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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.

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.

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 (p p 2/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.

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 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.