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 The criteria for exclusion of sources were low relevance and outdated information.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 effects of highly contagious coronaviruses (including SARS-CoV-2) on the central nervous system: neurodegeneration (including cytokine- induced); cerebral thrombosis and thromboembolism; damage to the neurovascular 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. Accordingly, 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.

Aim. To provide a rationale for the feasibility of using the succinate-containing drugs to treat hypoxia associated with COVID-19 based on the analysis of experimental and clinical studies.

Materials and methods. 84 Russian and international literature sources concerning the pathogenesis of COVID-19 and the pathogenetic role of succinate in the management of COVID-19 associated hypoxia, oxidative stress and diaphragmatic dysfunction were analyzed. The literature search was performed using Pubmed and ELIBRARY.ru databases.

Results. The literature analysis showed that tissue hypoxia, triggering the pathomorphological cascade of events and resulting in multiple organ failure is a central element of COVID-19 pathogenesis. Experimental and clinical studies show the positive impact of tissue hypoxia correction using succinate in both adult patients and children with various conditions associated with acute respiratory failure.

Conclusion. The literature data provide a rationale for using succinate-containing drugs in the treatment of severe COVID-19.

The aim of the study was to identify the pathomorphology of brain damage in patients who died of COVID-19.

Material and methods. Autopsy reports and autopsy brain material of 17 deceased patients with premortem confirmed COVID-19 infection were analyzed. Fatal cases in which COVID-19 was the major cause of death were included in the study. Five people were diagnosed with cerebral infarction. Organ samples were taken for histological examination during autopsy. Sections were stained with hematoxylin and eosin and by Nissl to assess brain histopathology. To study the vascular basal membranes the PAS reaction was used, to detect fibrin in vessels phosphotungstic acid-hematoxylin (PTAH) staining was used, to determine DNA in nuclei sections were stained according to Feulgen, to detect RNA in neuronal nuclei and cytoplasm sections were stained with methyl green-pyronin. Immunohistochemical study of a neuronal marker, nuclear protein NeuN, was performed to assess neuronal damage.

Results. The signs of neuronal damage found in patients who died of COVID-19 included nonspecific changes of nerve cells (acute swelling, retrograde degeneration, karyolysis and cytolysis, ‘ghost' cells, neuronophagia and satellitosis) and signs of circulatory disorders (perivascular and pericellular edema, diapedesis, congested and engorged microvasculature).

Conclusion. Brain histopathological data indicate damage to the central nervous system in COVID-19 patients. Ischemic stroke in patients with COVID-19 is mostly caused by a combination of hypoxia resulting from respiratory failure and individual risk factors, including cerebrovascular atherosclerosis and hypertension.

The search for sensitive and specific markers enabling timely identification of patients with a life-threatening novel coronavirus infection (COVID-19) is important for a successful treatment.

The aim of the study was to examine the association of molecular biomarkers of air-blood barrier damage, surfactant proteins SP-A and SP-D and Club cell protein CC16, with the outcome of patients with COVID-19.

Materials and methods. A cohort of 109 patients diagnosed with COVID-19 was retrospectively divided into two groups. Group 1 comprised survivor patients discharged from the ICU (w=90). Group 2 included the patients who did not survive (w=19). Association of disease outcome and SP-A, SP-D, and CC16 levels in blood serum, clinical, and laboratory data were examined taking into account the day of illness at the time of biomaterial collection.

Results. The non-survivors had higher SP-A (from days 1 to 10 of symptoms onset) and lower CC16 (from days 11 to 20 of symptoms onset) levels vs survivors discharged from ICU. No significant differences in SP-D levels between the groups were found.

Conclusion. According to the study results, the surfactant protein SP-A and Club cell protein CC16 are associated with increased COVID-19 mortality.

Aim of the study. To examine the effect of prone positioning on hemodynamics in patients with COVID-19.

Materials and methods. The study enrolled 84 patients of both sexes with community-acquired multisegmental viral and bacterial pneumonia associated with COVID-19, who were divided into groups according to the type of respiratory support. The tests were performed using the integrated hardware and software system for noninvasive central hemodynamic assessment by volumetric compression oscillometry.

Results. We found that the pulse blood pressure velocity decreased from 281 [242.0; 314.0] to 252 [209; 304] mm Hg/s in patients with severe COVID-19 on oxygen support (p=0.005); volume ejection rate decreased from 251 [200; 294] to 226 [186; 260] ml/s (P=0.03); actual/estimated normalized vascular resistance ratio dropped from 0.549 [0.400; 0.700] to 0.450 [0.300; 0.600] (P=0.002), while the arterial wall compliance increased from 1.37 [1.28; 1.67] to 1.45[1.10; 1.60] ml/mm Hg (P=0.009). Prone positioning of patients on noninvasive lung ventilation associated with a reduction of linear blood flow rate from 40.0 [34.0; 42.0] to 42.5 [42.5; 47.25] cm/s (7=0.04) and arterial wall compliance from 1.4 [1.24; 1.50] to 1.32 [1.14; 1.49] ml/mm Hg (7=0.03). Prone positioning of patients on invasive lung ventilation did not result in significant hemodynamic changes.

Conclusion. The greatest hemodynamic changes during prone positioning were found in patients on oxygen respiratory support, whereas the least significant alterations were seen in patients on invasive ventilatory support.

Coagulopathy and associated thrombotic complications are common conditions seen in COVID-19. Therefore, anticoagulants are an integral part of the treatment of patients with COVID-19.

The aim of the study was to compare the efficacy of oral anticoagulants and low molecular weight heparins in the prevention of pulmonary embolism and their safety in terms of major bleeding incidence, as well as to evaluate the cost-effectiveness of using oral anticoagulants in the treatment of COVID-19.

Materials and methods. Two stages of patient management were compared: before and after the start of a widespread use of oral anticoagulants (OAC). The incidence of pulmonary embolism and gastrointestinal bleeding during the compared time periods was analyzed to assess the efficacy and safety of anticoagulants. To assess the cost-effectiveness, we compared the cost of anticoagulants per day of treatment and per patient.

Results. The incidence of pulmonary embolism and gastrointestinal bleeding did not differ during the compared time periods. Despite the increased frequency of anticoagulant use, the costs per day of treatment and per patient decreased after the start of a widespread use of OACs.

Conclusion. According to the results of the study, inclusion of OACs in COVID-19 management protocols allows to reduce treatment costs without compromising its efficacy and safety. However, the short period of comparison does not allow drawing any firm conclusions. Additional large-scale comparative studies are needed.

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.

Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28^th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.

Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.

Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components.