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Lung transplantation for pulmonary fibrosis secondary to severe COVID-19
Ankit Bharat; Melissa Querrey; Nikolay S Markov; Samuel S Kim; Chitaru Kurihara; Rafael Garza-Castillon Jr.; Adwaiy Manerikar; Ali Shilatifard; Rade Tomic; Yuliya Politanska; Hiam Abdala-Valencia; Anjana V Yeldandi; Jon W Lomasney; Alexander V Misharin; GR Scott Budinger.
Afiliación
  • Ankit Bharat; Northwestern University
  • Melissa Querrey; Northwestern University
  • Nikolay S Markov; Northwestern University
  • Samuel S Kim; Northwestern University
  • Chitaru Kurihara; Northwestern University
  • Rafael Garza-Castillon Jr.; Northwestern University
  • Adwaiy Manerikar; Northwestern University
  • Ali Shilatifard; Northwestern University
  • Rade Tomic; Northwestern University
  • Yuliya Politanska; Northwestern University
  • Hiam Abdala-Valencia; Northwestern University
  • Anjana V Yeldandi; Northwestern University
  • Jon W Lomasney; Northwestern University
  • Alexander V Misharin; Northwestern University
  • GR Scott Budinger; Northwestern University
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20218636
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.
Licencia
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint