Editorial: COVID-19 immunology and organ transplantation.

PURPOSE OF REVIEW: The aim of this study was to provide a critical appraisal of the literature on the effects of the COVID-19 pandemic on organ transplantation, with a specific focus on lung transplantation given the predominant pulmonary involvement of the virus. RECENT FINDINGS: There was a significant decrease in lung transplant volumes during the first wave of the COVID-19 pandemic due to a combination of reduced availability of donors and an imbalance between waitlist additions and inactivations. SARS-CoV-2 infection was subsequently associated with an exuberant immune response that can lead to the development of postinfectious fibrotic lung disease. Few lung transplants have been performed in previously infected recipients and long-term outcomes remain unknown. Although the lung transplant volume rebounded during the second wave, it is unclear what the long-term effects of healthcare resource limitation and public health measures will have on transplant volumes in the future. Outcomes after SARS-CoV-2 infection in previous lung transplant recipients appear to be worse than the general public, and, although an immunosuppressed state likely contributes to these outcomes, whether immunosuppression should be altered in those exposed to or infected with SARS-CoV-2 remains unanswered in the absence of unequivocal data. SUMMARY: The COVID-19 pandemic has presented a number of challenges for lung transplant programs across the globe. Multiple research questions remain to be answered in order to optimally manage lung transplant recipients in the context of this pandemic.

Experiences and perceptions of receiving and prescribing rehabilitation in adults with cystic fibrosis undergoing lung transplantation.

BACKGROUND: Rehabilitation is prescribed to optimize fitness before lung transplantation (LTx) and facilitate post-transplant recovery. Individuals with cystic fibrosis (CF) may experience unique health issues that impact participation. METHODS: Patient and healthcare provider semi-structured interviews were administered to explore perceptions and experiences of rehabilitation before and after LTx in adults with CF. Interviews were analyzed via inductive thematic analysis. RESULTS: Eleven participants were interviewed between February and October 2021 (five patients, median 28 (IQR 27-29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare providers. Rehabilitation was delivered both in-person and virtually using a remote monitoring App. Six key themes emerged: (i) structured exercise benefits both physical and mental health, (ii) CF-specific physiological impairments were a large barrier, (iii) supportive in-person or virtual relationships facilitated participation, (iv) CF-specific evidence and resources are needed, (v) tele-rehabilitation experiences during the COVID-19 pandemic resulted in preferences for a hybrid model and (vi) virtual platforms and clinical workflows require further optimization. There was good engagement with remote data entry alongside satisfaction with virtual support. CONCLUSIONS: Structured rehabilitation provided multiple benefits and a hybrid model was preferred going forward. Future optimization of tele-rehabilitation processes and increased evidence to support exercise along the continuum of CF care are needed.

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation.

OBJECTIVE: The use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation. METHODS: The AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement. RESULTS: The expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively. CONCLUSIONS: Achieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.

Transplanting thoracic COVID-19 positive donors: An institutional protocol and report of the first 14 cases.

We present our institution's protocol for evaluating and transplanting thoracic organs from COVID-19 positive donors and report the outcomes to date. Hearts from donors testing positive for COVID-19 on any test were eligible for transplantation at our institution provided the donor exhibited no evidence of hypercoagulability or COVID-19 induced hyperinflammatory state during terminal hospitalization. Lungs were eligible if the donor first tested PCR positive on nasopharyngeal swab (NPS) for COVID-19 > 20 days prior to procurement and had a negative lower respiratory tract specimen. We performed 14 thoracic transplants in 13 recipients using organs from COVID-19 positive donors. None of the recipients or healthcare members acquired COVID-19. No recipients suffered unexpected acute rejection. Patient survival is 92% to date, with graft survival 93%. The use of hearts from COVID-19 positive donors may be safe and effective. Transplantation of lungs is unresolved but may be cautiously pursued under the restricted circumstances.

Heterotopic lung transplant: a feasible approach to compensate for organ shortages.

Lung transplants are still limited by the shortage of suitable donor lungs, especially during the coronavirus disease 2019 pandemic. A heterotopic lung transplant (HLTx), as a flexible surgical procedure, can maximize the potential of donor lungs in an emergency, but its widespread use is hindered by difficulties in anastomosis and paucity of outcome data. We performed a retrospective review of 4 patients, each of whom received an HLTxs over 1 year, including 1 left-to-right single HLTx, 2 right-to-left single HLTxs and 1 lobar HLTx (right upper lobe-to-left). The median recipient age was 58.5 years (46-68); 3 patients were male. The postoperative hospital stay was 33 days (30-42). One recipient lived for 10 years and died of bronchiolitis obliterans syndrome; the others were alive with no major morbidity at 12 to 31 months after the operation with a 1-year survival of 100%. The follow-up chest images showed that transplanted lungs could be inflated well and adapted morphologically to fill the thoracic cavity in the short and long term. This study demonstrates that an HLTx is a feasible alternative to a conventional lung transplant in emergency cases and could be considered in selected patients at advanced medical centres.

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 Severe Post-coronavirus Disease 2019 Respiratory Failure.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in >72 million cases and 1.6 million deaths. End-stage lung disease from COVID-19 is a new and growing entity that may benefit from lung transplant; however, there are limited data on the patient selection, perioperative management, and expected outcomes of transplantation for this indication. METHODS: A systematic review of the literature was performed with searches of MEDLINE and Web of Science databases as well as the gray literature. All manuscripts, editorials, commentaries, and gray literature reports of lung transplantation for COVID-related respiratory failure were included. A case from the University of Virginia is described and included in the review. RESULTS: A total of 27 studies were included: 11 manuscripts, 5 commentaries, and 11 gray literature reports. The total number of transplantations for COVID-related lung disease was 21. The mean age was 55±12 years, 16 (76%) were male individuals, and the acuity was high, with 85% on extracorporeal membrane oxygenation preoperatively. There was a 95% early survival rate, with 1 additional late death. There is growing histopathologic evidence for permanent structural damage with no replicating virus at the time of transplantation. CONCLUSIONS: Bilateral lung transplantation is an effective treatment option with reasonable short-term outcomes for patients with end-stage lung failure secondary to COVID-19. However, specific considerations in this new population require a multidisciplinary approach. As we move into the second wave of the COVID-19 global pandemic, lung transplantation will likely have a growing role in management of these complex patients.

Vaccination and their importance for lung transplant recipients in a COVID-19 world.

INTRODUCTION: Lung transplant patients are immunocompromised because of the medication they receive to prevent rejection, and as a consequence are susceptible to (respiratory) infections. Adequate vaccination strategies, including COVID-19 vaccination, are therefore needed to minimize infection risks. AREAS COVERED: The international vaccination guidelines for lung transplant patients are reviewed, including the data on immunogenicity and effectivity of the vaccines. The impact on response to vaccination of the various categories of immunosuppressive drugs, used in the posttransplant period, on response to vaccination is described. A number of immunosuppressive and/or anti-inflammatory drugs also is used for controlling the immunopathology of severe COVID-19. Current available COVID-19 vaccines, both mRNA or adenovirus based are recommended for lung transplant patients. EXPERT OPINION: In order to improve survival and quality of life, infections of lung transplant patients should be prevented by vaccination. When possible, vaccination should start already during the pre-transplantation period when the patient is on the waiting list. Booster vaccinations should be given post-transplantation, but only when immunosuppression has been tapered. Vaccine design based on mRNA technology could allow the design of an array of vaccines against other respiratory viruses, offering a better protection for lung transplant patients.

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.

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.

COVID-19 pneumonia in lung transplant recipients: Report of 2 cases.

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

Lung transplantation during the COVID-19 pandemic: Safely navigating the new "normal".

In the United States, an overall national decline in organ transplants has accompanied the substantial burden of COVID-19. Amidst significant regional variations in COVID-19, lung transplantation (LTx) remains a critical life-saving operation. Our LTx practice during the early pandemic may provide a blueprint for managing LTx in an era of continued community prevalence. Patients who underwent LTx at our institution between March 1 and May 20, 2020 were included. Recipient, operative, and donor characteristics were compared to those from our program in 2019, and COVID-19 testing practices were evaluated for March, April, and May to understand how our practice adapted to the pandemic. Our program performed 36 LTx, 33% more than the same period in 2019. Recipient, operative, and donor characteristics during COVID-19 were similar to those in 2019. By April 1, all donors and recipients underwent pretransplant COVID-19 testing, all returning negative results. To date, no recipients have developed posttransplant COVID-19. At our institution, pretransplant COVID-19 testing, use of local donor lungs, and avoidance of donors from areas of increased community penetration supported a safe and effective LTx practice during the early COVID-19 pandemic. Continued follow-up is required to ensure the long-term safety of these newly transplanted patients.

Current precautions and future directions in lung transplantation during the COVID-19 pandemic - a single center cohort study.

The unprecedented public health emergency caused by the acute viral respiratory coronavirus disease (COVID-19) has drastically changed current practices in solid organ transplantation, markedly so for transplantation of the lungs, the major target of the virus. Although national and state authorities do not recommend postponing transplant procedures, most specialists are reluctant to proceed due to substantial uncertainty and increased risks in the midst of the pandemic. There is an urgent need for evidence-based directions to move forward. Here, we offer our insights as specialists at a high-volume center located in a geographical area with high infection rates.

COVID-19 in lung transplant patients: A case series.

Several case reports and small case series have been published on coronavirus disease 2019 infection after solid organ transplantation; however, thus far there are limited data on coronavirus disease 2019 infections in lung transplant patients. In the present single-center case series we discuss 10 lung transplant patients with a documented severe acute respiratory syndrome coronavirus 2 infection, diagnosed with nasopharyngeal swab in 8 and bronchoalveolar lavage in 2. Eight of 10 patients needed hospital admission, of whom 1 was in the intensive care unit. He died after 2 weeks from multiple organ failure. The remaining nine patients recovered. Cell cycle inhibitors were withheld in all patients, whereas the calcineurin inhibitor and corticosteroids were continued at the same dose, with an acceptable outcome.