Lung Transplants and COVID
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This single-center case series describes the clinical characteristics, intraoperative procedures, postoperative complications, and survival of a cohort of lung transplant recipients who had COVID-19–associated ARDS, with data about non–COVID-19–related lung transplant recipients presented for context.
As the COVID-19 pandemic evolves across the globe, lung transplantation will continue to be considered as a salvage therapy for patients with COVID-19–associated ARDS who do not recover despite maximum ventilatory support, use of ECMO, and optimal medical care.17-19 To our knowledge, this single-center case series represents the largest series to date reporting the posttransplant survival of patients undergoing lung transplant for COVID-19–associated ARDS.
Prior to lung transplant, patients with COVID-19–associated ARDS have prolonged respiratory failure when compared with patients with pneumonia secondary to other respiratory pathogens,20,21 and as a result, they commonly develop complications of prolonged critical illness including malnutrition and neuromuscular deconditioning.22 Many patients with COVID-19–associated ARDS also develop severe pleural adhesions and secondary pneumonias from invasive nosocomial pathogens.23,24 These complications raise concerns about the technical feasibility of lung transplant as well as posttransplant outcomes in this critically ill cohort. The findings of this study suggest that despite these concerns, successful outcomes can be achieved in these patients following lung transplant.
All patients in this study with COVID-19–associated ARDS underwent double lung transplant due to the severity of lung damage and the high incidence of pulmonary necrosis, bronchiectasis, ventilator-associated pneumonia caused by multidrug-resistant pathogens, and pulmonary hypertension with concomitant right ventricular dysfunction observed among these patients.7,25 Use of cardiopulmonary bypass may be associated with worse outcomes following lung transplant.26 However, due to the high incidence of pulmonary hypertension and right ventricular dysfunction observed in patients with COVID-19–associated ARDS,7 and concerns about the severity of pleural adhesions, intraoperative cardiopulmonary support was necessary. In an attempt to reduce total blood loss and decrease the need for blood transfusion anticipated with cardiopulmonary bypass,27-29 venoarterial ECMO was routinely used for the patients with COVID-19 in this study.
Patients with COVID-19–associated ARDS can develop ventilator-associated pneumonia, often with resistant pathogens.24 However, during surveillance bronchoscopies performed at 1, 3, 6, 9, and 12 months after lung transplant, none of the patients with COVID-19 had evidence of nosocomial pathogens. In addition, none demonstrated recurrence of SARS-CoV-2 on bronchoscopy following lung transplant, suggesting that the preoperative approach of assessing for clearance of SARS-CoV-2 using polymerase chain reaction testing of 2 consecutive lower respiratory fluid samples 24 hours apart was appropriate.30,31
Patients with COVID-19–associated ARDS had high intraoperative blood loss that required transfusion of a large number of blood products, likely reflecting the increased technical complexity of the procedure in the COVID-19 cohort.27 Despite high rates of primary graft dysfunction, patients with COVID-19–associated ARDS had a substantial improvement in their Karnofsky Performance Status after lung transplant. This improvement in Karnofsky Performance Status may have resulted from their relatively young age and relatively healthy baseline medical condition prior to the onset of COVID-19 infection.
None of the COVID-19–associated ARDS lung transplant recipients demonstrated acute rejection or development of de novo donor-specific antibodies, known risk factors for chronic lung allograft dysfunction.32 Possible explanations for the lack of rejection and donor-specific antibodies may include development of immune “accommodation”33 resulting from dilution of HLA antibody titers due to high intraoperative blood loss and increased blood transfusion, which are mechanisms thought to protect cardiac allografts from acute rejection.34 However, follow-up of longer duration is necessary to better determine the incidence of allograft rejection in patients who have undergone lung transplant for COVID-19–associated ARDS. Additionally, patients with COVID-19 may develop long-term secondary effects from their critical illness such as kidney failure.35 In this study, a higher percentage of patients with COVID-19–associated ARDS required long-term hemodialysis (13.3%) after lung transplant compared with the non–COVID-19 cohort (5.5%). Follow-up is needed to determine the long-term effects of kidney failure on patients in this study who required hemodialysis after lung transplant.
The median time from onset of COVID-19–associated ARDS to lung transplant in this study was 104 days. Several factors explain this long duration, including allowance of time for possible lung recovery, delays in the transplant referral and evaluation process, and limited ICU bed availability during COVID-19 surges. As discussed in the data presented regarding the screening process for transplant, 36 patients died while being evaluated for transplant or awaiting transfer after completion of lung transplant evaluation. Additionally, 12 patients deemed to have potential for lung recovery who were receiving ECMO died. It cannot be determined whether those patients would have benefited from earlier consideration for lung transplant. This experience underscores the importance of future studies to better inform decision-making to maximize the benefit of lung transplant while avoiding premature consideration of lung transplant.7
While offering double lung transplants to patients with COVID-19–associated ARDS has the potential to increase demand-supply discordance, this effect has not been documented in the medical literature to date.7 During this study, no increase in waitlist mortality was observed in the non–COVID-19 cohort at our center with the introduction of lung transplant for patients with COVID-19–associated ARDS; however, this needs to be studied in other centers with a different supply of donor lungs.
Recommendations for consideration for lung transplant evaluation in patients with COVID-19–associated ARDS have been proposed but consensus guidelines are lacking.7,8,17,36 Given the lack of clinical tests or biomarkers that indicate irreversible lung damage, the decision to proceed with lung transplant evaluation should be made by a multidisciplinary care team that specializes in ARDS management and lung transplantation. Due to the inherent uncertainty in prognosis, the progress of each patient needs to be determined longitudinally over time. With advanced ventilatory and extracorporeal support, more than 50% to 60% of patients with COVID-19–associated ARDS can demonstrate lung recovery.37 Because both the pre- and posttransplant care of patients with COVID-19–associated ARDS is highly complex, expensive, and resource intensive, these patients should preferably undergo lung transplant at high-volume centers with experienced multidisciplinary teams to provide optimal care.
Limitations
This study has several limitations. First, it was performed at a single center and the COVID-19 lung transplant cohort had a sample size of only 30 patients. Second, the patients who had COVID-19–associated ARDS were carefully selected for lung transplant; a less stringent approach to lung transplant in patients with this condition would likely not yield similar results. Third, posttransplant outcomes in this critically ill cohort are likely to vary depending on patient heterogeneity and center experience. Therefore, outcomes reported in this study may differ from national registries.Conclusions
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. -
@jon-nyc , how many transplants do they do at Duke?
I was really surprised to see how many were done at Northwestern. About 10/month. I remember the first one done there, decades ago. Did not go well. I was fortunate enough to NOT be the cardiovascular anesthesiologist on call that night.
