Potential predictors of severe course and outcome of community-acquired pneumonia.

Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients. The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022. Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient's condition and expected outcome.Copyright © Volchkova E.V. et al., 2023.

Potential predictors of severe course and outcome of community-acquired pneumonia

Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients. The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 – 2022. Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient's condition and expected outcome. © Volchkova E.V. et al., 2023.

Potential predictors of severe course and outcome of community-acquired pneumonia.

Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients. The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022. Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient's condition and expected outcome.Copyright © Volchkova E.V. et al., 2023.

HIF-1a in immune pathogenesis of SARS-CoV-2-pneumonia

The review is devoted to cellular and molecular mechanisms of the course and progression of new coronavirus disease, in particular, the role of hypoxia and hypoxia-induced factor 1α (HIF-1α). Literature searching was performed in the PubMed, Medline and Web of Science databases for the period 2019—2022. Hypoxia is a direct consequence of lung damage due to COVID-19 infection. In the areas of SARS-CoV-2-induced damage, focal inflammation occurs, and tissue microenvironment becomes hypoxic («inflammatory hypoxia»). Possible causes of «silent», «happy» or «apathetic» hypoxia in patients with COVID-19 and no symptoms of respiratory discomfort are discussed. HIF-1α activated by hypoxia is generally considered to be the main regulator of cellular response to oxygen deficiency. There is no consensus regarding the role of its activation in pathogenesis of COVID-19. As a transcriptional factor, HIF-1α can reduce penetration of SARS-CoV-2 via proteins controlling its entry into cells. This protein also reduces angiotensin-converting enzyme 2 receptor (ACE2) and serine protease expression, as well as increases expression of ADAM17 enzyme, which cleaves ACE2 from surface membrane of alveolocyte. The reverse side of HIF-1α activation may be fulminant cytokine storm as a result of expression of immune cells releasing pro-inflammatory cytokines. Possible HIF-dependent approaches to the treatment and prevention of COVID-19 are considered. These approaches are aimed at either suppressing HIF-1α activity using HIF-1α suppressor drugs or activating and stabilizing HIF-1α using HIF prolyl hydroxylase inhibitors. © E.V. VOLCHKOVA1, N.A. KUZUBOVA2, YU.S. ALEKSANDROVICH1, E.S. LEBEDEVA2.

Cytokine patterns of fatal hyperinflammatory conditions, caused by secondary hemophagocytic lymphohistiocytosis, bacterial sepsis and COVID-19

Introduction. In severe cases of coronavirus disease 2019 (COVID-19) pulmonary infiltration is accompanied by cytokine storm syndrome (CSS) development. Besides COVID-19, CSS can be triggered by the range of pathologies, which include hemophagocytic lymphohistiocytosis (sHLH) and septic shock (SS). The aim of this study was to compare immunological profiles in fatal cases of COVID-19, sHLH and SS. Material and methods. Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17A, IL-18, IFN-γ, TNF-α, procalcitonin, neopterin, ferritin with percent of glycosylated fraction (% GF) were measured in 37 COVID-19 fatal cases, collected during 2020 year prospectively;and in 39 sHLH and 47 SS fatal cases, collected within 2018–2019 years retrospectively. Comparison groups also included 194 non-fatal COVID-19 cases and 20 healthy donors, collected during 2020 year. Cytokine concentrations, procalcitonin and neopterin were measured by enzyme-linked immunosorbent assay;the ferritin level was determined by the turbidimetry method. The percent of glycosylated ferritin fraction (% GF) was calculated by the modified method of M. Worwood et al. Results. Deceased patients with COVID-19 had higher IL-6, IL-8, IL-10, IL-18, procalcitonin median levels compared to the survived. Meanwhile IL-8, IL-18, IFN-γ, TNFα and ferritin concentrations were significantly lower in deceased COVID-19 patients compared to sHLH and SS. The levels of IL-6 and procalcitonin in fatal COVID-19 were comparable to SS, but significantly higher than in sHLH. Leucocytes were higher in COVID-19 compared to both SS and sHLH. Conclusion. Each fatal condition was accompanied by specific features of the cytokine profile: high IL-6 combined with low IFN-γ, TNFα in COVID-19;high IL-8, IL-6 with low IL-17A, IL-2 in SS;high IL-18, ferritin, IFN-γ with low IL-6, procalcitonin, % GF in sHLH.

[Pharmacoepidemiological research of COVID-19 in the Russian Federation EGIDA-2020].

AIM: An analysis of coronavirus infection in Russia and evaluation of different AVT regimens effectiveness. MATERIALS AND METHODS: The study involved a retrospective analysis of 1082 patient records with laboratory-confirmed COVID-19 in 17 regions of Russia. The number of men and women was equal, mean age 48.718.1 (median 50). Patients with moderate COVID-19 (85%) versus mild COVID-19 (15%) were characterized by higher age (median 54 vs 21 years; p0.001), higher body mass index (27.8 vs 23.4; p0.001), prevalence of chronic diseases (75.3% vs 8.5%; p0.001), including circulatory system diseases (37.8%). Moderate COVID-19 characterized higher intoxication (10.86.1 vs 4.22.7 days; p0.001) and catarrhal symptoms duration (10.25.4 vs 6.14.1 days; p0.001). RESULTS: During hospitalization 92% of the patients received AVT, 77% antibiotics, and 16% corticosteroids. Umifenovir therapy resulted in a significant reduction of intoxication (8.75.5 vs 11.75.5 days; p0.001) and catarrhal symptoms duration (8.85.1 vs 12.04.9 days; p0.001) compared to the group without AVT. The usage of INF reduced intoxication symptoms compared with the group without AVT (8.97.5 vs 11.75.5; p0.05). Therapy with hydroxychloroquine, imidazolylethanamide pentandioic acid, and lopinavir + ritonavir combination did not affect the course of COVID-19. Most of adverse reactions were related to antibiotics. CONCLUSION: Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients.

Endothelial progenitor cells in pathogenesis of new coronaviral infection

Pulmonary vascular endothelium dysfunction is one of the main pathogenic factors responsible for many clinical manifestations of the severe course of COVID-19. Circulating endothelial progenitor cells (EPCs) are the endogenous regenerative reserve that maintains the integrity of the vascular endothelium and its restoration in case of damage by pathogenic factors. A decrease in the circulating EPCs is regarded as a predictor of morbidity and mortality in conditions associated with development of endothelial dysfunction, including COVID-19. The exact phenotype of progenitor cells capable of differentiating into endothelial cells has not been determined. In most laboratories antigens CD133+, CD34+, VEGFR-2+ (CD 309) or combination of these are used to identify EPCs. The process of EPCs mobilization and migration is controlled by molecular signals from immune cells located in the damage area. Stromal cell factor 1 (SDF-1), produced by the bone marrow and many other tissues, is an important chemoattractant for EPCs which express its receptors. The results of studies carried out in 2020 indicate that SARS-Cov-2 infects both hematopoietic stem cells, transforming into EPCs, and directly circulating EPCs, causing inflammatory and procoagulant reactions that complicate the COVID-19 course. There is no consensus on the mechanism of EPCs infection with coronavirus – directly through the expression of angiotensin-converting enzyme (ACE2) receptor or through an ACE2-independent mechanism. Today there is no effective therapy for COVID-19. The use of the EPCs regenerative potential, and the search for ways to enhance the EPCs mobilization from the depot, and increase their functional activity may become a promising approach to the prevention of severe complications and mortality from COVID-19. © 2021, Remedium Group Ltd. All rights reserved.

Pandemic COVID-19: Features of the mechanism of drug action

Main drugs used to treat COVID-19 and its complications are reviewed. Brief information about the molecular mechanisms of action of etiotropic, pathogenetic and symptomatic palliative drugs is given. A comparative analysis of data available on the efficacy and safety of drugs and the risks of drug interactions is carried out. There are currently no proven effective treatments for COVID-19. Rapidly expanding knowledge about the nature of SARS-CoV-2 is creating conditions for increase in the number of potential drug targets for the treatment of COVID-19.