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.

Real-life antimicrobial therapy in hospitalized patients with COVID-19 (preliminary results and recommendations).

Objective. Development of local clinical protocols for antibacterial therapy of COVID-19-associated bacterial pneumonia in the therapeutic department of the city clinical hospital based on an analysis of the treatment process in patients with COVID-19-associated pneumonia. Materials and methods. A retrospective analysis of 1382 cases of hospitalization in the therapeutic department of patients with COVID-19-associated pneumonia for the period from 2020 to 2021 was carried out. The structure of etiotropic therapy, the frequency and timing of microbiological studies of the biomaterial, the manifestations of the main markers of bacterial infection during dynamic monitoring of clinical and laboratory parameters in patients prescribed antibiotic therapy, as well as statistics of the stay of patients in the therapeutic department of the hospital were assessed. Based on the results obtained in the course of microbiological studies, an assessment was made of the microbial landscape of the lower respiratory tract of patients with an analysis of the sensitivity of strains of the leading microflora to a wide range of antibiotics. Results. The study found that the dominant flora in COVID-19-associated pneumonia in hospitalized patients was gram-negative bacteria - K. pneumoniae, P. aeruginosa and A. baumannii - their proportion was more than 50%. Among K. pneumoniae strains, 89.4% were ESBL producers, 63.5% of the strains were resistant to carbapenems, which with a high probability allows them to be considered carbapenemase-producing strains. Among the strains of P. aeruginosa, the proportion of strains resistant to carbapenems and with a high degree of probability being strains - producers of carbapenemase was 41.1%. Among strains of Acinetobacter spp. these were 76.4%, and associated resistance to fluoroquinolones and aminoglycosides was also demonstrated. Gram-positive microorganisms were found in 34.3% of cases and were mainly represented by strains of S. aureus (74.9%), only 26.4% of strains of this pathogen were methicillin-resistant. Conclusions. Microbiological monitoring conducted in 2020-2021 revealed the presence, among the pathogens of viral-bacterial pneumonia, at an early stage of hospitalization, a significant proportion of gram-negative bacteria with resistance of the MDR and XDR types. Based on the obtained microbiological data, starting empirical schemes for antibacterial therapy of secondary viral and bacterial pneumonia, which complicated the course of a new coronavirus infection COVID-19 caused by the SARS-CoV-2 virus, were developed and proposed.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Features of the Humoral Response to Infection, Vaccination, and Revaccination during COVID-19.

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.

Real-life antimicrobial therapy in hospitalized patients with COVID-19 (preliminary results and recommendations)

Objective. Development of local clinical protocols for antibacterial therapy of COVID-19-associated bacterial pneumonia in the therapeutic department of the city clinical hospital based on an analysis of the treatment process in patients with COVID-19-associated pneumonia. Materials and methods. A retrospective analysis of 1382 cases of hospitalization in the therapeutic department of patients with COVID-19-associated pneumonia for the period from 2020 to 2021 was carried out. The structure of etiotropic therapy, the frequency and timing of microbiological studies of the biomaterial, the manifestations of the main markers of bacterial infection during dynamic monitoring of clinical and laboratory parameters in patients prescribed antibiotic therapy, as well as statistics of the stay of patients in the therapeutic department of the hospital were assessed. Based on the results obtained in the course of microbiological studies, an assessment was made of the microbial landscape of the lower respiratory tract of patients with an analysis of the sensitivity of strains of the leading microflora to a wide range of antibiotics. Results. The study found that the dominant flora in COVID-19-associated pneumonia in hospitalized patients was gram-negative bacteria – K. pneumoniae, P. aeruginosa and A. baumannii – their proportion was more than 50%. Among K. pneumoniae strains, 89.4% were ESBL producers, 63.5% of the strains were resistant to carbapenems, which with a high probability allows them to be considered carbapenemase-producing strains. Among the strains of P. aeruginosa, the proportion of strains resistant to carbapenems and with a high degree of probability being strains – producers of carbapenemase was 41.1%. Among strains of Acinetobacter spp. these were 76.4%, and associated resistance to fluoroquinolones and aminoglycosides was also demonstrated. Gram-positive microorganisms were found in 34.3% of cases and were mainly represented by strains of S. aureus (74.9%), only 26.4% of strains of this pathogen were methicillin-resistant. Conclusions. Microbiological monitoring conducted in 2020–2021 revealed the presence, among the pathogens of viral-bacterial pneumonia, at an early stage of hospitalization, a significant proportion of gram-negative bacteria with resistance of the MDR and XDR types. Based on the obtained microbiological data, starting empirical schemes for antibacterial therapy of secondary viral and bacterial pneumonia, which complicated the course of a new coronavirus infection COVID-19 caused by the SARS-CoV-2 virus, were developed and proposed. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

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 °C), 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. © The Author(s), 2022.

Seroprevalence of anti-sars-cov-2 antibodies among healthcare professionals in Moscow in april-december 2020

We evaluated humoral immunity (presence of specific IgM and IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare professionals providing inpatient care for individuals with COVID-19. Objective. To detected and measure the level of anti-SARS-CoV-2 antibodies in healthcare professionals and to identify how many of them contacted with COVID-19 patients, including those who had asymptomatic or subclinical disease. Materials and methods. Anti-SARS-CoV-2 antibodies were detected using enzyme-linked immunosorbent assay (ELISA) with the ‘SARS-CoV-2-ELISA-Vector’ kit for IgG (State research Center of Virology and Biotechnology ‘Vector’) and ‘SARS-CoV-2-IgG- ELISA-BEST’ and ‘SARS-CoV-2-IgМ-ELISA-BEST’ kits for IgM and IgG (Vector-Best LLC). Samples were collected in several healthcare institutions of Moscow and in G.N.Gabrichevskiy Moscow Research Institute of Epidemiology and Microbiology. A total of 24,373 serum specimens from 74 healthcare institutions were tested. All study participants filled in special questionnaires. Results. Among 24,373 healthcare professionals tested in this study, 5,382 people were IgG-positive to SARS-CoV-2 (seroprevalence index 22.1%). The seropositivity rate was 21.5% in senior medical staff, 22.2% in nursing professionals, and 22.8% in medical assistants/technicians. We found that the proportion of SARS-CoV-2 seropositive individuals had changed over time, gradually increasing from 17.9% in April 2020 to 37.6% in December 2020. The proportion of SARS-CoV-2 seropositive people doubled among senior medical staff and nursing professionals during the year. The proportion of individuals with asymptomatic or subclinical COVID-19 was 13.8%. Conclusion. The methodological approaches used in this study allowed us to assess the humoral immunity to SARS-CoV-2 among healthcare professionals in Moscow. Our findings can be used for further improvement of anti-epidemic measures in healthcare institutions. © 2021, Dynasty Publishing House. All rights reserved.