[Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review].

Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The effect of COVID-19 on vascular elasticity and liver function in overweight patients.

Objective. To study the changes in the vascular wall, vascular age and metabolic parameters in polymorbid COVID-19 conva-lescents. Material and methods. The study included 62 patients with hypertension who reached the target blood pressure (BP) with dual an-tihypertensive therapy after severe and extremely severe COVID-19. The following examinations were performed: laboratory tests of metabolic parameters, assessment of changes in the vessel elasticity indices (pulse-wave velocity (PWV), augmentation index (AI), central systolic BP (cSBP), 24-hour BP monitoring, and non-invasive markers of liver fibrosis. Results. According to office BP measurements, after the coronavirus infection, an increase in systolic BP (SBP) by 29.6% and di-astolic BP (DBP) by 23.6%, as well as heart rate (HR) by 11.8% (p<0.05) was reported during regular antihypertensive therapy. In addition, 24-hour BP monitoring data indicated an increase in the average daily SBP, DBP, and heart rate. After the coronavirus infection, an increase in PWV by 35.4% (p<0.05), AI by 24.4% (p<0.05), cSBP by 22.1% were reported. Carbohydrate and lipid metabolism parameters deteriorated. A pronounced adverse effect of coronavirus infection on liver function was observed. The vascular age (according to the modified SCORE scale) increased by 6 years (p<0.05). Conclusion. Our study showed that patients after severe and extremely severe COVID-19 have a high risk of liver fibrosis, hypertension and lipid metabolism control worsening and accelerating vascular aging.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Blood pressure control, target organ protection and metabolic disorders control using a fixed combination of azilsartan medoxomil + chlorthalidone in hypertensive patients survived after severe and extremely severe COVID-19

Objective. Evaluation of the possibility of a fixed combination of azilsartan medoxomil + chlorthalidone in additional angioprotection in patients with arterial hypertension (HTN) and high pulse wave velocity (PWV) after confirmed severe or extremely severe COVID-19 (bilateral polysegmental viral pneumonia)treated by genetically engineered biological drugs, who had not previously received combined antihypertensive therapy. Design and methods. An open observational study lasting 12 weeks included 30 patients, 28-31 days after discharge from the hospital after a severe and extremely severe COVID-19, who received or had not previously received antihypertensive therapy. Patients underwent 24-hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), measurement of PWV, laboratory tests before and after prescription of a fixed combination of azilsartan medoxomil + chlorthalidone. Results. At baseline, patients showed an increase in office blood pressure to 153,06/92,2 mmHg. After treatment with a fixed combination of azilsartan medoxomil + chlorthalidone, a decrease in systolic BP by 18,47 % and diastolic BP by 16,24 % was observed. According to ambulatory BP monitoring, the decrease in systolic BP was 19,65 % and diastolic BP - 24,68 %, PWV decreased by 34,4 %, augmentation index - by 9,42 %, central systolic BP - by 15,48 % (p < 0,05). At baseline, vascular age (VA) was increased to 44,96 years compared to the passport age of 35,03 years. After treatment, there was a significant decrease in VA to 38,74 years (p < 0,01). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, blood urea nitrogen and uric acid significantly decreased. Conclusions. The fixed combination of azilsartan medoxomil + chlorthalidone provides better control of BP. It also helps to improve vascular elasticity (augmentation index, PWV, central systolic BP, decrease in VA) and to reduce post-infectious inflammation in HTN patients after a severe coronavirus infection. Copyright © 2021 All-Russian Public Organization Antihypertensive League. All rights reserved.

Effect of Antioxidants on the Production of MCP-1 Chemokine by EA.hy926 Cells in Response to IL-6.

An elevated level of circulatory interleukin 6 (IL-6) is a biomarker for cytokine storm of various etiologies, including COVID-19, and contributes to poor prognosis. Vascular endothelial cells are one of the main targets of pathological action of IL-6. IL-6 activates the trans-signaling pathway via the formation of the IL-6/sIL-6Ra/gp130 receptor complex and subsequent activation of the JAK/STAT3 signaling pathway and PI3K/AKT and MEK/ERK kinases in some cases. Previously, it was shown by the authors' group and other researchers that reactive oxygen species (ROS), including mitochondrial ROS (mito-ROS), contribute to the induction of IL-6 expression in the endothelium, mainly due to increased activation of the transcription factor NF-kB. We have also shown that the mitochondria-targeted antioxidant SkQ1 (Plastoquinolyl-10(6'-decyltriphenyl)phosphonium) prevented tumor necrosis factor (TNF)-induced cytokine storm and death in mice. In the aortas of these animals, SkQ1 also prevented the increase in the expression of NF-kB-dependent genes, including the cytokine IL-6 and the chemokine MCP-1. In the current work, the hypothesis of mito-ROS involvement in the IL-6-signaling-mediated proinflammatory gene expression in endothelial cells is tested. SkQ1 suppressed the expression and secretion of the MCP-1 chemokine, induced by IL-6 in combination with sIL-6-Ra, but not the expression of ICAM-1 adhesion molecules in EA.hy926 human endothelial cells. Using specific inhibitors, the authors have shown that, in EA.hy926 cells, IL-6-induced expression of MCP-1 and ICAM-1 depends on the signaling protein and transcription activator STAT3 and, in some cases, on JNK, PI3K, and MEK1/2 kinases and is independent of p38 kinase. In this model, IL-6 induced rapid STAT3 activation, while ERK1/2 activation was less pronounced, and there was no IL-6 effect on Akt and JNK activation. SkQ1 partially suppressed STAT3 and ERK1/2 activation. Thus, we have shown that SkQ1 suppresses not only NF-kB-dependent expression of IL-6 and other proinflammatory genes but also IL-6-induced activation of JAK/STAT3 and STAT3-dependent expression of MCP-1, which probably contributes to the overall therapeutic effect of SkQ1.

PAMAM DENDRIMERS AND PROSPECTS OF THEIR APPLICATION IN MEDICINE

Development of drug delivery systems based on branched biocompatible polymers is one of the most promising areas of modern nanopharmaceutics. Researchers have been exploring this area several decades now, and the results of their efforts quickly find their way into production. Dendrimers, a new class of universal synthetic polymers with a highly functional surface, have a number of unique properties: constant size, high degree of branching, multivalence, solubility in water, definite molecular weight, internal cavities. With the release of VivaSol gel, the first dendrimer-based commercialized product, the "model range" of dendrimer carriers has grown significantly. Poly(amide-amine) (PAMAM) dendrimers, which consist of an alkyldiamine core and tertiary amine branches, are believed to be among the most promising compounds that can be used in the development of the new generation drugs. However, they were kept out of the list of clinically acceptable compounds for a long time because of their toxicity, unclear behavior in living systems and pharmacokinetic profile, as well the difficulties associated with establishing a therapeutic dose. This review presents basic information about PAMAM dendrimers and attempts to assess the prospects of their application in treatment of various diseases, including COVID-19. © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

OPTIMIZATION OF BLOOD PRESSURE CONTROL AND ANGIOPROTECTION WITH FIXED COMBINATION OF LISINOPRIL + AMLODIPINE + ROSUVASTATIN IN PATIENTS AFTER A COVID-19

Objective: Evaluation of the capability of a fixed combination of lisinopril + amlodipine + rosuvastatin (ECWAMER) in achieving additional angioprotection in patients with arterial hypertension (AH) and high pulse wave velocity (PWV) in patients after confirmed COVID-19 had 75 - 95% lung involvement, complicated by bilateral polysegmental viral pneumonia, with genetically engineered biological drugs (GIBD) therapy, who had not previously received combined antihypertensive therapy (AHT). Design and method: An open-label observational study with a duration of 12 weeks has been carried out. 30 patients who not previously received combined AHT was included. Patients underwent daily monitoring of blood pressure (ABPM), applanation tonometry (determination of the augmentation index (IA) and central blood pressure (CSAD)), measurement of PWV, laboratory tests (lipid composition of blood, fasting glucose, C-reactive protein - CRP, OAC, ferritin, fibrinogen, D-dimer, ALT, AST, creatinine, uric acid) before and after prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin (ECVAMER). Results: At baseline, the patients had an increase in office blood pressure to 152.6 / 89.1 mm Hg. After prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15.8% and diastolic blood pressure (DBP) by 12.2%. According to ABPM data, the decrease in SBP was 15% and DBP - 9%, decreased PWV by 23.8%, IA by 9%, CSAP by 12.4% (p < 0.05 for all comparisons with the baseline value). Vascular age (SV) was initially increased to 41.9 years with a passport age of 35.03 years. After the end of therapy, there was a significant decrease in CO up to 36.5 years, LDL by 46.8%, triglycerides by 16.8% and an increase in HDL by 10.7% (p < 0.05 for all comparisons with the baseline value). In addition, the levels of CRP, fibrinogen, D-dimer, glucose, and uric acid significantly decreased. Conclusions: The fixed combination of lisinopril + amlodipine + rosuvastatin provides better blood pressure control, improved vascular elasticity, and also improves lipid and carbohydrate metabolism in patients, reduces inflammation in patients with hypertension and hyperlipidemia after suffering from severe and extremely severe COVID-19.

Structural Shifts on Derivatives Markets at the Time of Increasing Digitalization and Post-pandemic Transformation of the Market

The increasing pressure of exogenous factors on the activities of mega-regulators at the time of the post-pandemic transformation of the market and changing monetary policy leads to lower profitability of deposits at commercial banks and at the same rises the yield curve of weighted average interest rates on interbank loans granted in euros, dollars, pounds and other currencies. The trading processes on the futures market are being intensively digitalized and so the post-pandemic transformation of the market is causing market players seeking to hedge risks to change their behavior. Changes that occurred on the debt capital market during the pandemic have increased investors’ interest in international derivatives market instruments and sped up the transformation of regional features of the derivatives market. These changes are mainly caused by the spread of the coronavirus infection and its impact on the global economy, which contributes to the development of digital technologies as instruments of interregional trade. International economic activity has been transformed by the opening and closing cycles of the economies of different countries, which affects the logistics and business processes of economic agents. The transformation of economic activity manifested in structural shifts occurring on the derivatives markets is confirmed by the changes in the dynamics of underlying assets of the derivatives market, such as stock indices, stocks, commodities, currencies, interest rates and ETFs. The analysis of the condition and specifics of the international derivatives market has revealed two problems worthy of independent research: 1) identifying major structural shifts in the international derivatives market that occurred during the pandemic;2) evaluating the impact of the post-pandemic transformation of the market on the Russian derivatives market. The main parameters of the derivatives market, such as capitalization and trading activity, were determined in order to solve the indicated problems. The study of the dynamics of these indicators in the aggregate system of data of the international derivatives market allowed us to identify the main development trends on this market and assess the degree of influence of the pandemic on its main tools. The analysis of the regional characteristics of the international derivatives market made it possible to find out the main changes that took place on American, European, Asian, Middle Eastern and African exchange markets affected by growing digitalization. The data obtained made it possible to identify the place of the Russian derivatives market in the system of world economic relations on the derivatives markets during the period of post-pandemic transformation of the market and to compare the changes that took place in the Russian derivatives market with the trends of the international derivatives market. © 2022, Springer Nature Switzerland AG.

Digital Transformation of Organizations as a New Prerequisite for Effective Operations

The paper examines the digital transformation of organizations and the problem of low efficiency of organizations with a low level of digital development. The authors study the dependence of the growth rate of the company’s digitalization on demand for consumer interaction between the company and the consumer. Additionally, the authors note the relationship between the type of company and the rate of its digitalization, as well as the potential risks of digitalization and its benefits in the interaction between individuals and the government. The paper aims to review and identify the relationship between organizational performance and digital development. The data reviewed confirm this relationship. Moreover, the data indicate that digitalization provides new opportunities for organizations to interact with customers and users and increase the customer inquiry on the digital level of organizations, which creates the need for digitalization of organizations. The authors identify the risks of digitalization, such as the reduction of low-skilled jobs, which, combined with economic shocks, can lead to a significant social stratification of citizens without government intervention. It is also noted that the COVID-19 pandemic has been a significant impetus for accelerated digital development. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Optimization of blood pressure control, organ protection and metabolic disorders using a fixed-dose combination of lisinopril+amlodipine+rosuvastatin in hypertensive patients after COVID-19

Aim. To evaluate the potential of a fixed-dose combination of lisinopril+amlodi-pine+rosuvastatin (Equamer® ) in achieving additional vascular protection in patients with hypertension and high pulse wave velocity (PWV) after severe and very severe coronavirus disease 2019 (COVID-19), complicated by bilateral multisegmental viral pneumonia, with the use of biological therapy, who had not previously received combination antihypertensive therapy. Material and methods. This 12-week open-label observational study included 30 patients with or without antihypertensive therapy. The patients underwent 24-hour blood pressure monitoring, applanation tonometry (determination of the augmentation index (AI) and central blood pressure (CBP)), PWV measurement, blood laboratory tests (lipid profile, fasting glucose, C-reactive protein, complete blood count, ferritin, fibrinogen, D-dimer, alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid) before and after switch to a fixed-dose combination of lisinopril+amlodipine+rosuvastatin. Results. At baseline, the patients had an increase in office blood pressure (BP) up to 152,6/89,1 mm Hg. After prescribing a fixed-dose combination of lisinopril+amlo dipine+rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15,8% and diastolic blood pressure (DBP) by 12,2%. According to 24-hour blood pressure monitoring, the decrease in SBP was 15%, DBP — by 9%, PWV — by 23,8%, AI — by 9%, CBP — by 12,4% (p<0,05 for all compared to baseline values). Vascular age (VA) was initially increased to 41,9 years with a chronological age of 35,03 years. After the end of therapy, there was a significant decrease in VA to 36,5 years, low-density lipoproteins by 46,8%, triglycerides by 16,8% and an increase in high-density lipoproteins by 10,7% (p<0,05 for all compared to baseline values). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, and uric acid significantly decreased. Conclusion. The fixed-dosed combination of lisinopril+amlodipine+rosuvastatin provides better blood pressure control, improved vascular elasticity parameters (AI, PWV, CBP, decrease in VA), and also improves lipid and carbohydrate metabolism, reduces inflammation in patients with hypertension and hyperlipidemia after severe COVID-19.

Clinical case of COVID-19 in a patient treated with alemtuzumab

The need to review the guidelines for the management of patients with multiple sclerosis using multiple sclerosis disease modifying drugs has become acute enough since the beginning of 2020 following the outbreak of the COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2. Immunosuppressive drugs were also specifically addressed, as it is during administration of these drugs that the more severe course of COVID-19 disease was expected. Both the Russian and foreign teams published results of their research works. This article presents a retrospective analysis of the incidence rates of COVID-19 in patients with multiple sclerosis after selective immunosuppressive therapy with alemtuzumab and a clinical case when a patient was infected with coronavirus in the first days following the last infusion of the therapy course without clinical manifestations of the infectious disease. The author discusses the mechanisms underlying such a favourable outcome due to the CD52 lymphocyte depletion leading to the reduction of risks of developing hyperimmune reactions that underlie severe complications of COVID-19, and analyses previously published works of our foreign colleagues on the same theme. The review of the accumulated works and personal experience suggest that it is the CD52 lymphocyte depletion that makes it possible to avoid the cytokine storm and, as a result, the more severe course of COVID-19. Amidst the COVID-19 pandemic, during the prescription of multiple sclerosis disease modifying drugs, it should be borne in mind that patients should have access to all types of modern therapy and that the ben-efits should outweigh the sum of possible risks. © 2021, Remedium Group Ltd. All rights reserved.

The effect of “compassion fatigue” in practices of media consumption (The case of the attitude to the covid-19 problematization)

The article presents the main results of the empirical study of the effect of “compassion fatigue” in the media consumption practices of active users of the Internet and social networks, conducted in the spring of 2020 via an online survey. The strategies of problematization of COVID-19 using by the media in current Russia were in our focus. The relevance of addressing this topic is due to two main factors: the shortage of research of complex and nonlinear relations between the media and the audience in Russian sociological discourse, and the unprecedented medical and social situation, accompanied by infodemic. The manifestations of the public burnout, the main factors of its formation, as well as some socio-demographic differences, gender first, in the perception of news about coronavirus were discovered. As a result, an increase in tiredness and irritation among respondents in the first month of the epidemic is recorded. Its strongly statistical correlation with purposeful avoidance of information about the current situation indicates “compassion fatigue” of Internet users. The assessment of news about coronavirus as dramatic and sensational is a significant factor of negative emotions, while the intensity of media consumption does not play a key role. The obtained data indicate the resistance of active Internet users to strategies of dramatization of situation. The rather rapid emotional burnout of the audience in the first wave of the epidemic is explained by the fact that today “compassion fatigue” becomes an a priori attitude. So, modern media consumption practices can be described using the metaphor of surfing on the crest of information waves. © 2021, Russian Academy of Sciences. All rights reserved.

Clinical observation of the course of covid-19 in patients with multiple sclerosis during ocrelizumab therapy: Two clinical cases

The COVID-19 pandemic was announced in 2020, and many professional medical societies had to review their algorithms for the management of high-risk patients. In addition to risk factors such as overweight, age over 65 years, cardiovascular disease, diabetes mellitus, and bronchial asthma, other chronic diseases should also be emphasized, taking into account possible immuno-suppressive therapy. This publication presents two clinical cases of COVID-19 infection in patients with multiple sclerosis treated with ocrelizumab. During the course of the disease, both patients developed a cytokine storm and were treated with IL-6 blockers. Both cases ended with recovery and a subsequent return to anti-B-cell therapy. Given the mechanism of action of ocrelizumab, there are higher risks of infectious complications, including with COVID-19, but mortality is not higher than the population average. The information published to date may serve as a reason to consider the use of extended dosing intervals to minimize the possible risks of COVID-19 infection, which are probably highest in the first months after infusion. © 2021, Remedium Group Ltd. All rights reserved.

COVID-19 AND OXIDATIVE STRESS

Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body’s systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis. Патогенез новой коронавирусной инфекции COVID-19 является предметом активного изучения во всем мире. COVID-19, вызываемый SARS-CoV-2, представляет собой сложное заболевание, в котором тесно переплетено взаимодействие вируса с клетками-мишенями, действием иммунной системы и системной реакцией организма на эти события. Многие респираторные вирусные инфекции, включая COVID-19, вызывают смерть инфицированных клеток, активацию компонентов врожденного иммунитета и секрецию цитокинов воспаления. Все эти процессы ассоциированы с развитием окислительного стресса, который вносит важный вклад в патогенез вирусных инфекций. В данном обзоре проведен анализ информации об окислительном стрессе при инфекциях, вызываемых SARS-CoV-2 и другими респираторными вирусами. Основное внимание в обзоре уделено участию сосудистого эндотелия в патогенезе COVID-19.

Clinical outcomes of patients with COVID-19 admitted for respiratory support to the intensive care units in Russia

Aim. To evaluate mortality and risk factors for death in patients with COVID-19 who required admission to intensive care units (ICU) for respiratory support in Russia.Material and methods. In a retrospective study, we collected medical records of the consecutive ICU patients submitted by the local COVID-19 hospitals across Russia to the Federal Center at the Sechenov University (Moscow) betweenMarch 16 to May 3, 2020. All patients have completed their hospital stay (death or recovery). Diagnosis of SARS-CoV-2 pneumonia was established both by polymerase chain reaction (PCR) and CT. In patients with inconclusive or negative results of PCR, the SARS-CoV-2 pneumonia was defined as severe acute respiratory infection with typical CT findings and no other obvious aetiology. We used Cox proportional hazards regression model adjusted for age, sex and other risk factors to estimate hazard ratios (HR) and 95% confidence intervals (CI).Results. We studied 1522 ICU patients with SARS-CoV-2 induced acute respiratory distress syndrome (ARDS), including 864 males and 658 females at the median age of 62 years. Nine hundred twenty two records (60.1%) were submitted from Moscow and Moscow province, and 600 records (39.4%) were received from the hospitals located in 70 regions of Russia. SARS-CoV-2 was verified by PCR in 995 (65.4%) patients. Among 1522 patients enrolled in the study,995 patients (65.4%) died, and 527 (34.6%) patients recovered. The most common causes of death were ARDS (93.2%), cardiovascular events (3.7%) and pulmonary embolism (1.0%). The mortality rate was low in patients with less severe pneumonia requiring oxygen therapy (10.1%). However, it increased significantly in patients who were placed on noninvasive or invasive ventilation (36.8% and 76.5%, respectively). Risk of death increased with age, and in males older than 50 years it was significantly higher than in females of similar age. In a unvariate analysis, arterial hypertension, coronary artery disease (CAD), history of stroke, atrial fibrillation, type 2 diabetes, obesity and malignancies were associated with an increased risk of death. However, only CAD (HR1.257, 95% CI 1.064-1.485, p=0.007), type 2 diabetes (HR1.300, 95% CI 1.131-1.494, p<0.0001) and obesity (HR1.347,95% CI 1.166-1.556, p<0.0001) retained statistical signicance in multiple factor analysis.Conclusion. In ICU patients with COVID-19, severity ofARDS (i.e. requirement in mechanical ventilation), age, malegender, CAD, obesity and type 2 diabetes were associatedwith a higher risk of death. Цель. Изучение летальности и факторов рискасмерти больных с COVID-19, госпитализированных для респираторной поддержки в отделения реанимации и интенсивной терапии(ОРИТ) лечебных учреждений Российской Федерации.Материал и методы. Ретроспективноеисследование было выполнено в Федеральномдистанционном консультативном центре анестезиологии и реаниматологии для взрослыхпациентов с COVID-19 на базе Первого МГМУим. И.М. Сеченова. В исследование включаливсех пациентов с известными исходами (смертьот любых причин или выздоровление) SARS-CoV-2 пневмонии, осложнившейся острым респираторным дистресс синдромом (ОРДС),которые были проконсультированы с 16 мартапо 3 мая 2020 г. Факторы риска смерти анализировали с помощью многофакторной регрессионной модели Кокса.Результаты. В исследование были включены 1522 пациента, 864 (56,8%) мужчины и 658(43,2%) женщин. Медиана возраста - 62 года.922 (60,6%) больных находились в ОРИТ стационаров Москвы и Московской области, 600(39,4%) - лечебных учреждений в 70 регионахРоссийской Федерации. У 995 (65,4%) больных диагноз SARS-CoV-2 инфекции был подтвержден с помощью ПЦР. Умерли 995 (65,4%)пациентов, выжили 527 (34,6%). Основнымипричинами смерти были ОРДС (93,2%), сердечно-сосудистые осложнения (3,7%) и тромбоэмболия легочной артерии (1,0%).Летальность была низкой у пациентов, находившихся на оксигенотерапии (10,1%), изначительно повышалась у больных, которыхприходилось переводить на неинвазивную(36,8%) или инвазивную (76,5%) вентиляциюлегких. Риск смерти увеличивался с возрастоми в возрастных группах старше 50 лет у мужчинбыл достоверно выше, чем у женщин. В однофакторных моделях заболеваниями, ассоциировавшимися с развитием летального исхода,были артериальная гипертония, ИБС, инсульт,фибрилляция предсердий, сахарный диабет 2типа, ожирение и солидные опухоли, однако вмногофакторной модели, построенной по всемпризнакам с коррекцией по полу и возрасту,статистическое значение сохранили толькоИБС (отношение рисков [ОР] 1,257, 95% доверительный интервал [ДИ] 1,064-1,485,p=0,007), сахарный диабет 2 типа (ОР 1,300,95% ДИ 1,131-1,494, p<0,0001) и ожирение(ОР 1,347, 95% ДИ 1,166-1,556, p<0,0001).Заключение. Основными факторами рискасмерти больных с COVID-19, переведенных вОРИТ для респираторной поддержки, былитяжесть ОРДС, прежде всего необходимость вИВЛ, пожилой возраст, мужской пол, а такжеИБС, ожирение и сахарный диабет 2 типа.

COVID-19 and Oxidative Stress.

Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body's systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis.

[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.