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Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that occurs in susceptible individuals in response to various inhaled antigens. The fibrotic phenotype of HP is characterized by disease progression and can lead to pulmonary hypertension (PH). The aim of this study was to estimate the prevalence of PH and to identify predictors of PH in patients with chronic HP. Methods: We conducted an observational longitudinal study that included 85 patients with an established diagnosis of HP. Clinical examination, quality of life questionnaires, high-resolution computed tomography (HRCT) of the chest, arterial blood gases analyses, six-minute walking test (6-MWT), pulmonary function tests, and echocardiography were performed. Results: Patients were divided into groups with fibrotic (71.8%) and nonfibrotic phenotype (28.2%). PH was detected in 41 (48.2%) patients. Patients with PH had the predominant fibrotic phenotype of HP, were older, more symptomatic, and had a higher FVC/DLco ratio. The most significant predictors of PH were CT signs of fibrosis, finger clubbing, FVC/DLco, decreased distance, and SpO2 at the end of 6-MWT, as well as the presence of cardiovascular diseases. Conclusions: PH is a common condition in patients with chronic HP, especially with the fibrotic phenotype. Early detection of the PH predictors is necessary for the timely diagnosis of this complication of HP.

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.

This non-randomized controlled study aimed to assess the efficacy of tofacitinib in reducing the risk of invasive mechanical ventilation or death in patients with COVID-19. Patients with COVID-19 associated with reduced oxygen saturation, increased C-reactive protein (≥50 mg/L), and/or persisting fever were recruited. Tofacitinib was administered in addition to standard of care therapy. Study outcomes were evaluated separately in the groups of patients with oxygen saturation at rest ≤93% and >93%. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regression analysis adjusted for inverse propensity score weighting. Overall, 384 patients with COVID-19 (212 males; median age 60 years) were included in our study and were treated with tofactinib (n=131) or standard of care alone (n=253). The percentages of patients who started mechanical ventilation or died during hospitalization in the tofacitinib and control groups were 12.5% (9/72) vs. 14.1% (26/185) among patients who required respiratory support (HR 0.92, 95% CI 0.33-2.56), and 1.7% (1/59) vs. 4.4% (3/68) in those with normal oxygen saturation (HR 0.83; 95 CI 0.07-9.44). Tofacitinib did not reduce the risk of invasive mechanical ventilation or death in patients with COVID-19, although the analysis of these outcomes favored tofacitinib.

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

Background This systematic review and meta-analysis aimed to assess the association between the tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in COVID-19. Methods We performed a systematic literature search using PubMed, Embase, and Scopus databases with keywords "COVID-19" OR "SARS-CoV-2" OR “2019-nCoV” AND “Tricuspid annular plane systolic excursion” OR “TAPSE” up until 20 January 2021. The main outcome was mortality; the effect estimate was reported in hazard ratio (HR) which was pooled from the unadjusted and adjusted effect estimate retrieved from the included studies. Mean difference of the TAPSE (in mm) between non-survivors and survivors were pooled. Results There were 641 patients from 7 studies included in this systematic review and meta-analysis. TAPSE was lower in non-survivors compared to survivors (mean difference -3.74 [-5.22, -2.26], p

Bedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p

Highlights • COVID-19 may be characterized by an abnormal coagulation process and microvascular thrombosis of the lung vasculature. • COVID-19 may also be linked with acute respiratory distress syndrome (ARDS) and acute cor pulmonale (ACP). • We confirmed the development of ACP in a patient suffering from COVID-19. • We treated our patient with systemic thrombolysis and this resulted in a marked improvement in hemodynamics. • In addition, there was a significant reduction in hypercapnia, alveolar dead space, and ventilatory ratio., Existing literature highlights the fact that patients with COVID-19 exhibit alterations in the coagulation process and are associated with respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale. In this report, we describe the effects of systemic thrombolysis on acute cor pulmonale in a patient suffering from COVID-19. We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.

This study was designed to evaluate the usefulness of lung ultrasound (LUS) imaging to characterize the progression and severity of lung damage in cases of COVID-19.We employed a set of combined ultrasound parameters and histopathological images obtained simultaneously in 28 patients (15 women, 0.6-83 years) with fatal COVID-19 submitted to minimally invasive autopsies, with different times of disease evolution from initial symptoms to death (3-37 days, median 18 days). For each patient, we analysed eight post-mortem LUS parameters and the proportion of three histological patterns (normal lung, exudative diffuse alveolar damage [DAD] and fibroproliferative DAD) in eight different lung regions. The relationship between histopathological and post-mortem ultrasonographic findings was assessed using various statistical approaches.Statistically significant positive correlations were observed between fibroproliferative DAD and peripheral consolidation (coefficient 0.43, p = 0.02) and pulmonary consolidation (coefficient 0.51, p = 0.005). A model combining age, time of evolution, sex and ultrasound score predicted reasonably well (r = 0.66) the proportion of pulmonary parenchyma with fibroproliferative DAD.The present study adds information to previous studies related to the use of LUS as a tool to assess the severity of acute pulmonary damage. We provide a histological background that supports the concept that LUS can be used to characterize the progression and severity of lung damage in severe COVID-19.

The objective of research: to assess the complementarity of histological, clinical, functional and CT data in acute and chronic hypersensitive pneumonitis (HP). Materials and Methods: The study included 176 patients with a diagnosis of HP verified by a multidisciplinary discussion. Clinical, functional data, CT signs, and open biopsy histology were retrospectively evaluated. Results: Acute/subacute HP (aHP) was verified in 16,8%, chronic HP (cHP)– in 60,8%, and uncertain HP in 32,4% by multidisciplinary discussion. Histological signs in aHP group were as follows: non-necrotic granulomas and giant multinucleated cells (65,4%), bronchiolitis obliterans (61,5%), non-specific interstitial pneumonia (NSIP) (42,3%), foam cells (38,5%), organizing pneumonia (34,6%). Histological signs in cHP group: interstitial fibrosis (85%), honeycombing (68,5 %), signs of pulmonary hypertension (70%), non-specific interstitial pneumonia (15%), UIP-like fibrosis (73%), fibroblatic foci (43%). The classical triad of morphological signs of HP (non-specific interstitial pneumonia, bronchiolitis obliterans, non-necrotic granulomas and giant multinucleated cells) was more common in aHP than cHP (19,2% vs 5,6%; p = 0.04). Rare patterns of cHP were OIP-like fibrosis combined with evidential emphysema (1,1%), focal cholesterol (endogen lipid) pneumonia (2,2%), focal alveolar proteinosis (1,1%) or prominent angiomatosis in fibrotic areas (1,7%). Conclusion: Classical histological triada was not common, especially in cHP. NSIP-like fibrosis was less common in cHP than UIP-like one. Rare features have not excluded the diagnosis in the aspect of the multidisciplinary discussion.

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.

Several studies suggested about the role of chronic infflammation in the pathogenesis of PH related to COPD. The aim of study was to evaluate the levels of plasma C-reactive protein (CRP) and fibrinogen and to assess its diagnostic significance in patients with COPD and PH. The study included 63 patients with COPD (GOLD II-IV, age 59.5±10.2 yrs, smoking history 24.1±8.9 pack/years). Patients were divided into groups: 1) without PH (n=21); 2) with moderate PH (n=23); 3) with severe PH (n=19). Moderate PH was defined as a systolic pulmonary artery pressure (SPAP)≥40 mmHg assessed by Doppler echocardiography, severe PH - as SPAP≥55 mmHg. There was an increase in the plasma levels of CRP and fibrinogen in all patients with COPD with statistically significant intra-gpoup differences (p1-2=0.001, p2-3=0.001, p1-3=0.001; p1-2=0.05, p2-3=0.001, p1-3=0.006). Close correlations between SPAP and plasma concentrations of CRP (r=0.74,r=0.05) and fibrinogen (r=0.84,r=0,03) were shown. The area under the ROC curve in COPD and moderate PH for CRP was 0.884 (p 21.5 mg/ml and >4.05 g/l, respectively; for severe PH: >23.5 mg/ml and >5.2 g/l, respectively. In patients with COPD and PH there were positive corelations of plasma CRP and fibrinogen levels with SPAP. Plasma levels of CRP and fibrinigen coud be used to predict PH in COPD patients with good sensitive and specificity.