Tracking the time course of pathological patterns of lung injury in severe COVID-19

Abstract Background Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathway...

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Main Authors: Thais Mauad, Amaro Nunes Duarte-Neto, Luiz Fernando Ferraz da Silva, Ellen Pierre de Oliveira, Jose Mara de Brito, Ellen Caroline Toledo do Nascimento, Renata Aparecida de Almeida Monteiro, Juliana Carvalho Ferreira, Carlos Roberto Ribeiro de Carvalho, Paulo Hilário do Nascimento Saldiva, Marisa Dolhnikoff
Format: Article
Language:English
Published: BMC 2021-01-01
Series:Respiratory Research
Subjects:
Online Access:https://doi.org/10.1186/s12931-021-01628-9
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author Thais Mauad
Amaro Nunes Duarte-Neto
Luiz Fernando Ferraz da Silva
Ellen Pierre de Oliveira
Jose Mara de Brito
Ellen Caroline Toledo do Nascimento
Renata Aparecida de Almeida Monteiro
Juliana Carvalho Ferreira
Carlos Roberto Ribeiro de Carvalho
Paulo Hilário do Nascimento Saldiva
Marisa Dolhnikoff
author_facet Thais Mauad
Amaro Nunes Duarte-Neto
Luiz Fernando Ferraz da Silva
Ellen Pierre de Oliveira
Jose Mara de Brito
Ellen Caroline Toledo do Nascimento
Renata Aparecida de Almeida Monteiro
Juliana Carvalho Ferreira
Carlos Roberto Ribeiro de Carvalho
Paulo Hilário do Nascimento Saldiva
Marisa Dolhnikoff
author_sort Thais Mauad
collection DOAJ
description Abstract Background Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. Methods We analysed lung tissue from 41 COVID-19 patients that died in the period March–June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. Results Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0–8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. Conclusion Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.
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spelling doaj.art-7810d5b787fc424e946ed838e5367ada2022-12-21T22:24:32ZengBMCRespiratory Research1465-993X2021-01-0122111110.1186/s12931-021-01628-9Tracking the time course of pathological patterns of lung injury in severe COVID-19Thais Mauad0Amaro Nunes Duarte-Neto1Luiz Fernando Ferraz da Silva2Ellen Pierre de Oliveira3Jose Mara de Brito4Ellen Caroline Toledo do Nascimento5Renata Aparecida de Almeida Monteiro6Juliana Carvalho Ferreira7Carlos Roberto Ribeiro de Carvalho8Paulo Hilário do Nascimento Saldiva9Marisa Dolhnikoff10Departamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Cardiopneumologia, Instituto Do Coração, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Cardiopneumologia, Instituto Do Coração, Faculdade de Medicina da Universidade de São PauloDepartamento de Cardiopneumologia, Instituto Do Coração, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloDepartamento de Patologia, Faculdade de Medicina da Universidade de São PauloAbstract Background Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. Methods We analysed lung tissue from 41 COVID-19 patients that died in the period March–June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. Results Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0–8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. Conclusion Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.https://doi.org/10.1186/s12931-021-01628-9COVID-19Lung pathologyMinimally invasive autopsyDiffuse alveolar damagePulmonary thrombosis
spellingShingle Thais Mauad
Amaro Nunes Duarte-Neto
Luiz Fernando Ferraz da Silva
Ellen Pierre de Oliveira
Jose Mara de Brito
Ellen Caroline Toledo do Nascimento
Renata Aparecida de Almeida Monteiro
Juliana Carvalho Ferreira
Carlos Roberto Ribeiro de Carvalho
Paulo Hilário do Nascimento Saldiva
Marisa Dolhnikoff
Tracking the time course of pathological patterns of lung injury in severe COVID-19
Respiratory Research
COVID-19
Lung pathology
Minimally invasive autopsy
Diffuse alveolar damage
Pulmonary thrombosis
title Tracking the time course of pathological patterns of lung injury in severe COVID-19
title_full Tracking the time course of pathological patterns of lung injury in severe COVID-19
title_fullStr Tracking the time course of pathological patterns of lung injury in severe COVID-19
title_full_unstemmed Tracking the time course of pathological patterns of lung injury in severe COVID-19
title_short Tracking the time course of pathological patterns of lung injury in severe COVID-19
title_sort tracking the time course of pathological patterns of lung injury in severe covid 19
topic COVID-19
Lung pathology
Minimally invasive autopsy
Diffuse alveolar damage
Pulmonary thrombosis
url https://doi.org/10.1186/s12931-021-01628-9
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