By Elaine Chen, MD
Associate Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Section of Palliative Medicine, Rush University Medical Center, Chicago
At the time of this writing, 1 million American lives have been lost due to COVID-19.1 Many more people are experiencing ongoing symptoms and disability as a result of sequelae of their disease. As we have learned more about COVID-19, our ability to care for patients with severe disease has improved, and we are better able to manage and support patients through critical illness. Lung transplantation has been used as a life-saving measure in some patients with severe, persistent lung disease due to COVID-19 pneumonia. This article will explore the history and epidemiology of lung transplantation and discuss its application and ethics in the COVID-19 pandemic.
Background of Lung Transplant
A kidney was the first solid organ to be successfully transplanted in Boston in 1954.2 This was followed by successful liver, heart, and pancreas transplants in the 1960s. The first lung transplants in the United States also took place that same decade. The benefits of these lung transplants were limited in these early attempts, with the longest survival 10 months.3 Since then, lung transplantation outcomes have improved substantially.
Ethics has been a prominent topic of discussion since the field of transplantation began. Laws and policies in the United States have evolved to support ethical organ harvesting, patient selection practices, and improvements in transplantation outcomes. In 1968, the Uniform Anatomical Gift Act was adopted by all 50 states, representing the first national law passed to regulate transplantation. This was further strengthened in 1972, when uniform donor cards were recognized as legally binding nationwide. In 1984, the National Organ Transplant Act was passed. This act called for an Organ Procurement and Transplantation Network (OPTN) to be created and run by a private, nonprofit organization under federal contract. The United Network for Organ Sharing (UNOS) was established and awarded the OPTN contract in 1986 by the U.S. Department of Health and Human Services and has held this role continuously to the present day. Organ procurement organizations are regionally run nonprofit organizations that manage and coordinate the evaluation and procurement of deceased donor organs. All are certified by the Centers for Medicare and Medicaid Services as well as the Association of Organ Procurement Organizations.
The epidemiology of lung transplantation has evolved substantially over the years. Since UNOS has been collecting detailed information, more than 45,000 lung transplants have been completed in the United States.4 Numbers have increased steadily, with 2,530 transplants completed in 2018 and 2,714 completed in 2019. In 2020-2021, transplant volumes decreased because of COVID-19-related shifts in healthcare, but thus far in 2022, they appear to be rebounding. The most common indication for lung transplantation is chronic obstructive pulmonary disease (COPD), followed by interstitial lung disease (ILD) primarily due to idiopathic pulmonary fibrosis (IPF), bronchiectasis primarily due to cystic fibrosis (CF), and pulmonary hypertension.5 Post-transplant life expectancy varies, often because of the nature of the underlying lung disease and associated comorbidities. For example, patients with CF were among the earlier patients who often had longer post-transplant life expectancy due in large part to their younger age compared to transplant recipients with COPD and IPF. Post-transplant survival has increased significantly, with median survival increasing from 2.1 years before 1993 to 5.8 years after 2005.6 With these improving outcomes, lung transplantation is becoming an increasingly attractive option for patients with severe pulmonary disease to improve both quality and quantity of life.
Despite these promising gains, lung transplant volumes and outcomes lag behind kidney and liver transplant programs because of the many unique challenges. Compared to the 2,714 lung transplants in 2019, there were 23,401 kidney transplants and 8,896 liver transplants. Lungs are harder to retrieve in the donation after cardiovascular death (DCD) setting, and most transplanted lungs come from donors after death by neurologic criteria. The wait time for lung transplant remains long, and many patients die before transplantation. The Lung Allocation Score (LAS) was implemented in 2005 and is designed to weigh clinical factors that predict survival with and without transplantation. LAS has improved transplant outcomes, including decreased time to transplant, increased transplant volume, and increased one-year survival.7 The LAS includes factors such as oxygenation, pulmonary function, age, body mass index, comorbidities, age, and diagnosis, among others.
COVID-19 Pneumonia
There have been unprecedented levels of acute respiratory distress syndrome (ARDS) and severe hypoxic respiratory failure during the COVID-19 pandemic. Many people died of COVID-19-related complications despite our best efforts. Some deaths were the result of multi-organ failure, and others were because of refractory hypoxemia or hypercapnia due to ARDS or post-ARDS fibrosis. Since the beginning of the pandemic in early 2020, treatments and therapies have evolved and changed. Overall, the longstanding principles of detailed and thorough supportive critical care made the largest impact on patient survival. Many patients experienced prolonged mechanical ventilation and support with extracorporeal membrane oxygenation (ECMO), some of whom slowly recovered. Others experienced long-term sequelae, including post-COVID-19 pulmonary fibrosis despite these efforts.8 Post-COVID-19 pulmonary fibrosis (PCPF) is, as of now, a heterogeneous condition characterized by radiographic evidence of fibrosis impairment in diffusion capacity and total lung capacity. It is yet unknown whether PCPF is partially reversible or will be permanent, but its impact on patients is clearly substantial.
Lung Transplantation in COVID-19 Patients
Lung transplantation has been explored as a treatment for COVID-19-related lung disease. The first transplant was performed at Northwestern Memorial Hospital in Chicago with significant media fanfare. A 28-year-old paralegal, immunosuppressed on steroids due to neuromyelitis optica, had a bilateral lung transplant on June 5, 2020.9,10 Prior to transplant, she had multi-organ failure and had been supported by ECMO for six weeks. She experienced a prolonged recovery period after transplant, but soon she was breathing without oxygen support. One year later, she had returned to work as a paralegal but has continued to struggle with anxiety, panic attacks, persistent physical impediments, and her course was complicated by sternal wound infection.11 Her medical team cited her as the sickest patient they had ever transplanted, and they did not expect her to survive otherwise.10
Many more lung transplants have been performed subsequently in patients for COVID-19-related lung disease. Some were critically ill with ARDS similar to the index case, and others had chronic respiratory failure due to lung fibrosis leading to significant disability. A recent report describes COVID-19 lung transplants in the United States between Aug. 1, 2020, and Sept. 30, 2021. During this 14-month time frame, 3,039 total lung transplants were performed, of which 214 (7%) were for COVID-19-related respiratory failure: 149 (4.6%) for ARDS and 74 (2.4%) for pulmonary fibrosis.12 In this cohort, 183 patients had validated data, and there were nine post-operative deaths. Thirty-day mortality was 2.2%, and three-month survival was 95.6%, similar to outcomes among lung transplantation for reasons other than COVID-19.
Ethical Considerations
Because transplant is both a life-saving procedure and a scarce resource, ethics always have been a key consideration in this pioneering field, particularly with lung transplantation. The ethical principles of utility, justice, and efficiency must be considered in addition to the pillars of beneficence, non-maleficence, and autonomy.13 The four box method is an ethical framework described by Jonsen, Siegler, and Winslade that can be applied to many clinical situations, including the discussion of lung transplant in the era of COVID-19.15 These four boxes include Medical Indications, Patient Preferences, Quality of Life, and Contextual Features. Within each box, the ethical principles described earlier are applied for consideration.
The medical indications of transplant for COVID-19 pneumonia are complex. Recognizing the limited long-term data and resulting uncertainty of patient outcomes without transplantation, clinicians must extrapolate their assessment regarding whether an individual patient’s condition is acute, chronic, reversible, or terminal based on knowledge from other conditions. We have all been surprised by both the successes and poor outcomes in patients with severe COVID-19 pneumonia, with some patients surviving in whom death seemed certain, and others dying without warning. Patient preferences may be compromised in the setting of COVID-19 ARDS, when surrogate decision-making must be employed when patients lack decision-making capacity without the benefit of the usual full patient psychological and social assessment, often without the benefit of a prior conversation to determine the patient’s wishes and attitudes toward transplantation. The differences in quality of life with and without transplantation also are difficult to predict given the uncertainty of the natural course of the disease. A previously healthy patient with COVID-19 ARDS, for example, will need to manage both the disability and recovery from a prolonged clinical course often associated with post-intensive care syndrome and the new, chronic medical complexities of transplantation. Recall, as detailed earlier, the prolonged course of the first reported COVID-19 lung transplant.11
There also are contextual features that must be considered carefully in the setting of COVID-19 pneumonia. The Lung Allocation Score objectively assigns value in the setting of a very scarce resource, yet assigning a score to the diagnosis of COVID-19 may be disputed by various parties.16 Concerns about conflicts of interest, vaccination status, and confidentiality may arise. Will transplanting a patient with an acute, life-threatening illness from COVID-19 ARDS thus prevent a patient with longstanding chronic lung disease from receiving a transplant that could vastly improve their quality of life or who could die while awaiting their turn? Does it improve or worsen the overall societal benefit from lung transplantation, maximizing quality of life for the most number of person-years possible?13
Vaccination for COVID-19 pneumonia also must be considered in the contextual features associated with COVID-19 lung transplantation. Given the increased risk of serious illness because of infection from post-transplant immunosuppression, adherence to the Centers for Disease Control and Prevention (CDC) vaccination schedules prior to transplantation has long been a requirement for transplant listing.17 The first lung transplants for COVID-19 occurred prior to the introduction of the COVID-19 vaccine. Following widespread availability of the vaccine, many, if not most, patients with severe illness and sequelae were not vaccinated. Should vaccination status be a consideration for transplant, whether for acute ARDS or for fibrotic disease? In a survey of American transplant centers in the fall of 2021, 36% of responding centers reported a vaccine mandate prior to transplantation, while 61% had not (the remainder were unsure).18 Some transplant centers have recommended that COVID-19 vaccination be a requirement for both potential solid organ transplant recipients and their support person, and that such a recommendation should be easily received and consistent with current standard practices for other vaccinations prior to organ transplant.19 At the current time, there is no universal standard.
Early in the COVID-19 pandemic, the International Society of Heart and Lung Transplant (ISHLT) released a task force statement when allocation of intensive care unit resources, including ventilators and ECMO for critically ill COVID-19 patients, was at the forefront.14 Ethical considerations always have been complex in all organ transplantation, especially lung, given the desire to optimize the benefit of this incredibly scarce resource, and the pandemic has only increased this complexity. A 2021 consensus statement published by ISHLT provides guidance regarding patient selection for transplantation and suggests that for now COVID-19 ARDS likely should be evaluated like other causes of post-viral ARDS based on the preliminary experience to date.13
Conclusion
In the era of COVID-19, lung transplantation has emerged as a potentially life-saving intervention for both patients dealing with refractory acute lung disease requiring ECMO for ARDS and those who develop post-COVID-19 pulmonary fibrosis. Controversies will always exist surrounding lung transplantation, especially with COVID-19 pneumonia, and the medical establishment must continue to thoughtfully ask and reflect on these questions.20 Ultimately, our duty is to ensure that we deliver the best care to both this group and patients with other end-stage lung diseases on the waitlist, using the limited resource of lung transplant to provide the best possible outcomes. While I hope that continued advances in COVID-19 treatment will reduce the related morbidity and mortality, it seems that COVID-19 is here to stay, and lung transplants will continue to be performed for those who experience its severe sequelae.
REFERENCES
- Coronavirus in the U.S.: Latest map and case count. The New York Times. Published March 3, 2020. https://www.nytimes.com/interactive/2021/us/covid-cases.html
- Leeson S, Desai SP. Medical and ethical challenges during the first successful human kidney transplantation in 1954 at Peter Bent Brigham Hospital, Boston. Anesth Analg 2015;120:239-245.
- Veith FJ, Koerner SK. The present status of lung transplantation. Arch Surg 1974;109:734-740.
- U.S. Department of Health and Human Services. Organ Procurement and Transplantation Network. National data. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#
- Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart–Lung Transplant Report—2016; Focus Theme: Primary diagnostic indications for transplant. J Heart Lung Transplant 2016;35:1170-1184.
- Yusen RD, Shearon TH, Qian Y, et al. Lung transplantation in the United States, 1999-2008. Am J Transplant 2010;10:1047-1068.
- Egan TM, Edwards LB. Effect of the lung allocation score on lung transplantation in the United States. J Heart Lung Transplant 2016;35:433-439.
- Ambardar SR, Hightower SL, Huprikar NA, et al. Post-COVID-19 pulmonary fibrosis: Novel sequelae of the current pandemic. J Clin Med 2021;10:2452.
- Northwestern Memorial Hospital. Meet the two COVID-19 patients who received double-lung transplants at Northwestern Medicine. Northwestern Medicine. Published July 30, 2020. https://www.nm.org/about-us/northwestern-medicine-newsroom/press-releases/2020/meet-the-two-covid19-double-lung-transplant-patients
- Herman C. 1st-known U.S. lung transplant for COVID-19 patient performed in Chicago. NPR. Published June 12, 2020. https://www.npr.org/sections/health-shots/2020/06/12/875486356/first-known-u-s-lung-transplant-for-covid-19-patient-performed-in-chicago.
- Herman C. ‘Happy to be alive’ after surviving COVID and a double-lung transplant. Illinois Newsroom. Published March 9, 2021. https://illinoisnewsroom.org/im-happy-to-be-alive-covid-lung-transplant-survivor-reflects-on-the-past-year/
- Roach A, Chikwe J, Catarino P, et al. Lung transplantation for Covid-19–related respiratory failure in the United States. N Engl J Med 2022;386:1187-1188.
- Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2021;40:1349-1379.
- Holm AM, Mehra MR, Courtwright A, et al. Ethical considerations regarding heart and lung transplantation and mechanical circulatory support during the COVID-19 pandemic: An ISHLT COVID-19 Task Force statement. J Heart Lung Transplant 2020;39:619-626.
- Jonsen AR, Siegler M, Winslade WJ, eds. Introduction. In: Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine. 9th ed. McGraw-Hill; 2022. accessmedicine.mhmedical.com/content.aspx?aid=1186991627
- Lepper PM, Langer F, Wilkens H, et al. Lung transplantation for COVID-19-associated ARDS. Lancet Respir Med 2021;9:e88.
- Doheny K. No COVID vax, no transplant: Unfair or good medicine? WebMD. Published Feb. 4, 2022. https://www.webmd.com/lung/news/20220204/no-covid-vax-no-transplant-unfair-or-good-medicine
- Hippen BE, Axelrod DA, Maher K, et al. Survey of current transplant center practices regarding COVID-19 vaccine mandates in the United States. Am J Transplant 2022;22:1705-1713.
- Kuczewski M, Wasson K, Hutchison PJ, Dilling DF. Putting ethics and clinical decision making before politics: Requiring COVID-19 immunization for Solid Organ Transplantation (SOT) candidates and their support team. J Heart Lung Transplant 2022;41:17-19.
- Abelson D, Glanville AR. Controversies and emerging topics in lung transplantation. Breathe (Sheff) 2018;14:278-287.
This article will explore the history and epidemiology of lung transplantation and discuss its application and ethics in the COVID-19 pandemic.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content