Lung transplantation for patients with severe COVID-19

Sci Transl Med. 2020 Dec 16;12(574):eabe4282. doi: 10.1126/scitranslmed.abe4282. Epub 2020 Nov 30.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged, 80 and over
  • COVID-19 / diagnosis
  • COVID-19 / physiopathology
  • COVID-19 / surgery*
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing
  • Databases, Factual
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung / physiopathology
  • Lung / surgery*
  • Lung / virology
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Pulmonary Fibrosis / diagnosis
  • Pulmonary Fibrosis / physiopathology
  • Pulmonary Fibrosis / surgery*
  • Pulmonary Fibrosis / virology
  • RNA-Seq
  • Recovery of Function
  • Retrospective Studies
  • Severity of Illness Index
  • Single-Cell Analysis
  • Treatment Outcome