Lung transplantation for patients with severe COVID-19.


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
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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Auteurs

Ankit Bharat (A)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. abharat@nm.org.

Melissa Querrey (M)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Nikolay S Markov (NS)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Samuel Kim (S)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Chitaru Kurihara (C)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Rafael Garza-Castillon (R)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Adwaiy Manerikar (A)

Division of Thoracic Surgery, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Ali Shilatifard (A)

Department of Biochemistry and Molecular Genetics, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Rade Tomic (R)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Yuliya Politanska (Y)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Hiam Abdala-Valencia (H)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Anjana V Yeldandi (AV)

Department of Pathology, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Jon W Lomasney (JW)

Department of Pathology, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Alexander V Misharin (AV)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

G R Scott Budinger (GRS)

Division of Pulmonary and Critical Care Medicine, Northwestern Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

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Classifications MeSH