[en] 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.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Tomassetti, Sara; Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Ciani, Luca; Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Luzzi, Valentina; Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Gori, Leonardo; Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Trigiani, Marco; Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Giuntoli, Leonardo; Interventional Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Lavorini, Federico; Pulmonology Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
Poletti, Venerino; Department of Diseases of the Thorax, GB Morgagni Hospital, Forlì, Italy
Ravaglia, Claudia; Department of Diseases of the Thorax, GB Morgagni Hospital, Forlì, Italy
Torrego, Alfons; Respiratory Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Maldonado, Fabien; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
Lentz, Robert; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
Annunziato, Francesco; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Maggi, Laura; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Rossolini, Gian Maria; Department of Experimental Medicine, University of Florence, Florence, Italy ; Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy
Pollini, Simona; Department of Experimental Medicine, University of Florence, Florence, Italy ; Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy
Para, Ombretta; Internal Medicine Unit 1, AOU Careggi, Florence, Italy
Ciurleo, Greta; Internal Medicine Unit 2, AOU Careggi, Florence, Italy
Casini, Alessandro; Internal Medicine Unit 2, AOU Careggi, Florence, Italy
Rasero, Laura; Department of Health Science, Clinical Innovations and Research Unit, Careggi University Hospital, Florence, Italy
Bartoloni, Alessandro; Infectious and Tropical Diseases Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Spinicci, Michele; Infectious and Tropical Diseases Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Munavvar, Mohammed; School of Biological Sciences, The University of Manchester, Manchester, United Kingdom ; Department of Respiratory, Lancashire Teaching Hospital NHS Foundation Trust, Preston, United Kingdom
Gasparini, Stefano; Interventional Pulmonology Unit, University Hospital Riuniti di Ancona, Ancona, Italy
Comin, Camilla; Department of Experimental and Clinical Medicine Section of Surgery, Histopathology, and Molecular Pathology, University of Florence, Florence, Italy
Cerinic, Marco Matucci; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Peired, Anna; Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy
Wahidi MM Lamb C Murgu S Musani A Shojaee S Sachdeva A et al. American Association for Bronchology and Interventional Pulmonology (AABIP) statement on the use of bronchoscopy and respiratory specimen collection in patients with suspected or confirmed COVID-19 infection. J Bronchology Interv Pulmonol. (2020) 27:e52–4. doi: 10.1097/LBR.0000000000000681, PMID: 32195687
Meyer KC. Bronchoalveolar lavage as a diagnostic tool. Semin Respir Crit Care Med. (2007) 28:546–60. doi: 10.1055/s-2007-991527
Poletti V Chilosi M Olivieri D. Diagnostic invasive procedures in diffuse infiltrative lung diseases. Respiration. (2004) 71:107–19. doi: 10.1159/000076670
Costabel U Guzman J. Bronchoalveolar lavage in interstitial lung disease. Curr Opin Pulm Med. (2001) 7:255–61. doi: 10.1097/00063198-200109000-00002
Tomassetti S Colby TV Wells AU Poletti V Costabel U Matucci-Cerinic M. Bronchoalveolar lavage and lung biopsy in connective tissue diseases, to do or not to do? Ther Adv Musculoskelet Dis. (2021) 13:1759720X2110596. doi: 10.1177/1759720X211059605
Clerici B Muscatello A Bai F Pavanello D Orlandi M Marchetti GC et al. Sensitivity of SARS-CoV-2 detection with nasopharyngeal swabs. Front Public Health. (2020) 8:593491. doi: 10.3389/fpubh.2020.593491
Wang W Xu Y Gao R Lu R Han K Wu G et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. (2020) 323:1843–4. doi: 10.1001/jama.2020.3786, PMID: 32159775
Kucirka LM Lauer SA Laeyendecker O Boon D Lessler J. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med. (2020) 173:262–7. doi: 10.7326/M20-1495, PMID: 32422057
Ai T Yang Z Hou H Zhan C Chen C Lv W et al. Correlation of chest CT and RT-PCR testing for coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. (2020) 296:E32–40. doi: 10.1148/radiol.2020200642, PMID: 32101510
Fang Y Zhang H Xie J Lin M Ying L Pang P et al. Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. (2020) 296:E115–7. doi: 10.1148/radiol.2020200432, PMID: 32073353
Khatami F Saatchi M Zadeh SST Aghamir ZS Shabestari AN Reis LO et al. A meta-analysis of accuracy and sensitivity of chest CT and RT-PCR in COVID-19 diagnosis. Sci Rep. (2020) 10:22402. doi: 10.1038/s41598-020-80061-2, PMID: 33372194
Guiot J Vaidyanathan A Deprez L Zerka F Danthine D Frix AN et al. Development and validation of an automated radiomic CT signature for detecting COVID-19. Diagnostics (Basel). (2020) 11:41. doi: 10.3390/diagnostics11010041
Darwiche K Ross B Gesierich W Petermann C Huebner RH Grah C et al. Recommendations for performing bronchoscopy in times of the COVID-19 pandemic – update 12/2020. Pneumologie. (2021) 75:187–90. doi: 10.1055/a-1320-8250, PMID: 33307556
Pritchett MA Oberg CL Belanger A Cardenas JD Cheng G Nacheli GC et al. Society for advanced bronchoscopy consensus statement and guidelines for bronchoscopy and airway management amid the COVID-19 pandemic. J Thorac Dis. (2020) 12:1781–98. doi: 10.21037/jtd.2020.04.32, PMID: 32642084
Luo F Darwiche K Singh S Torrego A Steinfort DP Gasparini S et al. Performing bronchoscopy in times of the COVID-19 pandemic: practice statement from an international expert panel. Respiration. (2020) 99:417–22. doi: 10.1159/000507898, PMID: 32344422
Guedes F Boléo-Tomé JP Rodrigues LV Bastos HN Campainha S de Santis M et al. Recommendations for interventional pulmonology during COVID-19 outbreak: a consensus statement from the Portuguese Pulmonology Society. Pulmonology. (2020) 26:386–97. doi: 10.1016/j.pulmoe.2020.07.007, PMID: 32868252
Lentz RJ Colt H. Summarizing societal guidelines regarding bronchoscopy during the COVID-19 pandemic. Respirology. (2020) 25:574–7. doi: 10.1111/resp.13824, PMID: 32277733
Saha BK Saha S Chong WH Beegle S. Indications, clinical utility, and safety of bronchoscopy in COVID-19. Respir Care. (2022) 67:241–51. doi: 10.4187/respcare.09405
Agrawal S Goel AD Gupta N Gonuguntla HK Colt H. A systematic review and metanalysis of diagnostic yield of BAL for detection of SARS-CoV-2. Heart Lung. (2021) 52:95–105. doi: 10.1016/j.hrtlng.2021.11.011
Liu R Han H Liu F Lv Z Wu K Liu Y et al. Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020. Clin Chim Acta. (2020) 505:172–5. doi: 10.1016/j.cca.2020.03.009, PMID: 32156607
Turriziani O Sciandra I Mazzuti L di Carlo D Bitossi C Calabretto M et al. SARS-CoV-2 diagnostics in the virology laboratory of a University Hospital in Rome during the lockdown period. J Med Virol. (2021) 93:886–91. doi: 10.1002/jmv.26332, PMID: 32697357
Ramos KJ Kapnadak SG Collins BF Pottinger PS Wall R Mays JA et al. Detection of SARS-CoV-2 by bronchoscopy after negative nasopharyngeal testing: stay vigilant for COVID-19. Respir Med Case Rep. (2020) 30:101120. doi: 10.1016/j.rmcr.2020.101120, PMID: 32566476
de Clercq J Malfait T Malfait S Boelens J Coorevits L Padalko E et al. Diagnosing COVID-19; towards a feasible COVID-19 rule-out protocol. Acta Clin Belg. (2021) 77:368–76. doi: 10.1080/17843286.2021.1883362, PMID: 33586631
Taton O Papleux E Bondue B Knoop C van Laethem S Bauler A et al. Role of the bronchoalveolar lavage in noncritically Ill patients during the SARS-CoV-2 epidemic. Pulm Med. (2020) 2020:1–9. doi: 10.1155/2020/9012187
Mondoni M Sferrazza Papa GF Rinaldo R Faverio P Marruchella A D'Arcangelo F et al. Utility and safety of bronchoscopy during the SARS-CoV-2 outbreak in Italy: a retrospective, multicentre study. Eur Respir J. (2020) 56:2002767. doi: 10.1183/13993003.02767-2020, PMID: 32859682
Patrucco F Albera C Bellocchia M Foci V Gavelli F Castello LM et al. SARS-CoV-2 detection on bronchoalveolar lavage: an Italian multicenter experience. Respiration. (2020) 99:970–8. doi: 10.1159/000511964, PMID: 33075793
Barberi C Castelnuovo E Dipasquale A Mrakic Sposta F Vatteroni G Canziani LM et al. Bronchoalveolar lavage in suspected COVID-19 cases with a negative nasopharyngeal swab: a retrospective cross-sectional study in a high-impact Northern Italy area. Intern Emerg Med. (2021) 16:1857–64. doi: 10.1007/s11739-021-02714-y, PMID: 33770367
Geri P Salton F Zuccatosta L Tamburrini M Biolo M Busca A et al. Limited role for bronchoalveolar lavage to exclude COVID-19 after negative upper respiratory tract swabs: a multicentre study. Eur Respir J. (2020) 56:2001733. doi: 10.1183/13993003.01733-2020, PMID: 32764117
Ora J Puxeddu E Cavalli F Giorgino FM Girolami A Chiocchi M et al. Does bronchoscopy help the diagnosis in COVID-19 infection? Eur Respir J. (2020) 56:2001619. doi: 10.1183/13993003.01619-2020
Vannucci J Ruberto F Diso D Galardo G Mastroianni CM Raponi G et al. Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease. J Glob Antimicrob Resist. (2020) 23:67–9. doi: 10.1016/j.jgar.2020.07.030, PMID: 32810641
Oberg CL Ronaghi R Folch EE Channick CL He T Susanto I et al. Pre-procedural COVID-19 nasopharyngeal swab has good concordance with bronchoalveolar lavage in patients at low risk for viral infection. Respiration. (2021) 100:510–4. doi: 10.1159/000514928
Chang J Swenson KE Sung A Bedi H. Coronavirus disease 2019 test correlation between nasopharyngeal swab and BAL in asymptomatic patients. Chest. (2021) 159:2488–90. doi: 10.1016/j.chest.2020.11.006, PMID: 33217415
Pickens CO Gao CA Cuttica MJ Smith SB Pesce LL Grant RA et al. Bacterial superinfection pneumonia in patients mechanically ventilated for COVID-19 pneumonia. Am J Respir Crit Care Med. (2021) 204:921–32. doi: 10.1164/rccm.202106-1354OC, PMID: 34409924
Guarino C Cesaro C Fiorentino G Rossi F Polverino BM Fragranza F et al. Bronchoscopy in COVID-19 patients: when, how and why. Experience in clinical practice. Monaldi Arch Chest Dis. (2021) 91:91. doi: 10.4081/monaldi.2021.1744
Arenas-de Larriva M Martín-DeLeon R Urrutia Royo B Fernández-Navamuel I Gimenez Velando A Nuñez García L et al. The role of bronchoscopy in patients with SARS-CoV-2 pneumonia. ERJ Open Res. (2021) 7:00165–2021. doi: 10.1183/23120541.00165-2021, PMID: 34258257
Mehta R Bansal S Kumar A Thorbole A Chakravarthi L Kalpakam H. Bronchoscopy in COVID19 ARDS patients on mechanical ventilation – a prospective study. med Rxiv. (2021)
Yang Y Yang M Yuan J Wang F Wang Z Li J et al. Laboratory diagnosis and monitoring the viral shedding of SARS-CoV-2 infection. Innovation (N Y). (2020) 1:100061. doi: 10.1016/j.xinn.2020.100061
Gao CA Cuttica MJ Malsin ES Argento AC Wunderink RG Smith SB et al. Comparing nasopharyngeal and BAL SARS-CoV-2 assays in respiratory failure. Am J Respir Crit Care Med. (2021) 203:127–9. doi: 10.1164/rccm.202008-3137LE, PMID: 33125256
Mahmood K Abbott M van Nostrand K Bechara R Gonzalez AV Brucker A et al. Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience. BMJ Open Respir Res. (2021) 8:8. doi: 10.1136/bmjresp-2021-000962, PMID: 34301713
Baron A Hachem M Tran van Nhieu J Botterel F Fourati S Carteaux G et al. Bronchoalveolar lavage in patients with COVID-19 with invasive mechanical ventilation for acute respiratory distress syndrome. Ann Am Thorac Soc. (2021) 18:723–6. doi: 10.1513/AnnalsATS.202007-868RL, PMID: 33233944
Mangioni D Panigada M Palomba E Bobbio C Chatenoud L Alagna L et al. Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study. Crit Care. (2023) 27:369. doi: 10.1186/s13054-023-04658-5, PMID: 37749631
Fabbri L Moss S Khan FA Chi W Xia J Robinson K et al. Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis. Thorax. (2023) 78:191–201. doi: 10.1136/thoraxjnl-2021-218275, PMID: 35338102
Kumar K Ratnakumar R Collin SM Berrocal-Almanza LC Ricci P al-Zubaidy M et al. Chest CT features and functional correlates of COVID-19 at 3 months and 12 months follow-up. Clin Med (Lond). (2023) 23:467–77. doi: 10.7861/clinmed.2023-0059, PMID: 37775167
Ravaglia C Doglioni C Chilosi M Piciucchi S Dubini A Rossi G et al. Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection. Eur Respir J. (2022) 60:2102411. doi: 10.1183/13993003.02411-2021, PMID: 35301248
Graziani L Gori L Manciulli T Basile G Campolmi I Borchi B et al. Successful use of nirmatrelvir/ritonavir in immunocompromised patients with persistent and/or relapsing COVID-19. J Antimicrob Chemother. (2023) 78:555–8. doi: 10.1093/jac/dkac433, PMID: 36544352
Meyer KC Raghu G Baughman RP Brown KK Costabel U du Bois RM et al. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med. (2012) 185:1004–14. doi: 10.1164/rccm.201202-0320ST, PMID: 22550210
Vanbellinghen MC Atasever B van der Spoel HJI Bouman CCS Altenburg J van Dijk K. Mini-bronchoalveolar lavage for diagnosing coronavirus disease 2019-associated invasive pulmonary aspergillosis. Crit Care Explor. (2021) 3:e0601. doi: 10.1097/CCE.0000000000000601, PMID: 34939036
Torrego A Pajares V Fernandez-Arias C Vera P Mancebo J. Bronchoscopy in patients with COVID-19 with invasive mechanical ventilation: a single-center experience. Am J Respir Crit Care Med. (2020) 202:284–7. doi: 10.1164/rccm.202004-0945LE, PMID: 32412787
Mehta P McAuley DF Brown M Sanchez E Tattersall RS Manson JJ et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. (2020) 395:1033–4. doi: 10.1016/S0140-6736(20)30628-0, PMID: 32192578
Doglioni C Ravaglia C Chilosi M Rossi G Dubini A Pedica F et al. Covid-19 interstitial pneumonia: histological and Immunohistochemical features on cryobiopsies. Respiration. (2021) 100:488–98. doi: 10.1159/000514822, PMID: 33725700
Dentone C Vena A Loconte M Grillo F Brunetti I Barisione E et al. Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy. BMC Infect Dis. (2021) 21:353. doi: 10.1186/s12879-021-06015-9, PMID: 33858331
Pandolfi L Fossali T Frangipane V Bozzini S Morosini M D’Amato M et al. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. BMC Pulm Med. (2020) 20:301. doi: 10.1186/s12890-020-01343-z, PMID: 33198751
Gillot C Favresse J Mullier F Lecompte T Dogne JM Douxfils J. NETosis and the immune system in COVID-19: mechanisms and potential treatments. Front Pharmacol. (2021) 12:708302. doi: 10.3389/fphar.2021.708302, PMID: 34421600
Mozzini C Girelli D. The role of neutrophil extracellular traps in Covid-19: only an hypothesis or a potential new field of research? Thromb Res. (2020) 191:26–7. doi: 10.1016/j.thromres.2020.04.031
D’Amato M Vertui V Pandolfi L Bozzini S Fossali T Colombo R et al. Investigating the Link between alpha-1 antitrypsin and human neutrophil elastase in bronchoalveolar lavage fluid of COVID-19 patients. Curr Issues Mol Biol. (2022) 44:2122–38. doi: 10.3390/cimb44050143, PMID: 35678672
Reynolds D Vazquez Guillamet C Day A Borcherding N Vazquez Guillamet R Choreño-Parra JA et al. Comprehensive immunologic evaluation of bronchoalveolar lavage samples from human patients with moderate and severe seasonal influenza and severe COVID-19. J Immunol. (2021) 207:1229–38. doi: 10.4049/jimmunol.2100294, PMID: 34348975
Gelarden I Nguyen J Gao J Chen Q Morales-Nebreda L Wunderink R et al. Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes. Hum Pathol. (2021) 113:92–103. doi: 10.1016/j.humpath.2021.04.010, PMID: 33905777
Wauters E van Mol P Garg AD Jansen S van Herck Y Vanderbeke L et al. Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages. Cell Res. (2021) 31:272–90. doi: 10.1038/s41422-020-00455-9, PMID: 33473155
Liao M Liu Y Yuan J Wen Y Xu G Zhao J et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. (2020) 26:842–4. doi: 10.1038/s41591-020-0901-9, PMID: 32398875
He J Cai S Feng H Cai B Lin L Mai Y et al. Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients. Protein Cell. (2020) 11:680–7. doi: 10.1007/s13238-020-00752-4, PMID: 32671793
Chen H Liu W Wang Y Liu D Zhao L Yu J. SARS-CoV-2 activates lung epithelial cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients. EBioMedicine. (2021) 70:103500. doi: 10.1016/j.ebiom.2021.103500, PMID: 34311326
Karmaus PWF Tata A Meacham JM Day F Thrower D Tata PR et al. Meta-analysis of COVID-19 BAL single-cell RNA sequencing reveals alveolar epithelial transitions and unique alveolar epithelial cell fates. Am J Respir Cell Mol Biol. (2023) 69:623–37. doi: 10.1165/rcmb.2023-0077OC, PMID: 37523502
Garg M Li X Moreno P Papatheodorou I Shu Y Brazma A et al. Meta-analysis of COVID-19 single-cell studies confirms eight key immune responses. Sci Rep. (2021) 11:20833. doi: 10.1038/s41598-021-00121-z
Martens CP van Mol P Wauters J Wauters E Gangnus T Noppen B et al. Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19. EBioMedicine. (2022) 83:104195. doi: 10.1016/j.ebiom.2022.104195, PMID: 35939907
