Heart Transplantation With COVID-19 Positive Donors
- There is ample evidence that SARS-CoV-2 transmission in heart transplantation from asymptomatic donors with conflicting and/or positive COVID-19 testing with high PCR cycle threshold number is negligible.
- Several non-lung, solid organ transplantations from actively infected COVID-19 donors have also resulted in non-transmission of the virus.
- Short- to long-term graft function of transplanted organs from COVID-19 donors requires further study.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has profoundly impacted many aspects of patient care, including heart transplantation (HTx). Initially, a number of transplant societies, including the International Society of Heart and Lung Transplant,1 recommended against transplanting grafts from COVID-19 positive (COVID-19+) donors. Concerns about the use of organs from SARS-CoV-2 infected donors have included the potential risk for transmission of the virus through the allograft as well as SARS-CoV-2-mediated cardiac injury that might compromise short- and/or long-term allograft function. However, even early in the pandemic, the potential use of SARS-CoV-2 positive donors was proposed, based on autopsy data and information from related coronaviruses.2
Over time, transplant clinicians have become aware of important differences among COVID-19+ potential donors. Some individuals who test positive have significant clinical disease; these cases are clearly true positives. However, other asymptomatic individuals may have nasopharyngeal tests which yield conflicting results when repeated hours apart. In these situations, the polymerase chain reaction (PCR) test is usually positive at a high cycle threshold number, signifying the presence of little viral nucleic acid. Indeed, in these cases, infectious disease specialists view these COVID-19+ tests as either false positives or signals of either very early or remote infection with low likelihood of transmissibility with non-lung organ donation.
This concept has now been put to the test in multiple case reports and series. One report described transplanting a heart and two kidneys from a donor who contracted SARS-CoV-2 a month prior and had conflicting COVID-19 PCR tests at the time of donor offer.3 Another described a heart and liver donor who had remote COVID-19 with a positive nasopharyngeal COVID-19 PCR test that had a high cycle number just prior to organ procurement.4 A series of six donors with either history of COVID-19 or a COVID-19+ test at donation, from whom 13 organs (hearts, livers, and kidneys) were recovered and transplanted, was detailed in work by Neidlinger and colleagues.5 Dhand et al. also reported a heart and liver donor with a very recent COVID-19+ PCR test.6 Koval et al. described transplanting 10 kidneys from five donors who each had several COVID-19 tests with conflicting results.7 In all these cases, no transmission of SARS-CoV-2 from donor to recipient occurred (yet more cases can be found in the review by Kute et al.8).
Our own center has been using COVID-19+ donor hearts for transplantation (Table 1). Each had conflicting COVID-19 PCR results with positives having high cycle threshold numbers. None had a history of upper respiratory infection (URI) symptoms characteristic of COVID-19 in the time immediately preceding donation. Recipients were fully informed they were receiving a heart from a COVID-19+ donor and signed a consent specially formulated for this situation. No recipient declined the transplant. No additional infectious precautions for COVID-19+ patients were taken for these recipients post-surgery except routine weekly nasopharyngeal COVID-19 tests. No recipient developed COVID-19, and there were no reported outbreaks of any of the medical personnel involved in these cases. Recently, one HTx patient developed COVID-19 shortly after the procedure, but the donor never tested positive for the infection. Indeed, investigations of eight cases in which organ transplant recipients developed COVID-19 shortly after surgery concluded that these individuals contracted the virus from community or iatrogenic exposures rather than from their donors.9
Table 1: University of Washington Medical Center Experience with COVID-19+ Donors for Heart Transplantation
|Case 1||Case 2||Case 3||Case 4||Case 5|
|COVID-19 testing of donor||2 NP +, 1 NP -||2 NP + (2nd CT 35), 1 NP -||1 NP -, 1 BAL + (CT 30), 1 NP +||3 NP -, 1 NP + (CT 35), 2 BAL -, blood IgG spike +||1 NP -, 1 BAL -, 2 NP + (CT 37, 43)|
|Last UNOS status of recipient||3||4e||2e||3||4|
|Complications of the recipient||none||polymorphic VT requiring ICD||type B aortic dissection||primary graft dysfunction||none|
|Condition of the recipient (follow-up time)||alive (6 months)||alive (4 months)||alive (3 months)||alive (1 month)||alive (1 week)|
NP: nasopharyngeal COVID-19 PCR test
BAL: Bronchoalveolar lavage COVID-19 PCR test
CT: PCR cycle threshold number
ICD: implantable cardioverter defibrillator
VT: ventricular tachycardia
It should be noted that three out of five of our transplant patients experienced complications peri-operatively. For one of them (Case 3 involving a type B aortic dissection), the complication cannot be plausibly tied to the COVID-19 status of the donor. Whether the two remaining recipients with complications would have had a better outcome with another donor organ is debatable. The Case 2 patient who developed polymorphic ventricular tachycardia (VT) eventually underwent placement of an implantable cardioverter defibrillator (ICD), which to date, has yet to deliver any therapies. The Case 4 patient required extracorporeal membrane oxygenation (ECMO) for primary graft dysfunction (PGD) and was decannulated after 2 days. He had a lengthy hospital stay requiring inpatient rehabilitation but has been discharged home. Even for these two cases, the connection between COVID-19 and the complications is uncertain. What is incontrovertible in all these cases, though, is that they would have had to remain on the waiting list for longer periods of time had they declined the organs offered to them. Three out of the five had UNOS priority statuses at 3 or above at the time of transplant, so prolonging the wait time for those individuals in especially precarious hemodynamic states may have led to increased morbidity or even mortality.
The next frontier is to use organs from donors with known active disease. Reports have described several instances of liver, kidney, and HTx from SARS-CoV-2 positive donors with good outcomes and no evidence of transmission.8,10,11 On the other hand, inadvertent transmission via lung transplantation has also been reported.11 Thus far, it appears that transplantation involving donors with active COVID-19 for non-lung solid organs has been safe, with the caveat that only a small number have been done.
Beyond transmission, there is also a question over the long-term functional performance of grafts acquired from COVID-19+ donors. Xie and colleagues measured the burden of cardiovascular incidents including cerebrovascular accidents, arrhythmias, ischemic heart disease, and heart failure 30 days to a year after COVID-19 positivity on a large cohort of Veterans Affairs patients and found increased hazard ratios for these entities across the board.12 Whether this burden is conferred to recipients even after the heart is removed from its post-infection milieu and/or whether the risk of this increased burden of cardiovascular incidents overcomes the benefit of a timelier HTx will require further study.
In all, the field of HTx has continued to adjust in response to the COVID-19 pandemic. With the recognition that COVID-19 positivity has different gradations and that the risk of viral transmission is negligible, we routinely use grafts from donors who have had no recent URI symptoms immediately prior to donation and when their COVID-19+ tests have high PCR cycle numbers. We should also note that COVID-19 vaccination is mandated for all potential recipients at our institution. The boundaries in which we operate are likely to change as more data is accumulated and as the SARS-CoV-2 virus continues to evolve.
- Guidance from the International Society of Heart and Lung Transplantation regarding the SARS CoV-2 pandemic (ishlt.org). 2021. Available at: https://ishlt.org/ishlt/media/documents/SARS-CoV-2_Guidance-for-Cardiothoracic-Transplant-and-VAD-center.pdf. Accessed 04/15/2022.
- Kates OS, Fisher CE, Rakita RM, Reyes JD, Limaye AP. Use of SARS-CoV-2-infected deceased organ donors: should we always "just say no?" Am J Transplant 2020;20:1787–94.
- Sigler R, Shah M, Schnickel G, et al. Successful heart and kidney transplantation from a deceased donor with PCR positive COVID-19. Transpl Infect Dis 2021;23:e13707.
- de la Villa S, Valerio M, Salcedo M, et al. Heart and liver transplant recipients from donor with positive SARS-CoV-2 RT-PCR at time of transplantation. Transpl Infect Dis 2021;23:e13664.
- Neidlinger NA, Smith JA, D'Alessandro AM, et al. Organ recovery from deceased donors with prior COVID-19: a case series. Transpl Infect Dis 2021;23:e13503.
- Dhand A, Gass A, Nishida S, et al. Successful transplantation of organs from a deceased donor with early SARS-CoV-2 infection. Am J Transplant 2021;21:3804–05.
- Koval CE, Poggio ED, Lin Y-C, Kerr H, Eltemamy M, Wee A. Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: a report of 10 cases. Am J Transplant 2021;21:3743–49.
- Kute VB, Fleetwood VA, Meshram HS, Guenette A, Lentine KL. Use of organs from SARS-CoV-2 infected donors: is it safe? A contemporary review. Curr Transplant Rep 2021;8:281–92.
- Jones JM, Kracalik I, Rana MM, et al. SARS-CoV-2 infections among recent organ recipients, March-May 2020, United States. Emerg Infect Dis 2021;27:552–55.
- Hong H-L, Kim S-H, Choi DL, Kwon HH. A case of coronavirus disease 2019-infected liver transplant donor. Am J Transplant 2020;20:2938–41.
- Kumar D, Humar A, Keshavjee S, Cypel M. A call to routinely test lower respiratory tract samples for SARS-CoV-2 in lung donors. Am J Transplant 2021;21:2623–24.
- Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022;28:583–90.
Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Interventions and Imaging, Interventions and Vascular Medicine, Computed Tomography, Nuclear Imaging
Keywords: COVID-19, COVID-19 Vaccines, SARS-CoV-2, Waiting Lists, Extracorporeal Membrane Oxygenation, Pandemics, Heart Transplantation, Follow-Up Studies, COVID-19 Testing, Defibrillators, Implantable, Inpatients, Length of Stay, Patient Discharge, Preimplantation Diagnosis, Primary Graft Dysfunction, Tissue Donors, Tissue and Organ Procurement, Heart Failure, Hemodynamics, Polymerase Chain Reaction, Stroke, Tachycardia, Ventricular, Bronchoalveolar Lavage, Physical Functional Performance, Myocardial Ischemia, Lung Transplantation, Aneurysm, Dissecting, Communicable Diseases, Nucleic Acids, Vaccination, Arrhythmias, Cardiac, Iatrogenic Disease, Morbidity, Informed Consent, Immunoglobulin G, Tomography, X-Ray Computed
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