In a recent study published in the Journal of the American College of Cardiology, researchers investigated coronavirus disease 2019 (COVID-19)-infected donor use, donor and recipient characteristics, and early post-heart transplantation (HT) outcomes in the United States (US).
Study: Early Outcomes of Adult Heart Transplantation From COVID-19 Infected Donors. Image Credit: Explode / Shutterstock
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has created multiple challenges for heart transplantation facilities, adversely affecting all aspects of HT, including wait-list mortality, recipient survival, and donor heart procurement. Recent case series and single-center studies have reported acceptable outcomes in the short term, i.e., over a few weeks or months, of heart transplants using SARS-CoV-2-infected donors.
However, large-scale trials assessing long-term outcomes are required since SARS-CoV-2 infections can result in subclinical endothelial dysregulation and myocardial damage among probable donors. Studies including non-heart transplant recipients have reported an elevated risk for poor cardiovascular outcomes after the initial month of acute SARS-CoV-2 infections among hospitalized and non-hospitalized individuals.
About the study
In the present retrospective, registry-based study, researchers evaluated the early outcomes of adult HT from SARS-CoV-2-infected donor individuals.
Patient-level de-identified data from 27,862 donor individuals were obtained from the national-level United Network for Organ Sharing (UNOS) database Organ Procurement and Transplant Network (OPTN) from May 2020 to June 2022. Only individuals with data available on SARS-CoV-2 nucleic acid amplification tests (NATs) and organ donation in the database were included.
In total, 60,699 COVID-19 NATs were performed using nasopharyngeal swab specimens, bronchoalveolar lavage (BAL), or tracheal aspirate samples before organ donation. Individuals with NAT-positive reports at any timepoint during their terminal hospital admission were considered “COVID-19 donors”.
SARS-CoV-2-infected donors were subcategorized into “active COVID-19” (aCOV) and “recently resolved COVID-19” (rrCOV) donors. The aCOV group included individuals with NAT-positive reports in the initial two days following organ donation. The rrCOV group included those with NAT-positive reports during the initial period but who showed NAT-negative results before organ donation.
Individuals who were NAT-positive more than two days before organ donation was included in the aCOV group unless the presence of evidence of subsequent adverse reports within two days of the most recent NAT-positive report. The team excluded donor individuals with COVID-19 antibody or antigen testing reports other than NAT. They compared heart transplantation outcomes and performed Cox proportional hazards regression modeling to calculate the hazard ratios (HRs).
The participants were followed up until 30 September 2022. Pediatric transplant recipients, adults who received multiorgan transplants or re-transplants, and those with missing HT follow-up data were eliminated from the analysis. The primary study outcome was death due to any cause up to six months and 12 months into the follow-up period. The secondary study outcomes included stroke, pacemaker use, hemodialysis, and post-heart transplant hospital stay duration.
Results
Of 1,445 SARS-CoV-2-infected donors identified, 428 and 1,017 were rrCoV and aCOV, respectively, and of 309 heart transplants using SARS-CoV-2-infected donors, 239 HTs among adults (150 and 89 aCOV and rrCOV, respectively) satisfied the eligibility criteria. SARS-CoV-2-infected donors were of lower age and predominantly male compared to non-COV donor individuals.
Compared to transplant recipients using non-COV donor individuals, those using aCOV donor individuals had higher mortality at six months and 12 months, with HR values of 1.7 and 2.0, respectively. Transplant recipients who used non-COV and rrCOV donor individuals had comparable mortality at six and 12 months. HTs from SARS-CoV-2-infected and uninfected donors yielded comparable secondary study outcomes.
In addition, rrCoV and aCOV donor individuals had comparable secondary outcomes. Similar findings were observed for propensity score (PS)-matched study cohorts. SARS-CoV-2-infected donor HT counts increased during the study period. Of interest, peaks for HTs with SARS-CoV-2-infected donor individuals followed the surges in SARS-CoV-2 infections in community settings in the US.
Conclusions
Overall, the study findings showed HT recipients from aCOV donor individuals had higher mortality at six months and 12 months, whereas the mortality rates were comparable among those who received hearts from rrCOV and non-COV donor individuals. The findings indicated that heart transplants from rrCOV donor individuals appear safe, whereas HTs from aCOV donors might be related to increased mortality.
Significant trends of increases in SARS-CoV-2-infected (rrCoV and aCOV) donor use were observed during the study period. HT facilities selectively selected SARS-CoV-2-infected donors, who were predominantly younger and male. Probable donors underwent multiple SARS-CoV-2 NATs before organ donation, with greater numbers for NAT-positive individuals than those testing NAT-negative for SARS-CoV-2 (three versus two tests per donor, respectively).
The increase in mortality at six months and 12 months among adult transplant recipients from aCOV donors was concerning. Heart transplantation facilities must thoroughly evaluate the risk-benefit ratio of transplanting hearts from aCOV donor individuals. Further research must incorporate analysis of data including cycle threshold (Ct) values (to assess viral loads), donor infection history (including diagnosis date, symptomatology, and causative SARS-CoV-2 strain), COVID-19 vaccination status, and specific therapies administered to HT recipients from COVID-19 donors.
CRISPR-based therapy shown to be safe, effective for people with transthyretin amyloidosis