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Despite numerous clinical studies conducted over the past year, we have to admit that today we still have a very limited list of effective drugs for the treatment of Novel coronavirus disease 2019 (COVID-19). Dexamethasone improves survival in hospitalized patients requiring supplemental oxygen or respiratory support (1Collaborative Group RECOVERY Horby P Lim WS Emberson JR Mafham M Bell JL Linsell L et al.Dexamethasone in Hospitalized Patients with Covid-19.N Engl J Med. 2021; 384: 693-704https://doi.org/10.1056/NEJMoa2021436Crossref PubMed Scopus (1645) Google Scholar), and in the presence of systemic inflammation, tocilizumab may provide additional benefits (2Collaborative Group RECOVERY Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.Lancet. 2021; 397: 1637-1645https://doi.org/10.1016/S0140-6736(21)00676-0Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). Thus, there remains an unmet need for therapeutic interventions that prevent disease progression and improve prognosis in patients with COVID-19.

The need for safe and effective treatment is becoming increasingly urgent due to the high COVID-19 mortality rates observed worldwide. The choice of drug products for COVID-19 treatment regimens is based on the efficacy and safety data, the mechanism of action, and potential interactions. N-acetylcysteine's (NAC) pharmacological activity and its potential to suppress the progression of COVID-19 make it a promising therapeutic agent for COVID-19.Aimof the study was to evaluate the efficacy of NAC in the complex treatment of moderate COVID-associated pneumonia.Methods. The study included adult patients (n= 46) with moderate COVID-associated (the 2nddegree on CT) pneumonia (age 57 (51; 71) years, body mass index - 30 (27.1; 32.3) kg/m2, duration of the disease before hospitalization - 7 (6; 8) days, body temperature at the admission - 37.5 (37.1; 37.8)°С). The patients were randomized into two study groups. The 1stgroup (n= 22) received standard COVID-19 treatment [1]. The 2ndgroup (n= 24) additionally received NAC 1,200 - 1,500 mg/day intravenously. Treatment with NAC was started together with the standard therapy.Results. Our study showed that the inclusion of NAC in the complex treatment of moderate COVID-associated pneumonia led to a statistically significant increase in blood oxygen saturation, oxygenation index, the difference in delta increase in oxygenation index, a quicker reduction in the volume of lung damage and the difference between the groups in delta reduction of this index. Also, the rate of reduction of C-reactive protein and reduction of the duration of hospitalization in the group of patients who received NAC was statistically significantly more profound than in the standard treatment group.Conclusion. The study confirmed the effectiveness of NAC as a part of the complex treatment of moderate COVID-associated pneumonia.

In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19.We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure.We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70).The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.Цель. Анализ факторов, ассоциированных с ранним развитием септического шока у больных с тяжелым течением COVID-19. Материалы и методы. В исследование включены данные всех пациентов, проконсультированных до 1 мая 2020 г. на базе Федерального дистанционного консультативного центра анестезиологии и реаниматологии на базе ФГАОУ ВО Первый МГМУ им. И.М. Сеченова (Сеченовский Университет). Критерием септического шока считали снижение артериального давления, требовавшее введения вазопрессорных средств. Результаты. В исследование включены 1078 пациентов, 611 (56,7%) мужчин и 467 (43,3%) женщин. Средний возраст составил 61,013,7 года; 525 (48,7%) заявок на консультацию получены из стационаров Москвы, 159 (14,7%) Московской области, 394 (36,5%) лечебных учреждений в 58 регионах Российской Федерации. У 613 (56,9%) больных диагноз SARS-CoV-2-инфекции подтвержден с помощью полимеразной цепной реакции, а в остальных случаях установлен на основании клинической картины и результатов компьютерной томографии органов грудной клетки. Развитие септического шока отмечено у 214 (19,9%) из 1078 больных. В логистической регрессионной модели риск его развития у пациентов старше 50 лет выше, чем у больных более молодого возраста (отношение шансов 2,34; 95% доверительный интервал 1,533,67; р0,0001). У пациентов с более тяжелым течением SARS-CoV-2 отмечалось увеличение частоты сердечно-сосудистых заболеваний в целом, ишемической болезни сердца, фибрилляции предсердий, сахарного диабета 2-го типа, частота злокачественных опухолей выше. Риск развития септического шока у пациентов с тремя и более сопутствующими заболеваниями оказался выше, чем у пациентов без сопутствующих болезней (отношение шансов 1,76; 95% доверительный интервал 1,762,70). Заключение. Риск развития септического шока у пациентов с острым респираторным дистресс-синдромом, вызванным SARS-CoV-2, выше у пациентов старше 50 лет, страдающих несколькими сопутствующими заболеваниями, хотя тяжелое течение заболевания возможно и у более молодых людей без какой-либо сопутствующей патологии.

The objective: to evaluate the effectiveness of inhaled surfactant therapy in the integrated treatment of severe COVID-19 pneumonia in a multicenter prospective clinical trial of surfactant-BL.Subjects and methods. 122 patients with severe COVID-19-associated pneumonia treated in two treatment centers were enrolled in the study. All of them received antiviral, anticoagulant and anti-inflammatory therapy. 56 patients also received inhalation therapy with surfactant-BL (OOO Biosurf, St. Petersburg, Russia) at a dose of 1 mg/kg 2-3 times a day. The remaining 66 patients received no surfactant-BL inhalation. When included into the study, all patients were divided into two groups based on severity of the condition at the time of inclusion: 62 people (Group I) needed oxygen inhalation through a face mask with the flow of 6-8 L/min for hypoxemia correction (27 received surfactant therapy and 35 did not); other 60 patients (Group II) required non-invasive respiratory support (constant positive airway pressure, non-invasive mechanical ventilation, high-flow oxygen therapy), of them 29 received surfactant therapy, while 31 patients did not.Results. In Group I, switching to invasive mechanical ventilation was required for 3/27 (11.1%) patients who received surfactant therapy, and 10/35 (28.6%) who received no surfactant therapy (p = 0.085); lethality made 3/27 (11.1%) and 9/35 (25.7%) (p = 0.131), respectively. In Group II, among those who received surfactant therapy, 5/29 (17.2%) were switched to invasive mechanical ventilation and 18/31 (58.1%) among those who did not receive it (p = 0.001); lethality made 5/29 (17.2%) and 18/31 (58.1%) (p = 0.001), respectively. In the pooled group of 122 patients with severe COVID-19-associated pneumonia, 8 (14.3%) of 56 patients who received surfactant died, and 27 (40.9%) of 66 died among those who did not receive it, (p = 0.001).Conclusion: Inhalation surfactant therapy can reduce the frequency of switching patients to mechanical ventilation and statistically significantly reduce lethality caused by severe pneumonia associated with SARS-CoV-2.

Acute Respiratory failure (ARF) is the leading cause of death in patients with severe COVID-19, who have been admitted to the hospital. Tradition - ally, it has been believed that with severe pneumonia complicated by ARF, survival can improve with the use of early intubation and artificial lung ventilation (ALV) in patients. However, according to recently published studies, COVID-19 has a very high death rate among patients receiving ALV. In case of early (pre-life support) start of oxygen therapy and respiratory support in patients with COVID-19 the need for transfer to the intensive care unit, tracheal intubation and ALV decreases, and therefore the prognosis improves. This article presents practical guidelines for oxygen therapy and respiratory support at the pre-life support in patients with COVID-19 infection complicated by ARF.

To evaluate the efficacy of mechanical bacterial lysate on the prevention of infectious exacerbations of chronic obstructive pulmonary disease in patients with frequent exacerbations.The study included patients (n=60) with frequent exacerbations of COPD (groups C and D according to the GOLD classification). All COPD patients were divided into two groups by blind method. The first group (n=30) received conventional therapy for COPD plus MBL (the course included 3 cycles of 10 days therapy with 20-day intervals between them). The second group of patients (control, n=30) received conventional therapy for COPD without MBL.We evaluated the severity of symptoms, frequency of recurrence of COPD exacerbations, readmissions, need for emergency care and changes in basic therapy of COPD. Evaluations were done on 10 days, 1, 3 and 6 months from the start of the study.Adding of MBL to the therapy list of COPD resulted in a significant decrease of biomarkers of systemic inflammation and sputum purulence during compared to the control group. After 6 months of observation MBL group demonstrated statistically significant improvement of respiratory function, decrease in frequency of COPD exacerbations, needs for emergency medical service, reduced changes in basic therapy and hospitalization for exacerbation of COPD. Therapy with MBL showed a high degree of safety and low incidence of adverse events.The results of the study indicate that MBL may be used for the prevention of severe infectious exacerbations of COPD.Цель. Изучить влияние поливалентного механического бактериального лизата (ПМБЛ) на снижение общего числа инфекционных обострений хронической обструктивной болезни легких (ХОБЛ) у пациентов с частыми обострениями в анамнезе. Материалы и методы. В исследование включены больные (n=60) с частыми обострениями ХОБЛ (в возрасте 40 лет, группы C и D по классификации GOLD). Все пациенты слепым методом разделены на две группы. Первая группа пациентов (n=30) получала ПМБЛ (курс включал 3 цикла по 10 дней с 20-дневными интервалами между ними). Вторая группа пациентов (контроль, n=30) получала комплексную терапию ХОБЛ без иммуностимуляторов. Наблюдение осуществлялось через 10 дней, 1, 3 и 6 мес от начала исследования. Оценивались выраженность симптомов, частота рецидивов обострений ХОБЛ, повторных госпитализаций, вызовов скорой медицинской помощи; изменения в базовой схеме терапии ХОБЛ. Результаты. Включение ПМБЛ в стандартную терапию ХОБЛ привело к статистически значимому уменьшению выраженности клинических проявлений, уровня маркеров системного воспаления, объема и степени гнойности мокроты во время обострений и в течение 6 мес после обострения по сравнению с группой контроля. Через 6 мес наблюдения в группе больных, получавших ПМБЛ, отмечались статистически значимое улучшение функции внешнего дыхания, снижение частоты повторных обострений, вызовов скорой медицинской помощи по поводу обострения ХОБЛ, изменений проводимой базисной терапии и госпитализаций по поводу обострения ХОБЛ. Препарат показал высокую степень безопасности и низкую частоту нежелательных явлений. Заключение. Результаты проведенного исследования свидетельствуют о целесообразности клинического применения ПМБЛ для профилактики тяжелых инфекционных обострений ХОБЛ.

Idiopathic pulmonary fibrosis (IPF) is usually characterized by a chronic and slowly progressive course. According to several studies, a small number of patients with IPF (about 515%) develops an acute deterioration of deasese exacerbation of IPF. Exacerbations of IPF can occur at any time of the disease and sometimes becomes the first manifestation of IPF. Pulmonary hypertension in IPF is a fairly frequent complication, which leads to severe violations of gas exchange and reduced tolerance to physical stress. Currently, proven effective treatments for exacerbations of IPF do not exist, the management of this condition is based on supportive therapy (oxygen, respiratory support) and interventions with inadequate evidences (corticosteroids, immunosuppressant). During exacerbation of IPF a careful search of all the possible triggers is justified. In the presented clinical case of exacerbation of IPF there was demonstrated the efficacy of complex therapy including antifibrotic therapy, PAH-specific medicines and enhanced oxygen therapy.Идиопатический легочный фиброз (ИЛФ) обычно характеризуется хроническим и медленно прогрессирующим течением. Согласно исследованиям, у небольшого числа (порядка 515%) больных ИЛФ наблюдаются острые ухудшения состояния обострения ИЛФ, которые могут развиваться на фоне пневмонии, аспирации, тромбоэмболии легочной артерии, пневмоторакса, сердечной недостаточности. Обострение может возникать в любой момент заболевания и иногда становится первым проявлением ИЛФ. Легочная гипертензия при ИЛФ является довольно частым осложнением, приводит к тяжелым нарушениям газообмена и снижению толерантности к физическим нагрузкам. В настоящее время доказанные эффективные методы лечения обострений ИЛФ отсутствуют: рассматривается только поддерживающая терапия (кислородотерапия, респираторная поддержка) и вмешательства, не имеющие достаточной доказательной базы (глюкокортикостероиды, иммуносупрессанты). При обострении ИЛФ необходимы тщательный поиск всех возможных причин обострения ИЛФ и их коррекция. В представленном клиническом случае продемонстрирована эффективность комплексной терапии базисной, ЛАГ-специфической и усиленного режима кислородотерапии у пациента с обострением ИЛФ и тяжелой легочной гипертензией.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that combines various clinical manifestations and pathophysiological mechanisms. It underlies the separation of patients with COPD by phenotypes, endotypes and a personalized therapy of this disease. The implementation of this approach is possible only with the use of appropriate biomarkers. One of the most important biomarkers of COPD is eosinophilia of blood and/or sputum, which is considered as a predictor of frequent exacerbations and the effectiveness of inhaled glucocorticosteroids in patients with COPD. The literature discusses the impact of eosinophilic inflammation on the prognosis, clinical and functional parameters in COPD, and the role of the targeted therapy in the treatment of eosinophilic COPD.Хроническая обструктивная болезнь легких (ХОБЛ) - гетерогенное заболевание, сочетающее в себе различные клинические проявления и патофизиологические механизмы, что лежит в основе разделения больных ХОБЛ по фенотипам, эндотипам и персонифицированной терапии этого заболевания. Реализация данного подхода возможна только при использовании соответствующих биомаркеров. Одним из наиболее важных биомаркеров при ХОБЛ является эозинофилия крови и/или мокроты, рассматриваемая как предиктор частых обострений и эффективности ингаляционных глюкокортикостероидов у пациентов с ХОБЛ. В литературе обсуждаются вопросы влияния эозинофильного воспаления на прогноз, клинические и функциональные показатели при ХОБЛ, а также роли таргетной терапии в лечении эозинофильной ХОБЛ.

Awake prone positioning (PP) has been used to avoid intubations in hypoxic COVID-19 patients, but there is limited evidence regarding its efficacy. Moreover, clinicians have little information to identify patients at high risk of intubation despite awake PP. We sought to assess the intubation rate among patients treated with awake PP in our Emergency Department (ED) and identify predictors of need for intubation.We conducted a multicenter retrospective cohort study of adult patients admitted for known or suspected COVID-19 who were treated with awake PP in the ED. We excluded patients intubated in the ED. Our primary outcome was prevalence of intubation during initial hospitalization. Other outcomes were intubation within 48 h of admission and mortality. We performed classification and regression tree analysis to identify the variables most likely to predict the need for intubation.We included 97 patients; 44% required intubation and 21% were intubated within 48 h of admission. Respiratory oxygenation (ROX) index and P/F (partial pressure of oxygen / fraction of inspired oxygen) ratio measured 24 h after admission were the variables most likely to predict need for intubation (area under the receiver operating characteristic curve = 0.82).Among COVID-19 patients treated with awake PP in the ED prior to admission, ROX index and P/F ratio, particularly 24 h after admission, may be useful tools in identifying patients at high risk of intubation.

Background: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. Methods: This was a prospective observational study in critically ill mechanically ventilated patients (n=116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum» positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21.Results: The «optimum» PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p=0.002). In survivors, PaO2/FiO2 rose on Day 3 (p=0.008) and then between Days 7 and 10 (p=0.046). Conclusion: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate» PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS.Trial registration: ClinicalTrials.gov, NCT04445961. Registered 24 June 2020 - Retrospectively registered, http://https://clinicaltrials.gov/ct2/show/NCT04445961?cond=COVID-19&cntry=RU&city=Moscow&draw=3&rank=23

A 61-year-old woman, an ex-smoker with a 10 pack year smoking history, was referred to our clinic for the evaluation of insidious dyspnea and diffuse, bilateral infiltrates on a chest radiograph. She reported that she had been experiencing dyspnea on exertion and dry cough for the past 1.5 years. She denied fevers, chills, hemoptysis, or weight loss. Aside from a smoking history, there were no comorbidities or environmental exposures. She had no family history of lung diseases or other disorders. She worked as a school teacher and had no occupational exposures. There were no pets in the home and no prior occupational exposures.

Background One of the main pathophysiological mechanisms underlying the severe course of COVID-19 is the hyper-inflammatory syndrome associated with progressive damage of lung tissue and multi-organ dysfunction. IL-17 has been suggested to be involved in hyper-inflammatory syndrome. Objective To evaluate the efficacy and safety of the IL-17 inhibitor netakimab in patients with severe COVID-19. Study design. In our retrospective case-control study we evaluated the efficacy of netakimab in hospitalized patients with severe COVID-19 outside the intensive care unit (ICU). Patients in the experimental group were treated with standard of care therapy and netakimab at a dose of 120 mg subcutaneously. Results 171 patients with severe COVID-19 were enrolled in our study, and 88 of them received netakimab. On the 3 day of therapy, body temperature, SpO2/FiO2, NEWS2 score, and CRP improved significantly in the netakimab group compared to the control group. Other clinical outcomes such as transfer to ICU (11.4% vs 9.6%), need for mechanical ventilation (10.2% vs 9.6%), 28-day mortality (10.2% vs 8.4%), did not differ between the groups. Conclusion In hospitalized patients with severe COVID-19, anti-IL-17 therapy might mitigate the inflammatory response and improve oxygenation, but do not affect the need for mechanical ventilation and mortality.

Background We have investigated the use of nebulized surfactant as a potential therapeutic option for the patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) undergoing non-invasive ventilation. Methods The patients were divided into 2 groups: surfactant (n = 33) and control (n = 32). The subjects in the surfactant group received the inhaled surfactant at daily dose of 150–300 mg. The oxygenation parameters and several clinical outcomes were analyzed. Results On the 5 day of therapy, PaO2/FiO2 improved significantly in the surfactant group compared to the control group (184 (155–212) mmHg vs 150 (91–173) mmHg, p = 0.02). The inhaled surfactant significantly reduced the need for transfer of patients to intensive care units (24.2% vs 46.9%, p = 0.05) and invasive mechanical ventilation (18.2% vs 40.6%, p = 0.04). Even more, the nebulized surfactant shortened the length of non-invasive ventilation (7 (3–13) days vs 11 (5–22) days, p = 0.02) and time spent in hospital (18 (16–27) days vs 26 (21–31) days, p = 0.003) in patients suffering from COVID-19-linked ARDS. Conclusions Our preliminary data provided indications that inhaled surfactant therapy may represent a promising option for patients with COVID-19-associated ARDS. However, larger clinical trials are crucially needed.