Evaluation of clinical outcomes of COVID-19 in patients taking remdesivir in complex therapy in routine clinical practice

Remdesivir (GS-5734) is a new direct-acting antiviral drug in the nucleotide analogue class with antiviral activity against SARS-CoV-2 and the ability to inhibit RNA-dependent RNA polymerase. Preliminary results from phase III randomized clinical trials of remdesivir are inconsistent. Understanding the fact of the limited world experience with the use of remdesivir in COVID-19 required further study of its efficacy and safety in real clinical practice. The aim of the study is to evaluate the efficacy and safety of remdesivir in the treatment of patients with COVID-19. Material and methods. The study included 1422 patients with a novel coronavirus infection (COVID-19) who received remdesivir as part of complex therapy in a hospital setting at medical organizations of the Moscow public health system. Additionally, standard therapy was carried out, regulated by the Interim Guidelines "Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19)" of the Ministry of Healthcare of the Russian Federation, the current version. The efficacy of the drug was assessed based on primary and secondary efficacy points. Primary variable: 1) cumulative incidence of clinical outcomes in patients with COVID-19 treated with remdesivir as part of complex therapy;2) median time to clinical improvement according to the World Health Organization ordinal categorical scale (under clinical improvement, the patient is assumed to move >2 categories towards improvement in clinical condition). Secondary variables: 1) median time to achieve <2 NEWS scores lasting at least 24 hours or hospital discharge;2) mortality from all causes;3) duration of fever (>38 degreeC), days;4) duration of hospitalization, days;5) time to achieve elimination of the pathogen from the upper respiratory tract (no SARS-CoV-2 RNA), days. The safety of remdesivir was assessed based on the registration of adverse events using the method of spontaneous reports. Results. The analysis of clinical outcomes of treatment showed that 1195 (84.1%) patients recovered, death from all causes occurred in 227 (15.9%) patients. The median improvement in clinical status on the World Health Organization ordinal categorical scale was 6 days. The median time to reach a NEWS score of <2, lasting at least 24 hours, or hospital discharge was 4 days. The median duration of fever was 3 days from the start of remdesivir administration. The median length of hospital stays for patients included in the Register was 9 days. Adverse reactions associated with the use of remdesivir were recorded in 11 (0.7%) patients. Serious adverse reactions were not registered. During hospitalization, all adverse reactions were resolved. Conclusion. A retrospective analysis of data from the Registry of 1422 patients with COVID-19 who received remdesivir as part of complex therapy in medical organizations of the state healthcare system of Moscow in routine clinical practice showed clinical efficacy and a favorable safety profile of remdesivir (Remdeform, lyophilizate for solution for intravenous administration 100 mg, manufactured by JSC Pharmasyntez, Russia). The data obtained are consistent with previous randomized clinical trials of remdesivir and allow us to recommend its further use in patients with COVID-19 as part of complex therapy.Copyright © The Author(s), 2022.

Efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia: a systematic review based on current and previous antiviral therapy.

Objective: To systematically evaluate the efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia (COVID-19). Method(s): Randomized controlled trials (RCTs), cohort studies, and case-control studies on the efficacy and safety of arbidol for COVID-19, influenza, andother respiratory virus infections were collected by searching related database at home and abroad and network platform for preprint of Health Science Papers (medRxiv) (up to April 25, 2020). Quality of the enrolled studies was evaluated by bias risk assessment tool of Cochrane collaboration network and Newcastle-Ottawa Scale (NOS). Meta-analysis and descriptive analysis of relevant outcome indicators were performed using RevMan 5.3 software. Result(s): A total of 15 studies were enrolled in the study, including 7 cohort studies with high-quality and 8 RCTs, 6 of which were with low bias risk and the other 2 of which were with medium bias risk. Among these studies, 8 were on arbidol treatment for COVID-19, including 5 retrospective cohort studies, 2 prospective cohort studies, and 1 RCT, and involving 809 patients (479 patients in the arbidol group and 330 in the control group);7 were RCTs on arbidol treatment for influenza or other respiratory virus infections, involving 1 471 patients (745 patients in the arbidol group and 726 in the control group).In these studies, patients were treated with arbidol (0.15-1.2 g daily for 5-21 d) in the arbidol group while with the other antiviral agents or without any antiviral drug in the control group. Meta analysis on the efficacy and safety of arbidol in treatment for COVID-19 showed that the novel coronavirus (2019-nCoV) nucleic acid negative conversion rate in the arbidol group was significantly higher than that in the control group [71.7% (109/152) vs. 58.8% (94/160), relative risk (RR)=1.30, 95% confidence interval (CI): 1.01-1.67, P=0.04];the difference of time taken for 2019-nCoV nucleic acid negative conversion between the 2 groups was not statistically significant (standardized mean difference=-0.17, 95%CI: -0.72-0.38, P=0.55);the difference of disease improvement rate shown by chest CT on day 7 after treatment between the 2 groups was not statistically significant [46.2% (30/65) vs. 50.7% (36/71), RR=0.88, 95%CI: 0.39-1.98, P=0.76];and the difference of incidence of adverse reactions between the 2 groups was not statistically significant [16.9% (39/231) vs. 19.2% (47/245), risk difference (RD)=-0.03, 95%CI: -0.10-0.04, P=0.44]. Meta analysis on the safety of arbidol in treatment for influenza and other respiratory virus infections showed that the incidence of adverse reactions in the arbidol group was significantly lower than that in the control group [5.9% (44/745) vs. 11.3% (82/726), RR=0.52, 95%CI: 0.37-0.74, P<0.01]. Conclusion(s): Arbidol could effectively increase the 2019-nCoV nucleic acid negative conversion rate and it might be safe to treat COVID-19 using arbidol.Copyright © 2020 by the Chinese Medical Association.

Efficacy and safety of ivermectin in patients with mild and moderate COVID-19: A randomized controlled trial

Objective: To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19. Method(s): This study was a single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19. According to the 1:1 ratio between the study groups (ivermectin group and standard treatment group), patients were randomly admitted to each intervention arm. Result(s): The mean age of the participants in the ivermectin group was (48.37+/-13.32) years. Eighteen of them were males (54.5%) and the participants in the control group had a mean age of (46.28+/-14.47) years, with nineteen of them being males (59.4%). As a primary outcome, after 5 days of randomization, there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital (P=0.168). ICU admission (P=0.764), length of stay in ICU (P=0.622), in-hospital mortality (P=0.427), adverse drug reactions, and changes in the mean difference of laboratory data had not any significant difference between the two groups (except for urea change). In addition, the radiologic findings of the two groups of patients were not significantly different. Linear regression analysis showed that for every 10 years increase of age, 0.6 day of hospitalization duration was increased. There was no statistically significant association between other variables and clinical outcomes. Conclusion(s): Among adult hospitalized patients with moderate to severe COVID-19, there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement, and mortality of the participants.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

ATTITUDES OF THE BULGARIAN POPULATION TOWARD THE SAFETY OF COVID-19 VACCINES.

At the beginning of the COVID-19 pandemic, humanity hoped for the rapid development of vaccines against the coronavirus infection, but it turned out that the fight against the virus will also include the challenge of dealing with negative attitudes and the refusal of vaccination among many people. Vaccine hesitancy is a global problem that has intensified in the context of the coronavirus pandemic. The aim of this publication is to explore the attitudes of Bulgarian citizens toward the safety of COVID-19 vaccines and their willingness to report adverse reactions after vaccination, if any. We conducted a survey on people's attitudes about the safety of COVID-19 vaccines, peoples' willingness to report adverse reactions after vaccination, and their knowledge of the need for such reporting. A 28-question survey was developed, which was aimed at all current and future users of the vaccines against COVID-19, regardless of whether they have a medical education or not. To create and distribute the survey, we used Google Forms. From the statistical analysis of the answers of the 427 respondents, we formulated the following conclusions: People with higher education are more aware of the possibility to report adverse drug reactions (ADRs);Among people who report ADRs, the proportion of women is greater;Respondents are concerned that COVID-19 vaccines have been developed in a short time;The most used sources of information regarding the safety of COVID-19 vaccines are specialized medical internet-sites and general practitioners (GPs);Advice from the GP is one of the main factors in choosing a vaccine;Over 90% of those who believe in the safety of vaccines have higher education;The share of people with higher medical education who are afraid of the vaccine and adverse reactions is the smallest. These and other findings from the survey would be useful in developing a communication campaign to increase vaccination coverage in Bulgaria against the coronavirus infection.Copyright © 2022, Central Medical Library Medical University - Sofia. All rights reserved.

POST-GAM-COVID-VAC COMBINED VECTOR VACCINE CELLULAR AND HUMORAL IMMUNE RESPONSE.

Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose - to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points - prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1-2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3-CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection.Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.