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Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19

Erjefält, Jonas S. LU ; de Souza Xavier Costa, Natália ; Jönsson, Jimmie ; Cozzolino, Olga LU ; Dantas, Katia Cristina ; Clausson, Carl Magnus LU ; Siddhuraj, Premkumar LU ; Lindö, Caroline LU ; Alyamani, Manar LU and Lombardi, Suzete Cleusa Ferreira Spina , et al. (2022) In EBioMedicine 83.
Abstract

Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses... (More)

Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autopsy, COVID-19, Diffuse alveolar damage, Immunopathology, SARS-Cov-2
in
EBioMedicine
volume
83
article number
104229
publisher
Elsevier
external identifiers
  • pmid:36027872
  • scopus:85136471284
ISSN
2352-3964
DOI
10.1016/j.ebiom.2022.104229
language
English
LU publication?
yes
id
c3823b96-2279-49bb-8cbe-9002e7c0d202
date added to LUP
2022-12-28 13:54:24
date last changed
2024-04-18 17:17:21
@article{c3823b96-2279-49bb-8cbe-9002e7c0d202,
  abstract     = {{<p>Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart &amp; Lung Foundation.</p>}},
  author       = {{Erjefält, Jonas S. and de Souza Xavier Costa, Natália and Jönsson, Jimmie and Cozzolino, Olga and Dantas, Katia Cristina and Clausson, Carl Magnus and Siddhuraj, Premkumar and Lindö, Caroline and Alyamani, Manar and Lombardi, Suzete Cleusa Ferreira Spina and Mendroni Júnior, Alfredo and Antonangelo, Leila and Faria, Caroline Silvério and Duarte-Neto, Amaro Nunes and de Almeida Monteiro, Renata Aparecida and Rebello Pinho, João Renato and Gomes-Gouvêa, Michele Soares and Verciano Pereira, Roberta and Monteiro, Jhonatas Sirino and Setubal, João Carlos and de Oliveira, Ellen Pierre and Theodoro Filho, Jair and Sanden, Caroline and Orengo, Jamie M. and Sleeman, Matthew A. and da Silva, Luiz Fernando Ferraz and Saldiva, Paulo Hilário Nascimento and Dolhnikoff, Marisa and Mauad, Thais}},
  issn         = {{2352-3964}},
  keywords     = {{Autopsy; COVID-19; Diffuse alveolar damage; Immunopathology; SARS-Cov-2}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2022.104229}},
  doi          = {{10.1016/j.ebiom.2022.104229}},
  volume       = {{83}},
  year         = {{2022}},
}