The SARS‐CoV‐2‐positive donor in pediatric organ transplantation

Abbreviations

COVID‐19

coronavirus disease 2019

C _t

cycle threshold

OPTN

Organ Procurement and Transplantation Network

PCR

polymerase chain reaction

SARS‐CoV‐2

severe acute respiratory syndrome coronavirus 2

SOT

solid organ transplantation

COVID‐19 has had an undeniable impact on the transplant population, including with regards to organ allocation. Due to poor outcomes from SARS‐CoV‐2 infection in some transplant recipients and the initial uncertainty regarding the risk of transplantation with donors with prior or active infection, several transplant societies had initially advised against using organs from SARS‐CoV‐2‐positive donors, and to wait several weeks after an episode of COVID‐19 for organ donation. ¹ Although there have now been reports on the outcomes of transplantation using organs from donors with a positive SARS‐CoV‐2 polymerase chain reaction (PCR) test in adults, data are limited in the pediatric population. ² , ³ In the current issue of the Journal, two centers describe their experiences with using SARS‐CoV‐2 positive donors in non‐lung pediatric solid organ transplantation (SOT). ⁴ , ⁵ These reports provide important insights on the clinical trajectory of children who have received an organ from a SARS‐CoV‐2 positive donor, contributing to the data needed to inform potential strategies for organ allocation in pediatric populations in the context of ongoing SARS‐CoV‐2 circulation.

Emerging evidence has shown that the risk of developing COVID‐19 in SOT recipients following non‐lung transplantation from SARS‐CoV‐2 positive donors appears to be low in adults, with the transmission of SARS‐CoV‐2 from positive donors having only been reported in lung transplant recipients. A study using data from the Organ Procurement and Transplantation Network (OPTN) in the United States between March 2020 and March 2021 reported that amongst 19 recipients who received organs from nine SARS‐CoV‐2 positive donors, only one lung transplant recipients developed COVID‐19 potentially from a donor organ. ⁶ Although three cases of COVID‐19 occurred in lung transplant recipients, two were thought to be due to secondary transmission events (one from a healthcare worker documented by whole genome sequencing, and one from a family member). ⁶ Further, the 16 recipients of the extrapulmonary organs had no evidence of COVID‐19 after transplantation, with multiple negative PCR tests by nasopharyngeal swabs. Another study utilizing OPTN data, which included 269 organ transplants from 150 SARS‐CoV‐2‐positive donors (including two lung transplants) with follow‐up until September 2021 showed that survival of patients receiving grafts from positive donors was comparable to those receiving grafts from negative donors between 30 to 365 days after transplantation. ² This study also included four SARS‐CoV‐2‐positive pediatric deceased donors, as well as three pediatric recipients who received two kidneys and one heart from SARS‐CoV‐2‐positive adult donors. Although these studies provided reassuring insights on the risk of SARS‐CoV‐2 transmission from SOT and on the recipients' prognosis, details that would inform individualized risk stratification (e.g., donors' symptoms, timing of infection and level of positivity of SARS‐CoV‐2 PCR) and data in children were limited.

The article published by Clark et al reports on the outcomes in seven recipients (three children <18 years) of non‐lung organ transplantations from two asymptomatic SARS‐CoV‐2‐positive pediatric donors. ⁴   None of the recipients developed COVID‐19 after SOT. Unfortunately, the timing of the infection in the first donor is unclear, as multiple PCRs prior to transplant were found to be negative, with PCRs from autopsy (nasopharyngeal and plasma) being unexpectedly positive. This could have represented a newly hospital‐acquired infection immediately before organ recovery, or reactivation from a previous infection at the time of death. No information on the cycle threshold (C _t) from the post‐mortem PCR was provided, and no serologies appeared to have been previously drawn, which limits the assessment of the timing of infection for the donor. C _t values relate to the number of PCR amplification cycles required to generate enough copies of viral RNA to be detected by the assay. ⁷ C _t values are inversely related to the viral load and may provide insights into the timing of the patient's infection and their infectiousness in conjunction with clinical picture. ⁸ , ⁹ In the second donor, SARS‐CoV‐2 infection may have been remote given the reported high C _t, although the values were not provided.

Pizzo et al. reported successful short‐term outcomes in two pediatric kidney transplant recipients from asymptomatic SARS‐CoV‐2‐positive donors, with no recipients having developed COVID‐19 after SOT. ⁵ Both donors were found to have positive SARS‐CoV‐2 PCR by nasopharyngeal swab with high C _t values (33.4 and 37.2 at 3 and 16 days prior to donation), and negative tracheal SARS‐CoV‐2 PCR, making remote infection more likely as the trend in C _t value was increasing with time; further declines in viral load expected by the time of organ donation, which may in part explain the lack of transmission from SOT. Interestingly, the second donor in the report by Clark et al was managed using monoclonal antibodies (casirivimab/imdevimab) and remdesivir prior to organ recovery. Further data on the role of antiviral medications (e.g., remdesivir or nirmatrelvir/ritonavir) or monoclonal antibodies (e.g., casirivimab/imdevimab) are, however, needed to draw meaningful conclusions on the impact of this practice on reducing the viral replication in SARS‐CoV‐2‐positive donors and on the risk of SARS‐CoV‐2 transmission from SOT.

Overall, the cases described in both articles suggest that it may be safe for pediatric donors who are SARS‐CoV‐2 positive to donate non‐lung organs for transplantation, and for pediatric patients to receive non‐lung organs from SARS‐CoV‐2 positive donors for transplantation under certain circumstances. Conclusions regarding the broad use of organs from SARS‐CoV‐2‐positive donors remain limited, and a careful case‐by‐case evaluation of the donor and recipient with individualized risk stratification is still needed in the pediatric population. As demonstrated in these reports, factors that may influence risk assessment include donor and recipient characteristics [symptoms, severity of infection, the timing of SARS‐CoV‐2 infection (including assessment of C _t values and antibody testing with either antispike in unvaccinated or antinucleocapsid in vaccinated individuals), cause of death, co‐infections], and (underlying illness of the recipient, anticipated degree of immunosuppression, the urgency of transplantation), respectively. More information is required to determine the degree to which each factor may influence transmission risk. Informed consent from parents of the potential recipients should also be obtained, acknowledging the evolving evidence around the risk of transmission. Ongoing assessment of the risk of transmission of SARS‐CoV‐2 from positive organ donors is of particular importance in the context of evolving recommendations on organ allocation, as well as emerging Omicron sublineages that could influence the potential for transmission.

AUTHOR CONTRIBUTIONS

PPPR and TK wrote the first draft of the manuscript. AC, CWT, and UA critically reviewed and revised the manuscript. All authors read and approved the final manuscript.

CONFLICT OF INTEREST

All authors declare that they have no conflicts of interest related to this study.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.