Lung Transplant for COVID-19-Associated Lung Failure: The Pandemic’s Next Challenge

Written by: Pablo Sanchez, MD, PhD, FACS

As the COVID-19 pandemic has progressed and evolved worldwide, lung transplant surgeons have observed, adapted, and persevered to provide life-saving care to patients with end-stage lung disease. The challenges faced in the first half of 2020 have been replaced with those posed by debilitated patients with end-stage lung damage caused by COVID-19. Throughout, lung transplant recipients with COVID-19 infections have required care.

In 2020, lung transplant surgeons were tasked with continuing to transplant lungs to patients who desperately needed them in the midst of a highly contagious virus with no vaccine and few effective treatments. As of late 2022, vaccines and boosters against COVID-19, antiviral therapeutics, and a better understanding of COVID-19 illness have allowed us to overcome most of these hurdles. Instead, we are facing new challenges as we are increasingly caring for debilitated patients with end-stage lung damage as a result of COVID-19 infection, some of whom have spent months supported by mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

Lung Transplant in Patients With Lung Failure Due to COVID-19

Although many patients recover from acute respiratory distress syndrome due to COVID-19, some with and some without the use of ECMO, other patients may never recover sufficiently to be weaned from respiratory support. Additionally, COVID-19 illness can lead to pulmonary fibrosis, necessitating lung transplant. Despite concerns, thoracic surgeons began to perform lung transplants in selected patients who required ECMO for COVID-19-associated lung failure in 2020, and perhaps somewhat surprisingly, outcomes have been good in these patients. Currently, approximately 10% of lung transplants in the United States are being performed for COVID related respiratory failure from either COVID-associated acute respiratory distress syndrome (CARDS) or post- COVID pulmonary fibrosis.

The International Society of Heart and Lung Transplantation recommends carefully selecting patients for post- COVID lung transplant only if severe lung injury has been present for more than 28 days and there are indications of irreversibility noted in imaging and ventilatory studies. Lung dysfunction should be the only COVID-19-related morbidity in the potential recipient, and they must be free of active COVID infection and meet all of the center’s criteria to be admitted to candidacy.

The COVID-19 pandemic is changing practice in the field as we navigate lung transplant in severely debilitated patients.

More than 50% of recipients of a lung transplant for COVID-19-associated lung failure have been placed on ECMO support as a bridge to transplant, so consideration for lung transplant candidacy must reflect the deconditioning that occurs while sick for several months on ECMO. We have needed to adopt different thresholds for the ability to walk and participate in reconditioning exercises while on ECMO when considering these patients for lung transplant candidacy. Additionally, we must consider transplant in patients who have myopathy or neuropathy that would have been a deterrent from listing for transplant prior to the COVID-19 pandemic. We also have learned that dual-organ lung-kidney transplants are associated with successful outcomes in patients with both respiratory and renal failure, but that lung-liver transplants should be approached with extreme reserve.

Both in Pittsburgh and nationally, posttransplant outcomes have been good, but the effort required by both the care team and the patient is immense. When outcomes were examined in patients who underwent lung transplant from August 2020 through September 2021 using national data from the United Network for Organ Sharing (UNOS) database, survival rates three months after double lung transplant was 95.6% in 183 patients from the United States with validated data who underwent lung transplant for COVID-19-associated lung disease. In a propensity-matched analysis of all lung transplants for CARDS vs. lung transplants for non-COVID lung diseases from 2006 through 2021 using the UNOS database, similar posttransplant outcomes were observed in COVID-19 lung transplant recipients as compared with other lung transplant recipients with similar lung function pretransplant, including similar survival six months posttransplant (94% COVID vs. 88% non-COVID, p=0.26).

A large, single-center analysis from Northwestern University Medical Center in Chicago compared the outcomes of 30 patients who underwent lung transplantation for CARDS and 72 lung transplant recipients without COVID-19 from January 2020 through September 2021. Median time from onset of CARDS to lung transplant was 104 days, typically due to the need to assess whether lung function was recoverable. Posttransplant ICU and hospital stays were twice as long on average as compared with patients transplanted for non-COVID lung failure, and primary graft dysfunction (PGD) occurred three-times more frequently in the first 72 hours posttransplant. Nonetheless, with a median follow-up of 351 days for patients with COVID-19 and 488 days for non-COVID patients, 100% survival was seen in the 30 patients who underwent lung transplant for CARDS compared to 83% in the patients with transplant for non-COVID lung failure.

Our experiences in Pittsburgh have been concordant with these published reports. At most transplant centers in the United States, it has been common for patients to be supported with ECMO for at least three months before COVID-19 lung disease was considered unrecoverable. Many of these patients were quite debilitated when they were being considered for transplant but were, on average, significantly younger than lung transplant recipients with non-COVID lung failure. Posttransplant, they require extensive physical therapy, and their hospital stays posttransplant have been considerably longer overall.

COVID-19 in Lung Transplant Recipients

As we have cared for lung transplant recipients, we have observed that if a patient is vaccinated prior to transplant, it is highly likely that they will only develop mild disease if they are infected with COVID-19 posttransplant. If a lung transplant recipient is vaccinated after transplant, a mild disease course following COVID-19 infection is less assured due to impact of the immunosuppressive regimens needed to prevent allograft rejection on vaccine-induced immunity. Even though outcomes have improved with access to other therapies (e.g., antiviral therapies) and most COVID-19 therapies have a low potential for interaction with immunosuppressive medication, lung transplant recipients with posttransplant administration of vaccines can still get very sick or die from COVID-19. Additionally, COVID infection is associated with increased episodes of graft rejection. Managing rejection by increasing immunosuppression in the setting of the COVID virus is difficult. Vaccination before transplant is the best way to avoid this clinical tight spot requiring challenging multidisciplinary care. We very strongly recommend that all lung transplant candidates get vaccinated and maintain their fully vaccinated status with boosters even though vaccination is not required for listing as transplant candidate.

Late Referral for Lung Transplant Evaluation in the Third Year of the COVID-19 Era

At UPMC, the number of patients that we evaluate and transplant annually is almost back to pre-COVID levels, but unfortunately, the proportion of patients who are referred for lung transplant evaluation late in the progression of their lung disease has increased. Most of these patients have pulmonary fibrosis, which is tricky to manage in and of itself because symptoms get worse very gradually as the lung segments become more and more affected. Fibrotic disease can be very advanced by the time a patient realizes that he or she is significantly out of breath. Some patients are referred after it is too late for us to be able to list them as lung transplant candidates. Additionally, urgent evaluations present their own complexities, especially if a patient is behind on recommended preventative screenings (e.g., colonoscopy) or is not vaccinated. We might have days to get someone transplanted but need to catch up on years of health care. Overcoming patient reluctance to engage the health care system, especially reluctance driven by the COVID-19 pandemic, should be prioritized to promote earlier evaluation for lung transplant candidacy.

In 2021 and 2022, eight lung transplants were performed at UPMC for end-stage lung failure caused by COVID-19 infection, and we are continually evaluating patients and listing potential recipients for lung transplant candidacy. To date, all of the patients we have transplanted for COVID-associated lung failure are doing well. In the UPMC Department of Cardiothoracic Surgery Division of Lung Transplant and Lung Failure, we are continuing to rise to the challenges posed by COVID-19 as we offer life-saving lung transplants.