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      Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium

      review-article
      1 , * , , 1 , 1 , 2 , 1 , 1 , 2 , 3 , 3 , 4 , 5 , 5 , 6 , 6 , 7 , 8 , 7 , 8 , 9 , 10 , 10 , 11 , 12 , 12 , 13 , 14 , 15 , 16 , 6 , 17 , 18 , 18 , 18 , 18 , 19 , 18
      Frontiers in Medicine
      Frontiers Media S.A.
      COVID-19, bronchoalveolar lavage, interstitial pneumonia, infections, interventional pulmonology

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          Abstract

          Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

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          Most cited references64

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          COVID-19: consider cytokine storm syndromes and immunosuppression

          As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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            Detection of SARS-CoV-2 in Different Types of Clinical Specimens

            This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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              Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

              Background Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.
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                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                02 February 2024
                2024
                : 11
                : 1259570
                Affiliations
                [1] 1Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital , Florence, Italy
                [2] 2Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital , Florence, Italy
                [3] 3Department of Diseases of the Thorax, GB Morgagni Hospital , Forlì, Italy
                [4] 4Respiratory Department, Hospital de la Santa Creu i Sant Pau , Barcelona, Spain
                [5] 5Division of Allergy, Pulmonary and Critical Care Medicine, Department of Thoracic Surgery, Vanderbilt University Medical Center , Nashville, TN, United States
                [6] 6Department of Experimental and Clinical Medicine, University of Florence , Florence, Italy
                [7] 7Department of Experimental Medicine, University of Florence , Florence, Italy
                [8] 8Microbiology and Virology Unit, Florence Careggi University Hospital , Florence, Italy
                [9] 9Internal Medicine Unit 1, AOU Careggi , Florence, Italy
                [10] 10Internal Medicine Unit 2, AOU Careggi , Florence, Italy
                [11] 11Department of Health Science, Clinical Innovations and Research Unit, Careggi University Hospital , Florence, Italy
                [12] 12Infectious and Tropical Diseases Unit, Department of Experimental and Clinical Medicine, University of Florence , Florence, Italy
                [13] 13School of Biological Sciences, The University of Manchester , Manchester, United Kingdom
                [14] 14Department of Respiratory, Lancashire Teaching Hospital NHS Foundation Trust , Preston, United Kingdom
                [15] 15Interventional Pulmonology Unit, University Hospital Riuniti di Ancona , Ancona, Italy
                [16] 16Department of Experimental and Clinical Medicine Section of Surgery, Histopathology, and Molecular Pathology, University of Florence , Florence, Italy
                [17] 17Department of Clinical and Experimental Biomedical Sciences, University of Florence , Florence, Italy
                [18] 18Department of Respiratory Medicine, Universitary Hospital of Liège , Liège, Belgium
                [19] 19Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, University of Florence , Florence, Italy
                Author notes

                Edited by: Paschalis Steiropoulos, Democritus University of Thrace, Greece

                Reviewed by: Ilias C. Papanikolaou, General Hospital of Corfu, Greece; Maria D. I. Manunta, ASL Nuoro, Italy; Vasilios Tzilas, Sotiria General Hospital, Greece

                *Correspondence: Sara Tomassetti, s.tomassetti@ 123456gmail.com
                Article
                10.3389/fmed.2024.1259570
                10869531
                25df2ec9-c1df-493c-b7ae-26ce898f8f89
                Copyright © 2024 Tomassetti, Ciani, Luzzi, Gori, Trigiani, Giuntoli, Lavorini, Poletti, Ravaglia, Torrego, Maldonado, Lentz, Annunziato, Maggi, Rossolini, Pollini, Para, Ciurleo, Casini, Rasero, Bartoloni, Spinicci, Munavvar, Gasparini, Comin, Cerinic, Peired, Henket, Ernst, Louis, Corhay, Nardi and Guiot.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 July 2023
                : 09 January 2024
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 64, Pages: 11, Words: 10098
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Medicine
                Review
                Custom metadata
                Pulmonary Medicine

                covid-19,bronchoalveolar lavage,interstitial pneumonia,infections,interventional pulmonology

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