Lung transplantation for patients with severe COVID-19.
Adult
Aged, 80 and over
COVID-19
/ diagnosis
COVID-19 Nucleic Acid Testing
Databases, Factual
Disease Progression
Female
Humans
In Situ Hybridization, Fluorescence
Lung
/ physiopathology
Lung Transplantation
Male
Middle Aged
Pulmonary Fibrosis
/ diagnosis
RNA-Seq
Recovery of Function
Retrospective Studies
Severity of Illness Index
Single-Cell Analysis
Treatment Outcome
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
16 12 2020
16 12 2020
Historique:
received:
21
08
2020
accepted:
23
11
2020
pubmed:
2
12
2020
medline:
29
12
2020
entrez:
1
12
2020
Statut:
ppublish
Résumé
Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19-associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonresolving COVID-19-associated respiratory failure. We performed single-molecule fluorescence in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single-cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm postmortem lung biopsies from two patients who had died from COVID-19-associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single-cell RNA sequencing data from the lungs of patients with late-stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.
Identifiants
pubmed: 33257409
pii: scitranslmed.abe4282
doi: 10.1126/scitranslmed.abe4282
pmc: PMC8050952
pii:
doi:
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CSRD VA
ID : I01 CX001777
Pays : United States
Organisme : NIH HHS
ID : HL147290
Pays : United States
Organisme : NIH HHS
ID : HL145478
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135964
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153312
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145478
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147290
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147575
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
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