Lung transplantation for patients with severe COVID-19

Some patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.
A surgical solution for severe COVID-19 Despite optimal medical therapy, some patients with severe COVID-19 develop irreversible lung injury. In these patients who cannot be weaned from mechanical ventilation or extracorporeal life support, lung transplantation may be the only life-saving option. Bharat et al. now report the results of lung transplantation in three patients who had COVID-19–associated respiratory failure. SARS-CoV-2 RNA could not be detected in the explanted lungs of these patients, but fibrotic pathology and transcriptional changes resembling those of lungs from patients with pulmonary fibrosis were observed.
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.