The purpose of this research is to study the characteristics of the change in the circadian rhythm of macrophage colony-stimulating factor (M-CSF) content in the peripheral blood serum of patients with stage II essential hypertension (EH) based on 5 time points (8:00, 14:00, 20:00, 2:00, and 8:00) and analyze its connection with the frequency of cardiovascular events. Identified levels of M-CSF in the peripheral blood serum of 60 patients with stage II EH, before and after 1 year of antihypertensive therapy using enzyme-linked immunoassays (at 8:00, 14:00, 20:00, 2:00, and 8:00). The research demonstrated that stage II EH patients with a medical case history lasting 10–14 years have a greater content of M-CSF in their peripheral blood serum (p > 0.001). Before the start of antihypertensive therapy, they also have an increased variability in the circadian rhythm of M-CSF content in the bloodstream (when compared with healthy individuals) due to an increase at 20:00, decrease at 2:00 and recovery at 8:00. In 70% of those patients taking antihypertensive medication and have reached their target arterial blood pressure, the cytokine decrease stabilizes at 2:00 but the increase at 20:00 remains unchanged. Thirty percent of patients retained the rhythm characteristics of M-CSF content in the blood serum typical of patients before the start of therapy. This is a predictor of an increase in the five-year risk of developing cardiovascular complications, particularly myocardial infarction and acute cerebrovascular accident, in individuals with a comparable risk of cardiovascular complications or death on the Framingham risk score.

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.

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 aimof 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 5^thday 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.

Since the beginning of the pandemic, repeated attempts have been made to develop etiotropic therapy for a novel coronavirus infection. Hydroxychloroquine, lopinavir/ritonavir, etc. derivatives were used as antiviral agents, however, they demonstrated a low efficiency and an insufficient safety. In this connection, other groups of drugs with a more effective and safe pharmacological profile are currently being actively used.The aimof the study was to analyze the literature references on the efficacy and safety of antiviral drugs for the COVID-19 treatment.Materials and methods.When searching for the materials for the review article writing, such abstract databases as PubMed, Google Scholar, e-Library were used. The search was carried out on publications for the period from January 2020 to september 2022. The key queries were: COVID-19, etiotropic therapy; immunological drugs; antiviral drugs; interferons.Results.Currently, there are various degrees of effective etiotropic drugs for the treatment of COVID-19 patients. The review has considered a few groups of drugs that are of interest from the point of view of etiotropic therapy: immunological drugs (anticovid plasma, the drugs based on antiviral antibodies, the drugs of recombinant interferons-α2 and -β1, as well as interferon inducers, i.e., the drugs based on double-stranded RNA sodium salt, and others); drugs that block the penetration of the virus into the cell (umifenovir); the drugs that disrupt the process of the viral replication (favipiravir, remdesivir, molnupiravir, nirmatrelvir/ritonavir).Conclusion.Synthetic antivirals, in particular favipiravir, molnupiravir, remdesivir, and nirmatrelvir/ritonavir, have the largest evidence base for their efficacy and safety. The search for new effective and safe etiotropic drugs for the treatment of COVID-19, as well as the collection and analysis of post-registration data on the drugs already used in clinical practice, continues.

In this paper, the erythrocytes of healthy donors and people with a confirmed diagnosis of COVID-19 were tested by Raman spectroscopy and laser interference microscopy. We argue that erythrocytes (red blood cells) in COVID-19 patients have an irregular shape, and their morphometric characteristics are impaired in comparison to healthy red blood cells. Raman spectroscopy also allows us to detect a decreased oxygen transport function of these erythrocytes. The combination of these methods—Raman spectroscopy and laser interference microscopy—is a highly effective method for the diagnosis of SARS-CoV-2.

Essential hypertension (EH) is one of the most common modifiable risk factors for cardiovascular diseases and death. The aim of this study was to investigate a correlation between the levels of some cytokines (interleukins, adhesion molecules, tumor necrosis and growth factors, etc.) in the peripheral blood of patients with stage II EH and the rate of complications (myocardial infarction, acute cerebrovascular events, and transient ischemic attacks) occurring in a 5-year follow-up period. Twenty-eight cytokines were measured using ELISA, including IL1β, IL1α, IL1ra, IL18, IL18BP, IL37, IL6, sIL6r, LIF, sLIFr, IGF-1, IGFBP-1, TNFα, sTNF-RI, sVCAM-1, IL17, IL2, IL4, IL10, TGF-β1, IL8, CX3CL1, CXCL10, INFγ, M-CSF, IL34, VEGF-A, and erythropoietin, and a few vasoactive peptides, including NО, iNOS, eNOS, ADMA, SDMA, Nt-proСNP, and Nt-proBNP, in the peripheral blood samples of 200 patients with stage II EH who had been suffering from this condition for 10 to 14 years and were receiving comparable therapies to bring their blood pressure down. The patients were followed up for 5 years to keep track of complications. The retrospective analysis revealed that the group of patients who developed complications during the 5-year follow-up period exhibited a decline in the levels of IL1ra (р < 0.001) and IL10 (р < 0.001) and a rise in IL1β (р < 0.001), TNFα (р < 0.001) and M-CSF (р < 0.001) in comparison with the group of those who did not develop any complications. The multivariate Cox regression analysis was applied to the following parameters: IL1β > 18.8 pg/ml; IL1ra < 511 pg/ml; IL6 > 23.8 pg/ml; IL10 < 26.3 pg/ml; 389 pg/ml < M-CSF < 453 pg/ml; ADMA > 0.86 μmol/L; total cholesterol > 4.9 mmol/L; LDL> 3.0 mmol/L; HDL in men < 1.0 mmol/L; HDL in women < 1.2 mmol/L. The analysis revealed that M-CSF in the range from 389 to 453 pg/ml (р < 0.001) and LDL above 3.0 mmol/L (р < 0.01) correlated with an increase in the risk for end-organ damage in stage II EH. Changes in the cytokine levels can be regarded as a predictor of myocardial and cerebral damage in patients with stage II EH. Measurement of peripheral blood M-CSF can be included into the classic risk assessment schemes for the cardiovascular complications in the studied cohort of patients.