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INTRODUCTION: Since the early pandemic, prone positioning (PP) has been broadly utilized for non-intubated COVID-19 patients, but results from recently published randomized controlled trials (RCTs) are contradictory. We aimed to systematically synthesize the outcomes associated with PP for non-intubated COVID-19 patients. METHOD(S): Two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, and ClinicalTrials.gov for RCTs of PP in nonintubated adult patients with COVID-19 and published in English from January 1st, 2020 to July 1st, 2022. The same two independent groups extracted the data and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies and the GRADE approach to assess certainty/quality of the evidence. The primary outcome was the reported cumulative intubation risk, while secondary outcomes included mortality, need for escalating respiratory support, hospital length of stay, ICU admission, and adverse events. The study protocol was prospectively registered with PROSPERO, CRD42022343625. RESULT(S): 12 RCTs with 2,886 patients were included. For non-intubated COVID-19 patients, PP significantly reduced the intubation risk (risk ratio [RR] 0.85, 95%CI 0.75 to 0.96), compared to supine position. Subgroup analysis showed a significant reduction in intubation risk among patients supported by high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) (RR 0.83, 95%CI 0.73 to 0.94) but not in patients with conventional oxygen therapy (RR 1.02, 95%CI 0.67 to 1.56). No significant reduction was seen in mortality (RR 0.96, 95%CI 0.82 to 1.13), need for escalating respiratory support (RR 1.03, 95%CI 0.77 to 1.37), hospital length of stay (MD 0.35 days, 95%CI -0.57 to 1.26), ICU admission (RR 0.75, 95%CI 0.51 to 1.10), and adverse events. No obvious risk of bias and publication bias was found for the primary outcome. CONCLUSION(S): In non-intubated COVID-19 patients, PP reduced the need for intubation, in particular among those requiring respiratory support with HFNC or NIV, but did not reduce mortality, need for escalating respiratory support, hospital length of stay, and ICU admission.
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S44 Table 1Summary of significant medical events, thoracic computed tomography (CT) and pulmonary function tests (PFTs) in ORBCEL-C and placebo groups at 1 year follow upORBCEL-C Placebo Number of patients followed up 20 21 Significant medical events Number of patients with SMEs 6/20 9/21 Total SME events 7 11 Classification Respiratory,thoracic and mediastinal disorders 4 6 Neoplasm - benign, malignant, unspecified 1 0 Infections and infestations 1 1 Cardiac disorders 1 0 Metabolism and nutrition disorders 0 1 Injury, poisoning and procedural complications 0 1 Renal and urinary disorders 0 1 Gastrointestinal disorders 0 1 Thoracic CT Number of CTs available 5 8 Time to CT (Median, IQR) 181 (157–198) 203 (95–233) Evidence of ILD on CT 4 6 PFTs Number of PFTs available 10 8 Time to PFTs (Median, IQR) 184.5 (117.5–292.75) 203.5 (118.25–242.5) FEV1 (Mean, SD) 84.9 (13.6) 80.5 (13.3) FEV1 <80% predicted (n,%) 4/10 (44%) 4/8 (50%) FVC (Mean, SD) 78.4 (13.2) 79.3 (16.5) FVC <80% predicted (n,%) 5/10 (55%) 5/8 (62.5%) FEV1/FVC ratio (Mean, SD, n) 0.88 (0.12) N=8 0.76 (0.05) N=5 FEV1/FVC <0.7 (n,%) 0 (0%) 0 (0%) TLCO (Mean, SD, n) 78.9 (14.8) N=9 61.9 (13.4) N=7 TLCO <80% (n,%) 6/9 (66.7%) 7/7 (100%) ConclusionsOne year follow up supports the safety of ORBCEL-C MSCs in patients with moderate to severe ARDS due to COVID-19. A similar incidence of pulmonary dysfunction is reported in both groups at long term follow up.Please refer to page A?? for declarations of interest related to this .
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Acute respiratory distress syndrome (ARDS) is a critical illness characterized by a severe hypoxemic respiratory failure, caused by an inflammatory response which results in diffuse lung damage. Despite decades of research, the treatment of ARDS remains supportive. However, in recent years, cell-based therapies have been the subject of intensive ongoing research efforts, showing relevant therapeutic potential in preclinical ARDS models. Among all the different cells that have been identified as suitable candidates for use, mesenchymal stromal cells (MSCs) have been the most attractive candidates and have generated significant interest. MSCs are multipotent adult stem/stromal cells that can modulate the immune response and enhance repair of damaged tissue in multiple in vivo models. Their promising effect seems to be not primarily mediated by MSCs differentiation and engraftment but more by the paracrine release of different soluble mediators and cellular components such as extracellular vesicles (EVs). Preclinical experiments have provided encouraging evidence for the therapeutic potential of MSCs, leading to the launch of several phase I and II clinical trials that have shown safety of MSCs in ARDS, which became very common nowadays due to the Coronavirus disease (COVID-19) pandemic. However, some translational challenges have yet to be solved, such as the reproducibility of cell harvest, storage, reconstitution, and administration of cells/cell-products, before the therapeutic potential of stem cells therapies can be realized. ©2022 The Author(s). Published by MRE Press.
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Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to 'licence' or 'pre-activate' these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.
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Introduction: The AFTERCOR study was developed by the COVID-19 Critical Care Consortium (>7000 intensive care unit [ICU] and >400 extracorporeal membrane oxygenation [ECMO] patients currently) to enhance understanding of occurrence and progression of long-term dysfunction post-COVID-19. Design: Prospective longitudinal (24 months) study of ICU survivors of COVID-19 to describe recovery of the following aspects: a) health-related quality of life b) dynamics of organ dysfunction and recovery and c) pulmonary function. Countries involved Italy, Spain, Ireland, Austria, South Africa, Australia, USA, Argentina, Brazil, Colombia. Protocol specifics available at https://www.aftercorstudy.com. Inclusion Criteria: 1) COVID-19 infection requiring ICU admission;2) informed consent;3) age ≥18 years. Exclusion Criteria: 1) pregnancy;2) pre-COVID paralysis;3) history of pulmonary resection;4) prior lung transplant;5) inability to perform 6-min walk test or participate in interview. Methods: Goal enrollment is 1000 patients. Follow-up visits are at 3, 6, 12, 18 and 24-month post-ICU discharge. Assessments include: 1) Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36);2) Montreal Cognitive Assessment;3) any subsequent admission 4) St. George's Respiratory Questionnaire;5) Pulmonary function testing;6) chest radiography;7) 6-minute-walk test;8) Patient Health Questionnaire 9 (PHQ-9) and 9) full blood count and biochemistry. CT chest at 6 months and repeat ECHO at 3, 12 and 24 months if performed during COVID-19 hospitalization. If results are normal, subsequent testing will not be performed. Summary: The AFTERCOR study represents a comprehensive evaluation for long-term effects from COVID-19. Interested centers are sought and invited to participate.
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This paper reports on the progress in the project COVIGILANT, which is aimed at developing an evaluation taxonomy for Contact Tracing Applications (CTAs) for COVID-19. Specifically, this article describes the development of Usability, one pillar of the COVIGILANT taxonomy, discussing the classification and decision-making processes, and the initial model validation. The validation process was undertaken in two stages. First, we validated how the Usability pillar could be used to evaluate the Irish Health Services Executive (HSE) COVID-19 CTA. While this supported many of the attributes that we had within the Usability pillar, it also identified issues. We made amendments based on these, and undertook a second study, this time evaluating 4 CTAs used in other countries. This has led to the completion of the Usability pillar, which can now be used to evaluate global CTAs.
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Rationale Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous smallcase series or studies conducted at a national level.Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe the impact of CRS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two CRS groups. CRS was calculated as: tidal volume/[airway plateau pressure-positive endexpiratory pressure (PEEP)] and available within 48h from commencement of MV in 318 patients. Patients were mean±SD of 58.0±12.2, predominantly from Europe (54%) and males (68%). Median CRS (IQR) was 34.1 mL/cmH2O (26.5-45.5) and PaO2/FiO2 was 119 mmHg (87.1-164) and was not correlated with CRS. Female sex presented lower CRS than in males (95% CI:-13.8 to-8.5 P<0.001) and higher body mass index (34.7±10.9 vs 29.1±6.0, p<0.001). Median (IQR) PEEP was 12 cmH2O (10-15), throughout the range of CRS, while median (IQR) driving pressure was 12.3 (10-15) cmH2O and significantly decreased as CRS improved (p<0.001). No differences were found in comorbidities and clinical management between CRS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between CRSgroups.Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV-predominantly males or overweight females, in their late 50s-admitted to ICU during the first international outbreaks. Phenotypes associated with different CRS upon commencement of MV could not be identified.
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Rationale: Patients with COVID-19 commonly develop severe hypoxemic respiratory failure and require invasive mechanical ventilation (MV). The disease burden and predictors of mortality in this population remain uncertain. Methods: Prospective observational cohort study from 139 intensive care units of the international COVID-19 Critical Care Consortium. Patients enrolled from January 14th through November 31st 2020 were included in the analysis. Patient's characteristics and clinical data were assessed. Multivariable Cox proportional hazards analysis was conducted to identify indipendent predictors of mortality within 28 days from commencement of MV. Results: 1578 patients on MV were included into the analysis. Mean±SD age was 59 years±13 and patients were predominantly males (66%). 542 Patients (34.4%) died within 28 days from commencement of MV. Nonsurvivors were slightly older (mean age±SD 62±13 vs. 59±13) and presented more frequently hypertension, chronic cardiac disease and diabetes. Median (IQR) PaO2/FiO2 upon commencement of MV was 96 (68-135) and 111 (81-173) in patients who did not survive vs. survivors, respectively (p=0.04). ECMO (13% vs 25%, p<0.01), inhaled nitric oxide (11% vs 15%, p=0.02) and recruitment manoeauvres (26% vs 31%, p<0.01) were used less frequently in patients who did not survive. Independent risk factors associated with 28-day mortality included age older than 70 years (hazard ratio [HR], 2.83;95% CI, 1.32-6.07), higher creatinine levels upon ICU admission (HR, 1.20;95% CI, 1.03-1.40), and lower pH within 24h from commencement of MV (HR, 0.12;95% CI, 0.02-0.62), while a shorter period (day) from early symptoms to hospitalisation reduced mortality risks (HR, 0.96;95% CI, 0.93-0.99). Conclusions: Our findings from a large international cohort of critically-ill COVID-19 patients on mechanical ventilation emphasises that elderly patients, not promptly admitted to the hospital, and who present higher creatinine levels and acidosis are at higher risk of mortality.
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Recent estimates suggest that up to 34% of frontline workers in healthcare (FLWs) at the forefront of the COVID-19 pandemic response are reporting elevated symptoms of psychological distress due to resource constraints, ineffective treatments, and concerns about self-contamination. However, little systematic research has been carried out to assess the mental health needs of FLWs in Europe, or the extent of psychological suffering in FLWs within different European countries of varying outbreak severity. Accordingly, this project will employ a mixed-methods approach over three work packages to develop best-practice guidelines for alleviating psychological distress in FLWs during the different phases of the pandemic. Work package 1 will identify the point and long-term prevalence of psychological distress symptoms in a sample of Irish and Italian FLWs, and the predictors of these symptoms. Work package 2 will perform a qualitative needs assessment on a sample of Irish and Italian FLWs to identify sources of stress and resilience, barriers to psychological care, and optimal strategies for alleviating psychological distress in relation to the COVID-19 pandemic. Work package 3 will synthesise the findings from the preceding work packages to draft best practice guidelines, which will be co-created by a multidisciplinary panel of experts using the Delphi method. The guidelines will provide clinicians with a framework for alleviating psychological distress in FLWs, with particular relevance to the COVID-19 pandemic, but may also have relevance for future pandemics and other public health emergencies.
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Bacterial infection remains the main cause of acute respiratory distress syndrome and is a leading cause of death and disability in critically ill patients. Here we report on the use of purified ß-glucan (lentinan) extracts from Lentinus edodes (Shiitake) mushroom that can reduce infection by a multidrug-resistant clinical isolate of Klebsiella pneumoniae in a rodent pneumonia model, likely through immunomodulation. Adult male Sprague-Dawley rats were subjected to intra-tracheal administration of K. pneumoniae to induce pulmonary sepsis and randomized to three groups; vehicle control (Vehicle, n = 12), commercial lentinan (CL, n = 8) or in-house extracted lentinan (IHL, n = 8) were administered intravenously 1 h postinfection. Physiological parameters and blood gas analysis were measured, bacterial counts from bronchoalveolar-lavage (BAL) were determined, along with differential staining of white cells and measurement of protein concentration in BAL 48 h after pneumonia induction. Use of IHL extract significantly decreased BAL CFU counts. Both CL and IHL extractions reduced protein concentration in BAL. Use of IHL resulted in an improvement in physiological parameters compared to controls and CL. In conclusion, administration of lentinan to treat sepsis-induced lung injury appears safe and effective and may exert its effects in an immunomodulatory manner.