Transplanting Children with Organs from Covid-Positive Donors

COVID has been a difficult time for all. It has brought about new challenges and opportunities to the field of transplantation. There are many unanswered questions surrounding the novel corona virus and only recently have some of the answers started appearing in the literature. Data on the immunogenicity of the COVID-19 vaccines among SOT recipients have just started to emerge. Feingold et al. reported SARS-CoV-2 antibody responses following the use of COVID-19 mRNA vaccines among pediatric and young adult heart-transplant recipients ¹. In their study, 61% had SARS-CoV-2 spike protein antibody responses after a 2-dose vaccination series. A subset received a third dose of an mRNA vaccine and 57% of those patients who were seronegative after the second dose of vaccine developed antibody responses after the third dose. Luigi et al. reported that 44% of adolescent/young adult kidney transplant patients who received 2 doses of the COVID mRNA vaccine seroconverted and 92% seroconverted after the third dose ². The Center for Disease Control just recently published interim clinical considerations for COVID 19 vaccines recommending a 3-dose primary mRNA COVID-19 vaccine series for moderately or severely immunocompromised persons 5 years of age and older, followed by a booster dose for those 12 years of age and older ³.

More recently we are learning about newer antiviral drugs in SOT patients with COVID-19 infection. Prikis and Cameron recently published a paper on Paxlovid (Nirmatelvir/Ritonavir) and Tacrolimus Drug-Drug Interaction leading to incredibly high tacrolimus levels ⁴. We have also had a pediatric heart transplant patient reach a tacrolimus level of >60 ng/ml after receiving Paxlovid from their pediatrician.

Now that we are 2 years into this pandemic, the newest question is “Can we accept organs from COVID positive donors.” There are differing opinions on this in different organs. At least for kidney, I accepted my first positive donor recently. It was a perfect donor. Twenty-three-year-old male, head trauma, asymptomatic for COVID, terminal creatinine 0.8mg/dl, no pressors, no protein in the urine, no drugs, no past medical history. Completely healthy. BAL was positive for COVID with a cycle count of 35. I accepted the offer and 3 weeks later the child is still asymptomatic and doing great. I started asking around to other centers and some are transplanting kidneys from asymptotic donors with a cycle count of 18. I think we have a lot to learn in this area, and I hope to see some papers in the near future that address this topic. Maybe even some data will be presented at IPTA 2023 in Austin, TX. I hope to see you all there!!

1. Responsiveness to second and third dose of mRNA COVID-19 vaccination in adolescent and young adult heart transplant recipients [published online ahead of print
   Feingold B, Berman P, Moninger A, et al.
   [published online ahead of print, 2022 Mar 27]. Pediatr Transplant. 2022; e14272. doi:10.1111/petr.14272
2. Response to Third Dose of Vaccine Against SARS-CoV-2 in Adolescent and Young Adult Kidney Transplant Recipients
   Cirillo, Luigi; Citera, Francesco; Mazzierli, Tommaso MD1; Becherucci, Francesca MD; Terlizzi, Vito; Lodi, Lorenzo; Buti, Elisa; Romagnani, Paola
   Transplantation: May 18, 2022 - Volume - Issue - doi: 10.1097/TP.0000000000004199
3. Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States
   Accessed 6/14/2022
4. Paxlovid (Nirmatelvir/Ritonavir) and Tacrolimus Drug-Drug Interaction in a Kidney Transplant Patient with SARS-2-CoV infection: A Case Report
   Marios Prikis and Alexandra Cameron
   Transplant Proc. 2022 May 19; S0041-1345(22)00286-X. doi: 10.1016/j.transproceed.2022.04.015. Online ahead of print

IPTA is delighted to introduce our new IPTA Committee members, as outlined below for each Committee. We are proud to share that each Committee has Allied Health and Nursing Professionals represented.

It is also my pleasure to announce the merging of 2 Committees, the Communications Committee and the Membership Committee, to form the Membership Communications Committee. We decided to merge these 2 committees to serve the needs of our members as best possible, using all the means of communication at our disposal to both communicate Society news whilst helping retain and drive membership in terms of joining and staying current on payments of Society dues. This Committee will be jointly chaired by Dr. Pankaj Chandak (London, UK) and Dr. Manuel Rodriguez-Davalos (Salt Lake City, USA).

IPTA Committees 2022 – New Members

Allied Health and Nursing Professionals Committee
Louise Kipping, London, UK
Jemma Mears, Birmingham, UK
Jenny Prüfe, Essen, Germany

Education Committee
Gerri James – Stanford, USA (AHNP representative)

Ethics Committee
Hassina Mohammed, Trinidad & Tobago

ID Care Committee
Eunkyung Song, Columbus, USA

Membership Communications Committee
Lorraine Hamiwka, Calgary, Canada
Courtney Risley, Boston, USA (AHNP representative)

Outreach Committee
Dominique Jan, New York, USA
Jenny Wichart, Calgary, Canada (AHNP representative)

Publications Committee
Koji Hashimoto, Cleveland, USA
Jason Vanatta, Memphis, USA
Adrianne Sikora, Aurora, USA (AHNP representative)

Identifying a gap in our offer, I have decided to form a Multi-Organ Transplant Committee. This Committee will be jointly chaired by Dr. Irene Kim (Los Angeles, USA) and Dr. Alisha Mavis (Durham, USA). Please see the formation of this exciting new Committee below. We look forward to working together on new fresh and innovative initiatives.

Co-Chair: Irene Kim, Nashville, USA
Co-Chair: Alisha Mavis, Durham, USA
Council Liaison: Carlos Esquivel,Standford, USA
AHNP Correspondant: Louise Bannister, Toronto, Canada
Members:
Sophoclis Alexopoulos, Nashville, USA
Upton Allen, Toronto, Canada
Ane Andres, Madrid, Spain
Chesney Castleberry, Austin, USA
Abanti Chaudhuri, Sunnywale, USA
Amrita Dosanjh, San Diego, USA
Katsuhide Maeda, Philadelphia, USA
Cal Matsumoto, Washington DC, USA
Agnieszka Prytula, Ghent, Belgium
Lainie Ross, Chicago, USA
Marianne Samyn, London, UK
Thozama Siyotola, Cape Town, South Africa
Riccardo Superina, Chicago, USA
Jason Vanatta, USA

For full Committee formations, please go to www.tts.org/ipta-about/ipta-about-committees. We are excited to continue our good work! If you are interested in joining an IPTA Committee, the next call for new Committee members will be in January 2023.

Re-transplantation in non-adherent patients: Would You Consider These Patients for a Re-transplant?

Case #1
The patient is a 14 -year-old female who had a heart transplant 4 years ago and now has developed severely depressed cardiac function from grade 3 coronary allograft vasculopathy. She has mild symptoms of fatigue with ordinary activity but has frequent ventricular ectopy. She is currently hospitalized and inotrope dependent. From a noncardiac perspective, she also has stage 3 chronic kidney insufficiency (CKD) and obesity. She was only transplanted 4 years ago but has had a difficult time maintaining therapeutic levels of her immunosuppressants. The patient has had 3 episodes of grade 3 cellular rejection in the past 2 years. She has been admitted multiple times to the hospital for inadequate levels. Interestingly, the patient has felt comfortable in the hospital and does not mind being admitted.

Prior to transplant, her family and the patient were educated on transplantation. However, since the transplant, her parents have divorced and are now in new relationships. The patient has been coming to all her appointments and all scheduled visits; however, only one parent comes, and they are not always engaged and do not know the doses of her medicines. There have been multiple meetings with family and patient to address adherence concerns. When asked about why her drug levels are not therapeutic, the patient shrugs and says she always takes the medications, and she does not know why her levels are always low. Her parents state they have talked to her about the importance of medication and believe that she is taking them. They have tried to encourage adherence and have watched her take her medications intermittently but are not always consistent. Given her progressive decline, the likelihood of needing another transplant was brought up by the parents. Parents want her to live and are adamant that they will provide the necessary support.

Would you consider this child for re-transplantation?
What are the primary factors that influence your decision to offer re - transplantation?

The patient continued to decline. Social services became involved, and parents were deemed unsuitable guardians. She was placed on mechanical circulatory support and waited in the hospital for 8 months before getting a second heart transplant at age 15 years. She and her court appointed guardians were counseled extensively on heart transplant management and care. The patient was eventually discharged with guardian. However, the patient ran away from home 1 year after her second heart transplant for 6 months. She presented again with rejection that improved with augmented immunosuppression. After this rejection episode the patient became aware of her condition and, with significant social support and help, managed to change her life. She had therapeutic levels and perfect adherence with appointments and medications the past 3 months. She is now 17 years old, currently finishing high school and was accepted to college. She wants to become a nurse. However, the patient was found to have new grade 3 CAV with severely depressed cardiac function. She does have symptoms of fatigue, abdominal pain, and shortness of breath. Inotropic support with milrinone has helped her symptoms and she is currently inotrope dependent.

Would you offer this patient a third heart transplant?
Would you offer mechanical cardiac support?

Case #2
Patient is a 15-year-old male s/p Kidney transplant 8 years ago due to focal segmental glomerulosclerosis. The patient’s kidney is now failing, and he needs a second kidney transplant. The first few years after his transplant, the patient had adequate follow-up and maintained therapeutic levels of immunosuppression. However, he has missed appointments over the past 2 years. Due to loss of work from the COVID pandemic, the family had to move 3 hours away from the transplant center and they cannot come often. His mother died due to COVID complications. His father has been trying to work and care for the patient and his two sisters. For a time, they were homeless and that is why the kidney transplant team couldn’t reach the family. His family has not been able to pay for his medications and have been cutting his doses in half to try to extend the immunosuppression. The family does not have a car, so their only method of transportation is by train.

Would you consider this child for kidney re-transplantation?
What are the primary factors that influence your decision to offer re - transplantation?

ETHICS COMMENT
The IPTA Ethics Committee is in the process of developing a survey to assess our members practices regarding organ transplantation in the setting of poor medical adherence. In preparation for that survey, we invite the members to consider these cases as well as their responses to the questions posed. We plan to proceed with a formal survey on these issues in the coming months.