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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.
Monaldi Arch Chest Dis ; 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1534344

ABSTRACT

This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.

3.
Cells ; 10(3)2021 03 10.
Article in English | MEDLINE | ID: covidwho-1125934

ABSTRACT

We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs' GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.


Subject(s)
COVID-19/surgery , Chemokines/metabolism , Cytokines/metabolism , Leukocytes, Mononuclear/metabolism , Lung Transplantation , Lung/pathology , Respiratory Distress Syndrome/surgery , Adolescent , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/virology , COVID-19/blood , Gene Expression Profiling , Gene Expression Regulation/immunology , Genotype , Humans , Inflammasomes/metabolism , Interleukin-6/metabolism , Lung/immunology , Lung/metabolism , Lung/virology , Lymph Nodes/pathology , Lymph Nodes/virology , Male , Middle Aged , Plasma/virology , Polymorphism, Single Nucleotide , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Tumor Necrosis Factor-alpha/metabolism
4.
Int J Surg Case Rep ; 77: 80-85, 2020.
Article in English | MEDLINE | ID: covidwho-906683

ABSTRACT

Introduction: In addition to morbidity and mortality rate per se, COVID-19 outbreak leads to potential 'side effects', which are difficult to evaluate and predict. Lung transplantation is a consolidated treatment for end-stage chronic lung disease requiring significantly demanding management. Deciding whether to keep transplant programmes open during an epidemic of this size is not easy, as immunosuppressed subjects face the risk of infection and related mortality. Additionally, there is a chance for the patient's standard care process to be compromised. Presentation of case: We report the case of a patient undergoing bilateral lung transplantation during the explosion of COVID-19 epidemic in Lombardy; he died from definite early acute antibody-mediated rejection, clinically (persistent high fever, unresponsive to treatment) and radiologically mimicking viral pneumonia but persistently negative for SARS-CoV-2. Discussion: The diagnosis was difficult given this atypical presentation, confounded by global scenario. Grafts were procured from a donation after circulatory death donor in an uncontrolled setting and a donor-recipient transmission was possible. Our institute became a COVID-Hospital right during the first post-transplantation days. Radiological imaging had the same features of SARS-CoV-2 pneumonia. Conclusions: This is the first report of lung transplantation of the COVID-19 era in Europe. Our extremely fragile patient was COVID-19 free up to the end. Donor-recipient transmission is conceivable, but the risk should be assessed with respect to waiting list mortality. Ultimately, treating COVID-19 patients can be a resource-consuming activity but we decided to keep our centre open.

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