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.

The effectiveness of the antiviral immune response largely depends on the activation of cytotoxic T cells. The heterogeneous group of functionally active T cells expressing the CD56 molecule (NKT-like cells), that combines the properties of T lymphocytes and NK cells, is poorly studied in COVID-19. This work aimed to analyze the activation and differentiation of both circulating NKT-like cells and CD56− T cells during COVID-19 among intensive care unit (ICU) patients, moderate severity (MS) patients, and convalescents. A decreased proportion of CD56+ T cells was found in ICU patients with fatal outcome. Severe COVID-19 was accompanied by a decrease in the proportion of CD8+ T cells, mainly due to the CD56− cell death, and a redistribution of the NKT-like cell subset composition with a predominance of more differentiated cytotoxic CD8+ T cells. The differentiation process was accompanied by an increase in the proportions of KIR2DL2/3+ and NKp30+ cells in the CD56+ T cell subset of COVID-19 patients and convalescents. Decreased percentages of NKG2D+ and NKG2A+ cells and increased PD-1 and HLA-DR expression levels were found in both CD56− and CD56+ T cells, and can be considered as indicators of COVID-19 progression. In the CD56− T cell fraction, increased CD16 levels were observed in MS patients and in ICU patients with lethal outcome, suggesting a negative role for CD56−CD16+ T cells in COVID-19. Overall, our findings suggest an antiviral role of CD56+ T cells in COVID-19.

Введение. Анемия является распространённой проблемой у пациентов реанимации и интенсивной терапии. Причины анемий разнообразны и связаны не только с основным и сопутствующими заболеваниями, но и с ятрогенной кровопотерей, обусловленной частым и/или чрезмерным взятием крови для проведения лабораторных исследований. В условиях реани­мации у пациентов в критическом состоянии объем ежедневно отбираемой для исследования крови становится значимым фактором, способным влиять на исход заболевания. Поэтому у данной когорты пациентов актуальным является минимизация объёма и кратности отбора проб крови для выполнения необходимых лабораторных исследований. Цель исследования: оценить возможность минимизации объёма отбираемой крови и кратности отбора проб крови для лабораторных иссле­дований у реанимационных пациентов при использовании пробирок с уменьшенным объемом. Материалы и методы. Проведено одноцентровое, проспективное, открытое исследование. Все пациенты отделений реанимации были стратифицированы на 2 группы по временным интервалам по 10 дней каждый. Отбор проб венозной крови у группы 1 осуществляли в пробирки стандартного объема (BD Vacutainer); у группы 2 кровь отбирали в пробирки с уменьшенным объёмом (Sarstedt). Выполнены гематологические, биохимические, коагулогические лабораторные исследования, а также анализ газов и электролитов крови. Оценивали объёмы взятой крови, качество образцов крови и результаты исследований, полученных из пробирок двух типов. Результаты. При сравнении стандартных пробирок и пробирок с уменьшенным объемом достигнуто снижение на 41,8% объёма взятой на аналогичные исследования крови без потери качества и кратности исследования. Наиболее значительное снижение диагностических кровопотерь достигнуто в исследованиях газов и электролитов (на 58%) и в коагулологических исследованиях (на 48,1%). Кроме того, использование пробирок с уменьшенным объемом, адаптированных для реанимационных отделений, в сочетании с дополнительным обучением среднего медицинского персонала позволило снизить общее количество проб ненадлежащего качества с 37,13 до 9,77%. Заключение. Применение пробирок с уменьшенным объемом позволяет снизить долю проб ненадлежащего качества и сэкономить 41,8% объема крови, взятой на лабораторные исследования у реанимационных пациентов, что способствует профилактике ятрогенной анемии. Introduction. Anemia is a common issue in intensive care and critical care patients. The causes of anemia are diverse and are associated not only with underlying and concomitant diseases, but also with iatrogenic blood loss due to frequent and/or excessive blood sampling for laboratory tests. In intensive care in critically ill patients, the volume of blood taken daily for testing becomes a significant factor that can affect the outcome of the disease. Hence, minimizing volume and frequency of blood sampling becomes relevant for performing necessary laboratory tests in this cohort of patients. Aim: to evaluate the possibility of minimizing the volume of blood drawn and the frequency of blood sampling for laboratory tests in intensive care patients when using low-volume tubes. Materials and Methods. In a single center, prospective, open study, all patients in intensive care units were stratified into two groups at time intervals of 10 days each. Venous blood sampling from the first group was carried out in standard tubes (BD Vacutainer). In the second group, blood was collected in reduced-volume test tubes (Sarstedt). Hematological, biochemical, and coagulation laboratory tests, as well as analysis of gases and blood electrolytes were carried out. The volumes of blood taken, the quality of blood samples, and the test results obtained from test tubes of two types were evaluated. Results. When comparing standard tubes and tubes with a reduced volume, a 41.8% reduction in the volume of blood taken for the same tests was achieved, without loss of test quality and multiplicity. The most significant reduction in diagnostic blood loss was achieved in gas and electrolyte tests (by 58%) and tests coagulological tests (by 48.1%). In addition, the use of reduced-volume tubes adapted for intensive care units, combined with additional training for nurses, reduced the total number of samples of poor quality from 37.13 to 9.77%. Conclusion. The use of reduced-volume tubes reduces the proportion of samples of inadequate quality and saves 41.8% of the volume of blood taken for laboratory tests in intensive care patients, which contributes to more effective treatment and prevention of iatrogenic anemia.

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.

New variants of SARS-CoV-2 such as Omicron BA.2, BA.4/5, BA.2.12.1 and BA 2.75 are characterized by higher infectivity and the ability to escape virus-neutralizing antibodies against previous coronavirus variants. The S-trimer of BA.2 and its phylogenetic derivatives are characterized by a predominant Up-conformation, which facilitates the interaction with ACE2 on target cells and promotes the resistance to neutralizing antibodies. The immunity acquired from the infection with earlier strains is non-sterile for both early and later strains; the booster systemic immunization does not significantly affect the effectiveness of antiviral immunity, and its feasibility is currently being questioned. Studies of the mucosal immune response have shown that intranasal immunization with adenovirus vaccines provides more pronounced protective immunity than systemic reimmunization does. A promising approach is the creation of multivalent inhaled next generation vaccines containing immunoadjuvants that activate B- and T-cell mucosal immunity. Currently, a large number of intranasal vaccines are undergoing phase I/II trials, while the preclinical and preliminary clinical results indicate that this method of vaccination provides a better mucosal immune response at the entry site of the virus than systemic immunization does. This strategy may provide a long-term immune protection against the currently existing and yet unknown new strains of SARS-CoV-2.

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU. Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.

BACKGROUND: COVID-19 mediates activation of immunocompetent cells. Little is known about the phenotypic marker CD38 on the surface of T and NK cells and its association with the severity of COVID-19. AIM: To analyze the distribution of the surface marker CD38 in subsets of T and NK cells at the different stages of their differentiation in the groups of patients with COVID-19 and convalescents, and to reveal the relationship between the level of CD38 expression in subpopulations of T and NK cells with the severity of COVID-19. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) from patients and donors were isolated using ficoll density gradient followed by cytofluorimetric analysis of the surface markers: CD3, CD56, CD38. RESULTS: In PBMC samples the level of CD38 expression on NK cells (CD3CD56+), including CD56bright and CD56dim subsets, as well as on T lymphocytes, differentiating conventional CD56(CD3+CD56) and NKT-like (CD3+CD56+) cells, were analyzed. Among CD56 T cells and NKT-like cells the highest levels of CD38 expression were registered in the groups of patients of moderate severity and convalescents, and, in contrast, the decreased CD38 levels were detected in the group of patients from the intensive care unit. CONCLUSIONS: The findings suggest that the level of CD38+ T cell in COVID-19 may be of use as diagnostic value.

ЦЕЛЬ ИССЛЕДОВАНИЯ Определить частоту развития и структуру тромботических и геморрагических осложнений у пациентов с COVID-19 в отделении реанимации и интенсивной терапии (ОРИТ). МАТЕРИАЛ И МЕТОДЫ В ретроспективное исследование включили пациентов (n=442) с тяжелым и крайне тяжелым течением COVID-19, госпитализированных в ОРИТ. РЕЗУЛЬТАТЫ У 87 (19,7%) из 442 пациентов возникли тромботические осложнения, преимущественно представленные тромбозами в системе глубоких и поверхностных вен нижних конечностей (n=42; 9,5%). Артериальные тромботические осложнения развились у 34 (7,7%) пациентов. Ведущими в структуре данных осложнений были острое нарушение мозгового кровообращения (n=19; 4,3%) и инфаркт миокарда (n=11; 2,5%). Пациенты, у которых диагностированы тромботические осложнения, по сравнению с пациентами без тромботических осложнений чаще нуждались в респираторной терапии и введении норэпинефрина, имели большую продолжительность пребывания в ОРИТ и в стационаре. У пациентов с тромботическими осложнениями определены более высокие концентрации ферритина, С-реактивного белка и тропонина Т при поступлении в ОРИТ, чем у пациентов без тромботических осложнений. По данным тромбоэластографии, у пациентов с тромботическими осложнениями отмечен профиль гиперкоагуляции, но различия между группами статистически незначимые. Геморрагические осложнения диагностированы у 23 (5,2%) пациентов, из них у 15 возникли большие кровотечения. В структуре геморрагических осложнений преобладали желудочно-кишечные кровотечения. ЗАКЛЮЧЕНИЕ У пациентов с тяжелым и крайне тяжелым течением COVID-19 отмечена высокая частота тромботических и геморрагических осложнений. Необходимо провести проспективные рандомизированные исследования для определения риска/пользы применения различных режимов антикоагулянтной терапии у пациентов с новой коронавирусной инфекцией в ОРИТ.

Пандемия COVID-19 характеризуется волнообразным течением, а также изменением подходов к лечению. Анализ клинико-лабораторных данных и их динамики позволит изучить особенности данной категории больных. ЦЕЛЬ ИССЛЕДОВАНИЯ Сравнить клинико-лабораторные характеристики пациентов реанимационного профиля первой и второй волн пандемии COVID-19. МАТЕРИАЛ И МЕТОДЫ Представлены данные 543 пациентов, госпитализированных в отделение реанимации и интенсивной терапии (ОРИТ) в первую и вторую волны пандемии. РЕЗУЛЬТАТЫ Сроки поступления пациентов в ОРИТ в первую волну были меньше, чем во вторую: от начала заболевания 10 [7; 13] и 11 [9; 17] дней, от поступления в стационар 2,5 [0; 5] и 4 [2; 8] дня соответственно. Пациенты второй волны были старше (74 [64; 82] и 68 [57; 79] лет, p=0,001). Длительность искусственной вентиляции легких (10 [5; 15] и 4 [1; 7] дня) была меньше во вторую волну; применение галоперидола (29,5 и 38,8%), глюкокортикостероидов (23 и 88,9%) отмечено чаще во вторую волну. Гемодиализ чаще проводили в первую волну (17,5 и 8,4%). Из лабораторных показателей выявлены различия между пациентами двух волн по числу лейкоцитов (p=0,001), тромбоцитов (p=0,025), нейтрофильно-лимфоцитарному соотношению (p=0,001), креатинину (p=0,043), С-реактивному белку (p=0,01), прокальцитонину (p=0,001). Во вторую волну длительность пребывания в ОРИТ была меньше (8 [4; 15] и 6 [3; 10] дней, p=0,003), а летальность больше (101 (50,5%) и 215 (62,7%), p=0,006). ЗАКЛЮЧЕНИЕ Длительность лечения в амбулаторных и стационарных условиях увеличилась, что привело к позднему поступлению пациентов в отделение реанимации и интенсивной терапии. Изменились подходы к респираторной и медикаментозной терапии. Средний возраст пациентов во вторую волну был больше с соответствующим увеличением летальности с каждым десятилетием.

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.

The aim of the study was to assess regional cerebral oxygenation (rScO₂) in patients with acute respiratory distress syndrome (ARDS) associated with COVID-19.Material and methods. The cross-sectional study was conducted. Twenty-eight patients with severe COVID-19 who were admitted in the intensive care unit were enrolled. Regional cerebral oxygenation was assessed using near-infrared spectroscopy, laboratory markers of cerebral damage, clinical and laboratory characteristics.Results. Median age of patients was 65 years, of whom 50% were men. Three (11%) patients had severeARDS, 8 (29%) patients had moderate ARDS, and 17 (60%) patients had mild ARDS. Mechanical ventilation was performed in 20 (71%) patients, vasopressors were used in 14 (50%) patients. The median levels of cerebral saturation were normal and did not differ between the left (rScO₂l) and right (rScO₂r) hemispheres (68 (58–75) and 69 (59–76), respectively). The level of S-100 protein was increased (0.133 (0.061–0.318) µg/l) in contrast to the normal level of neuron-specific enolase (12.5 (8.0–16.5) µg/l). A correlation was found only between rScO₂ and hemoglobin level (rho=0.437, P=0.02) and between rScO₂ and lymphocyte count (rho=–0.449, P=0.016). An increase in S-100 negatively correlated with a decrease in Glasgow Coma Scale score (rho=–0.478, P=0.028).Conclusion. Near-infrared spectroscopy did not reveal a decrease in rScO₂ among patients with ARDS associated with COVID-19. The S-100 protein is a useful marker for the assessment of impaired consciousness. Further study of the causes of cerebral dysfunction in patients with severe COVID-19 and methods for its early identification is warranted.

Early rehabilitation in the intensive care unit is a promising component of post-intensive care syndrome (PICS) treatment and prevention. However, the optimal time to start mobilizing critically ill patients is still to be determined.OBJECTIVE:To evaluate the effect of rehabilitation initiation timing on outcomes in patients with pneumonia.MATERIAL AND METHODS:The study included 106 patients with pneumonia (27 patients with community-acquired pneumonia and 79 patients with early-onset healthcare associated pneumonia) who received daily rehabilitation treatment for at least 7 days in the intensive care unit. All patients were retrospectively assigned to the early rehabilitation (ER) group if rehabilitation treatment was started within the first 48 hours of admission to the intensive care unit or the delayed rehabilitation (DR) group if mobilization was not initiated within this time frame.RESULTS:The baseline clinical and demographic characteristics of the patients did not differ between the groups. During rehabilitation, rates of catecholamine use and the psychiatric signs of PICS frequency were also comparable. The duration of mechanical ventilation was 1.5 times shorter in ER group patients than in DR group (8 vs. 6 days and 13 vs. 9 days, respectively; p=0.003). The ICU and hospital stay were also significantly shorter in ER group compared with the DR group (12 (9-16) vs. 19 (13-30), respectively; p<0.001; 23 (12) vs. 31 (13) as inpatients, respectively; p=0.005). Mortality and severe complications rate were comparable between the groups.CONCLUSIONS:The earliest possible start of rehabilitation provided the patient's condition is stable, can reduce the duration of respiratory support and hospital stay for patients with pneumonia.

Objective. To analyze the incidence and predictors of venous thromboembolic complications (VTEC) in COVID-19 patients ad-mitted to intensive care unit (ICU). Material and methods. A retrospective study recruited 200 ICU patients presenting with severe or critical COVID-19. Results. VTEC were found in 67 (33.5%) out of 200 patients. In 63 patients, deep and superficial vein thrombosis was observed. Four patients had pulmonary embolism. In 41 (20.5%) patients, VTEC occurred within the first day after admission to ICU. Patients presenting with VTEC had more extensive lung damage (CT data) and more common need for vasopressors (79.1% vs 59.4%, p=0.005) and mechanical ventilation (89.6% vs 60.2%, p=0.0001). Survival of these patients was lower (23 (34.3%) vs 76 (57.1%), p=0.003). There were significant differences in levels of von Willebrand factor antigen (vWF: Ag), interleukin 6 (IL-6), antithrombin III (AT III) and protein C. According to ROC analysis, vWF: Ag above 455% (AUC — 0.852 (0.69;1.00), p=0.008) was highly predictive for the risk of VTEC after 1 and 7 days. AT III below 72% (AUC — 0.77 (0.55;0.99), p=0.04) and IL-6 above 256 pg/ml (AUC — 0.85 (0.65;1.00), p=0.053) were prognostic factors of VTEC after the first day. Protein C below 81.5% at admission (AUC — 0.79 (0.59-0.99), p=0.042) was predictive regarding VTEC by the seventh day. Conclusion. Incidence of VTEC in ICU patients was 33.5%. In 60% of patients, VTEC developed before admission to ICU. vWF: Ag, AT III, IL-6, and protein C serve as predictors of VTEC in patients with severe or critical COVID-19. © 2021, Media Sphera Publishing Group. All rights reserved.

Background Vitamin D deficiency has been associated with an increased risk of respiratory infections. Objectives The study aimed to evaluate the serum 25-hydroxyvitamin D [25(OH)D] concentration in patients admitted to the intensive care unit (ICU) as a predictor of coronavirus disease 2019 (COVID-19) mortality. Methods A single-center retrospective observational study was conducted. Forty adult patients (50% men) with confirmed COVID-19 who were admitted to the ICU were enrolled. The primary endpoint was mortality at day 60. Serum 25(OH)D concentration was measured on the day of admission to the ICU. We used the Mann–Whitney test, Fisher's exact test, Kaplan–Meier analysis, and receiver operator characteristic (ROC) analysis to assess serum 25(OH)D concentration as a predictor of COVID-19 mortality. Results All 40 patients had a low median (IQR) serum 25(OH)D concentration at admission [12 (9–15) ng/mL]. The median (IQR) serum 25(OH)D concentration was greater in survivors [13.3 (10.0–17.1) ng/mL, n = 22] than in nonsurvivors [9.6 (7.9–14.2) ng/mL; n = 18], P = 0.044. The area under the ROC curve was 0.69 (95% CI: 0.52, 0.86; P = 0.044). The 60-d mortality rate of those with serum 25(OH)D concentrations ≤9.9 ng/mL (n = 14, 71%) tended to be greater than that of those with concentrations >9.9 ng/mL (n = 26, 31%) (P = 0.065), and they had a 5.6-fold higher risk of death (OR: 5.63; 95% CI: 1.35, 23.45; P = 0.018). Conclusions The ICU patients had a low serum 25(OH)D concentration. Serum 25(OH)D concentrations ≤9.9 ng/mL on admission can be used to predict in-hospital mortality in patients with COVID-19. This trial was registered at clinicaltrials.gov as NCT04450017.

Обоснование. Распространенность гиповитаминоза D в Российской Федерации у пациентов с COVID-19 изучена недостаточно, и совсем не изучена у пациентов с тяжелым и крайне тяжелым течением в отделении реанимации и интенсивной терапии (ОРИТ). Цель — изучить распространенность гиповитаминоза D у пациентов с COVID-19, находившихся на лечении в ОРИТ, и определить взаимосвязь статуса витамина D с исходом болезни. Методы. В ретроспективное одноцентровое исследование включены 103 взрослых пациента с тяжелым и крайне тяжелым течением COVID-19, госпитализированных в ОРИТ. Результаты. Из 103 пациентов в 94% случаев (n=97) выявлено существенное снижение концентрации 25(OH)D в сыворотке крови — 11 (7–15) нг/мл, в 46% (n=47) — тяжелый дефицит витамина D ( 10 нг/мл (66 и 42% соответственно; р=0,018). Эти две группы также достоверно различались по возрасту (р=0,018), наличию сахарного диабета в анамнезе (р=0,059), числу лейкоцитов (p=0,045), нейтрофильно-лимфоцитарному соотношению (р=0,017), уровню D-димера (р=0,05) и тропонина Т (р=0,054). Заключение. Выявлена высокая частота дефицита витамина D у пациентов с COVID-19, находящихся на лечении в ОРИТ. Тяжелый дефицит витамина D чаще определялся у пациентов пожилого возраста с сахарным диабетом и ассоциировался с повышенной летальностью среди больных. Выявленная взаимосвязь дефицита витамина D с нейтрофильно-лимфоцитарным соотношением позволяет предположить иммуноопосредованное влияние на исход у пациентов с COVID-19.

Background:Most patients with severe respiratory failure in intensive care unit (ICU) require bed rest. The limitation of physical activity leads to some adverse consequences such as ICU Acquired Weakness (ICUAW). Progression of respiratory failure, including that caused by the new coronavirus infection (COVID-19), can lead to the development of acute respiratory distress syndrome, the treatment of which contributes to a combination of risk factors for the development of ICUAW. Traditional diagnostic methods have certain limitations. Muscle ultrasonography is a modern tool for early detection of muscle mass loss.Aims:To compare different methods of early ICUAW screening and to estimate the incidence and peculiarities of ICUAW in patients with respiratory failure of infectious genesis.Methods:31 patients with severe coronavirus pneumonia (COVID-19+) and 13 patients with viral and/or bacterial lung infection (COVID-19 -) were included in the study. The muscle mass loss percent from day 1 to day 7 was higher in the COVID-19 - group (p=0.022). These patients also had longer durations of the ICU and hospital stay but a significantly lower mortality (2.5 times).Results:The analysis of the parameters of deceased and living patients regardless of the lung damage etiology showed a correlation between the indices of hand grip strength dynamometry (handgrip test) and ultrasonography of the thigh muscles: F1 and D1 (rho=0.6, p=0.003), F1 and S1 (rho=0.6, p=0.005), D1 and F7 (rho=0.9, p=0.001). In addition, the examined levels of the ICUAW markers were associated with age - F1 (rho=-0.6, p=0.001), D1 (rho=-0.4, p=0.003), S1 (rho=-0.4, p=0.004).Conclusions:During the critical illness, ICUAW develops by the 3d day of bed rest in two thirds of patients with respiratory failure of different infectious genesis. The correlation between the investigated markers of ICUAW and age indicates that elderly patients are the most vulnerable category in respect to the formation and progression of muscle weakness in the ICU. The handgrip test can serve as a reliable and simple method of ICUAW screening. Early identification of patients with ICUAW should provide the improvement of nutritional support and individualization of rehabilitation.

Background: Mortality in patients with severe COVID-19 remains high. Finding therapies that can improve the outcome in these patients is an urgent task. Aims: To evaluate the clinical efficacy of dexmedetomidine in the complex treatment of patients with a severe course of COVID-19. Methods: The retrospective study included 50 adult patients with severe COVID-19 admitted to the intensive care unit (ICU). The primary outcome of the study was the incidence of delirium. The secondary results of the study were the dynamics of gas exchange indicators (PaO2 and PaCO2) and inflammatory markers (C-reactive protein, CRP; procalcitonin, lymphocyte count, and neutrophil-lymphocyte ratio, NLR) on day 3 and day 5 of the treatment, as well as the duration of mechanical ventilation (MV), length of stay (LOS) in the ICU and in the hospital and mortality. Results: The incidence of delirium did not differ between the dexmedetomidine group and the control group (41 and 48%, respectively; p=0.661). The LOS in the ICU and in the hospital, as well as the MV duration, was comparable between the groups. However, the hospital mortality in the dexmedetomidine treatment group was lower than that in the control group (10.3% and 42.9%, respectively; p=0.008). The addition of dexmedetomidine to the therapy complex did not affect the blood gas composition but contributed to the increase in the number of lymphocytes (p=0.006) and to the NLS decrease (p=0.002) by the fifth day of treatment. At the same time, no significant changes in the CRP and procalcitonin levels were observed. Conclusion: In the treatment group, the mortality was statistically significantly lower than it was in the control group. At the same time, the use of dexmedetomidine did not reduce the incidence of delirium, the length of stay in the ICU and in the hospital, and the duration of mechanical ventilation in patients with severe COVID-19. The revealed relationship between the use of dexmedetomidine and NLR and the number of lymphocytes suggests an immune-mediated effect on the outcome in this category of patients. Prospective randomized trials are needed to confirm the beneficial effects of dexmedetomidine on the immune system and mortality.

Background: The prevalence of hypovitaminosis D has not been studied in the Russian Federation for the group of patients with severe and extremely severe COVID-19 in the intensive care unit (ICU). Aims: To study the prevalence of hypovitaminosis D in patients with COVID-19 treated in the ICU and to determine the relationship between the vitamin D status and disease outcome. Methods: The retrospective study included 103 adult patients with severe and extremely severe COVID-19 hospitalized in the ICU. Results: 94% patients (n = 97) showed a significant decrease in the concentration of 25 (OH) D in their blood serum 11 ng/ml [7; 15 ng/ml]. 37% (n = 38) of patients showed vitamin D deficiency, 46% (n = 47) had severe vitamin D deficiency, 12% (n = 12) had vitamin D insufficiency, 5% (n = 6) had normal vitamin D levels. In the group of patients with vitamin D levels less than 10 ng/ml, the mortality rate was significantly higher than that in the group of patients with the levels of vitamin D exceeding 10 ng/ml (66% and 42%, p = 0.018). These two groups of patients also significantly differed in their age (p = 0.018), history of diabetes mellitus (p = 0.059), white blood cell count (p = 0.045), neutrophil to lymphocyte ratio (p = 0.017), D-dimer level (p = 0.05) and troponin T level (p = 0.054). Conclusion: A high incidence of vitamin D insufficiency in patients with COVID-19 treated in the ICU has been identified. Severe vitamin D deficiency was more often found in elderly patients with diabetes mellitus, and was associated with the increased mortality. The identified relationship of the vitamin D deficiency with the neutrophilic-lymphocytic index suggests an immuno-mediated effect on the outcome of patients with COVID-19.