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Lung transplantation for pulmonary fibrosis secondary to severe COVID-19

Authors :
G. R. Scott Budinger
Ali Shilatifard
Ankit Bharat
Samuel Kim
Rade Tomic
Hiam Abdala-Valencia
Chitaru Kurihara
Rafael Garza-Castillon
Melissa Querrey
Yuliya Politanska
Nikolay S. Markov
Adwaiy Manerikar
Anjana V. Yeldandi
Alexander V. Misharin
Jon W. Lomasney
Source :
medRxiv
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 acute respiratory distress syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-induced pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report the results of the first two successful lung transplantation procedures in patients with non-resolving COVID-19 associated acute respiratory distress syndrome in the United States. We performed smFISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. Single cell RNA-Seq of the explanted native lungs from transplant and paired warm post-mortem autopsies showed similarities between late SARS-CoV-2 acute respiratory distress syndrome and irreversible end-stage pulmonary fibrosis requiring lung transplantation. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation in either patient. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.Single sentence summarySome patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.

Details

Language :
English
Database :
OpenAIRE
Journal :
medRxiv
Accession number :
edsair.doi.dedup.....7df10c56c0c3541803a6a16eacd50961