%), cheilitis (23.31%). Incidence of OM lesions in ID: catarrhal stomatitis - HI - 52.8%, ARVI - 64.1%, AEI - 67.9%; catarrhal gingivitis: in patients with HI, it is 1.7 times less frequent than in patients with AEI (p<0.001), and in ARVI - 1.6 times more often than in patients with HI (p<0.001). Cheilitis: HI - 25.9%, ARVI - 18.3%, AEI - 23.7%; catarrhal glossitis: AEI - 65.1%, ARVI - 23.2%, HI - 17.0%; candidiasis of the oral mucosal and tongue: HI - 11.1%, ARVI - 27.5%, AEI - 26.9%. A direct relationship between the lesions of OM and the severity of the course of HI, ARVI and AEI was established. CONCLUSION: Thus, dental pathology in infectious patients is pathogenetically determined by combined and interrelated disorders of the functional state of each organ of the oral cavity, the dental system and the body as a whole. Due to the relatively short duration of inpatient treatment for acute ID, priority should be given to the prevention of postinfectious complications of oral mucosal diseases.

[Evaluation of Photo- and Cytotoxicity of Chlorin e6 Ester Derivatives and Their Liposomal Forms].

Photophysical characteristics and photosensitizing activity of the chlorin e6 dimethyl and trimethyl ester derivatives in various solution and their liposomal forms were studied. It was shown that in lipid vesicles chlorin e6 ester derivatives are predominantly in the monomeric state and possess optimal photophysical properties and high photochemical activity. The rate of redistribution of the chlorin e6 dimethyl ester from lipid vesicle to cells was higher as compared with that one of the chlorin e6 trimethyl ester. The increase of the serum concentration in the incubation medium has a different effect on processes of accumulation of the liposomal forms of the chlorin e6 dimethyl and trimethyl ester derivatives by the cells. Cell culture studies showed that application of liposomal forms of the chlorin e6 dimethyl and trimethyl ester derivatives significantly decreases their cytotoxicity but keeps high cytotoxic effect of photodynamic activity of the chlorin e6 ester derivatives.

Generation of iPS Cells from Human Hair Follice Dermal Papilla Cells.

Dermal papilla (DP) cells are unique regional stem cells of the skin that induce formation of a hair follicle and its regeneration cycle. DP are multipotent stem cells; therefore we supposed that the efficiency of DPC reprogramming could exceed that of dermal fibroblasts reprogramming. We generated induced pluripotent stem cells from human DP cells using lentiviral transfection with Oct4, Sox2, Klf4, and c-Myc, and cultivation of cells both in a medium supplemented with valproic acid and at a physiological level of oxygen (5%). The efficiency of DP cells reprogramming was ~0.03%, while the efficiency of dermal fibroblast reprogramming under the same conditions was ~0.01%. Therefore, we demonstrated the suitability of DP cells as an alternative source of iPS cells.

[Genetic characteristic of toxigenicity of group A streptococci cultures isolated from patients with tonsillitis].

Twenty-eight strains of group A streptococci (GAS) isolated from patients with lacunar and fibrinous-necrotic forms of tonsillitis during its 1st or recurrent episode were tested for presence of genes of erythrogenictoxins A, B, C, and Fusing PCR assay. Obtained results allow to consider that clinical features of the disease (severity, repeatedness, clinical form) can be determined by toxigenicity of GAS. Express identification of S. pyogenes on the basis of detection of erythrogenic toxins genes spe B and spe F (mf) can be used for etiologic confirmation of diagnosis, whereas detection of erythrogenic toxins genes spe A and spe C can be recommended for prediction of the disease's course.