When Andrew Heyman, 50, last saw his cardiologist at NewYork-Presbyterian/Columbia University Medical Center on March 6, COVID-19 coronavirus barely entered the conversation about his heart transplant waitlist status.
"I was actually supposed to come into the hospital Monday this week to get another right heart cath," he told 鶹ý. "If the trend continued, I was going to be admitted at a level 2 or 3."
However, the unfolding tidal wave of COVID-19 undid those plans. His center and surgeries as of March 16th, including his.
It's a scenario playing out across the country as centers are making tough decisions on just what constitutes "essential."
"We have to balance the risks of postponing surgery with the risks of not only the surgical procedure but also the risk of potentially being exposed or potentially contracting the virus," said Joseph Vassalotti, MD, of the Icahn School of Medicine at Mount Sinai in New York City.
Every transplant takes some of a hospital's precious ICU and mechanical ventilator capacity, along with a substantial medical team in scarce personal protective equipment.
"The answer to whether a should be performed or not is going to be different depending on where you live and what the epidemiology is of the virus in your area," said Vassalotti, who is also chief medical officer of the National Kidney Foundation.
Adapting to Circumstances
Recent guidance from the Centers for Medicare & Medicaid Services recommended limiting all nonessential planned surgeries and procedures until further notice, but identified transplants as Tier 3b procedures that should not be postponed if possible.
At the same time, though, the United Network for Organ Sharing (UNOS) also smoothed the way for transplant hospitals to "temporarily inactivate candidates who, in their medical judgment, cannot or should not receive organ offers due to COVID-19 issues."
The Organ Procurement and Transplantation Network Executive Committee established an to keep patients like Heyman from getting "downgraded" on the organ waitlist if their clinical data can't be updated on the normally required schedule due to the pandemic.
Scaling back is inevitable, though, noted Atul Humar, MD, MSC, director of the transplant center at the University Health Network in Toronto, speaking at a multi-society organ donation and transplant on March 23.
Most U.S. and Canadian centers are at the point where a 50% reduction in transplant activity is required and only urgent or semi-urgent cases are moved forward, such as highly sensitized kidney transplant patients unlikely to get another offer, he said.
However, some transplant hospitals are already so overwhelmed with COVID-19 that all living and deceased donor transplants are halted, noted Humar, whose proposed was published simultaneously in the American Journal of Transplantation.
From the Italian centers getting a pounding by the virus, Luciano Potena, MD, PhD, of the University of Bologna, said that even before the peak in cases is reached, centers need to start considering alternatives to transplant where feasible, like left ventricular assist devices for heart transplant candidates, and accepting only "good" quality organs to minimize the risk of early graft dysfunction and a long ICU stay.
He also spoke at the town hall webinar held on behalf of the Association of Organ Procurement Organizations, American Society of Transplantation, American Society of Transplant Surgeons, International Society for Heart and Lung Transplantation, the UNOS, and others.
Choosing Candidates
Both the type of donor and the need of the recipient should inform the decision on a patient level, said Mandeep Mehra, MD, heart transplant surgeon and medical director of the Brigham and Women's Hospital Heart and Vascular Center in Boston.
Living donor transplants pose a nosocomial risk to both patients and can often be rescheduled, he noted in an interview with 鶹ý. And some patients on the waitlist fall in a semi-elective category that make sense to postpone putting them into an immunosuppressed state during a pandemic, he added.
Conversely, doing certain transplants actually reduces some patients' overall morbidity and mortality risk and conserves hospital resources, Mehra pointed out.
"We've got two patients currently at the Brigham waiting in high urgency status. These are patients on non-dischargable biventricular assist devices. It's absolutely essential that if we find a suitable donor we must move ahead," he said. "It would be not only unethical but crazy to not proceed with that under current circumstances when a patient is just sitting in the hospital unable to move as a result of being bound to mechanical circulatory support."
Assessing Risk
There have not been any confirmed transmissions of coronavirus reported from untested donors or any reports of transplanting known COVID-positive donors, which "prior to the development of a reliable treatment is unacceptably high" in risk,
"We're not there yet, where every OPO [organ procurement organization] is routinely testing every organ donor, but I think it's safe to say we're rapidly moving in that direction," said Kevin O'Connor, MS, president and CEO of one such organization, LifeCenter Northwest, who also spoke at the webinar.
Part of the problem is still variable availability of COVID-19 tests across the country, noted Anne Paschke, a public relations manager at UNOS. "As OPOs work toward acquiring sufficient testing for all donated organs, transplant surgeons are using their best clinical judgment about the potential risk associated with any untested donors."
That's created some angst, said Mehra, citing one case from Stanford where an infant was offered a heart from a donor in a COVID-19 endemic area who had an illness in the lung that looked like COVID-19, but the coronavirus test results took several days. "How do they make a choice? Ultimately, they transplanted the child and the test turned out to be negative. But still..."
Organ procurement, too, is running into issues both due to hospitals closing down access and hurrying transplants to free up ventilators and other resources as well as travel restrictions, O'Connor noted.
Risk Post-Transplant
The one bright spot in all of this has come from case reports.
"There's a reasonable expectation based on analogy with other viruses in this setting that our organ transplant patients with their immunosuppression might be at increased risk," both for acquiring the virus and progressing to more severe disease, noted Ajit Limaye, MD, director of the transplant infectious disease program at the University of Washington in Seattle, speaking at the webinar.
However, the five transplant recipient cases found to have the SARS-CoV-2 virus under his center's protocol for real-time onsite testing of all patients with signs or symptoms that could be consistent with COVID-19 did as well as those with similar underlying comorbidities, he said. Two have been managed on an outpatient basis, and all survived at least to the short, 1-week follow-up so far without changes to their immunotherapy being required.
It at least raises the possibility that the host response may be as important as the virus in determining the course of disease, and may even suggest that the low-dose maintenance regimens these patients were on a median of 15 years post-transplant were , Limaye said.
"It's highly speculative at this point, but I was surprised based on that very limited experience that none of the patients -- with 7 days of follow-up, to be clear -- have progressed to requiring intubation or have progressed to death, as has been described in many people with those same comorbidities who are not necessarily receiving immunosuppression," he said.
In a , only four of the 87 heart transplant recipients at one center in the epicenter of the outbreak in Hubei Province, China, developed an upper airway infection from Dec. 20, 2019 to Feb. 25, 2020. All were mild. Three of those tested negative for SARS-CoV-2, and one recovered before testing was launched.
"What's so unique about those patients?" Mehra said, citing the findings. "It turns out that patients who have had a heart transplant are already used to social distancing. They are already used to practicing sanitization measures. They are already used to practicing good hand hygiene. These measures in these patients work."
Conversely, the post-transplant patients on more substantial immunosuppression described on the webinar by Attilio Iacovoni, MD, of the heart transplantation unit at the ASST Papa Giovanni XXIII in Bergamo, Italy, haven't done as well.
Of the six COVID-19-positive transplant patients at his center, two were 4 months post-op when they tested positive but didn't develop symptoms and were managed on an outpatient basis. Another tested positive when he was ready for discharge 3 months post-op and went on to develop symptoms and now is stable on mask oxygen. At 4 months post-op, a woman was admitted after developing symptoms in the community and is in critical condition.
The other two -- 5 and 29 years post-transplant, respectively -- died. One came in late when he was already in some respiratory distress; the other died after the second dose of immune-suppressing rituximab (Rituxan).
"We may, over time, actually ," Mehra suggested, adding, "Don't give up your academic hats during a crisis like this."
Heyman, for his part, said he is happy to extend his now 18 months on the waitlist for a heart rather than increase his COVID-19 risk by going on intensive immunosuppression required after transplant at a hospital at the center of the worst-hit region of the U.S.
"We'll play it by ear," he said.