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.

Changes in pulmonary microcirculation after COVID-19

The endothelium is a tissue most vulnerable to the SARS-CoV-2 virus. Systemic endothelial dysfunction leads to the development of endothelitis which causes the main manifestations of the disease and systemic disturbance of microcirculation in various organs. Pulmonary microcirculatory damage, the most striking clinical manifestation, was the reason to perform SPECT to detect microcirculation disorders. Aim. To assess microcirculatory changes in the lungs of patients who had no previous respiratory diseases and had a COVID-19 infection at different times from the onset of the disease. Methods. SPECT data were analyzed in 136 patients who had a proven coronavirus infection of varying severity from May 2020 to June 2021. Results. All patients showed changes in microcirculation in the lungs in the post-COVID period. The severity of microcirculation disorders had a significant correlation (rs = 0.76;p = 0.01) with the degree of damage to the pulmonary parenchyma and an average correlation (rs = 0.48;p = 0.05) with the timing of the post-COVID period and the degree of residual lesions on CT (rs = 0.49;p = 0.01). The examined patients with persistent clinical complaints had pulmonary microcirculatory lesions, which may indicate the development of vasculitis, at all stages of the post-COVID period. Despite regression of the lesions confirmed by CT in 3 to 6 months after the acute COVID-19 infection, specialists from Russian and other countries report that 30–36% of patients develop pulmonary fibrosis. Similar changes were identified in 19.1% of the examined patients in our study. Conclusion. Microcirculation disorders are detected in all patients in the post-COVID period, irrespective of the severity according to CT. Progressive decrease in microcirculation in the lower parts of the lungs, local zones of hypoperfusion with the critically low accumulation of radiopharmaceuticals, persistent areas of compaction of the lung tissue (so-called “ground glass”), reticular changes, and the development of traction bronchiectasis, a decrease in the diffusion capacity of the lungs and alveolar volume may indicate fibrotic lesions with subsequent development of virus-associated interstitial lung disease. © 2021 Medical Education. All rights reserved.

Single-photon emission tomography of the lungs in the diagnosis of coagulopathyin patients in the postcovid period

Introduction. Exposure to SARS-CoV-2 leads to damage and dysfunction of the microvasculature of the lungs. The development of vasculitis, an increase in the permeability of the vessel wall, changes in the vascular-platelet and coagulation hemostasis, lead to the development of thrombosis / thromboembolism and hemorrhages. Single-photon emission tomography of the lungs is optimal for assessing changes in microcirculation in the lungs of patients with COVID-19 infection, since CT angiography can detect these formidable complications only in the large vessels of the lungs. Objective of the work. To assess changes in the microvasculature of the lungs in patients with the development of postcovid syndrome and to assess the possibilities of single photon emission computed tomography in the diagnosis of thromboembolism, thrombosis and hemorrhages. Material and methods. The data of radiological studies performed in 138 patients in the postcovid period were analyzed, directed for examination to assess changes in blood circulation in the lungs and identify complications of the disease (thromboembolism, thrombosis, hemorrhages). Results. In patients who underwent an infection caused by the SARS-CoV-2 virus in a mild form, we identified changes in microcirculation most characteristic of manifestations of vasculitis and small local blood flow defects close to a triangular shape (microthrombosis), which correlated with an increase in fibrinogen (4.32 ± 0.21 g/L) (rs = 0.97;p = 0.001). Signs of microthrombosis, pulmonary embolism were detected in 35.9% of moderately severe patients who did not receive anticoagulant therapy or was prescribed it on day 10-12 of illness, and in 67.2% of severe and extremely severe patients who received anticoagulant therapy during the illness. Signs of postthromboembolic changes were detected in 16 patients (59.2%) in the late postcovid period, which correlated to a high degree (rs = 0.81;p = 0.03) with an increase in the level of fibrinogen (4.5 ± 1.9 mg/l). Conclusions. The severity of microcirculation disorders in the lungs depends on the severity of the disease and the timing of the postcovid period. Signs of small branch thromboembolism / thrombosis are detected in the early postcovid period. In patients who have undergone COVID-19 with the development of thrombosis, signs of postponed pulmonary embolism are revealed and zones of local pneumosclerosis are formed. © 2021, Remedium Group Ltd. All rights reserved.

The effectiveness of combination of 7% hypertonic saline and 0.1% natrii hyaluronas in patients with chronic obstructive pulmonary disease who have suffered a new coronavirus infection

Introduction. New coronavirus infection (COVID-19) contributes to the aggravation of respiratory symptoms in patients with COPD, including affecting the intensity and nature of cough. Hypertonic solution (HS) has a positive effect on the rheological properties of sputum and mucociliary clearance. However, there are no studies in the available literature on the use of HS in patients who have undergone COVID-19. Goal. To evaluate the effect of the combination of 7% hypertonic saline and 0.1% natrii hyaluronas on the intensity and productive nature of cough in patients with COPD who have undergone a new coronavirus infection and the safety of its use in this cohort of patients. Materials and methods. 50 patients with severe COPD in remission who suffered a new coronavirus infection were examined. The rehabilitation stage of treatment was carried out in the conditions of the pulmonology department. From the moment of receiving the last negative PCR result for SARS-CoV-2 to admission to the hospital for rehabilitation, it took from 2 to 3 weeks. The duration of follow-up of patients was 10 days. The patients were divided into two groups: group 1 (n = 25) - patients who received combination of 7% hypertonic saline and 0.1% natrii hyaluronas 7% by inhalation through a nebulizer;group 2 (n = 25) - patients who did not receive combination of 7% hypertonic saline and 0.1% natrii hyaluronas. The severity of cough was assessed (cough severity scale;shortness of breath, cough and sputum scale), clinical and biochemical blood tests, ECG, spirometry. Results. In patients treated with combination of 7% hypertonic saline and 0.1% natrii hyaluronas, a significant decrease in the severity of cough, the amount of sputum was revealed. The tendency to reduce shortness of breath and improve the quality of life is determined. No serious adverse events were detected when using the drug. Conclusions. The use of the combination of 7% hypertonic saline and 0.1% natrii hyaluronas in patients with COPD who have suffered a new coronavirus infection at the rehabilitation stage leads to a decrease in the intensity of cough and improved sputum discharge, which helps to reduce the severity of shortness of breath and improve the quality of life. The use of the drug is safe and does not lead to clinically significant adverse events. © 2021, Remedium Group Ltd. All rights reserved.

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.