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Diffuse alveolar da...
Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19
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- Erjefält, Jonas S. (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- de Souza Xavier Costa, Natália (author)
- University of São Paulo
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- Jönsson, Jimmie (author)
- Medetect AB
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- Cozzolino, Olga (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Dantas, Katia Cristina (author)
- University of São Paulo
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- Clausson, Carl Magnus (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Siddhuraj, Premkumar (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Lindö, Caroline (author)
- Medetect AB
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- Alyamani, Manar (author)
- Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups
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- Lombardi, Suzete Cleusa Ferreira Spina (author)
- University of São Paulo
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- Mendroni Júnior, Alfredo (author)
- University of São Paulo
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- Antonangelo, Leila (author)
- University of São Paulo
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- Faria, Caroline Silvério (author)
- University of São Paulo
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- Duarte-Neto, Amaro Nunes (author)
- University of São Paulo
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- de Almeida Monteiro, Renata Aparecida (author)
- University of São Paulo
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- Rebello Pinho, João Renato (author)
- University of São Paulo,Albert Einstein Israelite Hospital
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- Gomes-Gouvêa, Michele Soares (author)
- University of São Paulo
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- Verciano Pereira, Roberta (author)
- University of São Paulo
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- Monteiro, Jhonatas Sirino (author)
- University of São Paulo
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- Setubal, João Carlos (author)
- University of São Paulo
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- de Oliveira, Ellen Pierre (author)
- University of São Paulo
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- Theodoro Filho, Jair (author)
- University of São Paulo
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- Sanden, Caroline (author)
- Medetect AB
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- Orengo, Jamie M. (author)
- Regeneron Pharmaceuticals, Inc.
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- Sleeman, Matthew A. (author)
- Regeneron Pharmaceuticals, Inc.
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- da Silva, Luiz Fernando Ferraz (author)
- University of São Paulo
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- Saldiva, Paulo Hilário Nascimento (author)
- University of São Paulo
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- Dolhnikoff, Marisa (author)
- University of São Paulo
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- Mauad, Thais (author)
- University of São Paulo
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
- Related links:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- Autopsy
- COVID-19
- Diffuse alveolar damage
- Immunopathology
- SARS-Cov-2
Publication and Content Type
- art (subject category)
- ref (subject category)
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Erjefält, Jonas ...
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de Souza Xavier ...
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Jönsson, Jimmie
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Cozzolino, Olga
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Dantas, Katia Cr ...
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Clausson, Carl M ...
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show more...
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Siddhuraj, Premk ...
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Lindö, Caroline
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Alyamani, Manar
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Lombardi, Suzete ...
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Mendroni Júnior, ...
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Antonangelo, Lei ...
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Faria, Caroline ...
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Duarte-Neto, Ama ...
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de Almeida Monte ...
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Rebello Pinho, J ...
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Gomes-Gouvêa, Mi ...
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Verciano Pereira ...
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Monteiro, Jhonat ...
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Setubal, João Ca ...
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de Oliveira, Ell ...
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Theodoro Filho, ...
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Sanden, Caroline
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Orengo, Jamie M.
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Sleeman, Matthew ...
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da Silva, Luiz F ...
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Saldiva, Paulo H ...
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Dolhnikoff, Mari ...
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Mauad, Thais
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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EBioMedicine
- By the university
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Lund University