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      VENTILATORY ASSOCIATED BAROTRAUMA IN COVID-19 PATIENTS: A MULTICENTER OBSERVATIONAL CASE CONTROL STUDY (COVI-MIX-STUDY).

      research-article
      a , b , * , c , c , d , e , f , g , h , i , l , m , n , o , p , q , a , r , s , t , u , v , w , o , x , y , z , 1 , 2 , 3 , 3 , d , c , the Italian COVI-MIX Study Group a
      Pulmonology
      Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U.
      COVID-19, acute respiratory failure, barotrauma, pneumothorax, High Flow Nasal Cannula, Invasive Mechanical Ventilation, C-PAP, continuous positive airway pressure, PSV, pressure support ventilation, COT, conventional oxygen therapy, HFNO, high flow nasal oxygen, C-ARDS, coronavirus acute respiratory distress syndrome, ICU, intensive care unit, NIV, non-invasive ventilation, IMV, invasive mechanical ventilation, NIRS, non invasive respiratory support, P-SILI, patients self-inflicted lung injury, VILI, ventilator induced lung injury, PNX, pneumothorax, PMD, pneumomediastinum, qCSI, Quick COVID-19 Severity Index, ECMO, Extra-Corporeal Membrane Oxygenation, HRCT, high-resolution computed tomography

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          Abstract

          Background

          The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication.

          Methods

          This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death.

          Results

          We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001).

          Conclusions

          C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality.

          Trial registration

          this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

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          Most cited references47

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          Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

          Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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            Dysregulation of immune response in patients with COVID-19 in Wuhan, China

            Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Methods Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. Results Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. Conclusions The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
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              Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

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                Author and article information

                Journal
                Pulmonology
                Pulmonology
                Pulmonology
                Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U.
                2531-0429
                2531-0437
                24 November 2022
                24 November 2022
                Affiliations
                [5 ]Division of Infectious Diseases, Departments of Medicine, Hospital Santa Croce e Carle, Cuneo, Italy
                [6 ]Anesthesia and Intensive Care, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
                [7 ]Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy
                [8 ]Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola, Bologna, Italy
                [9 ]Respiratory Disease and Lung Function Unit, Departments of Medicine and Surgery, University of Parma, Parma, Italy
                [12 ]Department of Medical Sciences, University of Turin, Infectious Diseases, City of Health and Sciences, Turin, Italy
                [13 ]Infectious Diseases Unit, Cardinal Massaia Hospital, Asti, Italy
                [14 ]Division of Infectious Diseases, Department of Medicine, Hospital Santa Croce e Carle, Cuneo, Italy
                [15 ]Pulmonary Medicine Unit, Lodi General Hospital, Lodi
                [16 ]Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
                [17 ]Infectious Diseases Division, Diagnostics and Public Health Department, University of Verona, Verona, Italy
                [18 ]Department of Infectious Diseases "Santa Maria della Misericordia" Hospital, University of Perugia, Perugia, Italy
                [19 ]Anaesthesia and Intensive Care, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
                [20 ]Azienda USL Toscana Nord Ovest, U.O. Medicina Interna, Felice Lotti Hospital, Pontedera, Pisa, Toscana, Italy
                [21 ]Department of Clinical, Integrated and Experimental Medicine (DIMES), University of Bologna, Bologna, Italy
                [22 ]Respiratory and Critical Care Unit, Sant Orsola University Hospital, Bologna, Italy
                [23 ]UOC Malattie Infettive ad Indirizzo Neurologico, AORN Ospedali dei Colli, P.O. "D. Cotugno", Naples, Italy
                [24 ]Respiratory Disease Unit, "Santa Maria degli Angeli" Hospital, Pordenone, Italy
                [25 ]Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
                [# ]University Hospital of Perugia, S. Andrea delle Fratte, Perugia, Italy
                [$ ]Department of Pulmonology, University Hospital of Cattinara., Trieste, Italy
                [^ ]Institute of Anaesthesia and Intensive Care., Padua University Hospital, Padua, Italy
                [+ ]Department of Health Sciences, University of Genoa., Genoa, Italy
                [& ]Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma., Parma, Italy
                []Institute of Anaesthesia and Intensive Care, Padua University Hospital., Padua, Italy
                []Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy
                []Department of Medicine and Surgery., Universiy of Perugia, Perugia, Italy
                []Department of Medicine, University of Udine, Udine, Italy
                []Department of Anesthesia and Intensive Care, Health Integrated Agency of Friuli Centrale, Udine, Italy
                []U.O. Medicina Interna, Felice Lotti Hospital, Pontedera, Azienda USL Toscana Nord-Ovest, Italy
                [a ]Department of Anesthesiology, Critical Care Medicine and Emergency, SS. Annunziata Hospital, Chieti, Italy
                [b ]Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy
                [c ]Pulmonology unit, Department of Cardiothoracic Surgery, Health Integrated Agency of Friuli Centrale, Udine, Italy
                [d ]Department of Anesthesia and Intensive Care., Health Integrated Agency of Friuli Centrale, Udine, Italy
                [e ]Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy
                [f ]Department of Anesthesia Intensive Care and Emergency. Policlinico Paolo Giaccone, Palermo, Italy
                [g ]Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
                [h ]Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, AOUP-Pisa, Italy
                [i ]University Hospital of Perugia., S. Andrea delle Fratte, Perugia, Italy
                [l ]Department of Medicine and Surgery, Universiy of Perugia, Perugia, Italy
                [m ]Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy
                [n ]Department of Anesthesia, Emergency and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
                [o ]Department of Medicine., University of Udine, Udine, Italy
                [p ]Institute of Anaesthesia and Intensive Care, Padua University Hospital, Padua, Italy
                [q ]Department of Medicine (DIMED), University of Padua, Padua, Italy
                [r ]Department of Innovative Technologies in Medicine and Dentistry, Gabriele d'Annunzio University of Chieti Pescara, Chieti, Italy
                [s ]Infectious Diseases Unit, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
                [t ]Department of Health Sciences, University of Genoa, Genoa, Italy
                [u ]Respiratory Disease and Lung Function Unit., Department of Medicine and Surgery, University of Parma, Parma, Italy
                [v ]Department of Pulmonology., University Hospital of Cattinara, Trieste, Italy
                [w ]University of Trieste, Trieste, Italy
                [x ]Pneumologia E Unità Di Terapia Semi Intensiva Respiratoria, AO Umberto I Mauriziano, Turin, Italy
                [y ]Department of Infectious Diseases "Santa Maria della Misericordia" Hospital., University of Perugia, Perugia, Italy
                [z ]Infectious Disease Unit, University Hospital of Trieste, Trieste, Italy
                [1 ]U.O. Medicina Interna, Felice Lotti Hospital., Pontedera, Azienda USL Toscana Nord-Ovest, Italy
                [2 ]Respiratory High Dependency Unit - General Hospital Lodi, Lodi, Italy
                [3 ]Infectious Diseases Division, Health Integrated Agency of Friuli Centrale, Udine, Italy
                Author notes
                [* ]Corresponding author: Luigi Vetrugno, Associate Professor, Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini n 33, 66100, Chieti, Italy
                Article
                S2531-0437(22)00260-4
                10.1016/j.pulmoe.2022.11.002
                9684110
                36669936
                a91c9659-aadc-4c87-8bc0-15dbe5136d4d
                © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 28 July 2022
                : 25 October 2022
                : 2 November 2022
                Categories
                Original Article

                covid-19,acute respiratory failure,barotrauma,pneumothorax,high flow nasal cannula,invasive mechanical ventilation,c-pap, continuous positive airway pressure,psv, pressure support ventilation,cot, conventional oxygen therapy,hfno, high flow nasal oxygen,c-ards, coronavirus acute respiratory distress syndrome,icu, intensive care unit,niv, non-invasive ventilation,imv, invasive mechanical ventilation,nirs, non invasive respiratory support,p-sili, patients self-inflicted lung injury,vili, ventilator induced lung injury,pnx, pneumothorax,pmd, pneumomediastinum,qcsi, quick covid-19 severity index,ecmo, extra-corporeal membrane oxygenation,hrct, high-resolution computed tomography

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