The legacy of the COVID-19 pandemic may represent an even more serious global health challenge than the acute infection itself. The neurological consequences of SARS-CoV-2 infection may progress to chronic brain tissue damage, leading to clinical manifestations of neurodegenerative diseases. Post-COVID-19 neurological syndrome and neurodegenerative disorders, such as Alzheimer disease and Parkinson disease, share common pathological features, risk factors, and underlying mechanisms. Immune-mediated mechanisms constitute a key component of the post-COVID-19 neurological syndrome and may initiate a neurodegenerative cascade. Chronic inflammatory processes triggered by SARS-CoV-2 infection promote the aggregation of misfolded proteins and neuronal loss, which are hallmark features of neurodegeneration. Given the high global prevalence of COVID-19 during the pandemic, health care systems should be prepared for a potential increase in the incidence of neurodegenerative diseases in the coming years. Addressing this challenge requires interdisciplinary collaboration integrating immunology, neurology, virology, and systems biology to develop effective individualized therapeutic strategies for one of the most persistent consequences of the COVID-19 pandemic. This review examines the complex relationship between COVID-19 and neurodegenerative diseases. SARS-CoV-2, its RNA, and proteins act as potent immunomodulatory agents capable of inducing chronic neuroinflammation even after viral clearance. Advances in modern biomedical technologies have enabled the identification of proteomic, genetic, and imaging biomarkers that may serve as predictors of risk and potential therapeutic targets. Elucidation of these molecular interactions provides important insights for future research aimed at developing innovative therapeutic and rehabilitation interventions.

The development and progression of cardiovascular diseases such as atherosclerosis, hypertension, coronary heart disease, heart failure, and others is determined by the interaction of genetic, environmental, and behavioral factors. In recent years, epigenetic mechanisms have been considered key regulators of the cardiovascular system, influencing gene expression without altering the DNA sequence. The expression of disease-associated genes is regulated by epigenetic mechanisms. The epigenome plays a key role in executing cellular programs, regulating gene transcription and altering chromatin structure and accessibility to transcription factors. Epigenetic enzymes depend on metabolites to perform their modifying functions, thereby establishing a link between metabolism and epigenetics. Cellular metabolic processes include glycolysis and β-oxidation of fatty acids, as well as energy metabolism. Cardiovascular metabolic dysfunction contributes to the development of cardiovascular disease through inappropriate epigenetic modifications of histone proteins, DNA, and RNA. Key elements of this process are transcription factors that interact with regulatory DNA sequences, altering gene expression. Advances in epigenome analysis have provided insights into the pathogenesis of cardiovascular diseases by identifying disease-associated epigenetic changes in cardiomyocytes and other cardiac cell types. This review examines recent discoveries in the field of epigenetic regulation of cardiac disease, highlighting the role of epigenetic enzymes and non-coding RNAs, which offer new opportunities for personalized medicine in cardiology. Understanding these epigenetic pathways is critical for the development of new biomarkers and epigenetic therapies and cardiac rehabilitation aimed at slowing or reversing maladaptive cardiac remodeling and improving clinical outcomes.

INTRODUCTION. Physiotherapy interventions are typically employed during the rehabilitation phase or as an adjunct to primary therapy, such as pharmacological or surgical treatment, for patients with chronic or acute conditions. Interest in the immunological aspects of physiotherapy is growing rapidly. AIM. To summarize the data on the immunological aspects of physiotherapy presented in foreign publications of the last five years. MATERIALS AND METHODS. The search was conducted in the PubMed and Google Scholar databases using the following keywords: physiotherapy, immunology, innate immunity, acquired immunity, cellular immunity, humoral immunity, and clinical trials. Following the application of the exclusion criteria, 66 studies were selected from the initial 207 articles that were retrieved. THE MAIN CONTENT OF THE REVIEW. Chronic diseases, as well as the consequences of traumatic injuries, are characterized by chronic inflammation and immune imbalance. Despite impressive clinical successes of rehabilitation, it is not always effective in some patients, which highlights the need to understand and overcome the mechanisms of therapeutic refractoriness. Like other therapeutic modalities, physiotherapy faces the challenge of predicting patient response to intervention. It is assumed that the beneficial effects of physiotherapy are related to its anti-inflammatory, cytoprotective, and antioxidant properties and synergistic effects on immune functions. Our review article provides a concise overview of clinical studies exemplifying such effects, demonstrating the influence of physiotherapeutic manipulations on the population structure of the immune system and cytokine secretion. The review material is structured according to the main methods of physiotherapy, such as traditional methods (massage, treatment with heat, cold, water, mud, ultrasound, laser, magnetic field, hyperbaric oxygenation, pelotherapy), as well as newer ones (thermal and mechanical ablation with high-intensity ultrasound). CONCLUSION. The materials presented in the review offer a novel insight into the potential of physiotherapeutic interventions on both innate and acquired immunity, as well as their cellular and humoral components. The present state of research in this area is at an early stage. Further large-scale clinical studies are needed to develop recommendations for the safe use of immunomodulatory physiotherapy in the context of specific pathologies. In addition, physiotherapists should acquire additional knowledge in the field of immunology, which is currently beyond their competence, to accurately interpret and use the data.

INTRODUCTION. Regular physical exercise has a beneficial effect on health, affecting all body systems and reducing morbidity. Muscle fiber activity during exercise helps reduce levels of inflammatory markers and stimulate anti-inflammatory responses. The ability to maintain homeostasis while exercising and adaptation to exercises depend on physical fitness, comorbidities and other factors, so the exercise program should be tailored to the individual. THE MAIN CONTENT OF THE REVIEW. Immune system activation in response to exercise is mediated by cytokine signaling. The main source of cytokines during physical activity is the skeletal muscles themselves. Cytokines produced by myocytes (myokines) during muscle contraction play a key role in providing communication between working muscles and other organs and tissues. Numerous studies have shown a positive effect of moderate intensity exercise on myokine secretion. People with chronic infectious or non-infectious diseases often demonstrate low-grade systemic inflammation and low levels of circulating myokines. Moderate intensity exercise has anti-inflammatory effects in inflammatory conditions and diseases. Exercise is a popular non-pharmacological adjunct to traditional treatments and rehabilitation for many diseases. CONCLUSION. Understanding the relationship between exercise modalities and myokine response helps to optimize treatment and rehabilitation recommendations for populations with different needs, such as patients with cancer, chronic inflammatory diseases, or post-viral infection syndromes.

Epidemiologic data indicate that up to 30% of individuals surviving the acute phase of COVID-19 experience persistent cardiovascular symptoms, including dyspnea, chest pain and discomfort, palpitations, exercise intolerance, pathological fatigue, and sleep disturbances. Numerous investigations worldwide have shown that patients, regardless of age, race, sex, or cardiovascular risk factors, remain at increased risk for cardiovascular complications after recovery from COVID-19, including new-onset or progressive inflammatory heart diseases, heart failure, myocardial infarction, ischemic heart disease, cardiomyopathy, thromboembolism, cardiac arrhythmias, and ischemic stroke. SARS-CoV-2 not only induces direct cardiomyocyte injury or damages other cardiovascular system cells but also causes systemic inflammation and coagulopathy, which may exacerbate comorbid cardiovascular diseases. Functional and instrumental diagnostic methods have revealed various forms of subclinical and clinical cardiac injury in most patients with post-COVID syndrome, regardless of the severity of the acute COVID-19 phase or coexisting conditions. The high prevalence of post-COVID cardiovascular syndrome underscores the need for a comprehensive, multidisciplinary approach to diagnosis, treatment, and rehabilitation. Authors of published investigations, meta-analyses, and systematic reviews consistently emphasize the importance of monitoring cardiovascular status for at least one year after recovery from infection. This review article highlights the need to investigate the pathophysiology of post-COVID cardiovascular syndrome to identify potential therapeutic targets and develop targeted treatment strategies.

Intensified training is a widely accepted approach to improving athletic performance. To achieve consistently high performance, athletes require a balance between training and recovery. Without adequate recovery and muscle rest, an athlete may progress from optimal training to overreaching and, ultimately, to overtraining syndrome, which negatively affects physical health and performance. The issue of overtraining syndrome remains an underexplored area in sports medicine. Monitoring of pre-competition training is crucial for adjusting training programs. Various physiological and biochemical markers are commonly used to assess athletic conditioning. Changes in these markers help coaches and athletes understand physical status and training effects as they reflect muscle condition, endurance, fatigue, and inflammation response in tissues. However, the sensitivity of individual biomarkers in detecting overtraining is limited, and reference ranges for different training levels are not clearly defined. Systematic assessment of pre-competition preparation and diagnosis of overtraining syndrome remain challenging as the factors, signs/symptoms, and mechanisms of maladaptation are individualized, sport-specific, and understudied. Thus, identification of biomarkers that could aid in monitoring athletic conditioning and preventing and diagnosing overtraining syndrome is a critical research objective.

Chronic rhinosinusitis with nasal polyps is a heterogeneous disease characterized by local inflammation of the upper airways. Inflammation in chronic rhinosinusitis with nasal polyps is divided into 3 main endotypes with different pathophysiology and various forms of inflammation: T1, T2, and T3. Epithelial barrier dysfunction is a common feature in chronic rhinosinusitis induced by endotype-specific cytokines directly and indirectly. The sinonasal epithelium not only functions as a passive barrier but also is an active immunological organ with innate and adaptive components. Violation of the delicate balance of intercellular interactions in the sinonasal epithelium leads to the development of inflammation. The nasal polyp tissue contains numerous populations of immune cells that secrete many different cytokines and chemokines and interact with each other and with cells of the sinonasal epithelium. The most common is the T2 endotype, which is characterized by inflammation of the corresponding type. Inflammatory mediators such as cytokines, chemokines, and their receptors, are potential therapeutic targets for biologics (specific monoclonal antibodies). Several of these drugs have been clinically tested and are already being used in clinical practice. Further studies are aimed at detailing the pathogenetic mechanisms of nasal polyposis, studying the influence of genetic factors on the predisposition to the development of various endotypes, and creating new effective and safe biological preparations for various endotypes of nasal polyposis.

The SARS-CoV‑2 coronavirus has become a major global health concern. Infection with SARS-CoV‑2 has caused millions of deaths worldwide, and the case fatality rate has been found to be largely related to pre-existing clinical conditions. The main clinical manifestation of COVID‑19 is the presence of respiratory symptoms. Severe complications of COVID‑19 are most often observed in people with significant medical histories. The SARS-CoV‑2 virus primarily attacks the respiratory system, causing pneumonia and acute respiratory distress syndrome, which can lead to severe systemic inflammation, multiple organ dysfunction, and death, especially in patients with pre-existing comorbidities. A number of meta-analyses strongly suggest that comorbid respiratory diseases, including chronic obstructive pulmonary disease and interstitial lung diseases, are factors in the development of severe forms of COVID‑19, worsening patient outcomes and survival rates. Studies have shown an association between adverse outcomes of COVID‑19 and the expression level of the angiotensin-­converting enzyme 2 (ACE2) in these patients. Regarding other respiratory system pathologies, such as bronchial asthma and cystic fibrosis, it is known that the main unfavorable factor is long-term immunosuppressive pharmacotherapy preceding infection. In this article, we highlight the main respiratory comorbidities to better understand the pathogenesis of COVID‑19.

Сепсис — это тяжелая системная инфекция с дисфункцией органов, требующая неотложных действий. При недостаточно оперативном и эффективном вмешательстве летальность превышает 30 %. Неоднородность сепсиса является причиной неудач клинических испытаний иммуномодулирующей терапии пациентов с сепсисом. Из-за недостаточного понимания патогенеза этой неоднородности методы лечения, казавшиеся многообещающими в доклинических условиях, не имели успеха в клинических испытаниях. Отчасти отсутствие эффективности связано с применением универсального подхода ко всем пациентам с сепсисом. Диагностические и терапевтические стратегии, учитывающие индивидуальные особенности пациента, не получили широкого распространения в области сепсиса. Необходим переход к более персонализированному лечению по всем трем направлениям лечения сепсиса: антибиотикотерапии, реанимации и поддержке органов. Именно поэтому предпринимаются попытки стратифицировать пациентов на более однородные группы на основе общих для группы прогностических и предиктивных характеристик иммунного ответа. Такой подход является ключом к прецизионной медицине с отбором на основе патофизиологического механизма тех пациентов, кто с большей вероятностью ответит на специфическую терапию. Проблема заключается в относительно ограниченном понимании механизмов, управляющих иммунопатологией сепсиса. После десятилетий исследований сепсис остается нечетко определенным, и ни одно определение сепсиса не отражает сложность синдрома. Углубленный анализ фенотипических различий выявляет субгруппы пациентов, которым действительно помогают определенные вмешательства. Транскриптомный анализ цельной крови, плазмы и отдельных популяций иммунных клеток идентифицировал сигнатуры генной экспрессии, позволяющие не только отличить сепсис от синдрома неинфекционного системного воспалительного ответа, но и выделить эндотипы сепсиса с разными иммунными профилями и разными ответами на терапию, определяемые патобиологическим механизмом. Таким образом, растет интерес к более индивидуальному подходу к лечению сепсиса, но лучшие средства его реализации еще не определены, поэтому накопление информации продолжается.

COVID-19 is primarily a respiratory disease, but it brings a significant risk of acute kidney injury or exacerbation of pre-existing kidney disease, especially in patients with comorbidities such as hypertension, coronary artery disease, chronic liver disease, chronic kidney disease, and malignancies. We reviewed studies that assessed the association between chronic kidney disease and the risk of SARS-CoV-2 coronavirus infection and infection outcomes, including hospitalization, severe COVID-19, need for intensive care, COVID-19 progression, and patient death. The results of the studies are varied and often contradictory, as the baseline data differ in many parameters, such as the period of the pandemic, the quality and size of the sample, and the degree of comorbidity. Nevertheless, all authors conclude that, in general, chronic kidney disease is an unfavorable factor with regard to SARS-CoV-2 infection. In patients with COVID-19, the presence of concomitant chronic kidney disease predisposes to severe COVID-19, viral pneumonia, development of acute respiratory distress syndrome, acute kidney injury and other complications, which in turn are a negative prognostic factor for mortality. Patients with chronic kidney disease who survived COVID-19 are more likely to develop post-COVID syndromes with a variety of persistent or recurrent symptoms than convalescents without renal comorbidity. This category of patients requires long-term monitoring, optimization of therapy and priority for vaccination.

Extracorporeal blood purification is intended to eliminate dysregulation of the immune system. The concept of extracorporeal therapy is based on the nonspecific clearance of inflammatory mediators and triggers, which attenuates the systemic expression of inflammatory mediators. The main types of extracorporeal therapy are hemoadsorption and plasma exchange. Hemoadsorption is used primarily as an adjuvant treatment for septic shock and other severe inflammatory conditions, including severe forms of COVID-19 with cytokine storm. Reliable data demonstrating the benefit of hemoadsorption in critically ill patientsis is limited. Recommendations for the use of hemoadsorption devices are often based on incomplete data or questionable interpretations of available data. Given the lack of evidence for the benefit of hemoadsorption in the treatment of severe inflammation, sepsis, liver failure and rhabdomyolysis, its routine use in clinical practice is not justified until the mechanisms underlying these findings are fully elucidated. Plasma replacement is a potentially life-saving invasive extracorporeal blood purification procedure that replaces plasma with a substitute fluid (saline, albumin solution, fresh frozen plasma, or a combination of these) with the risk of side effects and complications. There is still uncertainty regarding the timing, type of plasma exchange, volume and frequency of plasma filtration. Although plasma replacement is considered to be relatively safe, there is still insufficient evidence to support its inclusion in sepsis treatment protocols. Reports of the use of extracorporeal methods in the treatment of patients with severe refractory systemic inflammation provide evidence of decreased levels of inflammatory biomarkers, improved hemodynamic parameters, and decreased organ failure. However, according to the results of randomized clinical trials, extracorporeal therapy does not affect clinical outcomes, and in some even increases mortality. To clarify the effectiveness of extracorporeal therapy, it is necessary to study the mechanisms of interaction of the devices used with target and non-target blood components and large-scale randomized controlled trials assessing the ability of this therapy to improve clinical outcomes.

Literature reports on the risk of SARS-CoV-2 in people with inflammatory rheumatisms are inconsistent. According to most studies, the risk of infection and development of severe COVID-19 is higher in rheumatism patients versus the general population, but largely depends on rheumatism type and activity. Thus, patients with severe rheumatism most often required artificial ventilation and died more often. It was associated with immune dysfunction caused by both the disease itself and antirheumatic therapy with immunomodulating agents. Immunosuppression, additional chronic comorbidities, and incomplete vaccination are progression factors of COVID-19, hospital stay, intensive care, and risk factors of severe COVID-19 outcomes and reinfection with coronavirus in rheumatism patients. During the spread of SARS-CoV-2 Omicron variant, they were still significant. Although there is no full consensus in the literature regarding the association of rheumatism with the severity of COVID-19, rheumatism is usually not considered a factor of increased severity and mortality of COVID-19. SARS-CoV-2 vaccines boost humoral response, and reduce the incidence and severity of COVID-19. Nevertheless, rheumatism patients show reduced or no antibody production in response to even completed vaccination, along with higher rates of post-vaccination breakthrough infection. Further research into specific rheumatic diseases and the use of antirheumatic drugs in the context of COVID-19 is required to reduce the severity of COVID-19 in this population.

И аллергические, и онкологические заболевания представляют собой две глобальные проблемы современной медицины, далекие от своего решения. Обе патологии являются иммуноопосредованными, но в случае аллергии имеет место гиперчувствительность вследствие срыва иммунной толерантности, а в случае онкологии заболевание развивается именно из-за иммунной недостаточности, связанной с избыточной толерантностью. Ключевым фактором роста злокачественной опухоли является формирование максимально «дружественной» среды со стороны ее микроокружения. Различные компоненты иммунитета, теоретически, должны эффективно распознавать и уничтожать клетки опухоли еще на начальных этапах ее развития, до образования клинически значимого опухолевого роста. Однако клинические исследования говорят об обратном. Различные компоненты иммунной системы (опухоль-ассоциированные макрофаги, цитокины — факторы роста, супрессорные клетки миелоидного происхождения) участвуют в патогенезе опухолевого роста, не противодействуя, а способствуя развитию новообразования, его инвазии и метастазированию. И поэтому одной из основных целей в области лечения онкологических заболеваний является разработка вмешательств, которые могут нарушить иммунологическую толерантность и остановить прогрессирование рака. Многочисленные эпидемиологические исследования предполагают обратную ассоциацию между аллергическими заболеваниями и развитием злокачественных новообразований. Немало также доказательств концепции способности клеток иммунной системы и IgE разрушать опухолевые клетки. Проводятся многочисленные исследования in vitro, которые «нацеливают» данный класс антител на соответствующие опухолевые антигены. Было продемонстрировано, что антитела класса IgE специфичны для сверхэкспрессированной опухоли, они превосходили любой другой класс иммуноглобулинов в отношении антителозависимой клеточной цитотоксичности (ADCC — antibody-dependent cell-mediated cytotoxicity) и фагоцитоза (ADCP — antibody-dependent cell-mediated phagocytosis). И поэтому эозинофилы, тучные клетки и макрофаги в совокупности с IgE могут стать мощными противоопухолевыми эффекторами. Специфичный к опухолевым антигенам IgE вызывает эозинофил-опосредованную гибель опухолевых клеток цитотоксическими механизмами. Характер влияния тучных клеток на опухоль определяется комплексом факторов. Установлено, что в зависимости от своей локализации по отношению к опухоли тучные клетки могут демонстрировать разнонаправленные эффекты. Неоднозначные свойства клеток иммунной системы, синтезируемых ими медиаторов и различных классов иммуноглобулинов привлекают внимание исследователей всего мира. Было установлено, что между наличием у пациента аллергии и риском развития некоторых видов рака (глиома, рак поджелудочной железы и детский лейкоз) прослеживается обратная зависимость. Данные проспективных исследований подтвердили также негативную ассоциацию аллергии с колоректальным раком. Both allergic and oncological diseases are two global problems of modern medicine, far from being resolved. Both pathologies are immune-mediated, but in case of allergy there is hypersensitivity due to a breakdown of immune tolerance, and in the case of oncology, the disease develops precisely due to immune deficiency associated with excessive tolerance. A key factor in the growth of a malignant tumor is the formation of the most “friendly” environment from its microenvironment. The various components of immunity, theoretically, should effectively recognize and destroy tumor cells even at the initial stages of its development, before the formation of clinically significant tumor growth. However, clinical studies suggest otherwise. Various components of the immune system (tumor-associated macrophages, cytokines — growth factors, suppressor cells of myeloid origin) participate in the pathogenesis of tumor growth, not counter-acting, but contributing to the development of neoplasm, its invasion and metastasis. Therefore, one of the main goals in the field of cancer treatment is the development of interventions that may impair immunological tolerance and stop the progression of cancer. Numerous epidemiological studies suggest an inverse association between allergic diseases and the development of malignant neoplasms. There is also considerable evidence of the concept of the ability of cells of the immune system and IgE to destroy tumor cells. Numerous in vitro studies are being conducted that “target” this class of antibodies to the corresponding tumor antigens. It has been demonstrated that antibodies of the IgE class are specific for an overexpressed tumor, they were superior to any other class of immunoglobulins in terms of antibody-dependent cell cytotoxicity (ADCC — antibody-dependent cell-mediated cytotoxicity) and phagocytosis (ADCP — antibody-dependent cell-mediated phagocytosis). Therefore, eosinophils, mast cells and macrophages in combination with IgE can become powerful antitumor effectors. IgE specific for tumor antigens causes eosinophil-mediated death of tumor cells by cytotoxic mechanisms. The nature of the influence of mast cells on the tumor is determined by a complex of factors. It has been established that, depending on their location with respect to the tumor, mast cells may exhibit multidirectional effects. The ambiguous properties of the cells of the immune system synthesized by mediators and various classes of immunologlobulin attract the attention of researchers around the world. It was found that between the patient’s allergies and the risk of developing certain types of cancer (glioma, pancreatic cancer and childhood leukemia), an inverse relationship is observed. Also, prospective studies have confirmed a negative association of allergies with colorectal cancer.

The COVID-19 pandemic has severely affected the healthcare system across the globe and caused significant morbidity and mortality. The occurrence and importance of the post-COVID-19 sequelae was realized when a sizable proportion of patients appeared to continue suffering from various symptoms for many months and years after having recovered from the acute phase of infection. These complications were observed in multiple organ systems and not only in the respiratory tract. Multidisciplinary efforts are required to manage these patients as the complications are variable in terms of location and severity. The post COVID-19 condition (long COVID) represents a number of different post-viral syndromes that require an appropriate classification. Collection of a large amount of data is required for all the physical and neuropsychiatric symptoms that persist for more than 12 weeks without an alternative explanation. The process of data collection and analysis should be controlled for all confounding factors including the consequences of intensive care hospitalization, social isolation, and other effects. The current absence of the effective treatment reflects the unclear causes of the post COVID-19 conditions which cannot be targeted properly until their mechanism is established. Timely collection of data and identification of physiological mechanisms underlying the long-term clinical manifestations of C0VID-19 are vital for the relevant design of effective therapies.

Sepsis is an unregulated host response to infection resulting in life-threatening organ dysfunction. As one of the most catastrophic surgical complications, sepsis remains a major public health problem worldwide, with increasing incidence despite sterile preoperative prophylaxis and administration of antibiotics. Sepsis mortality has remained unchanged for over a decade, and early recognition continues to be the most crucial factor in survival outcome. Early and accurate diagnosis of infection and organ dysfunction remains problematic, as evidenced by numerous interventional trials that have not resulted in improved outcomes. These failures are partly because of the belated intervention, when the patient developed multiple-organ failure and the therapeutic window of opportunity closed. The success of immunomodulatory and other therapeutic strategies, which is often achieved in preclinical models of sepsis, depends on their use in the early stages of sepsis development or even proactive action. Predicting the development of sepsis in surgical patients using laboratory analysis of plasma may be useful for doctors in the intensive care unit and resuscitation. Significant efforts are being made to develop biomarkers for the early stages of sepsis with high sensitivity and specificity. For early and accurate diagnosis, effective treatment of sepsis requires a deep understanding of the pathogenetic mechanisms. Dysregulation of the patients response to infection leading to sepsis and septic shock is studied using ohmic approaches: proteomics, transcriptomics, and metabolomics. Owing to the complexity and large volume of data sets, special data analysis tools, the so-called machine learning, become necessary.

Сепсис — это тяжелая системная инфекция с дисфункцией органов, требующая неотложных действий. При недостаточно оперативном и эффективном вмешательстве летальность превышает 30 %. Неоднородность сепсиса является причиной неудач клинических испытаний иммуномодулирующей терапии пациентов с сепсисом. Из-за недостаточного понимания патогенеза этой неоднородности методы лечения, казавшиеся многообещающими в доклинических условиях, не имели успеха в клинических испытаниях. Отчасти отсутствие эффективности связано с применением универсального подхода ко всем пациентам с сепсисом. Диагностические и терапевтические стратегии, учитывающие индивидуальные особенности пациента, не получили широкого распространения в области сепсиса. Необходим переход к более персонализированному лечению по всем трем направлениям лечения сепсиса: антибиотикотерапии, реанимации и поддержке органов. Именно поэтому предпринимаются попытки стратифицировать пациентов на более однородные группы на основе общих для группы прогностических и предиктивных характеристик иммунного ответа. Такой подход является ключом к прецизионной медицине с отбором на основе патофизиологического механизма тех пациентов, кто с большей вероятностью ответит на специфическую терапию. Проблема заключается в относительно ограниченном понимании механизмов, управляющих иммунопатологией сепсиса. После десятилетий исследований сепсис остается нечетко определенным, и ни одно определение сепсиса не отражает сложность синдрома. Углубленный анализ фенотипических различий выявляет субгруппы пациентов, которым действительно помогают определенные вмешательства. Транскриптомный анализ цельной крови, плазмы и отдельных популяций иммунных клеток идентифицировал сигнатуры генной экспрессии, позволяющие не только отличить сепсис от синдрома неинфекционного системного воспалительного ответа, но и выделить эндотипы сепсиса с разными иммунными профилями и разными ответами на терапию, определяемые патобиологическим механизмом. Таким образом, растет интерес к более индивидуальному подходу к лечению сепсиса, но лучшие средства его реализации еще не определены, поэтому накопление информации продолжается. Sepsis is a severe systemic infection with organ dysfunction that requires urgent action. With insufficiently prompt and effective intervention, mortality exceeds 30 %. The heterogeneity of sepsis is the reason for the failure of clinical trials of immunomodulatory therapy in patients with sepsis. Due to insufficient understanding of the pathogenetic causes of this heterogeneity, treatments that seemed promising in the preclinical setting have not been successful in clinical trials. The lack of effectiveness is somewhat due to the application of a one-size-fits-all approach to patients with sepsis. Diagnostic and therapeutic strategies that take into account the individual characteristics of the patient are not widely used in the field of sepsis. A shift to more personalized care is needed in all three areas of sepsis management: antibiotic therapy, resuscitation, and organ support. Therefore, attempts are being made to stratify patients into more homogeneous groups based on common prognostic and predictive characteristics of the immune response for the group. This approach is the key to precision medicine, with selection on the basis of pathophysiological mechanism of those patients who are more likely to respond to specific therapy. The problem lies in the relatively limited understanding of the mechanisms governing the immunopathology of sepsis. After decades of research, sepsis remains ill-defined, and no single definition of sepsis captures the complexity of the syndrome. An in-depth analysis of phenotypic differences reveals subgroups of patients who are actually helped by certain interventions. Transcriptome analysis of whole blood, plasma, and individual populations of immune cells identified gene expression signatures that not only distinguish sepsis from non-infectious systemic inflammatory response syndrome, but also distinguish sepsis endotypes with different immune profiles and different responses to therapy, which are determined by the pathobiological mechanism. Thus, there is growing interest in a more individual approach to the management of sepsis, but the best means of implementing it have not yet been identified, so information continues to accumulate.

Not all the patients diagnosed with COVID-19 can completely recover; some of them experience various persistent symptoms which wax and wane. As the COVID-19 pandemic continues, the number of people with long-term symptoms is rapidly increasing, adding to the burden on the healthcare and society. The prevalence of the COVID-19 consequences varies between studies, with some researchers reporting that more than half of hospitalized patients suffer from long-lasting symptoms for at least 6 months after the acute SARS-CoV-2 infection, and others observing such symptoms for more than 12 months. The overall prevalence of residual symptoms in patients infected with SARS-CoV-2 is currently estimated as 1030%. This clinical syndrome is commonly referred to as post-acute COVID syndrome (PACS) or long COVID. This multifactorial syndrome is characterised by a variety of debilitating symptoms, including fatigue, brain fog, postural hypotension with tachycardia, and post-exertional malaise. Many of the post COVID-19 condition observations, including changes in the immune, cardiovascular, gastrointestinal, nervous and autonomic systems, are shared with those for myalgic encephalitis/chronic fatigue syndrome (ME/CFS) patients. A comprehensive longitudinal symptom monitoring is required to confirm the diagnosis, uncover the mechanisms of post-COVID-19-associated ME/CFS, and develop the prevention and treatment measures. The current absence of an effective treatment reflects the unclear causes of the post COVID-19 conditions which cannot be targeted properly until the mechanism is established and confirmed. The multisystem aspects of long COVID remain poorly understood. The COVID-19 pandemic has exposed a significant gap in the knowledge about the post-acute consequences of infectious diseases and the need for a unified nomenclature and classification, diagnostic criteria, and a reliable assessment of post-COVID conditions. Unraveling the complex biology of PACS relies on the identification of biomarkers in the plasma and tissue samples harvested from individuals infected with SARS-CoV-2 that will allow classification of the phenotypes of patients who develop PACS. For a comprehensive treatment of patients with post-COVID syndrome, multidisciplinary therapy and rehabilitation are required. Understanding the physiological mechanisms underlying the long-term clinical manifestations of COVID-19 and the post-COVID-19 state is vital for the development of appropriate effective therapies.

COVID-19, the disease caused by SARS-CoV-2, has diverse long-term consequences of varying severity after recovery from the acute phase. As survivorship and therefore the number of individuals with long COVID continue to increase, the prevalence, origins, and mechanisms of post-acute sequelae manifestation must be critically elucidated. The inappropriate and unique inflammatory response in the acute phase of COVID-19 causes severe respiratory symptoms, which can be subsequently accompanied by multiple-organ damage, affecting the brain, heart, kidneys, etc. This review examines the role of an unregulated antigen-specific immune response to COVID-19 in the onset and development of its consequences. We discuss the potential role of virus persistence in tissue reservoirs, unresolved inflammation, cytokine hyperproduction, tissue damage, and molecular mimicry and autoimmunity in the pathogenesis of post-COVID syndrome the induction and maintenance of imbalanced immune responses after the resolution of acute COVID-19.

The SARS-CoV-2 coronavirus has been circulating among the world population for 3 years, infecting hundreds of millions of people. Numerous reports from all over the world indicate that the majority of infections are caused by the Omicron variant and its subvariants, which predominate over all the previously emerged variants. The genome of the Omicron strain has accumulated dozens of mutations that increase the viruss adaptability and cause the emergence of new variants and subvariants with the increased contagiousness, transmissibility, and ability to evade the immune response. This compromises the protection provided by vaccines or the humoral immunity induced by previous infections. Although the biology of SARS-CoV-2 is well understood, its ability to infect, replicate, and spread in a population depends on the specific immune context during different periods of the pandemic. It is assumed that new variants arise as a result of chronic infection in immunocompromised individuals. The intralineage recombination is an opportunity for the virus to gain phenotypic advantages from distantly related circulating variants. The last of the subvariants of the Omicron variant, named Kraken due to its unprecedentedly high transmissibility, is a descendant of the recombinant line. The virus is constantly evolving in the direction of evading immune neutralization by vaccines, therefore, a constant work is underway to develop new, more effective vaccines and other antiviral agents.

Severe COVID-19 shares pathophysiological, immunological, metabolic, and clinical features with classic bacterial sepsis. Patients with severe COVID-19 have sepsis-like manifestations, such as acute respiratory distress syndrome and multiple organ failure. However, research indicates that COVID-19 leads to acute respiratory distress syndrome and that septic syndrome is more fatal than septic syndrome of other etiologies. SARS-CoV-2 initially infects the lungs; however, in COVID-19-associated sepsis, the majority of deaths are caused by the subsequent involvement of multiple organs. Many patients who died because of COVID-19 died from sepsis, a life-threatening dysfunctional response to infection that is accompanied by respiratory and multiple organ failure. Overlapping molecular characteristics are found in patients with severe COVID-19 and sepsis from all causes. Endotypes that reflect different etiologies of sepsis have been identified in patients with severe COVID-19. Whole-blood proteomics and transcriptomics are useful in identifying the pathogenetic mechanisms and multimolecular signatures of COVID-associated sepsis and other sepsis, which allow for the development of more specific criteria for early diagnosis, patient classification, and therapeutic choices. The detection of sepsis endotypes in patients with COVID-19 implies that sepsis endotypes may be useful for clinical risk stratification in COVID-associated sepsis and the potential opportunity to treat these patients with targeted immunomodulatory therapies that can correct endotype-specific dysfunctional immune processes.