Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified.

(Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Keywords:
COVID-19; COVID-19/pathology; Pulmonary fibrosis; Respiratory function tests; Biopsy

Authorship

Bruno Guedes Baldi

. Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.Universidade de São PauloBrazilSão Paulo, SP, Brazil. Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.

https://orcid.org/0000-0002-9609-5117

Alexandre Todorovic Fabro

. Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - USP - Ribeirão Preto (SP) Brasil.Universidade de São PauloBrazilRibeirão Preto, SP, Brazil. Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - USP - Ribeirão Preto (SP) Brasil.

https://orcid.org/0000-0002-7687-3161

Andreia Craveiro Franco

. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil.Universidade Estadual PaulistaBrazilBotucatu, SP, Brazil. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil.

https://orcid.org/0000-0002-4927-9108

Marília Helena C Machado

https://orcid.org/0000-0001-7749-9872

Robson Aparecido Prudente

https://orcid.org/0000-0003-1175-1435

Estefânia Thomé Franco

https://orcid.org/0000-0002-3847-539X

Sergio Ribeiro Marrone

. Disciplina de Radiologia, Departamento de Dermatologia e Radioterapia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil.Universidade Estadual PaulistaBrazilBotucatu, SP, Brazil. Disciplina de Radiologia, Departamento de Dermatologia e Radioterapia, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP) Brasil.

https://orcid.org/0000-0003-0732-2814

Simone Alves do Vale

https://orcid.org/0000-0001-9876-847X

Talita Jacon Cezare

https://orcid.org/0000-0002-4183-8542

Marcelo Padovani de Toledo Moraes

https://orcid.org/0000-0001-7598-7768

Eloara Vieira Machado Ferreira

. Disciplina de Pneumologia, Departamento de Medicina, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP) Brasil.Universidade Federal de São PauloBrazilSão Paulo, SP, Brazil. Disciplina de Pneumologia, Departamento de Medicina, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP) Brasil.

https://orcid.org/0000-0002-3291-6473

André Luis Pereira Albuquerque

https://orcid.org/0000-0003-3486-5240

Marcio Valente Yamada Sawamura

. Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.Universidade de São PauloBrazilSão Paulo, SP, Brazil. Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil.

https://orcid.org/0000-0002-9424-9776

Suzana Erico Tanni

https://orcid.org/0000-0002-2587-2759

Correspondence to:
Suzana Erico Tanni. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Rubião Junior, CEP 18600-000, Botucatu, SP, Brasil. Tel.: 55 14 3880-1171. Fax: 55 14 3882-2238. E-mail: suzanapneumo@gmail.com

AUTHOR CONTRIBUTIONS

BB, ATF, and SET: study conceptualization; clinical, radiological, and histological interpretation; and drafting the manuscript. RAP, ETF, ACF, MHCM, SAV, TJC, and MPTM: performance of all procedures and data collection. MVYS and SRM: radiological interpretation. EVMF, ALPA, MVYS, BB, ATF, and SET: revision of preliminary and final versions; and approval of the final version.

CONFLICT OF INTEREST

None declared.

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (2)

Thumbnail

Figure 1
Chest CT scans of the patients studied. Patient 1: in A, a scan during the acute phase showing bilateral ground-glass opacities (GGO), consolidations, and parenchymal bands; in B, a scan after 15 months of follow-up showing subtle peripheral and posterior GGO. Patient 2: in C, a scan during the acute phase showing bilateral and peripheral GGO; in D, a scan after 7 months of follow-up showing subtle GGO with subpleural curvilinear lines and small dilated bronchioles in the right lower lobe. Patient 3: in E, a scan during the acute phase showing bilateral GGO and crazy-paving pattern; in F, a scan after 6 months of follow-up showing subtle scattered GGO. Patient 4: a scan during the acute phase showing bilateral and peripheral GGO and consolidations; in H, a scan after 4 months of follow-up showing subtle bilateral and peripheral GGO. Patient 5: in I, a scan during the acute phase showing bilateral GGO; in J, a scan after 10 months of follow-up showing subtle GGO and mosaic attenuation in the lung parenchyma. Patient 6: in K, a scan during the acute phase showing bilateral GGO and consolidations; in L, a scan after 7 months of follow-up showing bilateral GGO with some dilated bronchioles.

Thumbnail

Figure 2
Histopathological panel of transbronchial biopsy samples collected from the patients studied (H&E; low power field, ×4, and high power field, ×40). All of the patients showed hyaline peribronchial remodeling with septal extension. Patient 1: focal septal thickening by prominent extracellular matrix deposition (blue dashed ellipse in A) associated with architectural distortion of the bronchial smooth muscle layer (blue arrows in B). Patient 2: mild hyaline peribronchial remodeling with septal extension (red arrow in C). Note the focal septal thickening by prominent extracellular matrix deposition (red dashed ellipse in D). Patient 3: prominent peribronchial remodeling with extensive extracellular matrix deposition (double green arrow in E). The architectural distortion of the bronchial smooth muscle layer is highlighted (green arrow in F). Patient 4: the architectural distortion around hyaline peribronchial remodeling promoted focal simile-desquamative reaction (area enclosed by blue dashed line in G). Note the disarray and hypertrophy of the bronchial smooth muscle layer (double blue arrow in H). Patient 5: prominent peribronchial remodeling (red arrow in I) with extensive extracellular matrix deposition (double red arrow in J) and small calcification. Patient 6: prominent peribronchial remodeling (green arrow in K) with extensive extracellular matrix deposition (green arrow in L).

Figure 1 Chest CT scans of the patients studied. Patient 1: in A, a scan during the acute phase showing bilateral ground-glass opacities (GGO), consolidations, and parenchymal bands; in B, a scan after 15 months of follow-up showing subtle peripheral and posterior GGO. Patient 2: in C, a scan during the acute phase showing bilateral and peripheral GGO; in D, a scan after 7 months of follow-up showing subtle GGO with subpleural curvilinear lines and small dilated bronchioles in the right lower lobe. Patient 3: in E, a scan during the acute phase showing bilateral GGO and crazy-paving pattern; in F, a scan after 6 months of follow-up showing subtle scattered GGO. Patient 4: a scan during the acute phase showing bilateral and peripheral GGO and consolidations; in H, a scan after 4 months of follow-up showing subtle bilateral and peripheral GGO. Patient 5: in I, a scan during the acute phase showing bilateral GGO; in J, a scan after 10 months of follow-up showing subtle GGO and mosaic attenuation in the lung parenchyma. Patient 6: in K, a scan during the acute phase showing bilateral GGO and consolidations; in L, a scan after 7 months of follow-up showing bilateral GGO with some dilated bronchioles.

Figure 2 Histopathological panel of transbronchial biopsy samples collected from the patients studied (H&E; low power field, ×4, and high power field, ×40). All of the patients showed hyaline peribronchial remodeling with septal extension. Patient 1: focal septal thickening by prominent extracellular matrix deposition (blue dashed ellipse in A) associated with architectural distortion of the bronchial smooth muscle layer (blue arrows in B). Patient 2: mild hyaline peribronchial remodeling with septal extension (red arrow in C). Note the focal septal thickening by prominent extracellular matrix deposition (red dashed ellipse in D). Patient 3: prominent peribronchial remodeling with extensive extracellular matrix deposition (double green arrow in E). The architectural distortion of the bronchial smooth muscle layer is highlighted (green arrow in F). Patient 4: the architectural distortion around hyaline peribronchial remodeling promoted focal simile-desquamative reaction (area enclosed by blue dashed line in G). Note the disarray and hypertrophy of the bronchial smooth muscle layer (double blue arrow in H). Patient 5: prominent peribronchial remodeling (red arrow in I) with extensive extracellular matrix deposition (double red arrow in J) and small calcification. Patient 6: prominent peribronchial remodeling (green arrow in K) with extensive extracellular matrix deposition (green arrow in L).

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E-mail: jbp@sbpt.org.br

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Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

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[1] Correspondence to:
Suzana Erico Tanni. Disciplina de Pneumologia, Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Rubião Junior, CEP 18600-000, Botucatu, SP, Brasil. Tel.: 55 14 3880-1171. Fax: 55 14 3882-2238. E-mail: suzanapneumo@gmail.com