[Psychological, psychiatric and neurological aspects of COVID-19]. / Psikhologicheskie, psikhiatricheskie i nevrologicheskie aspekty COVID-19.

OBJECTIVE: To analyze neurological, psychological and psychiatric aspects of COVID-19, as well as to study the current state of the problem. MATERIAL AND METHODS: The study included 103 patients with COVID-19. The main research method was clinical/psychopathological. To study the impact of activities related to the care of patients with COVID-19 in a hospital setting, the medical and psychological state of 197 hospital workers involved in the treatment of patients with COVID-19 was assessed. The level of anxiety distress was assessed with the Psychological Stress Scale (PSM-25), distress indicators corresponded to values of more than 100 points. The severity of anxiety and depressive symptoms was assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: When considering psychopathological disorders in the context of COVID-19, it is necessary to distinguish between two main groups of disorders: mental disorders during the pandemic, and mental disorders directly caused by the causative agent SARS-CoV-2. The analysis of psychological and psychiatric aspects in various periods of the initial stage of COVID-19 showed that each of them was characterized by specific features depending on the nature of the influence of different pathogenic factors. In the structure of nosogenic mental disorders in patients with COVID-19 (103 patients), the following clinical forms were identified: acute reaction to stress (9.7%), anxiety-phobic disorders (41.7%), depressive symptoms (28.1%), hyponosognosic nosogenic reactions (20.5%). At the same time, the majority of the patients had manifestations of somatogenic asthenia (93.2%). A comparative analysis of neurological and psychological/psychiatric aspects of COVID-19 showed that the main mechanisms of the impact of highly contagious coronaviruses, including the SARS-CoV-2, on the central nervous system are: cerebral thrombosis and cerebral thromboembolism, damage to the neurovascular unit, neurodegeneration, including that induced by cytokines, and immune-mediated demyelinating nerve damage. CONCLUSION: Neurological and psychological/psychiatric aspects of COVID-19 should be taken into account both at the stage of disease treatment and in the post-infection period due to the pronounced neurotropism of SARS-CoV-2 and its effect on the neurovascular unit. Along with helping patients, an important aspect is the preservation of the mental health of medical personnel working in hospitals for infectious diseases, due to special working conditions and a high level of professional stress.

On a New Paradigm of the Development of Neurodegenerative Diseases by the Example of Alzheimer's Disease and Parkinson's Disease

The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies is investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation is established, but the role of various infectious agents in the development of this process is much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including long-term persistent in nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either A beta or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of proinflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. The reactivation of latent infection, such as herpes, in APOE4 carriers significantly increases the risk of development of Alzheimer's disease. Class-II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. An increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.

INFECTIOUS HYPOTHESIS OF NEURODEGENERATIVE DISEASES. WHAT WAITS US AFTER THE COVID-19 PANDEMIC?

Since the description of the first clinical cases of the most common neurodegenerative diseases, numerous hypotheses have been proposed for their development. At the same time, the failure of therapeutic strategies in various directions of clinical research indicates the fallacy of most theories. In this regard, in recent years, various infectious agents are increasingly considered as a trigger of neuronal inflammation and a factor inducing the onset of the neurodegenerative process. Infectious agents differ in their mechanisms of invasion into the central nervous system and can even enter the brain perineurally. Reactivation of latent viral infection induces the production of viral proteins and the accumulation of abnormal proteins that are markers of Alzheimer's disease and Parkinson's disease. Both bacterial (chlamydia, causative agents of chronic periodontitis, E. coli) and viral (herpes viruses, noroviruses) infectious agents are considered. However, for the development of neurodegeneration, it is not enough just a simple invasion and reactivation of the infectious process: the genetic characteristics of the main histocompatibility complex also play a huge role. Currently, several studies have been initiated on the possible efficacy of antibacterial and antiviral drugs in Alzheimer's disease. Data obtained over the past year suggests that the brain may act as a target for SARS-CoV-2. Neurological manifestations of COVID-19 can occur as a result of both the direct cytopathic action of the pathogen and the activation of neuroinflammation, accompanied by a violation of the integrity of the blood-brain barrier. Further study of the molecular and cellular mechanisms of neuroinflammation and neurodegeneration in COVID-19 will form the basis for the development of treatments for neurological complications.

[A new paradigm for the development of neurodegenerative diseases on the example of Alzheimer's disease and Parkinson's disease.]

The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies has been investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation has been established, but the role of various infectious agents in the development of this process has been much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including a long-term persistent in the nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either Aβ or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of pro-inflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. Reactivation of latent, such as herpes, infection in individuals who are carriers of APOE4 significantly increases the risk of developing Alzheimer's disease. Class II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. The increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to the intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.

[Some psychiatric and neurological aspects of the asymptomatic and mild course of COVID-19]. / Nekotorye psikhiatricheskie i nevrologicheskie aspekty bessimptomnogo i legkogo techeniya COVID-19.

OBJECTIVE: To study neurological and mental disorders associated with the inapparent and mild course of COVID-19. MATERIAL AND METHODS: The study included 50 patients (mean age 35.2±11.4 years) admitted to a psychiatric hospital due to depressive spectrum disorders. Patients were divided into two groups: patients (n=16) who had IgG antibodies to SARS-CoV-2 (main group) and patients (n=34) without a history of COVID-19 (comparison group). RESULTS AND CONCLUSION: Patients of the main group showed a difference in the structure of asthenic disorders compared with the comparison group. Also, there was a significant predominance of the severity of asthenic symptoms and anxiety in the structure of psychopathological disorders in depressive spectrum disorders. The viral intoxication contributes to the formation of a kind of asthenic «soil¼ (with characteristic manifestations). In the future, in the case of the development of any stress-associated disorder, more pronounced psychopathological disorders are noted compared with patients of the comparison group. The authors describe a variant of the course of COVID-19, in which the development of ischemic stroke was the first clinical manifestation of the disease. These disorders are based on the pronounced neurotropic effect of SARS-CoV-2 and its effect on the neurovascular unit.

Signs and symptoms of central nervous system involvement and their pathogenesis in covid-19 according to the clinical data (Review)

Detailed clinical assessment of the central nervous system involvement in SARS-CoV-2 infection is relevant due to the low specificity of neurological manifestations, the complexity of evaluation of patient complaints, reduced awareness of the existing spectrum of neurological manifestations of COVID-19, as well as low yield of the neurological imaging. The aim. To reveal the patterns of central nervous system involvement in COVID-19 and its pathogenesis based on clinical data. Among more than 200 primary literature sources from various databases (Scopus, Web of Science, RSCI, etc.), 80 sources were selected for evaluation, of them 72 were published in the recent years (2016–2020). The criteria for exclusion of sources were low relevance and outdated information. The clinical manifestations of central nervous system involvement in COVID-19 include smell (5–98% of cases) and taste disorders (6–89%), dysphonia (28%), dysphagia (19%), consciousness disorders (3–53%), headache (0–70%), dizziness (0–20%), and, in less than 3% of cases, visual impairment, hearing impairment, ataxia, seizures, stroke. Analysis of the literature data revealed the following significant mechanisms of the ef-fects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegen-eration (including cytokine-induced);cerebral thrombosis and thromboembolism;damage to the neurovas-cular unit;immune-mediated damage of nervous tissue, resulting in infection and allergy-induced demyelination. The neurological signs and symptoms seen in COVID-19 such as headache, dizziness, impaired smell and taste, altered level of consciousness, bulbar disorders (dysphagia, dysphonia) have been examined. Accord-ingly, we discussed the possible routes of SARS-CoV-2 entry into the central nervous system and the mechanisms of nervous tissue damage. Based on the literature analysis, a high frequency and variability of central nervous system manifestations of COVID-19 were revealed, and an important role of vascular brain damage and neurodegeneration in the pathogenesis of COVID-19 was highlighted.

Respiratory RNA Viruses: How to Be Prepared for an Encounter with New Pandemic Virus Strains

The characteristics of the biology of influenza viruses and coronavirus that determine the implementation of the infectious process are presented. With provision for pathogenesis of infection possible effects of serine proteinase inhibitors, heparin, and inhibitors of heparan sulfate receptors in the prevention of cell contamination by viruses are examined. It has been determined that chelators of metals of variable valency and antioxidants should be used for the reduction of replicative activity of viruses and anti-inflammatory therapy. The possibility of a pH-dependent impairment of glycosylation of cellular and viral proteins was traced for chloroquine and its derivatives. The use of low-toxicity drugs as part of adjunct therapy increases the effectiveness of synthetic antiviral drugs and interferons and ensures the safety of baseline therapy.

Respiratory RNA Viruses: How to Prepare for Meeting with New Pandemic Strains

The biology features of influenza viruses and coronaviruses that determine the implementation of the infectious process are described. Taking into account the pathogenesis of infection, the possible effects of serine proteinase blockers, heparin and heparan sulfate receptor blockers in the prevention of cell contamination by viruses are considered. The necessity of using chelators of metals of variable valency and antioxidants to reduce the replicative activity of viruses and anti-inflammatory therapy is determined. The possibility of a pH-dependent violation of the glycosylation of cellular and viral proteins is traced for chloroquine and its derivatives. The use of low-toxic registered drugs as part of adjuvant therapy increases the effectiveness of antiviral synthetic drugs and interferons, ensures the safety of the use of basic therapy. Изложены особенности биологии вирусов гриппа и коронавирусов, определяющие реализацию инфекционного процесса. С учетом патогенеза инфекции рассмотрены возможные эффекты блокаторов сериновых протеиназ, гепарина и блокаторов гепарансульфатных рецепторов в профилактике контаминации клеток вирусами. Определена необходимость применения хелаторов металлов переменной валентности и антиоксидантов для снижения репликативной активности вирусов и противовоспалительной терапии. Возможность pH-зависимого нарушения гликозилирования клеточных и вирусных белков прослежена для хлорохина и его производных. Применение низкотоксичных лекарственных средств в составе вспомогательной терапии повышает эффективность противовирусных синтетических препаратов и интерферонов, обеспечивает безопасность применения средств базисной терапии.