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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Utilization of COVID-19 positive donors for Heart transplantation and associated short-term outcomes

  • Author Footnotes
    # Drs. DeFilippis and Wayda contributed equally to this manuscript as co-first authors
    Ersilia M. DeFilippis
    Footnotes
    # Drs. DeFilippis and Wayda contributed equally to this manuscript as co-first authors
    Affiliations
    Division of Cardiology, Columbia University Irving Medical Center, New York, New York
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  • Author Footnotes
    # Drs. DeFilippis and Wayda contributed equally to this manuscript as co-first authors
    Brian Wayda
    Footnotes
    # Drs. DeFilippis and Wayda contributed equally to this manuscript as co-first authors
    Affiliations
    Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California
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  • Anuradha Lala
    Affiliations
    Division of Cardiology, Mount Sinai Health System, New York, New York
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  • Michael M. Givertz
    Affiliations
    Division of Cardiology, Brigham and Women's Hospital, Boston, Massachsetts
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  • Kiran K. Khush
    Correspondence
    Reprint requests: Kiran K. Khush MD, MAS, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC 263, Stanford, CA, 94305. Telephone +650-721-3241.
    Affiliations
    Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California
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  • Author Footnotes
    # Drs. DeFilippis and Wayda contributed equally to this manuscript as co-first authors
Published:December 10, 2022DOI:https://doi.org/10.1016/j.healun.2022.12.006

      Background

      The safety and efficacy of using COVID-19 positive donors in heart transplantation (HT) are increasingly relevant, but not well established. The present study evaluated the characteristics and utilization of such donors and associated post-HT outcomes.

      Methods

      All adult (≥18 years old) potential donors and HT recipients in the United States from April 21, 2020 to March 31, 2022 were included. Donor COVID-19 status was defined by the presence (or absence) of any positive test within 21 days of organ recovery. Donor and recipient characteristics and post-HT outcomes, including a primary composite of death, graft failure, and re-transplantation, were compared by donor COVID-19 status.

      Results

      Of 967 COVID-19(+) potential donors, 19.3% (n = 187) were used for HT compared to 26.7% (n = 6277) of COVID-19(-) donors (p < 0.001). Transplanted COVID-19(+) vs COVID-19(-) donors were younger, but otherwise were similar. Recipients of hearts from COVID-19+ vs COVID-19(-) donors less frequently received pre-HT inotropes (24.1% vs 31.7%, p = 0.023) and ventricular assist device therapy (29.7% vs 36.8%, p = 0.040). There were no significant differences in any post-HT outcome by donor COVID-19 status, including the primary composite outcome at 90 days (5.4% vs 5.6%, p = 0.91). Among COVID-19(+) donors, the presence of a subsequent negative test prior to transplant was not associated with posttransplant outcomes.

      Conclusions

      Our results suggest that carefully selected COVID-19 positive donors may be used for HT with no difference in short-term post-transplant outcomes. Additional data regarding donor and recipient treatments and impact of vaccination should be collected to better inform our use of organs from COVID(+) donors.

      Keywords

      Abbreviations:

      COVID-19 (Coronavirus-19), HT (heart transplantation), OPTN (organ procurement and transplantation network), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), UNOS (united network of organ sharing)

      Introduction

      The novel coronavirus-19 (COVID-19) pandemic has posed immense challenges for heart transplant (HT) clinicians and their patients. Recommendations and practice have evolved rapidly regarding the use of donors with COVID-19 infection,
      • Schold JD
      • Koval CE
      • Wee A
      • Eltemamy M
      • Poggio ED.
      Utilization and outcomes of deceased donor SARS-CoV -2 positive organs for solid organ transplantation in the United States.
      which anecdotal reports suggest has become increasingly common.
      • Dhand A
      • Gass A
      • et al.
      Long-term and short-term outcomes of solid organ transplantation from donors with a positive SARS-CoV-2 test.
      • Ushiro-Lumb I
      • Callaghan CJ
      • Pettigrew GJ
      • et al.
      Transplantation of organs from SARS-CoV-2 RNA positive deceased donors: the UK Experience.
      • Eichenberger EM
      • Coniglio AC
      • Milano C
      • et al.
      Transplanting thoracic COVID-19 positive donors: an institutional protocol and report of the first 14 cases.
      • Madgula AS
      • Nestasie M
      • Link C
      • et al.
      Tackling the paradox of orthotropic heart transplantation from SARS-CoV-2 positive donors: asingle center experience.
      However, there has been no systematic evaluation to date of COVID-19 (+) donor utilization for HT in the United States (US) and its variation across centers and over time.
      The earliest and largest experience to date comes from the abdominal organ transplant literature.
      • Bock MJ
      • Vaughn GR
      • Chau P
      • Berumen JA
      • Nigro JJ
      • Ingulli EG.
      Organ transplantation using COVID-19-positive deceased donors.
      • Jayasekera CR
      • Vikram HR
      • Rifat Z
      • et al.
      Solid organ transplantation from SARS-CoV-2-infected donors to uninfected recipients: A single-center experience.
      • Koval CE
      • Poggio ED
      • Lin Y
      • Kerr H
      • Eltemamy M
      • Wee A.
      Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: areport of 10 cases.
      In an early cohort of 10 kidney transplants using five deceased donors with COVID-19 infection, all had excellent outcomes with no cases of donor-derived infection.
      • Koval CE
      • Poggio ED
      • Lin Y
      • Kerr H
      • Eltemamy M
      • Wee A.
      Early success transplanting kidneys from donors with new SARS-CoV-2 RNA positivity: areport of 10 cases.
      Per Organ Procurement and Transplantation Network (OPTN) data, the only three known cases of donor-derived COVID-19 infection in the US have occurred in the context of lung transplant – non-lung recipients from the same COVID-19(+) donors were not infected.
      Summary of current evidence and information–Donor SARS-CoV-2 testing & organ recovery from donors with a history of COVID-19 [Internet].
      Less data are available in HT recipients, although the largest case series to date (ranging from 3– 12 cases) have reported no instances of donor-derived COVID-19 infection.
      • Bhatt AS
      • Adler ED
      • Albert NM
      • et al.
      Coronavirus disease-2019 and heart failure: ascientific statement from the Heart Failure Society of America.
      • Clerkin KJ
      • Fried JA
      • Raikhelkar J
      • et al.
      COVID-19 and cardiovascular disease.
      OPTN approach to estimating the volume of COVID-19 positive deceased donors.
      • DeFilippis EM
      • Allen LA
      • Bhatt AS
      • et al.
      Vaccines, antibodies, and donors: varying attitudes and policies surrounding COVID-19 and heart transplantation.
      Less is known, however, regarding the risk of other adverse outcomes. Given the known cardiovascular manifestations of COVID-19 (e.g., myocarditis, arrhythmias, and thrombosis),
      • Bhatt AS
      • Adler ED
      • Albert NM
      • et al.
      Coronavirus disease-2019 and heart failure: ascientific statement from the Heart Failure Society of America.
      ,
      • Clerkin KJ
      • Fried JA
      • Raikhelkar J
      • et al.
      COVID-19 and cardiovascular disease.
      an effect on donor heart function is theoretically plausible, but data in this regard are limited. In light of these knowledge gaps, our current study examined 1) utilization of hearts from COVID-19(+) donors, including its variation across centers and over time; 2) the characteristics of COVID-19(+) donors and the patients who receive their hearts for transplant; and 3) short-term posttransplant outcomes among these recipients.

      Methods

      This study used the OPTN/United Network for Organ Sharing (UNOS) database and included data collected by OPTN on donor COVID-19 testing. The cohort consisted of all deceased donors from whom at least one organ was recovered for transplant between April 21, 2020 and March 31, 2022. Donors were classified as “COVID(+)” if they had a positive upper or lower respiratory tract nucleic acid (NAT) or antigen test within 21 days of organ recovery.
      OPTN approach to estimating the volume of COVID-19 positive deceased donors.

      Donor and recipient characteristics

      Adult (≥18 years) COVID(+) positive donors were compared with COVID(-) adult donors during the study period. Within the subset of COVID(+) donors, those used vs not used for heart transplantation (HT) were compared. Donor variables examined included demographics, comorbidities, cause of death, results of cardiac diagnostic tests, and other clinical characteristics. For COVID(+) donors, the timing (relative to recovery date) and source (upper vs lower respiratory tract) of positive tests were characterized. As multiple tests were available for some patients, secondary analyses were performed to compare COVID(+) donors with (vs without) a subsequent negative test prior to organ recovery.
      Additional analyses compared adult HT recipients by the COVID-19 status of their donor. Recipient characteristics included demographics, comorbidities, therapies administered prior to transplant, and other clinical characteristics. Variation across centers, by region, and over time in the utilization of COVID(+) donors was also examined.

      Post-Transplant outcomes

      The primary outcome was time to a composite of death, graft failure, or re-transplantation. Secondary outcomes included: 1) the above composite outcome assessed at 90 days post-HT, 2) time to discharge post-HT, 3) acute rejection, and 4) dialysis therapy occurring during the index hospitalization (i.e., post-HT but prior to discharge). Outcomes were compared among recipients of COVID(+) vs COVID(-) donors. Secondary analyses compared outcomes among COVID(+) donors with (vs without) a subsequent negative test prior to organ recovery.

      Statistical analysis

      In comparisons of donor and recipient characteristics, categorical and continuous variables were compared using chi-square and two-sample t-tests, respectively. Kaplan-Meier analyses were performed to assess differences in time to the primary outcome and time to discharge by subgroup, with significance assessed using the log-rank test. While our limited sample size precluded the use of robust multivariate adjustment in our primary analysis, we performed a secondary analysis using a Cox Proportional Hazards model to assess the association of donor COVID-19 status with the primary outcome after adjustment for selected donor and recipient risk factors that were chosen on the basis of clinical plausibility. Time to discharge analyses excluded patients transplanted after January 1, 2022 (i.e., those with less than 90 days of potential follow-up time); the rationale for their exclusion is further detailed in Supplemental Methods. Binary outcomes were compared using chi-squared tests. In comparisons of acute rejection and dialysis therapy, recipients who had not been discharged by the end of the study period (and thus lacked data on these outcomes) were excluded. In comparisons of the composite outcome at 90 days, those transplanted on or after January 1, 2022 were excluded due to lack of sufficient follow-up time.
      As data was obtained as part of routine care and de-identified by UNOS, Institutional Review Board approval was not required. Analyses were conducted using SAS version 9.4 and Microsoft Excel 2016.

      Results

      Comparison of donor characteristics, by COVID status and use for HT

      Of 24,488 adult donors with at least one solid organ recovered for transplant during the study period, 967 (4.0%) tested positive for COVID-19 (Figure 1). Most COVID-19 diagnoses were based on an upper respiratory sample (n = 742, 76.7%); 131 (13.6%) were positive on both upper and lower respiratory testing and the remaining 94 (9.7%) had a positive lower respiratory test only. The average duration between a donor's first positive test and organ recovery was 7.4 days, and 43.2% (n = 418) of COVID(+) donors had a subsequent negative test prior to organ recovery. COVID(+) donors with (vs without) a subsequent negative test were more often of non-White race, but did not differ significantly in other demographic or clinical characteristics (Supplemental Table S1).
      Figure 1
      Figure 1Flowchart depicting COVID-positive donors and recipients. The utilization of COVID(+) and COVID (-) donors for transplantation during the study period is shown. COVID-19 = novel coronavirus-2019; HT, heart transplantation.
      Of the 967 COVID(+) donors, 187 (19.3%) were used for HT compared to 26.7% of COVID(-) donors (p < 0.001). Among COVID(+) donors, those used (vs not used) for HT were significantly younger (mean age 31.4 vs 46.0 years, p < 0.0001), more often male (81.8% vs 60.0%, p < 0.001), and had fewer cardiovascular risk factors including hypertension and diabetes (Table 1). About two thirds (66.8%) of COVID(+) donors used for HT (vs 37.6% of those not used for HT) had a subsequent negative COVID test before recovery. Those used for HT had a longer average duration since their first positive test (8.1 vs 4.4 days, p < 0.0001).
      Table 1Characteristics of COVID-19 Positive Adult Donors, by Use (vs Non-Use) for Heart Transplantation (April 2020 - March 2022)
      All COVID(+)TransplantedNot transplantedp-value
      Based on chi-squared test for categorical variables and t-test for continuous variables.
      Total n967187 (19.3%)780 (80.7%)
      Demographics
       Female sex346 (35.8%)34 (18.2%)312 (40%)<0.0001
       Age (mean ± SD), years43.1 ± 13.431.4 ± 8.446.0 ± 12.8<0.0001
       Age 18 – 34283 (29.3%)124 (66.3%)159 (20.4%)<0.0001
       Age 35 – 49347 (35.9%)59 (31.6%)288 (36.9%)0.17
       Age 50+337 (34.9%)4 (2.1%)333 (42.7%)<0.0001
      Race/Ethnicity
       White641 (66.3%)113 (60.4%)528 (67.7%)0.059
       Hispanic163 (16.9%)37 (19.8%)126 (16.2%)0.23
       Black134 (13.9%)32 (17.1%)102 (13.1%)0.15
       Asian or Other29 (3%)5 (2.7%)24 (3.1%)0.77
      Comorbidities
       Obese (BMI ≥ 30 kg/m2)444 (45.9%)64 (34.2%)380 (48.7%)0.0004
       Coronary artery disease
      Includes either reported history of coronary artery disease or positive coronary angiogram.
      78 (8.1%)1 (0.5%)77 (9.9%)<0.0001
       Smoking
      Includes current or prior use.
      181 (18.7%)26 (13.9%)155 (19.9%)0.060
       Cocaine use
      Includes current or prior use.
      184 (19%)48 (25.7%)136 (17.4%)0.01
       Intravenous drug use
      Includes current or prior use.
      119 (12.3%)36 (19.3%)83 (10.6%)0.0013
       Diabetes mellitus143 (14.8%)9 (4.8%)134 (17.2%)<0.0001
       Hypertension324 (33.5%)25 (13.4%)299 (38.3%)<0.0001
      Cardiac diagnostic findings
       EF reported (%)
      Calculated prevalence of EF by strata (< 40, 40-49…) includes only donors for which EF was reported.
      580 (60%)187 (100%)393 (50.4%)<0.0001
       EF < 40%25 (8.5%)1 (0.5%)24 (12.2%)<0.0001
       EF 40-49%13 (2.5%)2 (1.1%)11 (5.6%)0.011
       EF ≥ 50%347 (89%)184 (98.4%)163 (82.2%)<0.0001
       Wall thickness reported (%)
      Calculated prevalence of LVH by strata (mild, moderate+) includes only donors for which either LV posterior or septal wall thickness was reported. LVH classification was based on the higher of these two measurements.
      382 (39.5%)130 (69.5%)252 (32.3%)<0.0001
       mild LVH (1.2-1.3cm)65 (17%)25 (19.2%)40 (15.9%)0.41
       moderate+ LVH (≥ 1.4 cm)32 (8.4%)3 (2.3%)29 (11.5%)0.0021
      Other clinical characteristics
       Blood type
       A368 (38.1%)60 (32.1%)308 (39.5%)0.061
       B107 (11.1%)20 (10.7%)87 (11.2%)0.86
       AB32 (3.3%)0 (0%)32 (4.1%)0.0049
       O460 (47.6%)107 (57.2%)353 (45.3%)0.0033
       Cardiac downtime
      Refers to the occurrence of cardiac arrest between the time of brain death and donor organ recovery. Calculated prevalence excludes 75 donors (19 transplanted, 56 not transplanted) for which downtime was coded as “unknown”.
      353 (39.6%)92 (54.8%)261 (36.1%)<0.0001
       Inotrope use236 (24.4%)47 (25.1%)189 (24.2%)0.80
       Acidemia (pH < 7.35)256 (26.5%)31 (16.6%)225 (28.9%)0.0006
      COVID test characteristics
      “Source of positive” is based only on tests performed within 21 days of donor recovery. “Days since first positive” is based on any tests performed within 60 days of donor recovery. “Subsequent negative” refers to any case where the last upper or lower respiratory test performed prior to donor recovery was negative.
       Source of positive test
       Upper respiratory- only742 (76.7%)142 (75.9%)600 (76.9%)0.77
       Lower respiratory- only94 (9.7%)23 (12.3%)71 (9.1%)0.19
       Both upper and lower respiratory131 (13.6%)22 (11.8%)109 (14.0%)0.43
       Days since first positive test (mean ± SD)7.4 ± 10.38.1 ± 11.14.4 ± 5.3<0.0001
       Subsequent negative test418 (43.2%)125 (66.8%)293 (37.6%)<0.0001
      Abbreviations: COVID, coronavirus-19; EF, ejection fraction; LVH, left ventricular hypertrophy.
      a Includes either reported history of coronary artery disease or positive coronary angiogram.
      b Includes current or prior use.
      c Calculated prevalence of EF by strata (< 40, 40-49…) includes only donors for which EF was reported.
      d Calculated prevalence of LVH by strata (mild, moderate+) includes only donors for which either LV posterior or septal wall thickness was reported. LVH classification was based on the higher of these two measurements.
      e Refers to the occurrence of cardiac arrest between the time of brain death and donor organ recovery. Calculated prevalence excludes 75 donors (19 transplanted, 56 not transplanted) for which downtime was coded as “unknown”.
      f “Source of positive” is based only on tests performed within 21 days of donor recovery. “Days since first positive” is based on any tests performed within 60 days of donor recovery. “Subsequent negative” refers to any case where the last upper or lower respiratory test performed prior to donor recovery was negative.
      g Based on chi-squared test for categorical variables and t-test for continuous variables.
      COVID(+) donors (n = 187) comprised 2.9% of the total number of adult donors (n = 6464) used for HT (Table 2). Transplanted COVID(+) donors were slightly younger (mean age: 31.4 vs 32.8 years, p = 0.0025), more often male (81.8% vs 71.6%, p = 0.0021), and less often had a cerebrovascular cause of death (8.0% vs 13.5%, p = 0.029) compared to COVID(-) donors. There were no significant differences by donor COVID status in other clinical characteristics, including left ventricular systolic dysfunction, smoking, diabetes, and hypertension. Similarly, there were no significant differences in demographics, comorbidities, or cardiac diagnostic findings among initially COVID(+) heart transplant donors with (vs without) a subsequent negative test result prior to organ recovery (Supplemental Table S2).
      Table 2Characteristics of Adult Donors Whose Hearts were Accepted for Transplantation, by COVID Status (April 2020 - March 2022)
      All transplanted donorsCOVID(+)COVID(-)p-value
      Based on chi-squared test for categorical variables and t-test for continuous variables.
      Total n6464187 (2.9%)6277 (97.1%)
      Demographics
       Female sex1818 (28.1%)34 (18.2%)1784 (28.4%)0.0021
       Age (mean ± SD), years32.8 ± 9.631.4 ± 8.432.8 ± 9.60.025
       Age 18 – 343852 (59.6%)124 (66.3%)3728 (59.4%)0.057
       Age 35 – 492219 (34.3%)59 (31.6%)2160 (34.4%)0.42
       Age 50+393 (6.1%)4 (2.1%)389 (6.2%)0.022
      Race/Ethnicity
       White4002 (61.9%)113 (60.4%)3889 (62%)0.67
       Black1195 (18.5%)37 (19.8%)1158 (18.5%)0.64
       Hispanic1070 (16.6%)32 (17.1%)1038 (16.5%)0.83
       Asian or Other197 (3.1%)5 (2.7%)192 (3.1%)0.76
      Comorbidities
       Obese (BMI ≥ 30 kg/m2)2006 (31%)64 (34.2%)1942 (30.9%)0.34
       Coronary artery disease
      Includes either reported history of coronary artery disease or positive coronary angiogram.
      111 (1.7%)1 (0.5%)110 (1.8%)0.21
       Smoking
      Includes current or prior use.
      773 (12%)26 (13.9%)747 (11.9%)0.41
       Cocaine use
      Includes current or prior use.
      1674 (25.9%)48 (25.7%)1626 (25.9%)0.94
       Intravenous drug use
      • Dhand A
      • Gass A
      • et al.
      Long-term and short-term outcomes of solid organ transplantation from donors with a positive SARS-CoV-2 test.
      1153 (17.8%)36 (19.3%)1117 (17.8%)0.61
       Diabetes mellitus257 (4%)9 (4.8%)248 (4%)0.55
       Hypertension978 (15.1%)25 (13.4%)953 (15.2%)0.50
      Cardiac diagnostic findings
       EF
      Calculated prevalence of EF by strata (< 40, 40-49…) includes only donors for which EF was reported.
       < 40%26 (0.4%)1 (0.5%)25 (0.4%)0.77
       40-49%56 (0.9%)2 (1.1%)54 (0.9%)0.76
       ≥ 50%6376 (98.7%)184 (98.4%)6192 (98.7%)0.81
       Wall thickness reported (%)
      Calculated prevalence of LVH by strata (mild, moderate+) includes only donors for which either LV posterior or septal wall thickness was reported. LVH classification was based on the higher of these two measurements.
      4663 (72.1%)130 (69.5%)4533 (72.2%)0.42
       any LVH (≥1.2 cm)774 (16.6%)28 (21.5%)746 (16.5%)0.12
       mild LVH (1.2-1.3cm)599 (12.8%)25 (19.2%)574 (12.6%)0.027
       moderate+ LVH (≥1.4 cm)175 (3.8%)3 (2.3%)172 (3.8%)0.38
      Other clinical characteristics
       Blood type
       A2185 (33.8%)60 (32.1%)2125 (33.9%)0.61
       B679 (10.5%)20 (10.7%)659 (10.5%)0.93
       AB105 (1.6%)0 (0%)105 (1.7%)0.075
       O3495 (54.1%)107 (57.2%)3388 (54%)0.38
       Cardiac downtime
      Refers to the occurrence of cardiac arrest between the time of brain death and donor organ recovery. Calculated prevalence excludes 767 donors (19 COVID(+), 748 COVID-) for which downtime was coded as “unknown”.
      2861 (50.2%)92 (54.8%)2769 (50.1%)0.23
       Inotrope use2025 (31.3%)47 (25.1%)1978 (31.5%)0.064
       Acidemia (pH <7.35)805 (12.5%)31 (16.6%)774 (12.3%)0.083
      Abbreviations: COVID, coronavirus-19; EF, ejection fraction; LVH, left ventricular hypertrophy.
      a Includes either reported history of coronary artery disease or positive coronary angiogram.
      b Includes current or prior use.
      c Calculated prevalence of EF by strata (< 40, 40-49…) includes only donors for which EF was reported.
      d Calculated prevalence of LVH by strata (mild, moderate+) includes only donors for which either LV posterior or septal wall thickness was reported. LVH classification was based on the higher of these two measurements.
      e Refers to the occurrence of cardiac arrest between the time of brain death and donor organ recovery. Calculated prevalence excludes 767 donors (19 COVID(+), 748 COVID-) for which downtime was coded as “unknown”.
      f Based on chi-squared test for categorical variables and t-test for continuous variables.

      Variation in COVID-19(+) donor utilization, by center and over time

      Of the 130 centers that performed at least one HT during the study period, 42 centers (32.3%) performed at least two transplants with COVID(+) donors over the study period. Seventeen (13.1%) only used one COVID(+) donor and 71(54.6%) centers did not use any COVID(+) donors for HT. Figure 2 shows the distribution of the number and percentage of HTs using a COVID(+) donor in the 42 centers that accepted hearts from at least 2 COVID(+) donors, which ranged from 2 to 19 HTs per center (1.2% to 17.0% of all transplants performed by each site).
      Figure 2
      Figure 2Variation across centers in the use of COVID-positive donors for heart transplant (April 2020 – March 2022). Centers that used at least 2 COVID(+) donors for HT were included. The green bars represent the absolute number of COVID(+) donors used during the study period, whereas the purple line represents the COVID(+) donors as a percentage of the total transplants by that center during the study period.
      COVID(+) donor utilization increased significantly over time (p < 0.001), as shown in Figure 3. COVID(+) donors were used in less than 1% of all HTs prior to March 2021. From March – September 2021, this percentage ranged from 1% – 3% of all HTs. Over the subsequent six months (October 2021 – March 2022), there were a total of 148 HTs using COVID(+) donors (9.1% of total HT volume). Use of COVID(+) donors varied by UNOS region with the greatest proportion of transplants with COVID(+) donors occurring in the Northeast US (UNOS regions 2 and 9) (Supplemental Figure S1).
      Figure 3
      Figure 3Use of COVID-19 positive donors for HT over time. Use of COVID(+) donors for heart transplantation is shown by month from April 2020 through March 2022. The green bars represent the absolute number of heart transplants performed using COVID(+) donors while the purple line represents the percentage of heart transplants from COVID(+) donors relative to the total number of heart transplants in the US.

      Recipient characteristics, by donor COVID-19 status

      During the study period, 6,421 patients underwent HT. Of these, 199 adults (3.1%) received a heart from a COVID(+) donor (Table 3). There were no significant differences in recipient age, race, etiology of heart failure, or UNOS status at transplant by donor COVID-19 status. Patients who received a COVID(+) donor had lower rates of inotrope use (29.7% vs 37%, p = 0.04), durable ventricular assist device (VAD) (24.1% vs 32%, p = 0.02), and intra-aortic balloon pump (20.6% vs 26%, p = 0.08) therapies at the time of transplant. Notably, our recipient sample includes 21 adults who received a heart from a COVID-19+ pediatric donor (with median age 15 years, range 10 – 17 years); one of these pediatric donors had hypertension, two were obese, and none had other comorbidities or cardiac diagnostic abnormalities (of those listed in Table 2).
      Table 3Characteristics of Heart Transplant Recipients, by Donor COVID Status (April 2020 - March 2022)
      All recipientsRecipients of COVID(+) donorsRecipients of COVID(-) donorsp-value
      Based on chi-squared test for categorical variables and t-test for continuous variables.
      Total n
      Differs from those reported in Table 1 and 2, due to difference in inclusion criteria, i.e., donor age ≥18 years in Table 1 and 2 and recipient age ≥ 18 years in Table 3.
      6421199 (3.1%)6222 (96.9%)
      Demographics
       Female sex1685 (26.2%)44 (22.1%)1641 (26.4%)0.18
      Age (mean ± SD), y ears
       Age 18 – 391017 (15.8%)38 (19.1%)979 (15.7%)0.20
       Age 40 – 592846 (44.3%)82 (41.2%)2764 (44.4%)0.37
       Age 60+2558 (39.8%)79 (39.7%)2479 (39.8%)0.97
      Race/Ethnicity
       White3831 (59.7%)122 (61.3%)3709 (59.6%)0.63
       Hispanic1602 (25.0%)46 (23.1%)1556 (25%)0.54
       Black659 (10.3%)21 (10.6%)638 (10.3%)0.89
       Asian or Other329 (5.1%)10 (5.0%)319 (5.1%)0.95
      Comorbidities
       Obese (BMI ≥30 kg/m2)2105 (32.8%)70 (35.2%)2035 (32.7%)0.47
       Smoking2580 (40.2%)85 (42.7%)2495 (40.1%)0.46
       Diabetes mellitus1882 (29.3%)58 (29.2%)1824 (29.3%)0.96
      Therapies prior to transplant
       Extra-corporeal membrane oxygenation375 (5.8%)10 (5.0%)365 (5.9%)0.62
       Intra-aortic balloon pump1672 (26.0%)41 (20.6%)1631 (26.2%)0.076
       Ventricular assist device2021 (31.5%)48 (24.1%)1973 (31.7%)0.023
       Inotropes2346 (36.5%)59 (29.7%)2287 (36.8%)0.040
       Dialysis397 (6.2%)9 (4.5%)388 (6.2%)0.30
       Prior heart transplant125 (1.9%)0 (0.0%)125 (2.0%)0.53
       Prior cardiac surgery (non-transplant)2267 (35.3%)68 (34.2%)2199 (35.3%)0.73
      Other clinical characteristics
      Etiology of heart failure
       Ischemic1764 (27.5%)55 (27.6%)1709 (27.5%)0.96
       Congenital300 (4.7%)11 (5.5%)289 (4.6%)0.56
       Hypertrophic/restrictive503 (7.8%)11 (5.5%)492 (7.9%)0.22
       Non-ischemic or other3854 (60.0%)122 (61.3%)3732 (60.0%)0.71
       Multi-organ transplant722 (11.2%)18 (9.1%)704 (11.3%)0.32
      UNOS status at transplant
       1639 (10.0%)18 (9.1%)621 (10.0%)0.66
       23107 (48.4%)94 (47.2%)3013 (48.4%)0.74
       3977 (15.2%)31 (15.6%)946 (15.2%)0.89
       41295 (20.2%)45 (22.6%)1250 (20.1%)0.38
       558 (0.9%)2 (1.0%)56 (0.9%)0.88
       6345 (5.4%)9 (4.5%)336 (5.4%)0.59
      a Differs from those reported in Table 1 and 2, due to difference in inclusion criteria, i.e., donor age ≥18 years in Table 1 and 2 and recipient age ≥ 18 years in Table 3.
      b Based on chi-squared test for categorical variables and t-test for continuous variables.

      Post-Transplant Outcomes

      Among the 199 adult recipients of COVID(+) donor hearts, median follow-up time was 35 days (IQR 15-166 days) and 131 (65.8%) had discharge outcomes available (Table 4). The prevalence of acute rejection prior to discharge was numerically lower among recipients of COVID(+) donors compared to COVID(-) donors, but did not meet statistical significance (11.4% vs 17.4%, p = 0.077). The prevalence of the composite outcome (death, graft failure or re-transplantation at 90 days post-HT) was similar among recipients of COVID(+) vs COVID(-) donors [5.4% (n = 5) vs 5.6% (n = 312), respectively; p = 0.91]. Kaplan-Meier analyses comparing recipients of COVID(+) and COVID(-) donors (Supplemental Figure S2) showed no difference in time to discharge (p = 0.23) or time to the composite outcome (p = 0.27). Whether or not a COVID(+) donor had a subsequent negative test prior to organ recovery had no association with the primary composite or any secondary outcome (Supplemental Table S3). Donor COVID-19 status was not associated with the primary composite outcome after multivariate adjustment (HR 0.69, 95% confidence interval 0.38 – 1.26; Supplemental Table S4).
      Table 4Selected Outcomes Among Heart Transplant Recipients, by Donor COVID Status (April 2020 - March 2022)
      All recipientsCOVID(+) donorsCOVID(-) donorsp-value
      Based on chi-squared test for categorical variables and t-test for continuous variables.
      Total (n) with discharge outcomes available57351315604
      Days from transplant to discharge (mean ± SD)23.4 ± 23.122.3 ± 20.123.4 ± 23.20.58
      Acute rejection prior to discharge988 (17.2%)15 (11.4%)973 (17.4%)0.077
      Dialysis prior to discharge883 (15.4%)23 (17.6%)860 (15.4%)0.49
      Total (n) with at least 90 days of potential follow-up
      i.e., date of transplant before January 01, 2022.
      5627935534
      Composite outcome (death, graft failure, or re-transplant) at 90 days317 (5.6%)5 (5.4%)312 (5.6%)0.91
      a i.e., date of transplant before January 01, 2022.
      b Based on chi-squared test for categorical variables and t-test for continuous variables.
      Ten recipients of hearts from COVID(+) donors experienced the composite outcome at any time after transplant, at a mean of 55.7 days after transplant (range 0 – 222 days); these cases are further detailed in Supplemental Table S5, and include two recipients with graft failure resulting in re-transplantation, three with graft failure resulting in death, and five with death from another cause.

      Discussion

      Our study sought to examine the utility and safety of using hearts from COVID(+) donors for transplantation. Our major findings are the following: 1) carefully selected COVID(+) donors comprise an increasing minority of heart transplants; 2) COVID(+) donors were more likely to be younger and male, but otherwise had similar characteristics compared to COVID(-) donors whose hearts were used for HT; 3) recipients of hearts from COVID(+) donors are similar to those who received hearts from COVID(-) donors, with comparable short-term outcomes; 4) there were no significant differences in clinical characteristics or post-transplant outcomes between those COVID(+) donors with a subsequent negative test and those without. Taken together, these findings suggest that COVID(+) donors, even in the absence of a subsequent negative test, can be safely used for heart transplantation.
      While the use of COVID(+) donors for HT has increased over time, they remain underutilized compared with COVID(-) donors. Moreover, we found that less than one third of US centers have used more than one COVID(+) donor for HT. This finding is consistent with a recent survey of heart transplant providers and medical directors of heart transplant centers, most of whom report that they would not consider accepting a donor with a positive COVID-19 nasopharyngeal PCR (even with a negative bronchoalveolar lavage).
      • DeFilippis EM
      • Allen LA
      • Bhatt AS
      • et al.
      Vaccines, antibodies, and donors: varying attitudes and policies surrounding COVID-19 and heart transplantation.
      Our study's findings suggest that this majority view should be reconsidered - especially as (despite our best public health efforts) COVID(+) donors are likely to comprise a significant proportion of the donor pool for the foreseeable future.
      Herein we describe the largest cohort of recipients of hearts from COVID(+) donors. Although the sample size is still relatively small and more data are needed, short-term graft outcomes appear acceptable. This is consistent with other recent reports. In two multi-organ analyses of OPTN data by Schold et al and Bock et al, 62 and 18 COVID-19 heart transplants were included, respectively.
      • Schold JD
      • Koval CE
      • Wee A
      • Eltemamy M
      • Poggio ED.
      Utilization and outcomes of deceased donor SARS-CoV -2 positive organs for solid organ transplantation in the United States.
      ,
      • Bock MJ
      • Vaughn GR
      • Chau P
      • Berumen JA
      • Nigro JJ
      • Ingulli EG.
      Organ transplantation using COVID-19-positive deceased donors.
      They similarly found that COVID-19 positive donor hearts were significantly less likely to be recovered despite similar outcomes. Notably, since the end of the Bock study period in August 2021, there have been an additional 137 heart transplants using COVID(+) donors included in this analysis. In addition to sample size, strengths of our analysis include more detailed characterization of donor and recipient characteristics and description of center- and region- level variation.
      There are limitations to our analysis that should be acknowledged. Given limited follow-up time, further studies are necessary to assess longer-term outcomes in this cohort. Markers of the severity of donor infection including symptoms and cycle threshold were unavailable; it remains possible that the subset of donors with severe infection confers additional risk. Additionally, data regarding specific COVID-19 variants, vaccination status of recipients, as well as use of antiviral therapies including monoclonal antibodies post-HT were not available. Furthermore, repeat test results were available for only a subset of the donors included. The donors without a subsequent negative test may not necessarily have been viremic at the time of recovery or transplant.
      However, data regarding the role of vaccination and COVID-related therapies can be gleaned from single center reports detailing their successful experience with HT. Westchester Medical Center described their experience with organs from 12 COVID(+) donors who were transplanted into 14 recipients, including 3 hearts.
      • Dhand A
      • Gass A
      • et al.
      Long-term and short-term outcomes of solid organ transplantation from donors with a positive SARS-CoV-2 test.
      None of the three HT recipients were vaccinated prior to transplantation. One was on extracorporeal membrane oxygenation at the time of transplant, one was on an intra-aortic balloon pump, and the third was Status 2 but not on mechanical circulatory support. There was no clinical or molecular evidence of transmission of SARS-CoV2 in any recipients.
      • Dhand A
      • Gass A
      • et al.
      Long-term and short-term outcomes of solid organ transplantation from donors with a positive SARS-CoV-2 test.
      At one month follow-up, all had excellent graft function. Another analysis from the United Kingdom assessed 24 COVID(+) donors whose organs were used for 64 transplants, including three heart transplants.
      • Ushiro-Lumb I
      • Callaghan CJ
      • Pettigrew GJ
      • et al.
      Transplantation of organs from SARS-CoV-2 RNA positive deceased donors: the UK Experience.
      There was only one case of donor-derived infection, in a lung recipient who tested positive 5 days after transplantation. The largest single center report describes 12 HT with donors who tested positive for COVID-19 on any test.
      • Eichenberger EM
      • Coniglio AC
      • Milano C
      • et al.
      Transplanting thoracic COVID-19 positive donors: an institutional protocol and report of the first 14 cases.
      Ten of the 12 recipients had received at least 2 doses of mRNA vaccine against COVID-19 prior to transplant. No recipients developed signs or symptoms of COVID-19 infection. One recipient received preexposure prophylaxis with tixagevimab and cilgavimab but none required treatment for COVID-19.
      • Eichenberger EM
      • Coniglio AC
      • Milano C
      • et al.
      Transplanting thoracic COVID-19 positive donors: an institutional protocol and report of the first 14 cases.
      A similar experience with 8 HT using COVID(+) donors had no evidence of viral transmission. All patients received preexposure prophylaxis with tixagevimab and cilgavimab prior to hospital discharge.
      • Madgula AS
      • Nestasie M
      • Link C
      • et al.
      Tackling the paradox of orthotropic heart transplantation from SARS-CoV-2 positive donors: asingle center experience.
      In summary, carefully selected COVID(+) donors can be used for HT with no difference in early post-transplant outcomes. These data suggest that donor COVID status should not be an isolated factor contributing to donor turndown, particularly given a limited donor pool. Data regarding longer-term outcomes will be needed.

      Conflicts of interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Disclosures

      Dr. Wayda receives support from the NIH/NHLBI F32 fellowship award titled “Narrowing the gap between supply and demand in heart transplantation” (Award #: 1F32HL154750-01A1).
      Dr. Khush receives support from the NIH grant R01 HL125303 entitled “Evidence Based Evaluation and Acceptance of Donor Hearts for Transplantation.”
      Dr. Lala is on the Editorial Board of the Journal of Cardiac Failure, on the Advisory Board for BioVentrix and Merck, the DSMB for Sequana Medical, and has received speaker honoraria from Abbott and Zoll.

      Acknowledgments

      We wish to thank Denise Tripp at the United Network for Organ Sharing for her assistance with the dataset used for this manuscript.

      Appendix. Supplementary materials

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