Lung transplantation for coronavirus disease 2019 acute respiratory distress syndrome/fibrosis: silver lining of a global pandemic.

PURPOSE OF REVIEW: The COVID-19 pandemic revolutionized the field of lung transplantation, as lung transplant is now an acceptable life-saving therapy for select patients with COVID-19-associated acute respiratory distress syndrome (ARDS), while prior to the pandemic, few transplants were performed for ARDS. This review article details the establishment of lung transplantation as a viable therapy for COVID-19-related respiratory failure, how to evaluate COVID-19 patients for lung transplant, and specific technical considerations for the operation. RECENT FINDINGS: Lung transplantation is a life-altering treatment for two distinct cohorts of COVID-19 patients: those with irrecoverable COVID-19-associated ARDS and those who recover from the initial COVID-19 insult but are left with chronic, debilitating post-COVID fibrosis. Both cohorts require stringent selection criteria and extensive evaluation to be listed for lung transplantation. As the first COVID-19 lung transplantation was recently performed, long-term outcomes are lacking; however, short-term outcome data of COVID-19-related lung transplants are promising. SUMMARY: Given the challenges and complexities associated with COVID-19-related lung transplantation, strict patient selection and evaluation are required with an experienced multidisciplinary team at a high-volume/resource center. With promising short-term outcome data, ongoing studies are needed to assess long-term outcomes of COVID-19-related lung transplants.

Lung Transplantation in Coronavirus-19 Patients: What We Have Learned So Far.

Coronavirus-19 (COVID-19) can result in irrecoverable acute respiratory distress syndrome (ARDS) or life-limiting fibrosis for which lung transplantation is currently the only viable treatment. COVID-19 lung transplantation has transformed the field of lung transplantation, as before the pandemic, few transplants had been performed in the setting of infectious disease or ARDS. Given the complexities associated with COVID-19 lung transplantation, it requires strict patient selection with an experienced multidisciplinary team in a high-resource hospital setting. Current short-term outcomes of COVID-19 lung transplantation are promising. However, follow-up studies are needed to determine long-term outcomes and whether these patients may be predisposed to unique complications.

Lung Transplantation for Acute Respiratory Distress Syndrome.

In this review, we discuss the outcomes of patients with severe acute respiratory distress syndrome (ARDS). We discuss evidence that suggests that a significant proportion of patients with ARDS develop end-stage lung disease and die of pulmonary complications. In carefully selected patients with permanent lung damage, lung transplant can be a life-saving treatment.

Clinical Characteristics and Outcomes of Patients With COVID-19-Associated Acute Respiratory Distress Syndrome Who Underwent Lung Transplant.

Importance: Lung transplantation is a potentially lifesaving treatment for patients who are critically ill due to COVID-19-associated acute respiratory distress syndrome (ARDS), but there is limited information about the long-term outcome. Objective: To report the clinical characteristics and outcomes of patients who had COVID-19-associated ARDS and underwent a lung transplant at a single US hospital. Design, Setting, and Participants: Retrospective case series of 102 consecutive patients who underwent a lung transplant at Northwestern University Medical Center in Chicago, Illinois, between January 21, 2020, and September 30, 2021, including 30 patients who had COVID-19-associated ARDS. The date of final follow-up was November 15, 2021. Exposures: Lung transplant. Main Outcomes and Measures: Demographic, clinical, laboratory, and treatment data were collected and analyzed. Outcomes of lung transplant, including postoperative complications, intensive care unit and hospital length of stay, and survival, were recorded. Results: Among the 102 lung transplant recipients, 30 patients (median age, 53 years [range, 27 to 62]; 13 women [43%]) had COVID-19-associated ARDS and 72 patients (median age, 62 years [range, 22 to 74]; 32 women [44%]) had chronic end-stage lung disease without COVID-19. For lung transplant recipients with COVID-19 compared with those without COVID-19, the median lung allocation scores were 85.8 vs 46.7, the median time on the lung transplant waitlist was 11.5 vs 15 days, and preoperative venovenous extracorporeal membrane oxygenation (ECMO) was used in 56.7% vs 1.4%, respectively. During transplant, patients who had COVID-19-associated ARDS received transfusion of a median of 6.5 units of packed red blood cells vs 0 in those without COVID-19, 96.7% vs 62.5% underwent intraoperative venoarterial ECMO, and the median operative time was 8.5 vs 7.4 hours, respectively. Postoperatively, the rates of primary graft dysfunction (grades 1 to 3) within 72 hours were 70% in the COVID-19 cohort vs 20.8% in those without COVID-19, the median time receiving invasive mechanical ventilation was 6.5 vs 2.0 days, the median duration of intensive care unit stay was 18 vs 9 days, the median post-lung transplant hospitalization duration was 28.5 vs 16 days, and 13.3% vs 5.5% required permanent hemodialysis, respectively. None of the lung transplant recipients who had COVID-19-associated ARDS demonstrated antibody-mediated rejection compared with 12.5% in those without COVID-19. At follow-up, all 30 lung transplant recipients who had COVID-19-associated ARDS were alive (median follow-up, 351 days [IQR, 176-555] after transplant) vs 60 patients (83%) who were alive in the non-COVID-19 cohort (median follow-up, 488 days [IQR, 368-570] after lung transplant). Conclusions and Relevance: In this single-center case series of 102 consecutive patients who underwent a lung transplant between January 21, 2020, and September 30, 2021, survival was 100% in the 30 patients who had COVID-19-associated ARDS as of November 15, 2021.

Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries.

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.

Lung Transplantation for End-Stage Respiratory Failure After Severe COVID-19: A Report of 2 Cases.

We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.

First lung transplantation as a treatment of a patient supported with extracorporeal membrane oxygenation (ECMO) after COVID-19 in Poland.

A 44-year-old male with no history of underlying diseases was referred to academic hospital due to ARDS with confirmed SARSCoV-2 infection after 7 days of mechanical ventilation. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated as no improvement was noted in prone position. Mechanical ventilation was continued with TV of 3-4 mL/kg. A gradual decline of static lung compliance was observed from baseline 35 mL/cm H20 to 8 mL/cm H2O. The chest CT scan revealed extensive ground-glass areas with a significant amount of traction bronchiectasis after 3 weeks since admission. When the patient was negative for SARS-CoV-2 during the 4th week of ECMO, the decision to perform an emergency lung transplantation (LTx) was made based on the ongoing degradation of lung function and irreversible damage to lung structure. The patient was transferred to the transplant center where he was extubated, awaiting the transplant on passive oxygen therapy and ECMO. Double lung transplantation was performed on the day 30th of ECMO. Currently, the patient is self-reliant. He does not need oxygen therapy and continues physiotherapy. ECMO may be life-saving in severe cases of COVID-19 ARDS but some of these patients may require LTx, especially when weaning proves impossible. VV ECMO as a bridging method is more difficult but ultimately more beneficial due to insufficient number of donors, and consequently long waiting time in Poland.

First lung and kidney multi-organ transplant following COVID-19 Infection.

As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

Experience of International Air Transportation and Subsequent Lung Transplant in a Patient with COVID-19-associated Acute Respiratory Distress Syndrome: a Case Report.

We report an inspiring case of a 55-year-old Korean female diagnosed with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) in Mexico. The patient was assessed for lung transplant as a salvage therapy for treatment-refractory ARDS following no signs of clinical improvement for > 7 weeks, despite best treatment. The patient was transported from Mexico to Korea by air ambulance under venovenous extracorporeal membrane oxygenation (ECMO) support. She was successfully bridged to lung transplant on day 88, 49 days after the initiation of ECMO support. ECMO was successfully weaned at the end of operation, and no bleeding or primary graft dysfunction was observed within the first 72 hours. The patient was liberated from mechanical ventilation on postoperative day 9 and transferred to the general ward 5 days later. Despite the high doses of immunosuppressants, there was no evidence of viral reactivation after transplant. At 3 months post-transplantation, she was discharged to home without complication. Our experience suggests that successful lung transplant for COVID-19-associated ARDS is feasible even in a patient with prolonged pre-transplant ECMO support. Lung transplant may be considered a salvage therapy for COVID-19-associated ARDS that does not respond to conventional treatments.

Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients.

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.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Lung transplantation during the outbreak of Coronavirus Disease 2019 in China.

OBJECTIVES: The study objectives were to illustrate our workflow for lung donation and transplantation during the Coronavirus Disease 2019 crisis and to report our preliminary experience with perioperative care. METHODS: We retrospectively analyzed data in the China Lung Transplantation Registration from January 23, 2020, to March 23, 2020 (2020 cohort), compared with the same period in 2019 (2019 cohort). Pre- and post-lung transplantation management strategies, including measures aiming to prevent severe acute respiratory syndrome coronavirus 2 infection, were applied to all recipients, including 5 post-Coronavirus Disease 2019 transplants during the Coronavirus Disease 2019 pandemic period in China. RESULTS: Twenty-eight lung transplant procedures were performed, including lung transplant for 5 patients with acute respiratory distress syndrome due to Coronavirus Disease 2019-related pulmonary fibrosis. Compared with the 2019 cohort, more patients with urgent conditions received transplantation in 2020, with a shorter pre-lung transplant admission time and early mobilization post-lung transplant. A large proportion (60%) of lung donations were transported on high-speed trains and commercial flights or highways and commercial flights. Grafts in the preservation containers were handed over to the receiving staff at the airport for 40% (10/25) of donations, which reduced the unnecessary quarantine of transporting staff entering the city. Listed candidates were urgently transferred to other qualified centers in 17.9% of cases (5/28), which reduced the risk of severe acute respiratory syndrome coronavirus 2 exposure in Coronavirus Disease 2019-designated hospitals. The 90-day survival of the transplant recipients in 2020 was 85.7%, including 3 of 5 recipients (60%) who had critically severe Coronavirus Disease 2019. CONCLUSIONS: Lung transplant and donation amid Coronavirus Disease 2019 can be performed safely with coordinated efforts on medical resource sharing and medical staff protection based on stratification of the infection risk. Outcomes were not compromised during the Coronavirus Disease 2019 outbreak. Lung transplantion can be regarded as salvage therapy for critical patients with Coronavirus Disease 2019 with a confirmed positive turned negative virology status.

Stem cell therapy in coronavirus disease 2019: current evidence and future potential.

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.