Conclusions.
BAL has been widely used during the SARS-Cov-2 pandemic for both clinical and research purposes. In clinical practice BAL can change management decisions in up to two-third of patients confirming a suspected SARS-Cov-2 infection when the NP swab is negative, detecting other infections or supporting alternative diagnosis. Although studies have a wide variability, a pooled estimates of 11% positive cases suggest that BAL can be used to confirm suspected SARS-Cov-2 infection when negative NP swab is negative.19 The prevalence of false negative BAL for SARS-Cov-2 detection can’t be accurately drawn from current studies, but seems to be very low (<2%).25 In both critically ill and non-critically ill patients, BAL detects coinfections a significant proportion of patients. BAL can help clinicians in difficult differential diagnosis including acute exacerbations of interstitial lung diseases (ILDs), connective tissue related ILDs, hypersensitivity pneumonitis, cryptogenic organizing pneumonia. BAL analyses are 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 the understanding of 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 health care 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 with great potential for research. Based on the evidences here summarized, we propose a simplified diagnostic algorithm in which BAL can be used in suspected COVID-19 cases when the NP swab is negative, and in COVID-19 cases to guide antimicrobial and steroid treatment when a coinfection is suspected (Figure 1). We acknowledge that this algorithm reflects the clinical practice only in selected centres properly equipped and experienced in the use of BAL and that further large prospective studies are needed to corroborate current knowledge before BAL can be widely recommended.
References
1. Wahidi MM, Lamb C, Murgu S, 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-e4.
2. Meyer KC. Bronchoalveolar lavage as a diagnostic tool. Semin Respir Crit Care Med 2007;28:546-60.
3. Poletti V, Chilosi M, Olivieri D. Diagnostic invasive procedures in diffuse infiltrative lung diseases. Respiration 2004;71:107-19.
4. Costabel U, Guzman J. Bronchoalveolar lavage in interstitial lung disease. Curr Opin Pulm Med 2001;7:255-61.
5. 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;13:1759720X211059605.
6. Clerici B, Muscatello A, Bai F, et al. Sensitivity of SARS-Cov-2 Detection With Nasopharyngeal Swabs. Front Public Health 2020;8:593491.
7. Wang W, Xu Y, Gao R, et al. Detection of SARS-Cov-2 in Different Types of Clinical Specimens. JAMA 2020;323:1843-4.
8. 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.
9. Ai T, Yang Z, Hou H, 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-E40.
10. Fang Y, Zhang H, Xie J, et al. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology 2020;296:E115-E7.
11. Khatami F, Saatchi M, Zadeh SST, et al. A meta-analysis of accuracy and sensitivity of chest CT and RT-PCR in COVID-19 diagnosis. Sci Rep 2020;10:22402.
12. Guiot J, Vaidyanathan A, Deprez L, et al. Development and Validation of an Automated Radiomic CT Signature for Detecting COVID-19. Diagnostics (Basel) 2020;11.
13. Darwiche K, Ross B, Gesierich W, et al. [Recommendations for Performing Bronchoscopy in Times of the COVID-19 Pandemic - Update 12/2020]. Pneumologie 2021;75:187-90.
14. Pritchett MA, Oberg CL, Belanger A, 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.
15. Luo F, Darwiche K, Singh S, et al. Performing Bronchoscopy in Times of the COVID-19 Pandemic: Practice Statement from an International Expert Panel. Respiration 2020;99:417-22.
16. Guedes F, Boleo-Tome JP, Rodrigues LV, et al. Recommendations for interventional pulmonology during COVID-19 outbreak: a consensus statement from the Portuguese Pulmonology Society. Pulmonology 2020;26:386-97.
17. Lentz RJ, Colt H. Summarizing societal guidelines regarding bronchoscopy during the COVID-19 pandemic. Respirology 2020;25:574-7.
18. Saha BK, Saha S, Chong WH, Beegle S. Indications, Clinical Utility, and Safety of Bronchoscopy in COVID-19. Respir Care 2022;67:241-51.
19. 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.
20. Liu R, Han H, Liu F, 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.
21. Turriziani O, Sciandra I, Mazzuti L, 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.
22. Ramos KJ, Kapnadak SG, Collins BF, 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.
23. De Clercq J, Malfait T, Malfait S, et al. Diagnosing COVID-19; towards a feasible COVID-19 rule-out protocol. Acta Clin Belg 2021:1-9.
24. Taton O, Papleux E, Bondue B, et al. Role of the Bronchoalveolar Lavage in Noncritically Ill Patients during the SARS-Cov-2 Epidemic. Pulm Med 2020;2020:9012187.
25. Mondoni M, Sferrazza Papa GF, Rinaldo R, et al. Utility and safety of bronchoscopy during the SARS-Cov-2 outbreak in Italy: a retrospective, multicentre study. Eur Respir J 2020;56.
26. Patrucco F, Albera C, Bellocchia M, et al. SARS-Cov-2 Detection on Bronchoalveolar Lavage: An Italian Multicenter experience. Respiration 2020;99:970-8.
27. Barberi C, Castelnuovo E, Dipasquale A, 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.
28. Geri P, Salton F, Zuccatosta L, 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.
29. Ora J, Puxeddu E, Cavalli F, et al. Does bronchoscopy help the diagnosis in COVID-19 infection? Eur Respir J 2020;56.
30. Vannucci J, Ruberto F, Diso D, 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.
31. Oberg CL, Ronaghi R, Folch EE, 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.
32. 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.
33. Pickens CO, Gao CA, Cuttica MJ, et al. Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia. Am J Respir Crit Care Med 2021;204:921-32.
34. Guarino C, Cesaro C, Fiorentino G, et al. Bronchoscopy in COVID-19 patients: When, how and why. Experience in clinical practice. Monaldi Arch Chest Dis 2021;91.
35. Arenas-De Larriva M Mn-DR, Urrutia Royo B, Ferna ndez-, Navamuel I GVA, Nun˜ez Garcı a L. The role of
bronchoscopy in patients with SARS-Cov-2 pneumonia. ERJ Open Res 2021;7:165.
36. Mehta R BS, Kumar A, Thorbole A, Chakravarthi L, Kalpakam H. ronchoscopy in COVID19 ARDS patients on mechanical ventila- tion – a prospective study. medRxiv 2021.
37. Yang Y, Yang M, Yuan J, et al. Laboratory Diagnosis and Monitoring the Viral Shedding of SARS-Cov-2 Infection. Innovation (N Y) 2020;1:100061.
38. Gao CA, Cuttica MJ, Malsin ES, et al. Comparing Nasopharyngeal and BAL SARS-Cov-2 Assays in Respiratory Failure. Am J Respir Crit Care Med 2021;203:127-9.
39. Mahmood K, Abbott M, Van Nostrand K, et al. Low utilisation of bronchoscopy to assess COVID-19 respiratory infection: a multicenter experience. BMJ Open Respir Res 2021;8.
40. Baron A, Hachem M, Tran Van Nhieu J, 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.
41. Meyer KC, Raghu G, Baughman RP, 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.
42. 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.
43. 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.
44. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.
45. Doglioni C, Ravaglia C, Chilosi M, et al. Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies. Respiration 2021;100:488-98.
46. Dentone C, Vena A, Loconte M, 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.
47. Pandolfi L, Fossali T, Frangipane V, et al. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. BMC Pulm Med 2020;20:301.
48. Reynolds D, Vazquez Guillamet C, Day A, 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.
49. Gelarden I, Nguyen J, Gao J, et al. Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes. Hum Pathol 2021;113:92-103.
50. Wauters E, Van Mol P, Garg AD, 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.
51. Liao M, Liu Y, Yuan J, et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 2020;26:842-4.
52. He J, Cai S, Feng H, et al. Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients. Protein Cell 2020;11:680-7.
53. 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.
54. Garg M, Li X, Moreno P, et al. Meta-analysis of COVID-19 single-cell studies confirms eight key immune responses. Sci Rep 2021;11:20833.