In many ways, arterial hypertension and obesity determine the likelihood of a severe course and lethal outcomes in COVID-19. This fact justifies the expediency of an early use of drugs with a direct antiviral action, the analysis of their efficacy not only in the acute, but also in the postcovid period.The aim of the research was to analyze the outpatient cards and case histories of the COVID-19 patients to study the effect of the early (up to the 5th day after the onset of the first symptoms of the disease) use of the drug based on favipiravir, on the frequency of patients’ hospitalizations with arterial hypertension and obesity, as well as to determine the cytokine status characteristics of this patient category in the postcovid period.Materials and methods. “An open prospective comparative study of the “Areplivir®” (favipiravir) efficacy in the debut of COVID-19 in comorbid patients” was carried out in the Republic of Mordovia (the analysis of the hospitalizations frequency and blood levels of M-CSF, EPO in 218 patients, in terms of the use of the antiviral preparation).Results. According to the results of the analysis, it was found out that, despite the presence of comorbid conditions that increase the risk of developing a severe course of COVID-19, i.e. obesity and essential arterial hypertension, in the group of patients taking favipiravir, the need for hospitalization was twice as low (p < 0.05), in relation to the comparison group. The analysis of the cytokine status revealed that in the postcovid period, in the group that took the drug based on favipiravir at the outpatient stage, the average level of M-CSF was significantly lower (p> 0.05), and EPO was higher (p> 0.05) than in the patients from the group “without antiviral drugs at the outpatient stage”. Indirectly, according to the previously obtained data, that acts as a potential marker for reducing the risk of long-term cardiovascular complications of COVID-19.Conclusion. This study showed that an early prescription of favipiravir contributes to a decrease in the rate of COVID-19 patients’ hospitalization even against the background of concomitant hypertension and obesity, due to a decrease in the likelihood of moderate and severe courses of the disease, and also leads to an earlier objective and subjective recovery. The results demonstrated a high potential benefit of an early favipiravir use in the novel coronavirus infection and in the prevention of postcovid complications.

The article presents modern scientific data on long-term clinical and pathogenetic effects of the antiviral drug Areplivir (Favipiravir) in patients with metabolic syndrome in the post-COVID period.The aim of the article is to study long-term cytokine-mediated (IL-6/sIL6r and LIF/sLIFr) pathogenetic effects of the favipiravir (Areplivir®) based drug on the incidence of complications in patients with metabolic syndrome in the post-COVID period.Material and methods. With the approval of the local ethics committee at the N.P. Ogarevs Mordovia State University (Protocol No. 5 dated May 17, 2020) “An open prospective comparative study of the Areplivir® (Favipiravir) drug effectiveness in reducing the risk of complications in the post-COVID period in patients with metabolic syndrome” in the Republic of Mordovia was carried out.The study included 190 metabolic syndrome patients who received the outpatient treatment for COVID-19 at Saransk polyclinics from February 2021 to March 2021. The case of COVID-19 was diagnosed in accordance with the current Temporary Guidelines for the prevention, diagnosis and treatment of the new coronavirus infection.Results. The analysis of the metabolic syndrome patients’ follow-up within 1 year after undergoing COVID-19, revealed significant differences in the incidence of complications depending on the intake of the favipiravir based drug. The patients who were administrated with favipiravir at the early stage of infection, were characterized by lower serum levels of four members of the interleukin 6 family – IL-6 (IL-6, sIL6r and LIF, sLIFr) 10, 30 and 180 days after a clinical and laboratory recovery (p<0.001). The average statistical changes in the IL-6 /sIL6r system of the group administrated with favipiravir, were 90%, and they were higher than in the group not administrated with antiviral drugs. In the group of the patients administrated with favipiravir, there was a significant (p<0.001) positive dynamic of the sLIFr indicator, while in the comparison group, there was an increase in this indicator.A protective effect of the early favipiravir use was characterized by a decrease in the frequency of cardiovascular complications, a 2.66-fold decrease in the risk of a stroke and the ACS in the post-COVID period.Conclusion. The areplivir therapy in the acute period of coronavirus infection made it possible to timely reduce the viral load. It helps to correct the pro-inflammatory vector of the immune response at the post-COVID stage and, accordingly, reduces the risk of progression of atherosclerosis, transient cerebrovascular accidents with a cognitive decline, an endothelial dysfunction, and can be considered a secondary prevention of life-threatening cardiovascular complications.

Данные о роли цитокинов в патогенезе артериальной гипертензии (АГ), обобщенные в настоящем обзоре, подчеркивают значимость поиска места терапии, направленной на регулирование цитокиновых схем иммунопатогенеза гипертонии. Цель исследования: охарактеризовать спектр научных данных, отражающих иммунопатогенетический потенциал цитокиновой и антицитокиновой терапии при АГ. Поиск и анализ научных работ, посвященных заявленной теме «Цитокины в терапии артериальной гипертензии», опубликованных в период с 1940 по 2021 гг. и представленных в базах данных PubMed, Scopus, WoS, CochraneLibrary, eLibrary. Ключевые слова: cytokines and hypertension therapy, anti-cytokine therapy for hypertension, interleukins and hypertension therapy, chemokines and hypertension therapy -были подобраны с учетом анализа публикаций, представленных в международных базах научного цитирования. По данным выполненного анализа наибольшее число исследований обозначают потенциальными мишенями цитокиновой и антицитокиновой терапии: IL-

COVID-19 is a multisystem disease, but the extent of its consequences is currently poorly understood, especially in the persons with metabolic disorders. The aim of the present study was to evaluate the special changes in the cytokines of IL-6 family (IL-6 and sIL-6, LIF and sLIFr), adiponectin and leptin within 360 days after SARS-CoV-2 infection in the patients with metabolic syndrome (MetS), to discern features of immunopathogenesis depending on previous vaccination against COVID-19. We have classified the patients in two groups: (1) patients with MetS who underwent COVID-19 6-12 months after full-course vaccination with a vector vaccine (n = 32); (2) patients with MetS who underwent COVID-19 without story of vaccination (n = 29). Control group included conditionally healthy individuals without MetS: (3) vaccinated, and (4) non-vaccinated, who also had COVID-19. The levels of IL-6 and sIL-6, LIF and sLIFr, leptin and adiponectin, NO, ADMA, SDMA were determined by ELISA technique. In patients with MetS, changes in cytokine regulation towards proinflammatory reactions were revealed (an increase in blood IL-6 and leptin levels), which was most pronounced in MetS within first 30 days post-COVID, but with a number of changes which remained for 12 months (e.g., increased leptin concentration in blood). Vaccination against COVID-19 reduced the severity of pro-inflammatory changes in the sIL- 6r/ IL-6 and leptin/adiponectin systems towards protective adiponectin. However, the persistent increase in leptin was not canceled. When interpreting these results, no negative differences were revealed in the group of once vaccinated individuals with MetS, concerning the mentioned cytokine regulations of MetS over 1 year after COVID-19. The univariate, and then multifactorial correlation analysis between serum contents of sIL- 6r/ IL- 6, LIF/ sLIFr, adiponectin and leptin and the levels of vasoactive substances (NO, ADMA and SDMA), glycated hemoglobin, LDL has shown that the increased ratio of sIL-6r/IL-6 is an independent factor for the NO reduction of (r = 0.74, p 0.01); an increase in sLIFr positively correlates with increase in glycated hemoglobin (r = 0.69, p 0.01), and an association with increase of ADMA (r = 0.82, p 0.001), leptin (in this model) are shown to be an independent factor of LDL increase (r = 0.69, p 0.05). Influence of pre-COVID modifiable factors, in particular, vaccination, is relevant in terms of reducing the likelihood of progression of pre-existing chronic diseases (hypertension, atherosclerosis, diabetes mellitus) in the persons with MetS after COVID-19 and has prospects for implementation into clinical practice.

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