PREDICTORS OF MORTALITY IN HOSPITALIZED COVID-19 PATIENTS

When treating patients with COVID-19, prognostic and diagnostic tests to assess the risk of severe disease and adverse outcome are particularly important. The analysis of demographic, clinical, laboratory and instrumental data obtained on ICU admission was performed on a sample of 109 patients to determine potential predictors of lethal outcome. The factors increasing the risk of adverse outcome included age =57 years (AUC = 0.777, P < 0.001), hypertension (RR = 3.073, P = 0.033), ARDS (RR = 17.455, P < 0.001), advanced chest CT severity score (HR = 1.569, P = 0.039), severe and critical COVID-19 (RR = 6.964, P = 0.016), neutrophilia (AUC = 0.729, P = 0.005), lymphopenia (AUC = 0.705, P = 0.023), thrombocytopenia (AUC = 0.713, P = 0.018), reduced MCHC (AUC = 0.700, P = 0.026), elevated RDW (AUC = 0.718, P = 0.007), LDH (AUC = 0.891, P = 0.005) and D-dimer (AUC = 0.806, P = 0.029).

Biomarkers of air-blood barrier damage in covid-19

The search for sensitive and specific markers enabling timely identification of patients with a life-threat-ening 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 (n=90). Group 2 included the patients who did not survive (n=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 bio-material 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.

CLINICAL AND HISTOPATHOLOGICAL FEATURES OF LUNG IN JURY IN COVID-19 INFECTION

The aim of the study was to evaluate the histopathological changes in the lungs of patients who died of a new coronavirus infection (COVID-19) in relation to the length of hospital stay. We evaluated lung autopsy material, autopsy reports, and death summaries of 39 patients who died of COVID-19. The length of hospital stay ranged from a few hours to 25 days. At all stages of the disease, lung alterations (desquamation of bronchial and alveolar epithelium), circulatory disorders (alveolar edema and hemorrhages, congestion in small blood vessels, thrombosis), compensatory response (fibrosis) were identified. The patients who died during the first week of hospitalization demonstrated predominant signs of circulatory disorders (alveolar edema, hyaline membranes, alveolar hemorrhages, congestion in small blood vessels). Fibrosis, usually not typical for the first week of acute respiratory distress syndrome, was detected in 46% of the deceased during the first week of hospitalization, which may be due to late hospitalization or patterns of fibrosis development in COVID-19. For those who died in the 2nd and 3rd weeks of hospitalization, the compensatory response and progression of fibrosis were noted. By the 3rd week, pulmonary fibrosis was detected in 91% of patients. Thrombotic complications (thrombosis, pulmonary artery thromboembolism) were observed in almost half of fatalities occurring during weeks 2-3. Hemorrhagic infarction was found in 43% (6 patients) who died during week 2 of hospitalization, three of them were diagnosed with pulmonary embolism, indicating progression of pulmonary vascular damage.

COVID-19 AND OXIDATIVE STRESS

Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body’s systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis. Патогенез новой коронавирусной инфекции COVID-19 является предметом активного изучения во всем мире. COVID-19, вызываемый SARS-CoV-2, представляет собой сложное заболевание, в котором тесно переплетено взаимодействие вируса с клетками-мишенями, действием иммунной системы и системной реакцией организма на эти события. Многие респираторные вирусные инфекции, включая COVID-19, вызывают смерть инфицированных клеток, активацию компонентов врожденного иммунитета и секрецию цитокинов воспаления. Все эти процессы ассоциированы с развитием окислительного стресса, который вносит важный вклад в патогенез вирусных инфекций. В данном обзоре проведен анализ информации об окислительном стрессе при инфекциях, вызываемых SARS-CoV-2 и другими респираторными вирусами. Основное внимание в обзоре уделено участию сосудистого эндотелия в патогенезе COVID-19.

COVID-19 and Oxidative Stress.

Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body's systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis.

Lithium chloride for the novel coronavirus infection covid-19

The novel coronavirus infection COVID-19 is associated with increased release of inflammatory cytokines (cytokine storm) and reactive oxygen species. These processes result a damage to the endothelium, pulmonary alveolar epithelium and their basal membranes (including the structures of blood-air barrier), increased vascular permeability and non-cardiogenic pulmonary edema. These mechanisms underlie the pathogenesis of acute respiratory distress syndrome in patients with coronavirus infection COVID-19. In this review, we have analyzed the data on the effect of lithium chloride on cytokine storm, increased vascular endothelial permeabili-ty, apoptosis of endotheliocyte and advanced activation of innate immune cells in patients with coronavirus infection COVID-19. © 2020, Media Sphera. All rights reserved.

TRANSCRIPTION FACTOR Nrf2 AS A THERAPEUTIC TARGET FOR THE PREVENTION OF CYTOKINE STORM IN COVID-19

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients. Nrf2 является ключевым фактором транскрипции, ответственным за антиоксидантную защиту во многих тканях и клетках, включая альвеолярный эпителий, эндотелий и макрофаги. Кроме того, Nrf2 функционирует как транскрипционный репрессор, подавляющий экспрессию цитокинов воспаления в макрофагах. Пациенты с COVID-19 в критическом состоянии зачастую имеют чрезвычайно высокие параметры окислительного стресса и системного воспаления, которое служит одной из основных причин летальности. В данной статье представлено обоснование использования индукторов транскрипционного фактора Nrf2 для предотвращения развития избыточного воспалительного ответа при COVID-19.

Transcription Factor Nrf2 as a Potential Therapeutic Target for Prevention of Cytokine Storm in COVID-19 Patients.

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.