Modern Directed Antiviral Covid-19 Therapy: Results of Multicenter Clinical Effectiveness and Safety Study of Fixed Nirmatrelvir+Ritonavir Combination

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.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Modern Directed Antiviral Covid-19 Therapy: Results of Multicenter Clinical Effectiveness and Safety Study of Fixed Nirmatrelvir+Ritonavir Combination

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 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 Copyright © 2022 Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute. All rights reserved.

EFFECTIVENESS AND SAFETY OF FAVIPIRAVIR INFUSION IN PATIENTS HOSPITALIZED WITH COVID-19

Research in the development of new therapeutic agents with a wide spectrum of the antiviral activity and a low ability to develop resistance remains the main dimension in combating the global threat to public health. The need for a parenteral form of favipiravir was dictated by the necessity to increase the efficacy of therapy in COVID-19 inpatients. This dosage form has expanded the possibilities of drug therapy in the inpatients, for whom a therapeutic effect acceleration and a high safety profile of the drugs used are especially important. The aim of the article is the evaluation of the efficacy and safety of a medicinal product containing favipiravir for the parenteral administration against the background of pathogenetic and symptomatic therapy, in comparison with standard therapy in hospitalized COVID-19 patients. Materials and methods. An open, randomized, multicenter comparative study was conducted in 6 research centers in the Russian Federation to evaluate the efficacy and safety of favipiravir, a lyophilisate for the preparation of a concentrate for the infusion solution administrated to the patients hospitalized with COVID-19. Screening procedures and randomization were completed in 217 patients, 209 of which had completed the study in accordance with the protocol. Results. Between the study groups, statistically significant differences have been found out, making it possible to consider the hypothesis of the drug Areplivir (favipiravir) superiority for the parenteral administration over the standard therapy, which included favipiravir (p. o.) and remdesivir. A comparative analysis has shown that a course of therapy with the parenteral favipiravir drug leads to a significant improvement in the condition of patients with COVID-19, significant benefits in terms of the speed and frequency of improvement in the clinical status of patients, as well as a reduction in the hospital stay length. It has been proven that therapy with a drug containing favipiravir for the parenteral administration does not adversely affect the parameters of clinical and biochemical blood tests, urinalysis, coagulograms, vital signs and ECG, which indicates the therapy safety. The study drug is characterized by a high safety profile and tolerability. Conclusion. The versatility and resistance to mutations of RNA-dependent RNA polymerase make it possible to consider it as the main target for combating the most common RNA viruses that cause ARVI, that determines the need further studies of favipiravir to expand the range of its indications.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

International register “dynamics analysis of comorbidities in sars-cov-2 survivors” (Aktiv sars-cov-2): Analysis of predictors of short-term adverse outcomes in covid-19

The international AKTIV register presents a detailed description of out-and inpatients with COVID-19 in the Eurasian region. It was found that hospitalized patients had more comorbidities. In addition, these patients were older and there were more men than among outpatients. Among the traditional risk factors, obesity and hypertension had a significant negative effect on prognosis, which was more significant for patients 60 years of age and older. Among comorbidities, CVDs had the maximum negative effect on prognosis, and this effect was more significant for patients 60 years of age and older. Among other comorbidities, type 2 and 1 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer and anemia had a negative impact on the prognosis. This effect was also more significant (with the exception of type 1 diabetes) for patients 60 years and older. The death risk in patients with COVID-19 depended on the severity and type of multimorbidity. Clusters of diseases typical for deceased patients were identified and their impact on prognosis was determined. The most unfavorable was a cluster of 4 diseases, including hypertension, coronary artery disease, heart failure, and diabetes mellitus. The data obtained should be taken into account when planning measures for prevention (vaccination priority groups), treatment and rehabilitation of COVID-19 survivors.

International register “dynamics analysis of comorbidities in sars-cov-2 survivors” (Aktiv) and the register “analysis of hospitalizations of comorbid patients infected during the second wave of sars-cov-2 outbreak” (aktiv 2)

The organizer of the registers “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients.

The efficacy of etiotropic therapy for a new coronavirus infection with Areplevir (favipiravir), depending on the time of initiation of treatment (clinical observation)

The current millennium has been marked by the emergence of 3 epidemics of coronavirus infection: severe acute respiratory syndrome (SARS, SARS-CoV or atypical pneumonia), Middle East respiratory syndrome (MERS-CoV) and, over the past year, severe acute respiratory syndrome caused by the new coronavirus infection (SARS). CoV2, COVID-19). COVID-19 turned out to be the most common, far ahead of other epidemics in terms of the number of infected and mortality. The use of a vaccine will undoubtedly become the most important method of combating a new pandemic, but its creation is associated with certain difficulties, both in terms of lack of time and due to the high rate of spontaneous mutations inherent in all RNA viruses and coronavirus in particular. In this regard, the development of effective treatment regimens aimed at inhibiting the virus, suppressing the secondary effects of the cytokine storm and/or modulating the body's immune system, as well as blocking some specific links in the pathogenesis of COVID 19 (for example, hypercoagulation) is a priority area of modern medicine. The article describes clinical observations demonstrating an improvement in the clinical status of patients while using the drug Areplivir (favipiravir), which blocks viral replication and has proven its efficacy in controlled trials. © 2021 Nutritec. All rights reserved.

Efficacy and safety of some etiotropic therapeutic schemes for treating patients with novel coronavirus infection (covid-19)

The aim of the study is to assess the efficacy and safety of the Favipiravir (Areplivir) drug, compared to the standard etiotropic therapy in the patients hospitalized with COVID-19. Material and methods. The research was conducted as a part of an open, randomized, multicenter comparative study of the efficacy and safety of Areplivir, 200 mg film-coated tablets ("PROMOMED RUS" LLC, Russia), in the patients hospitalized with COVID-19. The dosing regimen of Favipiravir was 1600 mg twice a day on the 1st day and 600 mg twice a day on days 2 14. Thirty nine patients were enrolled into the study with a laboratory-established diagnosis of a new type of Coronavirus infection caused by SARS-CoV-2 (confirmed) of moderate severity, with pneumonia. The group of comparison (22 patients) received standard etiotropic therapy, prescribed in accordance with the current version of the temporary guidelines for the diagnosis and treatment of COVID-19, represented mainly by Hydroxychloroquine with the dosage regimen of 800 mg on the 1st day, then 400 mg on days 2-7, and Azithromycin 500 mg once a day for 5 days. The main group (17 patients) received Favipiravir (Areplivir) as etiotropic therapy. Results. In the main group, the time period until fever disappeared was found to be 1.36 days shorter than in the group of comparison (p0.05);there was a higher rate of the reduction of inflammatory changes in the lungs according to the computer tomography data (38.4% vs 14.9%, p0.05). By the end of the treatment, there was also a lower lactate level in the blood (27.1%, p0.05) than in the patients of the group of comparison. The evaluation of the drug efficacy according to the Categorical Ordinal Scale of Clinical Improvement and measurements of oxygen saturation in the blood, manifested similar positive dynamics in the patients treated according to various etiotropic therapy regimens. By the end of the treatment, the RNA SARS-CoV-2 tests were also negative in all the patients. As for the overall frequency of adverse events (AEs), no relevant distinctions were found between the groups. A greater part of AEs was related to hepatotoxicity, with a predominantly clinically relevant increase in alanine aminotransferase (ALT). A clinically relevant prolongation of the corrected QT interval on the standard ECG was found to occur in the standard-Therapy group on day 5, while no serious AEs were registered in the main group. No serious adverse reactions were registered in patients of the main group. Conclusion. The efficacy of the Favipiravir (Areplivir) therapy for the novel coronavirus infection has proved to be superior to the efficacy of the standard etiotropic therapy in a number of aspects. Basing on the obtained findings, Favipiravir (Areplivir) drug can be recommended for treating patients with the novel coronavirus infection of moderate severity. © 2021 Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute. All rights reserved.

Serum macrophage colony-stimulating factor levels in patients with essential hypertension after SARS-CoV-2 infection

Understanding changes in the cytokine-mediated mechanisms in immunopathogenesis of essential hypertension (EH) after COVID-19 poses a pressing scientific issue. SARS-CoV-2 exerts direct effects on macrophages with high probability altering regulatory M-CSF-VEGF-A-IL-34 axis, thereby accounting for change in cytokine-mediated patterns of hypertension progression. Immunopathogenesis of complications after SARS-CoV-2 infection and a role of M-CSF in EH pathogenesis justify study objective - to compare the serum M-CSF and VEGF-A, IL-34 levels in stage II EH patients prior to COVID-19 and one month after recovery to assess modality of altered M-CSF-mediated mechanisms behind hypertension progression. Four groups of patients were stratified depending on EH and clinical characteristics of COVID-19 (without/with pneumonia). Blood sampling was performed one month after COVID-19. The serum M-CSF and VEGF-A, IL-34 level was measured by using enzyme-linked immunosorbent assay. The data were statistically processed by using Stat Soft Statistica 13.5. Comparative analysis of serum M-CSF level in patients with stage II EH prior and after COVID-19 revealed that regardless of clinical course (with/without pneumonia) they were featured with higher levels of M-CSF one month after recovery (p < 0.001) vs baseline level. The serum VEGF-A level in patients with stage II EH did not change in papallel with increased M-CSF (458 pg/ml or more) one month after SARS CoV 2 infection. However, M-CSF stimulated rise in serum VEGF-A level and accounted for formation of marked coronary collateral network prior to infection. A relationship between the increased serum M-CSF level (higher than 392 pg/ml) and elevated percentage of COVID-19 with pneumonia in patients with stage II EH prior to the infection might be related to the hypothesis about “a role of dysregulated activation of mononuclear phagocytes in development of lung tissue damage”. The data presented prove scientific and clinical value of assessing a role for M-CSF with respect to altered cytokine-mediated patterns of EH progression after COVID-19 recovery. Понимание изменения цитокин-опосредованных звеньев иммунопатогенеза ЭАГ после перенесенного COVID-19 является актуальным научным вопросом. SARS-CoV-2 обладает прямыми эффектами действия на макрофаги, что с высокой вероятностью вносит изменения в регуляторную систему M-CSF-VEGF-A-IL-34 у данной категории больных, а значит, определяет изменение цитокин-опосредованных схем прогрессирования гипертензии. Современное состояние исследования в области иммунопатогенеза осложнений SARS-CoV-2 инфицирования и собственные данные о роли M-CSF в патогенезе ЭАГ обосновывают цель исследования - сопоставить уровни M-CSF и VEGF-A, IL-34 в сыворотке крови больных ЭАГ II стадии до и через 1 месяц после перенесенного COVID-19 для оценки характера изменения M-CSF-опосредованных механизмов прогрессирования гипертензии. Для достижения поставленной цели было сформировано 4 группы пациентов в зависимости от наличия ЭАГ и формы COVID-19 (без пневмонии и с пневмонией). Забор крови проводился через 1 месяц после перенесенного COVID-19. Содержание M-CSF и VEGF-A, IL-34 определяли иммуноферментным методом в сыворотке крови. Статистическая обработка полученных данных проводилась с помощью Stat Soft Statistica 13.5. Сравнительный анализ содержания M-CSF в сыворотке крови больных ЭАГ II стадии до и после перенесенного COVID-19 определил, что, вне зависимости от формы заболевания (ОРВИ (без пневмонии) или с пневмонией), регистрируются более высокие уровни M-CSF через 1 месяц после выздоровления (р < 0,001). При этом у больных ЭАГ II стадии через 1 месяц после SARSCoV2 инфицирования отсутствует компенсаторное увеличение VEGF-A в сыворотке крови на фоне значительного роста M-CSF (выше 458 пг/мл), что было зарегистрировано в период до инфекционного заболевания у данной категории пациентов и определяло формирование более выраженной коронарной коллатеральной сети при сравнении лиц с гемодинамически значимым изменением коронарных сосудов. Выявленная в нашем исследовании ассоциация повышенного содержания M-CSF (более 392 пг/мл) в прединфекционном периоде у больных ЭАГ II стадии и увеличением процента развития COVID-19 с пневмоний, возможно, связана с гипотезой о роли дисрегулированной активации компартмента мононуклеарных фагоцитов при развитии поражения ткани легкого. Приведенные результаты доказывают научную и клиническую ценность изучения роли M-CSF в аспекте изменение цитокинопосредованных схем прогрессирования ЭАГ после перенесенного COVID-19.

EFFICACY AND SAFETY OF SOME ETIOTROPIC THERAPEUTIC SCHEMES FOR TREATING PATIENTS WITH NOVEL CORONAVIRUS INFECTION (COVID-19)

The aim of the study is to assess the efficacy and safety of the Favipiravir (Areplivir) drug, compared to the standard etiotropic therapy in the patients hospitalized with COVID-19. Material and methods. The research was conducted as a part of an open, randomized, multicenter comparative study of the efficacy and safety of Areplivir, 200 mg film-coated tablets ("PROMOMED RUS" LLC, Russia), in the patients hospitalized with COVID-19. The dosing regimen of Favipiravir was 1600 mg twice a day on the 1st day and 600 mg twice a day on days 2-14. Thirty nine patients were enrolled into the study with a laboratory-established diagnosis of a new type of Coronavirus infection caused by SARS-CoV-2 (confirmed) of moderate severity, with pneumonia. The group of comparison (22 patients) received standard etiotropic therapy, prescribed in accordance with the current version of the temporary guidelines for the diagnosis and treatment of COVID-19, represented mainly by Hydroxychloroquine with the dosage regimen of 800 mg on the 1st day, then 400 mg on days 2-14, and Azithromycin 500 mg once a day for 5 days. The main group (17 patients) received Favipiravir (Areplivir) as etiotropic therapy. Results. In the main group, the time period until fever disappeared was found to be 1.36 days shorter than in the group of comparison (p<0.05);there was a higher rate of the reduction of inflammatory changes in the lungs according to the computer tomography data (38.4% vs 14.9%, p<0.05). By the end of the treatment, there was also a lower lactate level in the blood (27.1%, p<0.05) than in the patients of the group of comparison. The evaluation of the drug efficacy according to the Categorical Ordinal Scale of Clinical Improvement and measurements of oxygen saturation in the blood, manifested similar positive dynamics in the patients treated according to various etiotropic therapy regimens. By the end of the treatment, the RNA SARS-CoV-2 tests were also negative in all the patients. As for the overall frequency of adverse events (AEs), no relevant distinctions were found between the groups. A greater part of AEs was related to hepatotoxicity, with a predominantly clinically relevant increase in alanine aminotransferase (ALT). A clinically relevant prolongation of the corrected QT interval on the standard ECG was found to occur in the standard-therapy group on day 5, while no serious AEs were registered in the main group. No serious adverse reactions were registered in patients of the main group. Conclusion. The efficacy of the Favipiravir (Areplivir) therapy for the novel coronavirus infection has proved to be superior to the efficacy of the standard etiotropic therapy in a number of aspects. Basing on the obtained findings, Favipiravir (Areplivir) drug can be recommended for treating patients with the novel coronavirus infection of moderate severity.