ABSTRACT
The aim of the study was to evaluate the efficacy and safety of an RNA double-stranded sodium salt drug, a lyophilisate for a solution preparation for an intramuscular and subcutaneous administration, as a means of post-exposure COVID-19 prophylaxis in comparison with placebo.Material and methods. A double-blind, placebo-controlled, multicenter, randomized phase III clinical trial was conducted to evaluate the efficacy and safety of a double-stranded sodium salt RNA drug (RADAM IN (R) VIRO), a lyophilisate for preparing a solution for intramuscular and subcutaneous administration as a means of post-exposure prophylaxis of COVID-19. The study was conducted in 10 research centers in the Russian Federation from May 31, 2022 to January 17, 2023. The study included men and women aged =18 years who cohabitate with a person with a documented COVID-19 diagnosis and do not have symptoms characteristic of COVID-19. At the randomization stage, the subjects were assigned to one of two groups: group 1 (n=400) received a study drug RADAM IN (R) VIRO 5 mg (1 vial) intramuscularly once a day;group 2 (n=400) received placebo 1 vial intramuscularly once a day. The total duration of the study for each subject was no more than 30 days.Results. By day 10-11, in the double-stranded sodium salt RNA drug group, the proportion of the subjects with confirmed COVID-19 and at least 1 symptom characteristic of COVID-19 was 5.76% (23/399), and in the placebo group - 11.03% (44/399). The difference in proportions between the study drug and placebo groups was 0.0526 (5.26%), the 95% confidence interval (CI) for the difference in proportions between the groups was [0.0123;0.0937]). More than 94% of single-dose subjects did not become infected with COVID-19 with any symptoms during the 11 days of the follow-up. As a result of a comparative analysis, it was shown that the infection frequency in the study drug group was statistically significantly (almost twice) less than in the comparison group, which indicates a high efficiency and expediency of using the double-stranded sodium salt RNA drug as a means of the post-exposure COVID-19 prophylaxis.Conclusion. Thus, regardless of the vaccination availability, the effectiveness and feasibility of using the study double -stranded sodium salt RNA drug as a means of the post-exposure COVID-19 prophylaxis was demonstrated not only in medical institutions (outpatient clinics and hospitals), but also in caregivers and/or the persons in contact with COVID-19 patients. The situation was the same in the organizations and enterprises in case of evolution of a mass infection threat and the availability of appropriate medical personnels.
ABSTRACT
The article presents the data from an open, two-stage, multicenter study on the efficacy and safety evaluation of a combined drug (a fixed combination of nirmatrelvir 300 mg, and ritonavir 100 mg) in the complex therapy in COVID-19 patients. The aim of the study was to assess the safety, tolerability and pharmacokinetic parameters of the fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg in healthy volunteers, the efficacy and safety assessment of the drug in the combination therapy compared with the standard therapy in COVID-19 patients. Material and methods. An open two-stage multicenter clinical study to assess the main pharmacokinetic parameters, safety, and efficacy against COVID-19 of the drug nirmatrelvir 300 mg and ritonavir 100 mg combination (Skyvira((R)) PROMOMED RUS LLC, Russia) in the adult population, included 2 stages. At stage 1, safety, tolerability and pharmacokinetic parameters were evaluated in healthy volunteers (over 18 years of age) in order to confirm their comparability with the literature data known for a set of active substances. Phase 2 assessed efficacy and safety in COVID-19 patients. As a part of the second stage, the study involved 264 patients (men and women aged 18 to 80 years), who had been divided into two groups. The first group patients (n=132) received the study drugs (nirmatrelvir 300 mg and ritonavir 100 mg) - 1 tablet twice a day with an interval of 12 +/- 2 hours for 5 days in combination with pathogenetic and symptomatic therapy. The second group patients (n=132) received standard therapy in accordance with the approved Temporary Guidelines for the Prevention and Treatment of Novel Coronavirus Infection (Version 15 dated February 22, 2022). Results. During the study, none of the patients from the (nirmatrelvir + ritonavir) group experienced a transition of the COVID-19 course to a heavier severity level, in contrast to the patients in the standard therapy group. The study participants included patients with comorbidities (68% of the general population), with risk factors for COVID-19 progression to a heavier severity level and the risk of hospitalization (75% of the general population). There were no cases of COVID-19 progression to a heavier severity level in the study drug group. By the 6th day, in the nirmatrelvir + ritonavir group, the proportion of the patients who had achieved a complete recovery was twice more and amounted to 35.61% (p=0.0001), and the proportion of the patients with a negative RNA analysis to SARS-CoV-2 was 20% higher than in the comparison group, and amounted to 82.58% (p=0.0001). The fixed nirmatrelvir + ritonavir combination therapy has a favorable safety profile comparable to the standard therapy. The identified adverse reactions were transient in nature and did not require discontinuation of therapy or changes in the treatment regimen. Conclusion. The fixed nirmatrelvir + ritonavir combination has a favorable safety profile in COVID-19 patients, comparable to the standard therapy. The data obtained demonstrate a clinical and pharmacoeconomic feasibility of including the fixed (nirmatrelvir + ritonavir) combination in the COVID-19 treatment regimen.
ABSTRACT
COVID-19 is a new highly contagious infectious disease caused by the SARS-CoV-2. The World Health Organization (WHO) on March 11, 2020, has declared the novel coronavirus (COVID-19) outbreak a global pandemic. More attention is currently paid to the fact that men are more at risk for worse outcomes. In addition, SARS-CoV-2 can infect the testes, potentially affecting testosterone production, as well as having a negative influence on the reproductive potential. Our aim was to review the current concepts of the possible influence of testosterone levels on the pathogenesis of COVID-19 in men and to present the available data on the impact of COVID-19 on the structure and function of the testis. Based on the analysis of 72 articles using the MEDLINE database (PubMed), it can be concluded that testosterone is involved in the co-regulation of the synthesis of angiotensin-converting enzyme-2 and transmembrane serine protease-2, facilitating the penetration of SARS-CoV-2 into target cells and promoting easier infection in men. On the other hand, low testosterone levels increase the risk of cardiopulmonary complications. Hypogonadism appears to be an important unfavorable prognostic factor for the disease. Orchitis is a reported complication of COVID-19. Damage to testicular tissue is possible due to direct invasion by a virus, a secondary autoimmune reaction, hyperthermia and thrombosis of testicular microvessels. Prophylaxis of possible vertical and sexual transmission of infection is recommended. Despite the available data, further studies are required to assess the definite role of androgens in the course of infection and the influence of SARS-CoV-2 on male reproductive potential.
ABSTRACT
Clinical practice shows that in addition to a life-threatening condition caused by lung damage, the SARS-CoV-2 virus provokes multiple organ damage and systemic endothelial inflammation, leading to serious, often fatal consequences. The complex pathophysiology of the virus and the mechanisms of its effect on the body require the development of complex therapy aimed at minimizing the systemic damage, as well as protecting the organs and tissues involved in order to improve the prognosis of the course of the disease. Early initiation of antiviral therapy aimed at inhibiting a specific mechanism of the SARS-CoV-2 virus is necessary to reduce the viral load and the risk of complications. The review provides information on the safety and clinical efficacy of favipiravir in the treatment of infectious diseases caused by RNA viruses, in particular COVID-19, as well as the possibility of using Areplivir (favipiravir) in patients with new coronavirus infection. © 2021 Nutritec. All rights reserved.
ABSTRACT
Severe Acute Respiratory Syndrome (SARS-CoV-2) has spread rapidly throughout the world, causing high morbidity and mortality. Analysis of clinical and autopsy data may allow to understand this disease. The results of pulmonary and renal autopsies in 37 deceased patients from COVID-19 are presented. MATERIALS AND METHODS: An autopsy was performed in Moscow in 37 deceased patients aged from 28 to 94 years. The microscopic features of the lungs and kidneys were examined using hematoxylin and eosin staining. RESULTS: Important findings include diffuse alveolar injury, pulmonary thrombosis and microangiopathy, as well as acute kidney injury in all cases, varying in severity. CONCLUSIONS: We report the presence of acute kidney injury in all cases, which requires correction of renal function in patients with SARS-CoV-2, with control of serum creatinine levels, urine volume, proteinuria and hematuria.
ABSTRACT
The aim of this study was to analyze the symptoms of depression, anxiety, and stress in urologists during the COVID-19 pandemic. MATERIALS AND METHODS: 90 urologists aged 25 to 60 years (M=37.27, S.D.=9.53), 93% of them were men, participated in the online survey. They answered questions about their attitude to their job as doctors and the impact of COVID-19. They filled out the Depression, Anxiety and Stress Scales (DASS-21), the Ten Item Personality Inventory (TIPI) and answered questions assessing their sense of control. RESULTS: The greatest concern among urologists is the risk of getting infected with COVID-19 (for 30% of the doctors). 43% of urologists state that their profession interesting. A positive attitude to work, as well as the Big Five traits (Conscientiousness, Emotional Stability and Agreeableness) are associated with lower levels of depression, anxiety, stress and lack of control. Working with COVID-19 patients reduces stress and increases the sense of control. Age and high levels of Emotional Stability predicted lower levels of anxiety, depression and stress. DISCUSSION: Working with COVID-19 patients allows doctors to feel more control over what is happening. A sense of control, in turn, and a positive attitude towards work are associated with a lower levels of depression, anxiety and stresssymptoms. CONCLUSION: The results of this study can be used in selection of therapeutic targets for psychotherapy, administered to doctors;in prevention of symptoms of anxiety, stress and depression among doctors;and in professional selection of doctors for working in crisis situations.