The COVID-19 epidemic has already come to be seen as an emergency of international concern. This relates not only to the wide occurrence of the infection, but also to a fairly high mortality rate, currently more than 6.5 million deaths in the world. The aim of this study was to analyze, generalize and systematize the currently available literary data on the study of the novel coronavirus infection pathogenesis in the human body and to determine key changes that occur after the SARS-CoV-2 penetration into cells. In this way to target physicians primarily based on the pathogenetic processes that occur in the human body, syndromes and symptom complexes that are observed in treatments. Results. The article presents a literature review demonstrating that the specific interaction between the virus and somatic cells is the triggering mechanism for the pathogenesis of coronavirus infection. The main route for SARS-CoV-2 entry into the body is the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed not only in type 2 alveolar epithelial cells, but also in cells of the kidney, heart, blood vessels and gastrointestinal tract, including endotheliocytes and pericytes. Expression of the ACE2 receptor has also been shown in various structures and parts of the brain, cells of the conjunctiva, limbus, cornea and cells of the substantia propria. A high expression of the ACE2 receptor has been found in the epithelial cells of the oral mucosa, salivary glands, tonsils and tongue. These factors explain a possible involvement of different organs and systems in the development of multiorgan failure. Conclusions. In the development of multiorgan disfunction, two components are important: first, direct cell tropism and viral load, that may be unique in each patient. Secondly, it is the development of immune-mediated reactions to infected cells. Under conditions of hyperimmune inflammation, that is, the development of cytokine storm, acute respiratory distress syndrome progresses, and multiple organ failure develops. Endothelial damage is directly involved in the pathophysiology of this process, that results in the development of endothelial dysfunction, disruption of microcirculation, as well as perivascular inflammation, which aggravates damage to the endothelium and can lead to thrombus formation. The use of modern knowledge about the immunopathogenesis of COVID-19 would help to estimate the risk for severe infection and the possible development of complications, allowing for the timely implementation of effective pathogenetic therapy.

Background:Long COVID syndrome has emerged as a new global healthcare challenge, with impaired physical performance being a prominent debilitating factor. Cardiopulmonary rehabilitation is a mainstay of management of symptomatic post-COVID patients, and optimization of candidate selection might allow for more effective use of available resources.Methods:In order to study the natural dynamics and to identify predictors of physical functional recovery following hospitalization for COVID-19, 6 min walk test was performed pre-discharge in 176 patients (40% hypertensive, 53% female, mean age 53.2 ± 13.5 years) with re-evaluation at 1 month.Results:Six min walk distance and the reached percent of predicted distance (6MWD%) were suboptimal at both visits-396 ± 71 m (68.7 ± 12.4%) pre-discharge and 466 ± 65 m (81.8 ± 13.6%) at 1 month. Associated changes included significant oxygen desaturation (2.9 ± 2.5 and 2.3 ± 2.2%, respectively) and insufficient increment of heart rate during the test (24.9 ± 17.5 and 28.2 ± 12.0 bpm) that resulted in low reached percent of individual maximum heart rate (61.1 ± 8.1 and 64.3 ± 8.2%). Automatic clusterization of the study cohort by the 6MWD% changes has allowed to identify the subgroup of patients with poor "low base-low increment" trajectory of spontaneous post-discharge recovery that were characterized by younger age (38.2 ± 11.0 vs. 54.9 ± 12.1, p < 0.001) but more extensive pulmonary involvement by CT (43.7 ± 8.8 vs. 29.6 ± 19.4%, p = 0.029) and higher peak ESR values (36.5 ± 9.7 vs. 25.6 ± 12.8, p < 0.001). Predictors of poor recovery in multivariate logistic regression analysis included age, peak ESR, eGFR, percentage of pulmonary involvement by CT, need for in-hospital oxygen supplementation, SpO2 and mMRC dyspnea score pre-discharge, and history of hypertension.Conclusion:COVID-19 survivors were characterized by decreased physical performance pre-discharge as assessed by the 6 min walk test and did not completely restore their functional status after 1 month of spontaneous recovery, with signs of altered blood oxygenation and dysautonomia contributing to the observed changes. Patients with poor "low base-low increment" trajectory of post-discharge recovery were characterized by younger age but more extensive pulmonary involvement and higher peak ESR values. Poor post-discharge recovery in the study cohort was predictable by the means of machine learning-based classification model that used age, history of hypertension, need for oxygen supplementation, and ESR as inputs.

Objective: To study the relation of hypertensive status and systolic blood pressure (SBP) pre-discharge values to the dynamics of functional re-conditioning as assessed by 6-minute walk distance during the 1-month follow-up after hospitalization for COVID-19. Design and method: 6-minute walk distance (6MWD) was assessed pre-discharge in 176 patients hospitalized for COVID-19 (40% hypertensive, 47% male, mean age 53,2 ± 13,5 years) using the 20 m walkway and an extended protocol that included monitoring of peripheral pulse and capillary blood oxygen saturation (SpO2) every 30 seconds via bluetooth-connected pulse oximeter. The repeated evaluation was performed after 1 month of follow-up. Results: Hypertensive participants were characterised by older age (57,8±11,8 vs 50,7±13,9, p < 0,001), higher weight and body mass index (31,7±5,3 vs 27,4±4,4 kg/m 2 , p < 0,001). As a result, 6MWD in them was shorter (378±57 vs 418±75 m, p = 0,001) but no difference in reached percent of predicted distance (6MWD%) was detected (63,0±8,5 vs 63,2±11,1 %, p = 0,939). The described relation persisted at 1 month, with no difference in absolute (72±43 vs 68±43 m, p = 0,324) and percentage gain of 6MWD (12,8±6,6 vs 11,2±7,5 %, p = 0,266) between groups. Multiple regression analysis has allowed to build the model that accounted for 94% of variability in the 6MWD% gain between visits (85% for dedicated hypertensive cohort model). After adjustment for age, sex, height, weight, Remdesivir treatment, minimal SpO2 levels during acute COVID-19, changes of SpO2 and pulse rate throughout the 6MWT, SBP remained a potent independent predictor of 6MWD% gain, with 10 mmHg higher values at baseline evaluation being associated with 21,5% lesser 6MWD% gain in hypertensive subjects and 8,2% lesser – in normotensives. Conclusions: Hypertensive status did not have an impact on 6MWD% in pre-discharge COVID-19 patients. Moderate-to-high quality multiple regression models have demonstrated an independent role of SBP, demographic and anthropometric data, changes of SpO2 and pulse rate throughout the 6MWT in prediction of 6MWD% gain during 1 month after discharge, both in hypertensive and normotensive patients.

Among the comorbid conditions that significantly worsen quality of life and life expectancy are the chronic obstructive pulmonary disease and heart failure. Difficulties of drug therapy are the mutually exclusive approaches in the treatment of chronic obstructive pulmonary disease and concomitant cardiovascular pathology. Aim of this study was to provide scientific evidence of the possible use of the combined drug LCZ696 (angiotensin receptor neprilysin inhibitor, ARNI), which contains neprilysin inhibitor sacubitril (AHU377) and angiotensin II blocker valsartan, in patients with congestive heart failure. The article presents a review of the literature. It was demonstrated that the cause of mortality in patients with chronic obstructive pulmonary disease could be both changes in the respiratory system and complications in the cardiovascular system. It has been shown that progressive chronic obstructive pulmonary disease leads to the formation of pulmonary hypertension, right ventricular hypertrophy, decrease in its systolic function, subsequent dilatation of the right ventricle, and development of right ventricular heart failure, which is one of the most serious and difficult tests in the treatment process. The further development of such a combined pathology is left ventricular heart failure. The role of the system of natriuretic peptides, namely brain natriuretic peptide, brain natriuretic propeptide, C-type natriuretic peptide, and N-terminal precursor of C-type natriuretic peptide, as markers of chronic obstructive pulmonary disease and heart failure has been discussed. Natriuretic peptide is currently a recognized marker of heart failure, the high value of which is achieved for determining the prognosis and stratification of the risk of heart failure. Natriuretic peptide acts as a vasodilator, provides antiproliferative activity through the G-dependent protein kinase pathway and promotes bronchodilation, causing the release of acetylcholine from bronchial epithelial cells. Conclusions. All these properties suggest that natriuretic peptides may be a potential treatment in patients with cardiac complications and chronic obstructive pulmonary disease. The best way to prolong life of natriuretic peptide is to inhibit degradation of the natriuretic peptide with the neprilysin inhibitor sacubitril.

Cardiovascular pathology is one of the frequent comorbidities in patients with chronic obstructive pulmonary disease, due to both genetic predisposition and common risk factors (smoking, senile age, male gender, sedentary lifestyle, obesity). The article shows that development of endothelial dysfunction is one of the earliest phases of pathogenesis in this setting. Endothelial dysfunction mechanisms are defined and characterized, including an imbalance of vasoconstricting and vasodilating agents with the emergence of "vicious circles" that violate hemo-vascular homeostasis. The role of nitric oxide, endothelin-1, intercellular adhesion molecule-1 (ICAM-1) in the development of endothelial dysfunction in COPD patients is discussed.The article defines the concept of oxidative stress, the most potent oxidants and mechanisms of their damaging effect arebeing listed. A particular attention is paid to 8-isoprostane as a golden standard in assessment of oxidative stress in patients with COPD.

The main cardiovascular diseases affect the processes of myocardial remodeling, which further contributes to the formation of systolic or diastolic heart dysfunction. The formation of myocardial dysfunction is primarily associated with left ventricular hypertrophy when under hemodynamic loading, firstly, wall rigidity increases, secondly, myocardial fibrosis is formed. The latter is one of the key factors of the hypertrophic process caused by the accumulation of collagen, which leads to a aggravation of the left ventricle relaxation processes. Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that are clinically manifested by alterations in the size, shape, and function of heart as a result of the heart muscle injury. It has been determined that fibrosis is an early morphological sign of injury in patients with left ventricular overload, as well as a factor in the development of diastolic and systolic dysfunctions. Compensatory left ventricular hypertrophy transforms into heart failure due to the fibrosis development. In hypertrophy the content of elastic collagen type III decreases and rigid collagen type I increases. The essential role of the extracellular matrix in myocardial fibrosis formation is emphasized. Cardiac fibrosis is a process of pathological remodeling of the extracellular matrix, which leads to abnormalities in its composition and dysfunction of the heart muscle. The extracellular matrix plays a key role in organogenesis and post−traumatic healing in tissue injuries. The study of intercellular interactions of the extracellular matrix will provide a better understanding of the mechanisms of changes in geometry and function of the heart, and investigation of the activity of matrix components will open new opportunities for targeted therapeutic effects on molecular mechanisms of cardiac remodeling. Key words: diastolic dysfunction, extracellular matrix, myocardial fibrosis, cardiomyocytes, fibroblasts.

Hypertension in its origin is a heterogeneous and multisystemic disease. Evaluation of oxidative stress activity based on the level of 8-iso-PgF2α, proinflammatory activity based on tumour necrosis factor-α, its type I soluble receptor, and C-reactive protein levels is relevant for further understanding of pathogenesis of hypertension and improvement of the early diagnostics of heart failure. 186 hypertensive patients were observed during a 2-months course of treatment, aged 30 to 65 years. Serum levels of 8-iso-PgF2α (n = 34), tumour necrosis factor-α and its type I soluble receptor were determined by ELISA before and after course of treatment. C-reactive protein level was determined by biochemical method. The control group included 16 clinically healthy individuals, aged 27 to 55 years. Hypertensive patients enrolled into the study were randomized into three groups that received different protocols of combined anti-hypertensive therapy: I clinical group – а combination of bisoprolol and indapamid, II – а combination of lacidipine and candesartan, III – а combination of fosinopril sodium and hydrochlorothiazide. On the background of combined antihypertensive therapy, we observed favourable dynamics of 8-iso-PgF2α, tumour necrosis factor-α and its type I soluble receptor, and C-reactive protein levels. Taking into account the insignificance of the correlations revealed, a one-factor dispersion analysis was applied which allowed us to determine the influence of the grade and duration of hypertension on the dynamics of the studied parameters. It has been found that the grade of hypertension is related to an increase in TNF-α and 8-iso-PgF2α serum levels, but not in TNF-α type I soluble receptor, and the duration of hypertension is related to an increase in C-reactive protein, TNF-α and its type I soluble receptor levels, with no relation to the level of 8-iso-PgF2α. Thus, oxidative stress possibly promotes the activation of potentially damaging immune mechanisms mediated by proinflammatory cytokines, nonspecific inflammation and drives the further progression of lesions in the target organs.

SUBCLINICAL CARDIAC DAMAGE IN CARDIOPULMONARY POLYMORBIDITY. (review). Part 1. Ashcheulova T., Ambrosova T., Kochubiei O., Honchar O., Sytina I. Hypertension and chronic obstructive pulmonary disease are one of the frequent comorbid conditions in internal medicine and are subject to meaningful cooperation among physicians, cardiologists, and pulmonologists. A combination of chronic obstructive pulmonary disease and hypertension presents certain diagnostic and therapeutic challenges. These conditions share common risk factors, similar clinical presentations and some common parts of pathogenesis. The problem of association between chronic obstructive pulmonary disease and hypertension may be currently discusses both as a simple combination of various clinical entities, and as chronic obstructive pulmonary disease resulting in development of factors contributing to hypertension. One way or another, either a simple combination, or a mutually aggravating syndrome, but we state there is a cardiorespiratory continuum where chronic obstructive pulmonary disease acts as a valid component of hypertension development, and vice versa. Thus, it seems to be relevant to study peculiarities of the structural and functional status of the cardiovascular system and microcirculation, systemic remodeling mechanisms, endothelial dysfunction and inflammation in presence of chronic obstructive pulmonary disease -associated hypertension. Problems of additional cardiovascular risk marker development, treatment efficiency assessment remain topical. Use of electrocardiography and echocardiography with dopplerometry has been an important diagnostic principle of subclinical cardiovascular damage in presence of hypertension and chronic obstructive pulmonary disease comorbidity. Non-invasive imaging methods play a central part in diagnostics of subclinical target organ damage. Wide implementation thereof is based on high diagnostic accuracy, common availability, safety and relatively low price. Key words: hypertension, chronic obstructive pulmonary disease, comorbidity, electrocardiography, echocardiography with dopplerometry Резюме. СУБКЛІНІЧНЕ УРАЖЕННЯ СЕРЦЯ ПРИ КАРДІОПУЛЬМОНАЛЬНІЙ ПОЛІМОРБІДНОСТІ (огляд). Частина 1. Ащеулова Т.В., Амбросова Т.М., Кочубєй О.А., Гончарь О.В., Ситіна І.В. Артеріальна гіпертензія і хронічне обструктивне захворювання легень - одне з частих коморбідних станів в клініці внутрішніх хвороб і є предметом конструктивної взаємодії терапевтів, кардіологів, пульмонологів. Поєднання хронічного обструктивного захворювання легень і артеріальної гіпертензії являє певні труднощі для діагностики і лікування. Ці захворювання мають загальні фактори ризику, схожі клінічні прояви і спільність деяких ланок патогенезу. Таким чином, представляється актуальним дослідження особливостей структурно-функціонального стану серцево-судинної системи і мікроциркуляції, вивчення системних механізмів ремоделювання, ендотеліальної дисфункції та запалення при артеріальній гіпертензії в поєднанні з хронічним обструктивним захворюванням легень. Залишаються актуальними питання розробки додаткових маркерів серцево-судинного ризику, оцінки ефективності проведеного лікування. В останні роки важливими принципами діагностики субклінічного ураження серця і судин при коморбідності хронічного обструктивного захворювання легень і артеріальної гіпертензії є використання електрокардіографії та ехокардіографії з доплерометрією. Неінвазивні методи візуалізації відіграють центральну роль в діагностиці субклінічного ураження органів-мішеней. Їх широке застосування обумовлено високою діагностичної точністю, повсюдною поширеністю, безпекою і відносно низькою вартістю. Ключові слова. Артеріальна гіпертензія, хронічне обструктивне захворювання легень, коморбідность, електрокардіографія, ехокардіографія з доплерометрією. Резюме. СУБКЛИНИЧЕСКОЕ ПОРАЖЕНИЕ СЕРДЦА ПРИ КАРДИОПУЛЬМОНАЛЬНОЙ ПОЛИМОРБИДНОСТИ (обзор). Часть 1. Ащеулова Т.В., Амбросова Т.Н., Кочубей О.А., Гончарь А.В., Сытина И.В. Артериальная гипертензия и хроническое обструктивное заболевание легких - одно из частых коморбидных состояний в клинике внутренних болезней и являются предметом конструктивного взаимодействия терапевтов, кардиологов, пульмонологов. Сочетание хронического обструктивного заболевания легких и артериальной гипертензии представляет определенные трудности для диагностики и лечения. Эти заболевания имеют общие факторы риска, схожие клинические проявления и общность некоторых звеньев патогенеза. Таким образом, представляется актуальным исследование особенностей структурно-функционального состояния сердечно-сосудистой системы и микроциркуляции, изучение системных механизмов ремоделирования, эндотелиальной дисфункции и воспаления при артериальной гипертензии в сочетании с хроническим обструктивным заболеванием легких. Остаются актуальными вопросы разработки дополнительных маркеров сердечно-сосудистого риска, оценки эффективности проводимого лечения. В последние годы важными принципами диагностики субклинического поражения сердца и сосудов при коморбидности хронического обструктивного заболевания легких и артериальной гипертензии является использование электрокардиографии и эхокардиографии с допплерометрией. Неинвазивные методы визуализации играют центральную роль в диагностике субклинического поражения органов-мишеней. Их широкое применение обусловлено высокой диагностической точностью, повсеместной распространенностью, безопасностью и относительно низкой стоимостью. Ключевые слова. Артериальная гипертензия, хроническое обструктивное заболевание легких, коморбидность, электрокардиография, эхокардиография с допплерометрией.

Over a long period, chronic heart failure was primarily associated with impaired contractility of the left ventricular myocardium, which is a manifestation of systolic dysfunction. Based on modern ideas about the pathophysiology of CHF syndrome, systolic dysfunction is considered as one of the etiological factors along with changes in wall tension and the structure of diastolic filling, i.e. everything that is included in the concept of “LV remodeling”. The objective is to present a review of the key parameters of chronic heart failure and left ventricular diastolic dysfunction according to the latest updates. The role and significance of diastolic dysfunction as the cause of chronic heart failure syndrome have only been determined over the past three decades, which can be explained by the difficulty of early diagnostics of diastolic dysfunction. The article describes the historical evolution of heart failure and left ventricular diastolic dysfunction estimation. It is important to note the high prevalence of diastolic dysfunction. The signs of myocardial diastolic dysfunction are detected in people with almost any heart disease. The universal review of the most important parameters which determine this disorder has been presented. It has been shown that Doppler echocardiography is now the noninvasive “gold standard” for estimation of diastolic dysfunction. We have presented methods of treatment for diastolic dysfunction according to the 2017AmericanCollegeof Cardiology/American Heart Association updated Guidelines for the management of heart failure Conclusions. The experimental studies demonstrate that the survival of HF patients with a preserved EF depends not so much on its indices, but on the severity of DD. DD is a more prognostic marker of mortality rate in patients with HF than EF, which requires further study for better therapeutic efficacy.

У статті представлено аналітичний огляд прогностичної значимості діагностики безсимптомного ураження органів-мішеней при артеріальній гіпертензії в контексті детальнішого визначення серцево-судинного ризику. Представлено основні інструментальні та функціональні проби для діагностики субклінічних стадій ураження органів-мішеней при артеріальній гіпертензії та визначено їх прогностичну значущість щодо основних кардіоваскулярних подій.

One of the main prerequisites for creation and dissemination of bioethics in the world was the concept of dual use in medical and biological sciences, which is defined as the direction of unintentional creation of biological threats in research or implementation of new biotechnologies. To determine the range of dual-use research that could potentially generate products, technologies, or knowledge whose misuse could harm large numbers of people or the environment and that are biosafety-relevant, the international term Dual Use Research of Concern (DURC) is used. Actualization of the debate on the dilemma of dual use in biomedical sciences is due to, on the one hand, the international community's attempt to minimize the potential for destructive use of biomedical research, on the other hand, the active search for effective ways to raise awareness of their social and moral responsibility for implementation of the results of scientific developments in the field of life. This article considers the definition of terms that define the field of DURC in the context of biosafety, which in recent decades have undergone a number of semantic changes. The article also outlines the modern general concept of DURC, defines the categories by which DURC is defined, and outlines the scope of policy on the implementation of control over DURC. Informing the scientific community engaged in biomedical research about the problem issues of DURC biotechnology is a key component of biosafety. Modern biotechnology and related biosafety issues should be applied to society needs, but without compromising human and environmental safety. Systematic consideration of all these disputable questions of the dual-use dilemma with the involvement of all stakeholders will allow to form a rational biosafety policy for biotechnology.

Relevance of the study of early repolarization syndrome is associated with a high degree of its occurrence among the general population, namely among young people and people doing sports. Objective is to generalize the data of experimental and clinical studies which have found that the early repolarization syndrome is an idiopathic electrocardiographic phenomenon, which is considered by various specialists ambiguously; to assess the state of the cardiovascular system in the subjects, both adults and children with early repolarization syndrome, and to propose a diagnostic algorithm for detecting this phenomenon on the ECG when admitting to physical exercise and sports. The history of the development of early repolarization syndrome has been shown since 1936 to present time, which was first described by R. Shipley and W. Halleran. Clinical interest in ERS appeared as a result of a clinically established relationship with lethal arrhythmias in healthy people without structural changes in the heart. According to existing recommendations, the opinions of leading experts, including members of Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), the Asia-Pacific Society for Heart Rhythm (2015), it should be distinguished between the pattern and the syndrome of early ventricular repolarization. The Shanghai scale for the diagnosis of early repolarization syndrome, as well as the etiology, electrophysiology of early repolarization syndrome, its modern classification and electrocardiographic signs are presented. The features of early repolarization syndrome in athletes and in children, as well as the features of its treatment and prevention are shown. Conclusions. Thus, the early repolarization syndrome is an important cardiac problem. Future clinical and experimental studies should focus on finding out the exact causes and mechanisms for the development of the early repolarization syndrome and, ultimately, on developing strategies to prevent premature death from cardiac causes in individuals with this electrocardiogram disorder.

Over a long period, chronic heart failure was primarily associated with impaired contractility of the left ventricular myocardium, which is a manifestation of systolic dysfunction. Based on modern ideas about the pathophysiology of CHF syndrome, systolic dysfunction is considered as one of the etiological factors along with changes in wall tension and the structure of diastolic filling, i.e. everything that is included in the concept of "LV remodeling". The objective is to present a review of the key parameters of chronic heart failure and left ventricular diastolic dysfunction according to the latest updates. The role and significance of diastolic dysfunction as the cause of chronic heart failure syndrome have only been determined over the past three decades, which can be explained by the difficulty of early diagnostics of diastolic dysfunction. The article describes the historical evolution of heart failure and left ventricular diastolic dysfunction estimation. It is important to note the high prevalence of diastolic dysfunction. The signs of myocardial diastolic dysfunction are detected in people with almost any heart disease. The universal review of the most important parameters which determine this disorder has been presented. It has been shown that Doppler echocardiography is now the noninvasive "gold standard" for estimation of diastolic dysfunction. We have presented methods of treatment for diastolic dysfunction according to the 2017 American College of Cardiology/American Heart Association updated Guidelines for the management of heart failure Conclusions. The experimental studies demonstrate that the survival of HF patients with a preserved EF depends not so much on its indices, but on the severity of DD. DD is a more prognostic marker of mortality rate in patients with HF than EF, which requires further study for better therapeutic efficacy.