BACKGROUND:The escalating global burden of stress and depression underscores an urgent need to unravel their complex interrelationships and underlying mechanisms. This investigation delves into the intricate dynamics between stress and depression, spotlighting the Neuroimmunoinflammatory Stress Model (NIIS), which elucidates the pivotal role of cellular and molecular pathways in mediating these conditions. METHODS:Through an exhaustive review of literature spanning epidemiology, neurobiology, and psychoneuroimmunology, this study synthesizes the current understanding of stress and depression. It accentuates the definitional scopes, interplay, and intricacies of the NIIS model, which integrates neuroimmune-inflammatory responses into the conceptual framework of the stress-depression interaction. RESULTS:By identifying stress as a multifactorial reaction to perceived adversities and depression as a manifestation of prolonged stress exposure, our analysis foregrounds the NIIS model. This paradigmatic model reveals the transition from normal stress responses to pathological neuroinflammatory pathways, highlighting neurotransmitter imbalances, disruptions in neuronal and glial homeostasis, and ensuing low-grade neuroinflammation as key factors in the pathogenesis of depression under chronic stress conditions. The NIIS model identifies prolonged cellular pro-inflammatory stress of neurons and microglia as a fundamental pathological subsystem of many neuropsychiatric disorders. In turn, neuroinflammation and associated neurodegenerative processes are complications of chronic psychoemotional stress, which can clinically manifest as depression. CONCLUSION:The NIIS model views depression as the terminal stage of chronic stress, pathogenetically linked to latent neuroinflammation. This insight not only advances our understanding of their etiopathogenesis but also paves the way for developing precise therapeutic interventions.

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

INTRODUCTION:This narrative review addresses the clinical challenges in stress-related disorders such as depression, focusing on the interplay between neuron-specific and pro-inflammatory mechanisms at the cellular, cerebral, and systemic levels.OBJECTIVE:We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors.METHODS:This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation.RESULTS:The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue.CONCLUSION:The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.

Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths and limitations of commonly used rat models, such as single prolonged stress (SPS), stress–re-stress (S-R), and predator-based paradigms, in replicating human PTSD pathology. While these models provide valuable insights into neuroendocrine responses, genetic predispositions, and potential therapeutic targets, they face challenges in capturing the full complexity of PTSD, particularly in terms of ethological relevance and translational validity. We assess the degree to which these models mimic the neurobiological and behavioral aspects of human PTSD, highlighting areas where they succeed and where they fall short. This review also discusses future directions in refining these models to improve their utility for translational research, aiming to bridge the gap between preclinical findings and clinical applications.

Neuroinflammation during intracerebral hemorrhage is initiated by blood breakdown products in the subarachnoid space and/or brain parenchyma. In this case, neuroinflammation can cause the development of systemic inflammation. In some cases, intracerebral hemorrhage is accompanied by the appearance of the phenomenon of ineffective cerebral blood flow and clinical manifestations of brain death. The purpose of the study is to identify markers of systemic inflammation in severe hemorrhagic stroke with or without effective cerebral blood flow. The study included patients with intracerebral hemorrhage and the presence of multiple organ failure syndrome, as well as coma on the first day of manifestation, to determine markers of systemic inflammation. A total of 3 groups were analyzed: patients with ineffective cerebral blood flow (Group 2); with effective cerebral blood flow (Group 3); and control group (Group 1) – healthy blood donors. Criteria for non-inclusion in the study: the presence in patients with hemorrhagic stroke of septic complications during hospitalization and acute infectious diseases during the manifestation of intracerebral hemorrhage. In frozen blood plasma samples (anticoagulant – citrate), the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, neuron-specific enolase, cortisol, myoglobin, troponin I and D-dimers were determined. Enzyme immunoassay was carried out on an automatic analyzer “Dynex Lazurite” (Dynex Technologies, VA, USA). The Kolmogorov–Smirnov test was used to confirm the normality of data distribution. Further comparison of quantitative data was carried out using the nonparametric Mann–Whitney U test. All results were considered statistically significant at p 0.05. In patients with effective and ineffective cerebral blood flow, statistically significant differences were observed in almost all studied markers of systemic inflammation, except for troponin I. However, in the presence of effective cerebral blood flow, significantly higher values of a number of indicators were noted, which may indicate a more rapidly occurring acute systemic inflammatory response in case of effective cerebral blood flow. At the same time, 28 day mortality and SOFA scores in the group with effective blood flow were lower than in the group with ineffective blood flow. This discrepancy may indicate a greater contribution to 28 day mortality and patient severity from direct loss of brain function than from systemic inflammation in patients with ineffective blood flow. On the other hand, the lack of severity of systemic inflammation in this category of patients is most likely due to impaired blood outflow from the damaged brain and the entry of tissue breakdown products and other pro-inflammatory factors into the systemic circulation. That is, intracerebral hemorrhage is accompanied by the development of neuroinflammation, which may be an important component of systemic inflammation. However, disruption of the inflow and outflow of blood in the main great vessels of the brain reduces the likelihood and severity of the development of systemic inflammation.

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1–3/5–8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood–brain barrier for tissue breakdown products and other neuroinflammatory factors.

Shocks of different origin (both septic and aseptic) be be considered clinical equivalents of systemic inflammation (SI) with following main manifestations : pronounced hypercytokinemia, other markers of systemic inflammatory response (SIR), coagulopathy, multiple organ failure (MOF), hypothalamic-pituitary-adrenal (HPA) distress, systemic tissue alteration. In general, these phenomena are directly and inversely related to systemic microcirculatory disturbances which determine the pathogenesis of distinct shock states. The aim of our study was to identify the features of SI phases in the development of two variants of septic shock, i.e., acute course (first week of the process) and prolonged/subacute sepsis (2 to 6 weeks from the onset of manifestations), as well as haemorrhagic shock studied 4-12 hours from the onset of massive blood loss. To verify the SI phases, we used the previously proposed SI scale, including the value of six SIR levels (RL-0-5), as well as additional criteria of SI, i.e., evaluation of clinical MOF grade (SOFA scale), plasma D-dimers ( 500 ng/mL), cortisol ( 1380 nmol/mL), tissue alteration markers, e.g., myoglobin ( 800 ng/mL) and/or troponin I ( 0.2 ng/mL). To calculate RL in SIR, plasma CRP and four cytokines (IL-6, IL-8, IL-10, TNF) were determined. The presence of SI was established if the SI scale exceeded 5 points (numerical RL values + presence of additional criteria, each equal to 1 point). The time and severity of the developing critical state, as well as the RL scores, were taken into account when reviewing the phases. There were three main SI phases: (1) evolving condition, (2) cytokine storm/phlogogenic hit (SD-4-5), and depressive (exhausting) phase. The latter was characterized by relatively low SIR values (RL-2-3). The lethality rate for shock in the presence of acute sepsis (n = 13) was 71.4%, reaching 94.1% in prolonged sepsis (n = 17). For haemorrhagic shock after massive blood loss, if not resolved within 24 hoursm the mortality rates was 53.8% (n = 13). Development of shock in acute sepsis, and haemorrhagic shock (within 4 to 12 hours after the onset of massive blood loss) is accompanied by the severity of critical-phase cytokine storm/PPS with a predominance of RL-5 in cases of lethal outcomes, and by a depression phase (RL-2-3) in prolonged sepsis. Overall mortality (for all groups) was 66.7% in the PS phase, 89.5% in the depressive phase and 15.4% in the evolvingl phase of haemorrhagic shock (with possible transition from this phase to the more critical SI phases until lethal outcome). Shock states of both septic and aseptic origin are based on a typical pathological process of SI, which should be distinguished from the signs of SIR characteristic of high-intensity canonical inflammation. It is characterized by higher cytokinemia (cytokine storm phase) or by the presence of additional SI phenomena with relatively moderate SIR levels (depressive SI phase). Thus, the depressive phase of SI is more fatal for disease outcome compared to the cytokine storm phase with higher intensity of SIR.

Background: Amniotic fluid embolism (AFE) is one of the main causes of maternal mortality in developed countries. The most critical AFE variants may be considered from the perspective of systemic inflammation (SI), a general pathological process that includes high levels of systemic inflammatory response, neuroendocrine system distress, microthrombosis, and multiple organ dysfunction syndrome (MODS). This research work aimed to characterize the dynamics of super-acute SI using four clinical case studies of patients with critical AFE. Methods: In all the cases, we examined blood coagulation parameters, plasma levels of cortisol, troponin I, myoglobin, C-reactive protein, IL-6, IL-8, IL-10, and TNF-α, and calculated the integral scores. Results: All four patients revealed the characteristic signs of SI, including increased cytokine, myoglobin, and troponin I levels, changes in blood cortisol, and clinical manifestations of coagulopathy and MODS. At the same time, the cytokine plasma levels can be characterized not only as hypercytokinemia, and not even as a “cytokine storm”, but rather as a “cytokine catastrophe” (an increase of thousands and tens of thousands of times in proinflammatory cytokine levels). AFE pathogenesis involves rapid transition from the hyperergic shock phase, with its high levels of a systemic inflammatory response over to the hypoergic shock phase, characterized by the mismatch between low systemic inflammatory response values and the patient’s critical condition. In contrast to septic shock, in AFE there is a much more rapid succession of SI phases. Conclusion: AFE is one of the most compelling examples for studying the dynamics of super-acute SI.

Riamilovir, a drug registered in Russia (chemical formula: methylthionitrooxodihydrotriazolotriazinide sodium, trade name: Triazavirin) is a synthetic analogue of guanine and a drug of direct antiviral action. Currently, there are conflicting data regarding usage of riamilovir as a preventive and therapeutic agent in coronavirus infections. The purpose of this study was to analyze some results of riamilovir usage, both for prevention of the SARS-CoV-2 infection and for the treatment of COVID-19 during the first wave of the new coronavirus pandemic. The analysis was based on a survey of 62 medical staff workers at a single medical institution in Ekaterinburg who was ill with COVID-19, being divided into 4 groups: (1) those who did not receive riamilovir (control), (2) persons who received riamilovir only as a disease prevention, (3) subjects who received the drug as a therapeutic agent, (4) those who received riamilovir before and during the disease. The data concerning usage of riamilovir for the prevention of infection with the SARS-CoV-2 virus have shown the following consequences: increased duration of hospitalization, an increased incidence of COVID-19 complications, i.e., fever, shortness of breath, pulmonary insufficiency, pneumonia, higher frequency of neurological disorders, which were not reported elsewhere. Severe clinical course of the disease was observed much more often in cases of prophylactic riamilovir administration, and the rehabilitation period was incomplete 2 months after the disease. Clinical symptoms of muscle and joint pain were documented at later terms in all persons who received riamilovir to prevent a new coronavirus infection. Usage of riamilovir for therapeutic purposes made it possible to avoid the development of pulmonary insufficiency, severe course of the infectious disease, and entirely restore the state of health. The study did not reveal the usefulness of riamilovir for prevention of COVID-19 complications when taking the drug before infection with the SARS-CoV-2 virus. However, the use of riamilovir for therapeutic purposes prevents development of severe clinical cases and is associated with 4-fold reduced risk of pain in muscles, joints, and spine among the COVID-19 patients.

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from a general pathology perspective, particularly with regard to atherogenesis patterns in the context of both canonical and non-classical inflammation types. In this review, we analyze various typical phenomena and outcomes of cellular pro-inflammatory stress in atherosclerosis, as well as the role of endothelial dysfunction in local and systemic manifestations of low-grade inflammation. We also present the features of immune mechanisms in the development of productive inflammation in stable and unstable plaques, along with their similarities and differences compared to canonical inflammation. There are numerous factors that act as inducers of the inflammatory process in atherosclerosis, including vascular endothelium aging, metabolic dysfunctions, autoimmune, and in some cases, infectious damage factors. Life-critical complications of atherosclerosis, such as cardiogenic shock and severe strokes, are associated with the development of acute systemic hyperinflammation. Additionally, critical atherosclerotic ischemia of the lower extremities induces paracoagulation and the development of chronic systemic inflammation. Conversely, sepsis, other critical conditions, and severe systemic chronic diseases contribute to atherogenesis. In summary, atherosclerosis can be characterized as an independent form of inflammation, sharing similarities but also having fundamental differences from low-grade inflammation and various variants of canonical inflammation (classic vasculitis).

The aim of this Special Issue is to analyze the key patterns of the 2019 coronavirus disease pandemic (COVID-19), the biology of SARS-CoV-2 (severe-acute-respiratory-syndrome-related coronavirus 2, formerly 2019-nCoV), and the characteristics of the human body's response to the invasion of this virus [...].

The relationship between the processes of coagulation and inflammation protects the organism from potentially dangerous biological agents. However, hyperinflammation leads to an increase in the procoagulation potential, and activation of hemostasis factors maintains the inflammatory process. This phenomenon is called “immunothrombosis” or “ thromboinflammation”. The study of thromboinflammatory mechanisms is an actual problem of modern medicine, because in the future it will help to improve the therapy of diseases, in the pathogenesis of which thromboinflammation plays a significant role. The aim: to carry out a comparative analysis of the severity of the systemic inflammatory response in patients with immuno- inflammatory rheumatic diseases depending on the manifestations of hypercoagulation.To achieve the aim, a comparative analysis of proinflammatory markers (IL-6, IL-8, IL-10, TNFα, sIL-2R, CRP, ECP, β2-microglobulin) in the blood of patients with immune-inflammatory rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, reactive arthritis, ankylosing spondylitis, psoriatic arthritis, rheumatic heart disease) was performed. Based on these inflammatory markers according to the authors' original methodology, the integral index of systemic inflammatory response (SIR) — Reactivity Level (RL) — was calculated. The cohort was divided into 2 groups: with the presence of signs of hypercoagulation and without signs of hypercoagulation according to the presence of elevated D-dimer level (> 500 ng/mL). Control group — healthy blood donors.The results of the study showed that SIR develops in patients with immuno-inflammatory rheumatic diseases regardless of the blood hemostatic potential. Patients with signs of hypercoagulation were characterized by higher values of most proinflammatory molecular markers, as well as increased integral level of SIR, which indicates a strong relationship between coagulation processes and inflammation at the systemic level. In addition, the probability of hypercoagulation increases with increasing severity of SIR (assessed by means of the integral index — RL). Thus, there is a transition of quantitatively more pronounced signs to a new qualitative level of pathological process development.The pathogenesis of immuno-inflammatory rheumatic diseases is characterized by the development of SIR (hypercytokinemia, acute phase response, intravascular leukocyte activation), the severity of which is closely related to intravascular microthrombosis.

This study examines an unexplored aspect of SARS-CoV-2 entry into host cells, which is widely understood to occur via the viral spike (S) protein’s interaction with human ACE2-associated proteins. While vaccines and inhibitors targeting this mechanism are in use, they may not offer complete protection against reinfection. Hence, we investigate putative receptors and their cofactors. Specifically, we propose CD46, a human membrane cofactor protein, as a potential putative receptor and explore its role in cellular invasion, acting possibly as a cofactor with other viral structural proteins. Employing computational techniques, we created full-size 3D models of human CD46 and four key SARS-CoV-2 structural proteins—EP, MP, NP, and SP. We further developed 3D models of CD46 complexes interacting with these proteins. The primary aim is to pinpoint the likely interaction domains between CD46 and these structural proteins to facilitate the identification of molecules that can block these interactions, thus offering a foundation for novel pharmacological treatments for SARS-CoV-2 infection.

The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological and pathological processes such as inflammation and stress. Dysregulation in this pathway can lead to severe immunodeficiencies and malignancies, and its role extends to neurotransduction and pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological and inflammatory disorders, their application has generally been limited to diseases with similar pathogenic features. Despite the modest expression of JAK-STAT in the CNS, it is crucial for functions in the cortex, hippocampus, and cerebellum, making it relevant in conditions like Parkinson's disease and other neuroinflammatory disorders. Furthermore, the influence of the pathway on serotonin receptors and phospholipase C has implications for stress and mood disorders. This review expands the understanding of JAK-STAT, moving beyond traditional immunological contexts to explore its role in stress-related disorders and CNS function. Recent findings, such as the effectiveness of Jakinibs in chronic conditions such as rheumatoid arthritis, expand their therapeutic applicability. Advances in isoform-specific inhibitors, including filgotinib and upadacitinib, promise greater specificity with fewer off-target effects. Combination therapies, involving Jakinibs and monoclonal antibodies, aiming to enhance therapeutic specificity and efficacy also give great hope. Overall, this review bridges the gap between basic science and clinical application, elucidating the complex influence of the JAK-STAT pathway on human health and guiding future interventions.

The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test. Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more often than others reported long-term fatigue, exacerbation of chronic and the appearance of new diseases (hypertension, cardialgia, bronchial asthma, allergies, decreased visual acuity), muscle, joint and vertebral pains that appeared for the first time. The phenomenon of arthralgia and other lesions of large joints in COVID-19 was described by us earlier. Studies by other authors also report frequent complaints of increased fatigue and joint pain. At the same time, the role of vitamin D is considered exclusively from the standpoint of vitamin deficiency in a new coronavirus infection and its potential role in inhibiting hyperinflammatory reactions, as well as accelerating the healing process of affected areas, especially in lung tissue. It was found that vitamin D intake did not affect the incidence of fever, the incidence of pneumonia, the volume of lung tissue damage (based on computed tomography data), the duration of hospitalization and the disease as a whole, and also did not prevent the development of anosmia and dysgeusia. The use of vitamin D as a protective agent to prevent infection with the SARS-CoV-2 virus has had an impact on reducing the frequency/ prevention of cases of respiratory distress syndrome during the disease. Also, those who took vitamin D recorded an increase in the formation of IgG to the SARS-CoV-2 virus 2 months after infection 3.8 times higher than the values recorded in respondents who did not take cholecalciferol. The participants who took cholecalciferol suffered the infection more severely, especially if they used any other protective substances. Also, with the preventive intake of vitamin D after COVID-19, increased fatigue persisted longer, the appearance of new and activation of chronic diseases and muscle, joint and vertebral pains that appeared for the first time were reported more often, which correlates with the data we received earlier.

Currently, there is rationale for separating the systemic manifestations of classical inflammation from systemic inflammation (SI) itself as an independent form of the general pathological process underlying the pathogenesis of the most severe acute and chronic diseases. With this aim in view, we used integral scales of acute and chronic SI (ChSI), including the following blood plasma parameters: interleukins 6, 8, 10; tumor necrosis factor alpha; C-reactive protein; D-dimer; cortisol; troponin I; myoglobin. The presence of multiple organ dysfunction according to the SOFA score was also taken into account. The effectiveness of the scales was tested in groups of intensive care patients during different periods of acute trauma, sepsis, and septic shock. The ChSI scale was applicable under systemic autoimmune diseases, chronic purulent infections, chronic limb threatening ischemia, and end-stage renal disease of various genesis. The number of examined patients was 764 in total. The scales allowed us to verify specific phases of acute SI and identify pathogenetic risk factors of lethal outcomes, as well as the most severe variants of the chronic pathologies course. These scales are open adaptable systems (in terms of the nomenclature and choice of indicators). They are primarily intended for scientific research. However, the SI verification methodology presented in this paper may be useful for developing advanced criteria for assessing both the typical links in the pathogenesis of many diseases and the severity of the overall condition of patients for clinical practice.

The purpose of this special issue is to highlight the main problems of the COVID-19 epidemic and to outline some ways to solve these problems, including research into the biology of the SARS-CoV-2 virus, general pathological and particular patterns of COVID-19 pathogenesis, acute and long-term complications of COVID-19, and evaluation of high-potential general and specific prevention methods and etiological and pathogenetic therapies for COVID-19 [...].

The issues of non-specific immunoprophylaxis in the patients with new coronavirus infection have been raised since the WHO announced the COVID-19 pandemic. According to numerous studies, the new coronavirus infection is accompanied by manifestations of anosmia and dysgeusia. The purpose of this study was to perform a retrospective study of the relationships between nonspecific immunoprophylaxis of COVID-19 and conditions of anosmia/dysgeusia in the persons who underwent this infection in Sverdlovsk region over 2020. We have studied clinical and laboratory data of 84 employees at the general medical institution providing emergency pediatric care. All participants suffered a single infection caused by SARS-CoV-2. Etiological diagnostics included mandatory virological PCR testing of biological samples. The concentration of antibodies to the virus was determined using a set of reagents for SARS-CoV-2-IgG detection (JSC Vector-Best, Novosibirsk, Russia). A sufficient part of this group (n = 41; 48.8% of total sample) reported self-administration of non-specific immunoprophylactic therapy of COVID-19 (without consulting a doctor) since the beginning of coronavirus pandemics. To this purpose, cholecalciferol, riamilovir, human recombinant IFNa-2b, umifenovir hydrochloride monohydrate, ascorbic acid, zinc acetate were used. In 58 cases (69% of total), clinical course of infection was complicated by loss of taste and sense of smell (group No. 1), in 26 people (31.0%), no changes in taste and sense of smell were detected (group No. 2). Statistical evaluation of the data was performed using STATISTICA v.12.5.192.5 package (StatSoft, Inc., USA). Along with basic statistics, cluster analysis was performed. The use of cluster analysis allowed us to establish that there is a connection between the incidence of anosmia/dysgeusia and usage of distinct immunoprophylactic agents. In particular, the use of human recombinant IFNa-2b is protective in terms of reducing the number complications in COVID-19, especially, anosmia/dysgeusia caused by the new coronavirus. The use of this drug was associated with 8.5-fold decrease in the number of complications by (p = 0.03). Moreover, invasive intranasal usage of interferon, was associated with decreased hospitalization terms by 14.3% (p = 0.01); lower volume of lung tissue damage (p = 0.03), higher concentrations of IgG to SARS-CoV-2 at 2 months after reconvalescence (p = 0.001). For the first time, data were presented on the relationship between usage of immunoprophylactic agents and manifestations of anosmia/dysgeusia in COVID-19. The protective role of human recombinant IFNa-2b has been shown in terms of reduced incidence of the disease complications, e.g., anosmia/dysgeusia, degree of lung damage, as well as development of an antiviral humoral immune response. The data obtained could be used to substantiate clinical recommendations for prevention of new outbreaks of coronavirus infection. The limitation of the obtained results is small number of cases, thus requiring additional studies in a wider sample of respondents.

The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It is defined by a number of universal components, including oxidative stress, cellular response to DNA damage, unfolded protein response to mitochondrial and endoplasmic reticulum stress, changes in autophagy, inflammasome formation, non-coding RNA response, formation of an inducible network of signaling pathways, and epigenetic changes. The presence of an inducible receptor and secretory phenotype in many cells is the cause of tissue pro-inflammatory stress. The key phenomenon determining the occurrence of a classical inflammatory focus is the microvascular inflammatory response (exudation, leukocyte migration to the alteration zone). This same reaction at the systemic level leads to the development of life-critical systemic inflammation. From this standpoint, we can characterize the common mechanisms of pathologies that differ in their clinical appearance. The division of inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects of inflammation are also described in the review. The aim of the review is to provide theoretical arguments for the need for an up-to-date theory of the relationship between key human pathological processes based on the integrative role of the molecular mechanisms of cellular and tissue pro-inflammatory stress.