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1.
Lancet Respir Med ; 9(5): 487-497, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537196

ABSTRACT

BACKGROUND: Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications. METHODS: We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed. FINDINGS: Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19. INTERPRETATION: The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients. FUNDING: National Institutes of Health. VIDEO ABSTRACT.


Subject(s)
COVID-19 , Critical Illness/therapy , Lung Transplantation/methods , Lung , Respiratory Distress Syndrome , Blood Transfusion/methods , COVID-19/complications , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/surgery , Critical Care/methods , Extracorporeal Membrane Oxygenation/methods , Female , Humans , Intraoperative Care/methods , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/pathology , Respiration, Artificial/methods , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/surgery , SARS-CoV-2/pathogenicity
2.
Artif Organs ; 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1480092

ABSTRACT

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) support is increasingly used in the management of COVID-19-related acute respiratory distress syndrome (ARDS). However, the clinical decision-making to initiate V-V ECMO for severe COVID-19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID-19 and non-COVID-19 patients undergoing V-V ECMO support. METHODS: Overall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID-19 and non-COVID-19 ARDS. RESULTS: The survival in patients with COVID-19 was statistically similar to non-COVID-19 patients (p = .16). However, the COVID-19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p < .001). The duration of V-V ECMO support was longer in COVID-19 patients compared to non-COVID-19 patients (29.0 ± 27.5 vs 15.9 ± 19.6 days, p < .01). Most notably, in contrast to the non-COVID-19 group, we found that COVID-19 patients who had been on a ventilator for longer than 7 days prior to ECMO had 100% mortality without a lung transplant. CONCLUSIONS: These findings suggest that COVID-19-associated ARDS was not associated with a higher post-ECMO mortality than non-COVID-19-associated ARDS patients, despite longer duration of extracorporeal support. Early initiation of V-V ECMO is important for improved ECMO outcomes in COVID-19 ARDS patients. Since late initiation of ECMO was associated with extremely high mortality related to lack of pulmonary recovery, it should be used judiciously or as a bridge to lung transplantation.

3.
Am J Transplant ; 21(12): 4073-4078, 2021 12.
Article in English | MEDLINE | ID: covidwho-1334386

ABSTRACT

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and "efficacy" of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.

5.
Sci Transl Med ; 12(574)2020 12 16.
Article in English | MEDLINE | ID: covidwho-1207479

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.


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