ABSTRACT
The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.Copyright © Team of Authors, 2022.
ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.
ABSTRACT
The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.
ABSTRACT
Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery. Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy. Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0. Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels). Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed. © 2022, Remedium Group Ltd. All rights reserved.
ABSTRACT
Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery. Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy. Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0. Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels). Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed. © 2022, Remedium Group Ltd. All rights reserved.
ABSTRACT
It was found that death from coronavirus infection is the more likely, the higher the degree of damage to the lung on the visual scale "CT 0-4". Thus, patients with pulmonary involvement of 75% or more are predictively poor in terms of outcome. Assessment of the influence of the rate of disease progression to CT-4 on mortality and the search for factors affecting this indicator may be of practical importance. The purpose of this study is comparison of the duration of progression of the CT picture to a critical degree in various "waves" of the pandemic, the search for factors influencing the interval of "debut diseases - CT 4", as well as the assessment of the state of the lung tissue after a total process in a long period of time. Materials and methods: a retrospective analysis of 708 patients (226 in the first wave, 482 in the second wave), hospitalized at City Clinical Hospital No. 15 and having a critical degree of lung. 25 discharged patients underwent a control CT scan 6 and 12 months after discharge from the hospital. Results: The study groups were comparable in terms of demographic characteristics and the degree of CT at admission in hospital. When comparing the interval "onset of the disease - detection of CT-4", no significant differences between the "waves" were found (p = 0.372). When assessing the CT-picture in the delayed period, there were no significant differences in the frequency of changes between the groups;an almost complete regression of inflammatory changes was observed. In the study of the entire sample, an increase in the interval "onset of the disease - detection of CT-4" (p = 0.033) was found in men (11 days (7-16)) compared with women for 10 days (6-15), and in discharged patients (12 days (8-18) compared with deaths (10 days (6-15)) (p <0.001). There was a significant reduction in the progression time with increasing age of patients (p = 0.003) Conclusions: Considering the data obtained on the possible influence of the timing of the progression of the CT picture on the mortality of patients, as well as the results of long-term observation, it is advisable to search for modifiable risk factors for the rapid progression of the disease.
ABSTRACT
Introduction. Mass vaccination of the population against SARS-CoV-2 in Russia and abroad has been going on for more than 2 years. Various types of vaccines are used for vaccination (vector vaccines, RNA vaccines, whole-virion vaccines). The first in the world was registered the Russian vector vaccine «Gam-COVID-Vac» («Sputnik V»), which is widely used in our country, as well as in many other countries of the world. An important area of research is the monitoring of the parameters of the vaccine-induced immune response their analysis in relation to the characteristics of the immune response caused by SARSCoV-2 infection/COVID-19. Such studies are important both for assessing the intensity and duration of post-vaccination immunity, and for improving strategies for immunoprophylaxis and immunotherapy of coronavirus infection. The article presents the results of a study of the humoral immune response in patients with COVID-19 and vaccinated with «Sputnik V» in the period from autumn 2020 till the present time. The aim of the work - a comparative study of the humoral immune response to SARSCoV-2 infection and vaccination against COVID-19. Material and methods. The content of antibodies against SARS-CoV-2 S- and N-proteins was studied in 449 blood serum samples of men and women (age 25-65 years). 5 groups of samples were formed: suffered from COVID-19 of mild and moderate severity, at different times after recovery (262 samples);immunized with the «Sputnik V» vaccine, at different times after injection of the 2nd component of «Sputnik V» (104 samples);suffered from COVID-19 of mild and moderate severity, and then vaccinated with «Sputnik V» (53 samples);vaccinated with «Sputnik V», and then suffered with COVID-19 (12 samples);revaccinated with the vaccine «Sputnik Light» (18 samples). Results. To assess the content of IgG antibodies to S-protein and to N-protein of SARSCoV-2 in human blood sera, an EIA diagnostic system was developed further certified by the Ministry of Health of Russian Federation. In people suffered COVID-19 in 90 % of cases the positive levels of IgG antibodies to SARS-CoV-2 S-protein persist 9 months after recovery, while the proportion of potential plasma donors and material for obtaining intravenous immunoglobulin with a high content of IgG antibodies to S-protein 1 month after the disease is 20 %. In 76 % of people vaccinated with «Sputnik V» high levels of IgG antibodies to S-protein are detected within 6 months after the course of vaccination. The content of IgG antibodies to S-protein in the blood sera of persons suffered COVID-19, and then 6 months after recovery vaccinated with the 1st component of the vaccine «Sputnik V» in 100 % of cases was high with a positivity coefficient above 8.1, regardless of the initial value, already on 7 and 21 days after injection. In persons vaccinated with «Sputnik V» and then passed COVID-19, a high content of S-specific IgG antibodies is observed in 100 % of cases. The examination of vaccinated persons who underwent revaccination with «Sputnik Light» showed a 100 % high level of antibodies against S-protein. Conclusion. The developed test system may be suitable for assessing the content of IgG antibodies to SARS-CoV-2 antigens in COVID-19 patients, vaccinated and revaccinated. The performed study demonstrated that there is a intensive post-vaccination immunity for 6 months and post-infectious immunity for 9 months.
ABSTRACT
The aim of the study is to validate the Russian version of the 4C Mortality Score scale and evaluate its accuracy in predicting the outcomes of severe COVID-19. Material and methods. The staff of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology received official permission from the authors to conduct a validation study of the 4C Mortality Score scale in Russia. In the course of the work, the linguistic and cultural ratification of the scale was carried out and its Russian-language version was prepared. Psychometric properties (reliability and validity) The Russian-language version was evaluated on a group of 78 patients (37 of whom were men, aged 34 to 88 years) with a confirmed diagnosis of COVID-19, hospitalized in the City Clinical Hospital No. 15 named after O.M. Filatov (Moscow) in the period from June to August 2021. Results. The linguocultural adaptation of the 4C Mortality Score scale was successfully carried out. High levels of reliability were obtained (Spearman correlation coefficient ρ=0.91, p<0.0001;Cronbach's alpha α=0.73, p=0.0002;Cohen's kappa κ=0.85, p<0.0001). It is shown that the 4C Mortality Score scores have a significant correlation with the COVID-GRAM scores (r=0.72, p=0.002) and NEWS2 (r=0.54, p=0.004). Conclusion. As a result of the validation study, the official Russian version of the 4C Mortality Score scale was developed. It is recommended for use by medical professionals of various specialties at all stages of providing medical care to patients with COVID-19. The scale is available for download on the website of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology (https://www.neurology.ru/reabilitaciya/centr-validacii-mezhdunarodnyh-shkal-i-oprosnikov). © 2022 by the authors.
ABSTRACT
Presented are two clinical cases of pregnancy, childbirth and the postpartum period in patients with a new coronavirus infection COVID-19 of the obstetric department of the Filatov City Clinical Hospital No.15. Despite the severe course of the disease, an extremely high risk of fatal complications, thanks to clear routing, a multidisciplinary approach and effective treatment tactics, it was possible to successfully solve the most difficult medical and diagnostic problems, save the lives and preserve the health of patients and newborns. © 2021, Media Sphera Publishing Group. All rights reserved.
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History of heart transplantation in combination with immunosuppressive therapy and acute viral respiratory infection overlay makes the patient difficult to manage. In case of COVID-19, the setting is complicated by unknown pathogenesis, including its effect on blood, coagulation system, and lung tissue. Current case report discusses the 60-year-old patient with a COVID-19 infection occurred in the immediate postoperative period after heart transplantation. Copyright © 2020, Silicea-Poligraf. All rights reserved.
ABSTRACT
Immunity against the novel coronavirus infection in neonates born to mothers with PCR-confirmed COVID-19 is an understudied field of research. The aim of this study was to analyze the levels of IgM and IgG antibodies against SARS-CoV-2. The study was carried out in 20 mothers aged 19 to 39 years and 21 neonates (including a pair of twins). Babies born to mothers with elevated IgM and IgG against SARS-CoV-2 also had elevated IgG. There is a hypothesis that anti-SARS-CoV-2 IgM are not passed on to the child across the placenta. In all cases studied in this work, neonates were PCR-negative for the virus, which suggests the absence of vertical COVID-19 transmission. Further research is needed.