Lung transplantation for patients with severe COVID-19

Ankit Bharat*, Melissa Querrey, Nikolay S. Markov, Samuel Kim, Chitaru Kurihara, Rafael Garza-Castillon, Adwaiy Manerikar, Ali Shilatifard, Rade Tomic, Yuliya Politanska, Hiam Abdala-Valencia, Anjana V. Yeldandi, Jon W. Lomasney, Alexander V. Misharin, G. R.Scott Budinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbereabe4282
JournalScience translational medicine
Volume12
Issue number574
DOIs
StatePublished - Dec 16 2020

ASJC Scopus subject areas

  • Medicine(all)

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