Нозокомиальная инфекция у пациентов с тяжелым и крайне тяжелым течением COVID-19

The aim of the study was to determine the etiology and frequency of nosocomial infections in patients with severe and critical COVID-19.Material and methods. A retrospective, single-center study included 168 patients with COVID-19 admitted to the intensive care unit (ICU). All episodes of infection, clinical and laboratory characteristics, and outcome were documented in patients.Results. Hospital-acquired infections were detected in 82 (48.8%) of 168 patients, more frequently in men (p = 0.028).  A total of 232 episodes of nosocomial infections were observed including ventilator-associated pneumonia (48.2%), bloodstream infection (39.2%), nosocomial pneumonia/tracheobronchitis (13.4%), and urinary tract infection (5.2%). The main causative agents of nosocomial infections were resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae. Infections developed on the average on day 6 [3; 9] of ICU stay and were associated with the initial severity of the patients assessed by SOFA (p=0.016), SpO2 (p=0.005), lymphopenia severity (p=0.003), Neutrophil-Lymphocyte Ratio (p=0.004), C-reactive protein (p=0.01), aspartate aminotransferase (AST) level (p=0.022), or vitamin D (p=0.035) levels. Patients diagnosed with infection were more likely than those without infections to require mechanical ventilation (67.6% vs 32.4%, p < 0.001), high-flow oxygen therapy (50.0% vs 31.0%, p = 0.020), renal replacement therapy (36.8% vs 9.3%, p = 0.003), and had longer ICU length of stay (13 [9; 18] vs 4 [2; 8], p < 0.001), hospital length of stay (19 [14; 29] vs 15 [11; 20], p = 0.001) and mortality (47 (57.3%) vs 25 (29.0%), p < 0.001).Conclusion. In patients with severe and critical COVID-19 a high incidence of nosocomial infections was found, which negatively affected the outcome. In more than half of the cases, the infection was caused by resistant strains of Gram-negative bacilli. Procalcitonin is a useful biomarker for identifying bacterial infection in patients with COVID-19.Цель исследования. Определить этиологию и частоту внутрибольничной инфекции у пациентов с тяжелым и крайне тяжелым течением COVID-19.Материалы и методы. В ретроспективное одноцентровое исследование включили 168 пациентов с COVID-19, госпитализированных в отделение реанимации и интенсивной терапии (ОРИТ). У пациентов регистрировали все случаи инфекции, клинико-лабораторную характеристику и исход.Результаты. Внутрибольничную инфекцию выявили у 82 (48,8%) из 168 пациентов, чаще у мужчин (р=0,028). Всего регистрировали 232 эпизода внутрибольничной инфекции: вентилятор-ассоциированную пневмонию (48,2%), инфекцию кровотока (39,2%), внутрибольничную пневмонию/трахеобронхит (13,4%) и мочевую инфекцию (5,2%). Основными возбудителями внутрибольничной инфекции были резистентные штаммы Acinetobacter baumannii и Klebsiella pneumoniae. Инфекция развивалась в среднем на 6-й [3; 9] день нахождения в ОРИТ, была ассоциирована с исходной тяжестью состояния, определяемой по ряду параметров: SOFA (p=0,016), SpO2 (p=0,005), выраженности лимфопении (p=0,003), нейтрофильно-лимфоцитарному соотношению (p=0,004), концентрации С-реактивного белка (p=0,01), аспартаминтрансферазы (p=0,022), витамина Д (p=0,035). Пациенты, у которых была диагностирована инфекция, в сравнении с пациентами без инфекции, чаще нуждались в проведении искусственной вентиляции легких (67,6 и 32,4%, p<0,001), высокопоточной кислородотерапии (50,0 и 31,0%, p=0,020), заместительной почечной терапии (36,8 и 9,3%, p=0,003), имели большую продолжительность нахождения в ОРИТ (13 [9; 18] и 4 [2; 8], p<0,001), большую продолжительность пребывания в стационаре (19 [14; 29] и 15 [11; 20], p=0,001) и летальность (47 (57,3%) и 25 (29,0%), p<0,001).Заключение. У пациентов с тяжелым и крайне тяжелым течением COVID-19 выявили высокую частоту внутрибольничной инфекции, которая негативно влияла на исход заболевания. Более чем в половине случаев возбудителями инфекции являлись резистентные штаммы грамотрицательных палочек. Прокальцитонин является полезным биомаркером для идентификации бактериальной ин-фекции у пациентов с COVID-19

Трудности лечения осложнений и реабилитации после COVID-19. Клинический случай

The severe course of the new coronavirus infection (COVID-19) is associated with multiple life-threatening complications that lead to delayed initiation of active rehabilitation and unfavorable long-term treatment outcomes. Tracheoesophageal fistula is one of these complications. The specific feature of this event in COVID-19 is delayed tissue regeneration which requires a non-standard approach to management of such patients.The article presents a clinical case of a pregnant patient after a complicated severe course of COVID-19 with the development of tracheoesophageal fistula, sepsis, and weakness syndrome acquired in ICU. The combination of complications of the disease led to a prolonged (about five months) period of rehabilitation.Modern standard components of intensive therapy of such patients including regular monitoring of endotracheal/tracheostomy tube cuff pressure, dynamic assessment of nutritional status and its correction, rational antimicrobial therapy, screening of psychiatric disorders and early rehabilitation, will minimize the number of both early and delayed complications of COVID-19.  Тяжелое течение новой коронавирусной инфекции (COVID-19) сопряжено со множеством жизнеугрожающих осложнений, которые приводят к отсрочке начала активных реабилитационных мероприятий и ухудшению долгосрочных результатов лечения. Одним из таких осложнений является формирование трахеопищеводного свища. Особенностью этой патологии при COVID-19 является замедленная регенерация тканей, что требует нестандартного подхода к тактике ведения таких пациентов.В статье представлен клинический случай лечения беременной пациентки после осложненного тяжелого течения COVID-19 с развитием трахеопищеводного свища, сепсиса, синдрома приобретенной в отделении реанимации и интенсивной терапии слабости. Комбинация осложнений заболевания привела к затяжному (около 5 мес.) периоду реабилитации.Современные стандартные компоненты интенсивной терапии таких пациентов, включая регулярный контроль давления в манжете эндотрахеальных/трахеостомических трубок, динамическую оценку нутритивного статуса и его коррекцию, рациональную антимикробную терапию, скрининг психических нарушений и раннюю реабилитацию, позволят минимизировать число как ранних, так и отсроченных осложнений COVID-19

Inhaled surfactant in patients with covid-19 who took high-flow oxygen: the results of a retrospective analysis

The article presents a comparative retrospective analysis of clinical, laboratory data and outcomes in 39 patients with severe COVID-19 complicated by acute respiratory distress syndrome, who received high-flow oxygen therapy. Of which, 19 patients additionally received 75 mg of inhaled surfactant BL twice daily for 5 days using a nebulizer. As a result, mortality rate in the group of patients receiving surfactant was 10.5%, while in the standard therapy group — 50%; the number of patients transferred to the mechanical ventilation was 21% and 70%, respectively. As the patients receiving the surfactant were injected with COVID-19 hyperimmune convalescent plasma and monoclonal antibodies to interleukin-6 receptors more often than those from the control group, we recalculated the results regardless of these patients. However, a significant difference between the mechanical ventilation rate (2.5 times less often in the surfactant group) and mortality rate (3.5 times less in the surfactant group) was observed. The duration of hospitalization and stay at the intensive care unit was not significantly different between patients with and without surfactant treatment. Inhalation therapy with surfactant BL was well tolerated even by patients with chronic obstructive pulmonary disease. In no case did therapy have to be stopped due to side effects, the most common of which was coughing during inhalation. This retrospective analysis shows that the prescription of an inhaled surfactant prior to transferring patients to mechanical ventilation can prevent the progression of respiratory failure, put down mechanical ventilation, and improve survival

Coordinated Loss and Acquisition of NK Cell Surface Markers Accompanied by Generalized Cytokine Dysregulation in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP). Our data confirmed that NK cell activation in patients with COVID-19 is accompanied by changes in circulating cytokines. The progression of COVID-19 was associated with a coordinated decrease in the proportion of NKG2D+ and CD16+ NK cells, and an increase in PD-1, which indicated their exhaustion. A higher content of NKG2D+ NK cells distinguished surviving patients from non-survivors in the ICU group. NK cell exhaustion in ICU patients was additionally confirmed by a strong negative correlation of PD-1 and natural cytotoxicity levels. In moderately ill patients and convalescents, correlations were found between the levels of CD57, NKG2C, and NKp30, which may indicate the formation of adaptive NK cells. A reduced NKp30 level was observed in patients with a lethal outcome. Altogether, the phenotypic changes in circulating NK cells of COVID-19 patients suggest that the intense activation of NK cells during SARS-CoV-2 infection, most likely induced by cytokines, is accompanied by NK cell exhaustion, the extent of which may be critical for the disease outcome

Coordinated Loss and Acquisition of NK Cell Surface Markers Accompanied by Generalized Cytokine Dysregulation in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP). Our data confirmed that NK cell activation in patients with COVID-19 is accompanied by changes in circulating cytokines. The progression of COVID-19 was associated with a coordinated decrease in the proportion of NKG2D+ and CD16+ NK cells, and an increase in PD-1, which indicated their exhaustion. A higher content of NKG2D+ NK cells distinguished surviving patients from non-survivors in the ICU group. NK cell exhaustion in ICU patients was additionally confirmed by a strong negative correlation of PD-1 and natural cytotoxicity levels. In moderately ill patients and convalescents, correlations were found between the levels of CD57, NKG2C, and NKp30, which may indicate the formation of adaptive NK cells. A reduced NKp30 level was observed in patients with a lethal outcome. Altogether, the phenotypic changes in circulating NK cells of COVID-19 patients suggest that the intense activation of NK cells during SARS-CoV-2 infection, most likely induced by cytokines, is accompanied by NK cell exhaustion, the extent of which may be critical for the disease outcome