After many weeks on a ventilator in the intensive care unit (ICU) at Chicago’s Northwestern Memorial Hospital, 28-year-old Mayra Ramirez was critically ill with COVID-19. A paralegal who had enjoyed running 5K races, her lungs were now ravaged. She developed severe acute respiratory distress syndrome (ARDS) and required extracorporeal membrane oxygenation (ECMO)—a respite for her lungs that provided oxygen by continuously pumping her blood through an artificial lung machine. She had sepsis and her kidneys and liver were beginning to fail.
Ankit Bharat, MD (left), and Samuel Kim, MD, perform a double lung transplant at Northwestern Medicine in Chicago in July 2020 for a patient with COVID-19.
Laura Brown/Northwestern Medicine
Ramirez couldn’t be weaned off of ECMO or sedation and was listed for a lung transplant. In June 2020, Ankit Bharat, MD, chief of thoracic surgery and surgical director of lung transplantation and respiratory ECMO at Northwestern, performed a bilateral lung transplant, giving Ramirez the distinction of being the first person in the US known to have undergone the procedure to treat COVID-19.
Since Ramirez’s surgery, other patients have followed suit. According to data from the United Network for Organ Sharing (UNOS), the nonprofit organization that manages the US organ transplant system, 134 lung transplants have been reported in the US for patients with COVID-19 through May 21. Among them, 82 patients had ARDS, 48 had developed pulmonary fibrosis, and 4 had unspecified lung failure due to COVID-19. In addition, 1 heart-lung transplant has been performed for COVID-19–related pulmonary fibrosis and heart failure. As of May 28, 22 patients with COVID-19–related lung failure were still on the lung transplant wait-list.
Bharat recently took time out from his surgical schedule to speak with JAMA about his experience performing Ramirez’s lung transplant for COVID-19. The following is an edited version of that conversation.
JAMA:On June 5, 2020, you performed the first successful double lung transplant in the US for a patient with ARDS due to COVID-19. Can you tell us about the decision-making process that occurred prior to the surgery?
Dr Bharat:At the start of the pandemic, we saw a number of patients progress to severe and catastrophic lung damage despite the best medical treatment available. At that point, we started to explore the possibility of lung transplant as a lifesaving intervention for these patients. But a number of questions remained unanswered, including “Can we definitively say these lungs are permanently damaged by coronavirus or the secondary effects of the virus?” So, we started a warm autopsy program, which to the best of our knowledge was the first of its kind in the nation. Within 1 hour of a patient’s death, we performed an autopsy to help understand the anatomy inside the chest and to collect tissues to study the structural framework of the lungs. In our research laboratories, we developed techniques that for the first time proved that some patients had permanent and much more severe structural framework damage than in end-stage lung diseases, such as pulmonary fibrosis and α1-antitrypsin deficiency.
Our second major question was “Can we be certain that the virus has been cleared from the host?” We didn’t want to perform a lung transplant, give these patients immunosuppressants, and then have the virus reactivate. So we did time-course studies, which informed us of the [average] duration of time needed for the virus to be cleared from the lungs. These findings were published as a scientific paper in Science Translational Medicine on December 16, 2020.
JAMA:How much time elapsed between placing your first COVID-19 patient on the transplant list and receiving the donor lungs?
Dr Bharat:For the first patient, it only took 2 days. Most patients receiving lung transplants for COVID-19 have been on ECMO with maximum ventilator support, so they get a high lung allocation score. Also, the majority of these patients have blood types O and A, which are 2 of the most frequent blood types in our donors, so they tend to get the organs pretty quickly.
JAMA:Can you describe how the operation and recovery process went for your first lung transplant for COVID-19 and what you have learned doing these operations?
Dr Bharat:Our first recipient had severe deconditioning, malnourishment, sepsis, acute kidney injury, a necrotizing pneumonia, and spontaneous bleeding into a lung and her liver. This is not the typical profile of standard lung transplant patients who, for the most part, are on oxygen but come from home and have participated in outpatient pulmonary and physical rehabilitation so are fairly strong. Also, the surgery itself is much more challenging for patients with COVID-19. While a typical double lung transplant takes about 6 hours, in patients with COVID-19 the average operative time is 10 to 12 hours. These patients have scar tissue in the chest that is actively inflamed and tends to bleed a lot, requiring an average of 10 units of blood transfusion in the operating room compared with 5½ units of blood for a typical double lung transplant recipient. Postoperatively, patients with COVID-19 have a higher incidence of primary graft dysfunction early on and tend to have a much longer ICU stay. But once they get beyond the first couple of weeks, they tend to recover quickly and catch up to the trajectory of a standard lung transplant by about 4 to 6 weeks. All the patients with COVID-19 in whom we’ve performed lung transplants so far have had 100% survival.
JAMA:As of now, in mid-May, how many lung transplants have you performed in patients with COVID-19?
Dr Bharat:We’ve done 19 so far.
JAMA:How long were these patients in the ICU on full support before undergoing a lung transplant?
Dr Bharat:Most patients with COVID-19 who have undergone lung transplant at our center have waited close to 3 months or longer. We’ve transplanted several patients who have been on ECMO for about 5 months.
JAMA:Lung transplants are being performed in the US for patients with COVID-19 who have developed ARDS or pulmonary fibrosis. Have you performed lung transplants for both of these COVID-19–related lung failure conditions?
Dr Bharat:The patients with ARDS have been the bulk of the patients with COVID-19 for whom we have performed lung transplants. We’ve focused on them because they have no other options and would die otherwise. But we have also done 2 lung transplants in patients who developed pulmonary fibrosis from COVID-19. I think the need for lung transplant will increase in that group of patients in the imminent future because we are seeing a significant surge in patients who recovered from moderate to severe COVID and are now coming to the outpatient setting with progressive oxygen requirements and pulmonary fibrosis.
JAMA:Are only double lung transplants being performed for patients with COVID-19?
Dr Bharat:Patients with ARDS due to COVID-19 need a double lung transplant because their lungs are severely damaged. But I do think that there may be a role for single lung transplants in patients who develop chronic pulmonary fibrosis from COVID-19.
JAMA:Do you currently have any patients with COVID-19 on the wait-list for a lung transplant?
Dr Bharat:Yes, we have at least 5 patients right now waiting for lung transplants. And we are in the process of evaluating a number of others as well.
JAMA:Can you describe important considerations for evaluating patients with COVID-19 for lung transplantation?
Dr Bharat:Lung transplantation obviously is a very resource-intensive treatment. There is a scarcity of donor lungs so we don’t want to perform a lung transplant in a patient who will not be compliant with medical guidance afterward. It’s important for the transplant centers to ensure that, from the psychosocial perspective, this is going to be a good fit.
The patients with COVID-19 generally being considered as candidates for lung transplant are, for the most part, young and healthy and without major comorbid conditions. So they haven’t ever been in a situation where they almost died or had to talk about a transplant vs no other option. Most of these patients agree to undergo lung transplant, but it’s our job to make sure they fully understand. And this also includes a financial assessment because these patients need to have health insurance, and since they will be taking medications for the rest of their lives, medication co-payments cannot be an impediment.
JAMA:Have you been able to obtain consent from all of your patients who have undergone lung transplant for COVID-19?
Dr Bharat:Our first patient who received a lung transplant for COVID-19 was so sick that we had to proceed to transplant using her medical power of attorney. But subsequently, every patient has been able to participate in the decision-making process.
JAMA:You recently published an article in The Lancet Respiratory Medicine about survival after lung transplantation for COVID-19 in 4 countries. Can you describe the major findings?
Dr Bharat:The main message was that despite how sick these patients are, in the experienced centers we can achieve excellent outcomes. The 12 patients included in our paper had a 30-day survival of 100%, and their long-term survival did not differ from patients without COVID-19 who received lung transplants in the same centers during the same period. A caveat is that these lung transplants need to be done at high-volume centers that have surgical and multidisciplinary expertise.
A second message of that paper was that the mortality of patients undergoing lung transplants at these centers has not changed. We can absolutely continue to perform transplants in patients without COVID-19 along with those with COVID-19. However, that does require some creative thinking by using expanded donor criteria, such as donors with hepatitis C infection, which is now a treatable disease.
JAMA:Can you discuss this paper’s proposed criteria for selecting patients with COVID-19 for lung transplant?
Dr Bharat:We typically use age 65 years as the cutoff for lung transplantation in patients with COVID-19, but up to 70 years of age may be considered if a patient was in exceptionally good condition prior to the illness. While for a standard transplant we would perhaps not consider patients with active infection or frailty, this is allowed with COVID-19 as long as other criteria for lung transplant are met. Additionally, because we know that patients with obesity are predisposed to severe COVID-19 and we didn’t want to exclude them solely based on body mass index (BMI), we relaxed the BMI criteria for lung transplant in these patients.
We proposed that every center wait a minimum of 4 weeks before considering transplantation in a patient with severe ARDS from COVID-19. We also emphasized that if a patient is still on a ventilator or ECMO at the end of 4 to 6 weeks but their lungs are getting better, centers should not rush to lung transplant but instead continue to give that patient a chance for lung recovery.
We strongly suggested that patients being considered for lung transplant should have 2 negative results of polymerase chain reaction tests of bronchoalveolar lavage fluid from the lungs performed 24 hours apart to ensure clearance of SARS-CoV-2.
JAMA:We do not yet have data about long-term survival for patients with lung transplants for COVID-19, but can you tell us about typical survival rates after lung transplant?
Dr Bharat:Of all the lung transplants performed in the US, both single and double transplants, the 30-day survival is about 98%, which is the same at our center. One-year survival approaches 90%, but obviously that number will vary based on the risk profiles of individual patients. At 3 years, survival after lung transplant is about 75% to 78%. By the 5-year mark, we expect 60% to 70% of these patients to be alive and independent in terms of their day-to-day activities.
JAMA:Did the cause of death of organ donors change substantially during the pandemic compared with prepandemic statistics?
Dr Bharat:Lung transplant donor deaths were less frequently due to car accidents and gunshot wounds during this time, but we saw a significant increase in the number of organ donor deaths from suicide, opioid overdose, and stroke.
JAMA:Has the number of donated organs changed substantially during the pandemic compared with prepandemic figures?
Dr Bharat:The number of organ donations absolutely decreased during the COVID-19 pandemic. Early on, the processes responsible for getting a brain-dead donor to an organ procurement organization were strained, and these organizations were short-staffed. As the pandemic evolved, organ donations started to slowly go up, but there was still a significant decline in the number of lungs available for transplant, partly because clinicians were initially worried about doing bronchoscopy on potential donors due to possible COVID-19 infection. Without bronchoscopy—an essential part of donor management—donor lungs were not being offered for transplant.
Additionally, while other organs from donors who had recovered from COVID-19 were being transplanted, there was a big concern about whether lungs from a patient who had COVID-19 could be used. To the best of our knowledge, we performed the first COVID-to-COVID transplant, which involved transplanting lungs from a donor who had recovered from COVID-19 and appeared not to have lung damage into another patient with COVID-19 infection.
As of today, close to 33 million people in the US have been diagnosed with COVID-19. Some reports have suggested that up to 80% of these patients, even many who were asymptomatic, can have demonstrable lung injury. It remains to be seen whether or not other patients who have recovered from mild, moderate, or even severe COVID-19 are going to be organ donors. If not, this may lead to a significant contraction of our donor pool.