Systematic computer analysis of the pharmacology of bioflavonoids in the context of increasing the body's antiviral defenses.

Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

[Pulmonary fibrosis in patients with COVID-19: A review].

The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, "cellular" degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma - oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase®) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea. © Chuchalin A.G. et al., 2023.

Changes in the proteomics of exhaled breath condensate under the influence of inhaled hydrogen in patients with post-COVID syndrome.

Aim. To study the effect of inhalation therapy with an active hydrogen (AH) on the protein composition of exhaled breath condensate (EBC) in patients with post-COVID syndrome (PCS). Material and methods. This randomized controlled parallel prospective study included 60 patients after coronavirus disease 2019 (COVID-19) with PCS during the recovery period and clinical manifestations of chronic fatigue syndrome who received standard therapy according to the protocol for managing patients with chronic fatigue syndrome (CFS). The patients were divided into 2 groups: group 1 (main) - 30 people who received standard therapy and AH inhalations (SUISONIA, Japan) for 10 days, and group 2 (control) - 30 medical workers who received only standard therapy. Patients in both groups were comparable in sex and mean age. All participants in the study were sampled with EBC on days 1 and 10. Samples were subjected to tryptic digestion and high-performance liquid chromatography combined with tandem mass spectrometry analysis using a nanoflow chromatograph (Dionex 3000) in tandem with a high-resolution time-of-flight mass spectrometer (timsTOF Pro). Results. A total of 478 proteins and 1350 peptides were identified using high resolution mass spectrometry. The number of proteins in samples after AH therapy, on average, is 12% more than before treatment. An analysis of the distribution of proteins in different groups of patients showed that only half of these proteins (112) are common for all groups of samples and are detected in EBC before, after, and regardless of hydrogen therapy. In addition to the qualitative difference in the EBC protein compositions in different groups, quantitative changes in the concentration of 36 proteins (mainly structural and protective) were also revealed, which together made it possible to reliably distinguish between subgroups before and after treatment. It is worth noting that among these proteins there are participants of blood coagulation (alpha-1-antitrypsin), chemokine- and cytokine-mediated inflammation, and a number of signaling pathways (cytoplasmic actin 2), response to oxidative stress (thioredoxin), glycolysis (glyceraldehyde-3- phosphate dehydrogenase), etc. Conclusion. The use of hydrogen therapy can contribute to the switching of a number of physiological processes, which may affect the success of recovery in PCS patients. In particular, the obtained results indicate the activation of aerobic synthesis of adenosine triphosphate in mitochondria by hydrogen therapy, which correlates well with the decrease in the blood lactate level detected by laboratory studies. At the same time, this therapy can inhibit pro-inflammatory activity, negatively affecting the coagulation and signaling pathways of integrins and apoptosis, and, in addition, activate protective pathways, tricarboxylic acid cycle, FAS signaling, and purine metabolism, which may be essential for effective recovery after COVID-19.Copyright © 2023 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

Bacterial ligands in the rehabilitation of healthcare workers after COVID-19

Immune defense mechanisms in survivors of the COronaVIrus Disease-19 (COVID-19) and development of their rehabilitation during the pandemic both portray a great scientific and practical interest. The aim of the study was to explore effect of Immunovac-VP-4 (I-VP-4), a vaccine based on bacterial ligands, on the clinical and airway mucosal immunity parameters, along with systemic immune response in a group of medical workers in post-COVID period and in persons who did not develop the disease. Methods. 82 healthcare workers aged from 18 to 65 years were included in a prospective open controlled study. The participants were divided into 4 groups: groups 1 (n = 20) and 2 (n = 27) included those with a history of COVID-19, and groups 3 (n = 18) and 4 (n = 17) included those who did not have the disease. Volunteers in groups 1 and 3 received I-VP-4. Samples of oral fluid, induced sputum, nasopharyngeal and oropharyngeal mucosa scrapings, and venous blood were examined. The levels of total secretory immunoglobulin class A (sIgA) and immunoglobulin G (IgG) were determined by enzyme immunoassay. The phagocytic index (PI) of leukocytes was assessed by flow cytometry. Results. The group of patients who did not have COVID-19 and received IVP-4 (Group 3) showed a tendency to a smaller number of COVID-19 cases, as well as some reduction in days of incapacity for work due to the acute respiratory infections (ARI). The vaccine improved airway mucosal immunity parameters and innate immune response. sIgA increased in the induced sputum (p < 0.005) and unchanged in the oropharyngeal mucosa samples in Group 1. The PI of macrophages in oral fluid doubled (p < 0.05) in this group. At the same time, those parameters decreased in Group 2. In non-infected vaccinated patients (Group 3), a significant increase of PI of blood monocytes was found on the day 90 of the study (p < 0.05). Also, a four-fold increase of PI of macrophages in oral fluid in comparison with Group 4 (p < 0.05) was noted. Conclusion. I-VP-4 improved airway mucosal immunity mechanisms and the systemic immune response. The vaccine can be recommended for rehabilitation programs for COVID-19 survivors and for prevention of ARIs. Copyright © 2022 Medical Education. All rights reserved.

[COVID-19 and human security].

The article was prepared after materials of the report at the 22.12.2020 International Scientific Forum COVID-19 and Human Safety in partnership with the World Academy of Arts and Science and the Rome Club on the virtual platform of the Faculty of Global Processes of the Federal State Budgetary Educational Institution of Higher Education Lomonosov Moscow State University.

Dyspnea: neurobiological and clinical aspects

The aim. The presented material reflects the results of studies by Russian specialists conducted under the auspices of the Russian Respiratory Society over the past 15 years. The article also includes the main provisions set out in the III Guidelines for dyspnea. A significant part of the manual is devoted to the recent achievements in studying neurophysiological processes in the brain structures during the development of dyspnea. These achievements were driven by image-diagnosis methods. An important aspect of this series of works for the clinical practice was identifying dyspnea domains and developing the instruments to assess severity. Results. Analysis of the data on dyspnea from the clinical practice showed a highly heterogenic clinical picture, which must be taken into account in the management of individual patients. A diagnostic algorithm for long-term follow-up of patients with dyspnea syndrome is also discussed. The attention of doctors is drawn to the features of dyspnea during COVID-19;the disproportion between the sensory perception of respiratory discomfort and the degree of oxygen desaturation is emphasized. Conclusion. It was concluded that in the Russian-speaking environment of patients, doctors should actively use a verbal characteristic of dyspnea – the “language of dyspnea”. © 2021 Medical Education. All rights reserved.

[Human placenta hydrolysates: from V.P. Filatov to the present day: Review].

Works of V.P. Filatov and his school laid the foundation for the study and clinical use of human placenta hydrolysates (HPH). To date, the PubMed database contains more than 5,000 publications on basic and clinical research on HPH. Studies of the peptide composition of HPH, carried out using the methods of modern proteomics, have made it possible to propose a complex of molecular mechanisms of the action of HPH in various pathologies. The article discusses the effects of HPH on the treatment of liver diseases, atopic dermatitis, viral infections (herpes, COVID-19, viral hepatitis), iron overload and chronic fatigue syndrome. Stimulation of HPH regenerative capabilities of the body is important for accelerating and improving the quality of wound healing, treatment of diseases of the joints and the reproductive system.

[Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19].

AIM: To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. MATERIALS AND METHODS: The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. RESULTS: It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

[Dyspnea: neurobiological and clinical aspects].

An analysis of the results of studies carried out by specialists of the Russian Respiratory Society over the past 15 years is given. The article also includes the main provisions set out in the III Guidelines for dyspnea. A significant part of the manual is devoted to the recent achievements in studying neurophysiological processes in the brain structures during the development of dyspnea. These achievements were driven by image-diagnosis methods. An important aspect of this series of works for the clinical practice was identifying dyspnea domains and developing the instruments to assess severity. Analysis of the data on dyspnea from the clinical practice showed a highly heterogenic clinical picture, which must be taken into account in the management of individual patients. A diagnostic algorithm for long-term follow-up of patients with dyspnea syndrome is also discussed. The attention of doctors is drawn to the features of dyspnea during COVID-19; the disproportion between the sensory perception of respiratory discomfort and the degree of oxygen desaturation is emphasized. It was concluded that in the Russian-speaking environment of patients, doctors should actively use a verbal characteristic of dyspnea the language of dyspnea.

[Biological activity of interferons in the novel coronavirus infection COVID-19].

INTRODUCTION: The immunopathogenesis of the novel coronavirus infection COVID-19 is usually associated with the development of imbalance in the immune response to its causative agent, SARS-CoV-2 virus (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). This is manifested, in particular, by interferons' (IFNs) deficiency at the beginning of the disease followed by hyperproduction of pro-inflammatory cytokines. The virus causes a decrease in IFN types I (α/ß) and III (λ) levels; changes in IFN type II (γ) are less studied. In this regard, it is relevant to assess the functional bioactive IFN (interferon status) in COVID-19. The aim of the study was to assess the antiviral potential of the body by testing the biologically active IFNs in COVID-19. MATERIAL AND METHODS: We used biological serum samples of COVID-19 patients taken in the acute phase (110 patients on the 1-5 days of the disease) and during rehabilitation (47 patients during 1-3 months after the disease onset). Assessment of interferon status was performed according to the technique developed by the authors and described earlier. RESULTS: The IFN status of patients with COVID-19 in the acute period and in the phase of post-infection rehabilitation was studied вduring the observation period. It was found that SARS-CoV-2 causes a pronounced inhibition of biological activity of IFN types I and II compared to the reference values by more than 20 and 7 times, respectively. During the post-COVID period, incomplete recovery of the IFN system activity was registered, which proceeded very slowly. No cases of reaching physiological indicators of interferon status were identified during the observation period. CONCLUSION: The obtained data on deficiency of the functional biologically active IFN confirm the hypothesis about the predominant role of impaired IFN production of different types in the immunopathogenesis of the novel coronavirus infection.

Peptides of Laennec® preparation that contribute to the elimination of endotheliopathy

Objective: identification of peptides in the composition of Laennec®, which can inhibit the development of endotheliopathy (endothelial dysfunction). Material and methods. Hybrid mass spectrometry followed by data analysis based on topological recognition theory was performed. The analysis of the peptide composition of Laennec® included four stages: purification of the drug, chromatographic separation of peptides, determination of the multidimensional mass spectrum of the peptide fraction, and de novo sequencing of the isolated peptides. Results. The preparation contains peptides-inhibitors of specific target proteins (PRKCZ, PKB, PKD1, MAPK14, IKKB, PDPK1) involved in the activation of the pro-inflammatory transcription factor NF-κB. Inhibition of CDK5 and SHC1 kinases helps to reduce endothelial cell apoptosis. The peptides of the drug also block enzymes involved in the synthesis and maturation of the tumor necrosis factor alpha (MAPKAPK2/3, ADAM17). Conclusion. In the composition of Laennec®, peptides have been found that contribute to a complex pathogenetic action against endotheliopathy. Endothelial regeneration is especially important in the rehabilitation of patients who have recovered from COVID-19. © 2021 IRBIS LLC. All Rights Reserved.

Questionnaire for initial self-assessment of health in post-COVID period Recommendations of Multidisciplinary expert board on screening of post-COVID syndrome during an expanded medical check-up

The post-COVID symptom complex is wide enough and requires special vigilance during clinical examination of patients after the novel coronavirus infection. The aim of the Multidisciplinary Expert Board study was to develop a standardized questionnaire for initial self-assessment by patients who had had COVID-19 before the expanded medical check-up. Methods. The existing validated international and national questionnaires and scales were analyzed to assess their relevance, convenience, and ease of filling out. Results of the analysis were used to set up a screening for post-COVID symptoms. Results. The work of the Multidisciplinary Expert Board in June-August 2021 resulted in a new screening questionnaire for the initial assessment of the health status of patients who have COVID-19. The questionnaire is intended for self-filling before the further clinical examination. Conclusion. A new standardized patient questionnaire to screen for post-COVID symptoms may significantly optimize the doctor’s working time, increase the efficiency of diagnosis, improve the principles of selection and formation of risk groups of patients during an expanded medical check-up. © 2021 Medical Education. All rights reserved.

Direct and Indirect Neurological Signs of COVID-19.

Objective. To systematize the neurological manifestations of COVID-19. Materials and methods. A systematic computerized analysis of all currently available publications on the neurological manifestations of COVID-19 was undertaken (2374 reports in PubMed) by topological data analysis. Results. A set of interactions between infection with SARS-CoV-2, metabolic impairments affecting neurotransmitters (acetylcholine, dopamine, serotonin, and GABA), enkephalins, and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia, and neurodegeneration (including demyelination) was described. The most typical neurological manifestations of COVID-19 were anosmia/ageusia due to ischemia, neurodegeneration, and/or systematic increases in proinflammatory cytokine levels. COVID-19 provoked ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis, and parkinsonism. Coronavirus infection increased the severity of multiple sclerosis and myopathies. The possible roles of the human virome in the pathophysiology of COVID-19 are considered. A clinical case of a patient with neurological complications of COVID-19 is described. Conclusions. In the long-term perspective, COVID-19 promotes increases in neurodegenerative changes, which requires special neurological rehabilitation programs. Use of cholinergic drugs and antihypoxic agents compatible with COVID-19 therapy is advised.

Thermovaccination: Thermoheliox as an Immune Response Stimulant. Kinetics of Antibodies and C-Reactive Protein Synthesis in Coronaviral Infection.

The high efficiency of using thermoheliox (inhalation with a high-temperature mixture of helium and oxygen) in the treatment of patients affected by COVID-19 was shown. The dynamics of accumulation of IgG, IgM, and C-reactive protein (CRP) in patients with coronavirus infection in the "working" and control groups was studied experimentally. It was shown that thermoheliox intensifies the synthesis of IgG, IgM, and CRP antibodies, while eliminating the induction period on the kinetic curves of the synthesis of specific antibodies in the IgG form and transfers the synthesis of CRP to a fast phase. The results of experiments confirm the previously obtained data based on the analysis of the kinetic model of the development of coronaviral infection in the human body.

[Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19].

A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).

Systematic computer analysis of published literature on nutritional support for vaccination

A range of 6700 publications from the PubMed database on the association of micronutrient supply and results of antibacterial and antiviral vaccination was reviewed by the method of topologic and metric analysis. This method allows for a selection of features (i.e. key words) by their informativity, the establishment of the most informative that provide the basis for “synthetic” features and algorithms, or the classification of the reviewed text by the relevance to the subject of the study. The results of fundamental studies showed that folates, vitamins A, D, and B12 are the regulators of mitosis of T and B-lymphocytes that exert the functions of the acquired immunity. Such microelements as zinc, iron, selenium, manganese, and omega-3 polyunsaturated fatty acid support the functioning of T and B-lymphocytes (energy metabolism, intracellular signal transmission, and transcription). Clinical studies showed that the support of vaccination with the specified micronutrients not only increases the titre of the respective antibodies to viral and bacterial pathogens but can also prevent unfavorable effects from vaccination. The administration of micronutrients before and after vaccination will contribute to a decrease in the mortality rate and severity of the pathology development (in case of disease). A systematic analysis allowed the authors to determine the perspectives of the proposed measures for an increase in the effectiveness and safety of vaccines, including COVID-19. Additional micronutrient supply contributes to an increase in the effectiveness and safety of vaccination. The application of specialized vitamin and mineral complexes during vaccination is economically feasible and reduces the vaccination risks for patients with polyhypoavitaminoses.

Chemoreactome screening of pharmaceutical effects on SARS-CoV-2 and human virome to help decide on drug-based COVID-19 therapy

Background. So-called rational drug design is suboptimal when it comes to finding effective and safe drug-based treatment for COVID-19. Another approach seems promising: to reprofile the pharmaceuticals registered in the Anatomical, Therapeutic, and Chemical Classifier (ATC). Material and methods. Chemoreactome screening, a method that simulates the results of inhibiting viral growth in a cell culture, models the effects of pharmaceuticals on the human virome, and estimates the adverse effects of medicines, was used to reprofile about 2700 pharmaceuticals from the ATC. The information technology behind chemoreactome analysis is based on the topological recognition theory advanced by the Institute of Pharmaceutical Informatics, Federal Research Center for Informatics and Control, Russian Academy of Sciences. Results. Sixty two pharmaceuticals and 20 micronutrients were found to have a pronounced antiviral effect with minimal side effects. Comparison against data of basic research and clinical trials showed 31 out of 62 pharmaceuticals to have been independently confirmed usable in COVID-19 treatment. These inhibit coronaviral proteins and/or function as adaptogenic molecules that improve the functioning of cells exposed to viral stress. Glucosamine sulfate was found to have the best safety profile and minimum effects on the healthy human virome out of all the tested anticoronaviral micronutrients. Conclusions. Reprofiling of pharmaceuticals registered in the ATC could significantly speed up the search for more effective and safer drug-based COVID-19 treatments. Several micronutrients show promise for long-term coronavirus prevention, especially in the elderly.