Rehabilitation Characteristics and Outcomes for Lung Transplantation for COVID-19: A Case Series.

OBJECTIVE: Severe coronavirus disease 2019 (COVID-19) can result in irreversible lung damage, with some individuals requiring lung transplantation. The purpose of this case series is to describe the initial experience with the rehabilitation and functional outcomes of 9 patients receiving a lung transplant for COVID-19. METHODS: Nine individuals, ranging in age from 37 to 68 years, received bilateral orthotopic lung transplantation (BOLT) for COVID-19 between December 2020 and July 2021. Rehabilitation was provided before and after the transplant, including in-hospital rehabilitation, postacute care inpatient rehabilitation, and outpatient rehabilitation. RESULTS: Progress with mobility was limited in the pretransplant phase despite rehabilitation efforts. Following transplantation, 2 individuals expired before resuming rehabilitation, and 2 others had complications that delayed their progress. The remaining 5 experienced clinically important improvements in mobility and walking capacities. CONCLUSION: Considerable rehabilitation resources are required to care for individuals both before and after BOLT for COVID-19. Rehabilitation can have a profound impact on both functional and clinical outcomes for this unique patient population. IMPACT: There is limited literature on the rehabilitation efforts and outcomes for patients who received BOLT for COVID-19. Occupational therapists and physical therapists play an important role during the pretransplant and posttransplant recovery process for this novel patient population. LAY SUMMARY: Patients with a bilateral orthotopic lung transplant due to COVID-19 require a unique rehabilitation process. They have significant difficulties with activities of daily living and functional mobility across the pretransplant and posttransplant continuum of care, but progressive gains in functional performance may be possible with a comprehensive multidisciplinary rehabilitation program.

OPTN/SRTR 2021 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

Periodontal Maintenance in a Patient with a Lung Transplantation Post-COVID-19 Infection.

Early dental screening and treatment before and after solid organ transplantation are recommended infection prophylaxis measures. Dental treatment after transplantation should only be rendered after a discussion with the patient's health-care provider and/or transplant surgeon to determine the patient's stability for dental care. Potential sources of acute or chronic oral infections should be evaluated at every visit. Periodontal evaluation and through dental prophylaxis should be performed. Oral hygiene instruction including the importance of maintaining excellent oral health after transplant should be reviewed.

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.

COVID-19 in Lung Transplant Recipients.

BACKGROUND: A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients. METHODS: Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed. RESULTS: Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02). CONCLUSIONS: For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%.

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.

Long-term extracorporeal membrane oxygenation - from SARS-CoV-2 infection to lung transplantation. / Oxigenação por membrana extracorpórea de longa duração - da infecção por SARS-CoV-2 ao transplante pulmonar.

A healthy 55-year-old woman unvaccinated for SARS-CoV-2 was admitted to the hospital with a SARS-CoV-2 infection with rapid clinical deterioration. On the 17th day of disease, she was intubated, and on the 24th day, the patient was referred and admitted to our extracorporeal membrane oxygenation center. Extracorporeal membrane oxygenation support was initially used to enable lung recovery and allow the patient to rehabilitate and improve her physical condition. Despite an adequate physical condition, the lung function was not adequate to discontinue extracorporeal membrane oxygenation, and the patient was considered for lung transplantation. The intensive rehabilitation program was implemented to improve and maintain the physical status throughout all phases. The extracorporeal membrane oxygenation run had several complications that hindered successful rehabilitation: right ventricular failure that required venoarterial-venous extracorporeal membrane oxygenation for 10 days; six nosocomial infections, four with progression to septic shock; and knee hemarthrosis. To reduce the risk of infection, invasive devices (i.e., invasive mechanical ventilation, central venous catheter, and vesical catheter) were removed whenever possible, keeping only those essential for monitoring and care. After 162 days of extracorporeal membrane oxygenation support without other organ dysfunction, bilateral lobar lung transplantation was performed. Physical and respiratory rehabilitation were continued to promote independence in daily life activities. Four months after surgery, the patient was discharged.

Mulher de 55 anos, saudável e não vacinada para SARS-CoV-2, foi admitida no hospital por infecção SARS-CoV-2 com rápida deterioração clínica. No 17º dia de doença, foi intubada e, no 24º dia, a paciente foi referenciada e admitida no nosso centro de oxigenação por membrana extracorpórea. Inicialmente, o suporte de oxigenação por membrana extracorpórea foi utilizado para possibilitar a recuperação pulmonar e permitir à paciente reabilitar e melhorar sua condição física. Apesar de apresentar uma condição física adequada, a função pulmonar não permitiu suspender a oxigenação por membrana extracorpórea, e a paciente foi aceita para transplante pulmonar. Um programa de reabilitação intensiva foi implementado para melhorar e manter o estado funcional da paciente em todas as fases. O curso de oxigenação por membrana extracorporal apresentou várias complicações que prejudicaram a reabilitação: falência ventricular direita, que exigiu oxigenação por membrana extracorpórea venoarterial-venosa durante 10 dias; seis infecções nosocomiais, sendo quatro com progressão para choque séptico; e hemartrose do joelho. Para reduzir o risco de infecção, sempre que possível removeram-se os dispositivos invasivos (ventilação mecânica invasiva, cateter venoso central e cateter vesical), mantendo-se apenas aqueles estritamente necessários à monitorização e tratamento. Após 162 dias de suporte de oxigenação por membrana extracorpórea sem outra disfunção orgânica, foi realizado o transplante pulmonar lobar bilateral. A reabilitação física e respiratória foi mantida para promover a autonomia nas atividades da vida diária. A paciente recebeu alta hospitalar 4 meses após a cirurgia.

Organ Donation, the Non-Perfect Lung Donor, and Variability in Conversion to Transplant.

Rates of lung donation have increased over the past several years. This has been accomplished through the utilization of donors with extended criteria, the creation of donor hospitals or centers, and the optimization of lungs through the implementation of donor management protocols. These measures have resulted in augmenting the pool of available donors thereby decreasing the wait time for lung transplantation candidates. Although transplant programs vary significantly in their acceptance rates of these organs, studies have not shown any difference in the incidence of primary graft dysfunction or overall mortality for the recipient when higher match-run sequence organs are accepted. Yet, the level of comfort in accepting these donors varies among transplant programs. This deviation in practice results in these organs going to lower-priority candidates thereby increasing the waitlist time of other recipients and ultimately has a deleterious effect on an institution's waitlist mortality.

First use of imlifidase desensitization in a highly sensitized lung transplant candidate: a case report.

Lung transplant candidates who are highly sensitized against human leucocyte antigen present an ongoing challenge with regards to finding immunologically acceptable donors. Desensitization strategies aimed at reducing preformed donor-specific antibodies have a number of limitations. Imlifidase, an IgG-degrading enzyme derived from Streptococcus pyogenes, is a novel agent that has been used to convert positive crossmatches to negative in kidney transplant candidates, allowing transplantation to occur. We present the first case of imlifidase use for antibody depletion in a highly sensitized lung transplant candidate who went on to undergo a successful bilateral lung transplant.

Advanced Cystic Fibrosis Lung Disease and Lung Transplantation in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have changed the clinical landscape of cystic fibrosis (CF) by improving clinically significant outcome measures and quality of life of people with CF (pwCF). There are now long-term data showing improved 5-year survival with the use of ivacaftor, and the field continues to evolve at a rapid pace with the continued development of highly effective CFTR modulators. While the randomized controlled trials of CFTR modulators excluded patients with severe lung disease (forced expiratory volume in 1 second <40% predicted), observational data based on case reports and registry data show similar benefits in those with advanced lung disease. This has altered clinical practice particularly as it pertains to the role of lung transplantation in CF. This article describes the impact of highly effective modulator therapy (HEMT) on the natural history of CF and the influence on the timing of referral and consideration of listing for lung transplantation. CF clinicians play a pivotal role to ensure that the impetus of the CF foundation consensus guidelines to facilitate timely referral for lung transplantation is not lost among the excitement of anticipated sustained benefit from HEMT. While the widespread availability of elexacaftor/tezacaftor/ivacaftor over the past 2 years has been associated with a sharp drop in the number of people referred for consideration for lung transplantation and the number of people wait-listed for lung transplantation, it is difficult to accurately determine the true impact due to the confounding effect of the coronavirus disease 2019 pandemic. It is expected that lung transplantation will remain an important treatment for a smaller number of pwCF. Lung transplantation offers survival benefits in CF, and there remains an imperative to ensure timely consideration of lung transplantation in patients with advanced disease to further reduce the number of pwCF dying without consideration of lung transplant.

Multimodal Remote Home Monitoring of Lung Transplant Recipients during COVID-19 Vaccinations: Usability Pilot Study of the COVIDA Desk Incorporating Wearable Devices.

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5-8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the RPM system deployment was proven by the rapid recruitment uptake, technical performance (i.e., low number of errors), favorable user experience questionnaires and detailed individual user feedback.

COVID-19 in pediatric lung transplant recipients: Clinical course and outcome.

BACKGROUND: COVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients. METHODS: Between March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded. RESULTS: Nineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p = 0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable. CONCLUSIONS: Unlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.

Case Report: Recurrence of Acute Respiratory Distress Syndrome After Bilateral Lung Transplantation.

BACKGROUND: The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. RESULTS: After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. CONCLUSION: With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.

Pediatric lung transplantation for COVID-19: Unique clinical and psychosocial barriers.

BACKGROUND: SARS-CoV-2 infection in the age group of 0-17 years contributes to approximately 22% of all laboratory-confirmed SARS-CoV-2 infections. Fortunately, this age group has a lower death rate (0.5 per 100 000) that accounts for only 4% of the total deaths due to COVID-19. Despite the low mortality rate in the pediatric population, children of minority groups represented 78% of the deaths highlighting the existing disparities in access to health care. METHODS: With the emergence of the more contagious COVID-19 variants and the relatively slow pace of vaccination among the pediatric population, it is possible to see more cases of significant lung injury and potential for transplantation for the younger age group. RESULTS: To our knowledge, our patient is the youngest to have undergone lung transplantation for SARS-CoV-2. CONCLUSION: The case presented unique challenges, particularly in relation to timing for listing and psychosocial support for parents who were his decision makers.