Faculty Bibliography

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

BACKGROUND AND OBJECTIVES:Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney transplantation due to restoration of kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:=190), and post-transplantation symptom score trajectories (mixed effects models). RESULTS:At evaluation, candidates reported being moderately to extremely bothered by fatigue (32%), xeroderma (27%), muscle soreness (26%), and pruritus (25%); 16% reported high and 21% reported very high symptom burden. Candidates with very high symptom burden were at greater waitlist mortality risk (adjusted subdistribution hazard ratio, 1.67; 95% confidence interval, 1.06 to 2.62). By transplantation, 34% experienced an increased symptom burden, whereas 42% remained unchanged. The estimated overall symptom score was 82.3 points at transplantation and 90.6 points at 3 months (10% improvement); the score increased 2.75 points per month (95% confidence interval, 2.38 to 3.13) from 0 to 3 months, and plateaued (-0.06 points per month; 95% confidence interval, -0.30 to 0.18) from 3 to 12 months post-transplantation. There were early (first 3 months) improvements in nine of 11 symptoms; pruritus (23% improvement) and fatigue (21% improvement) had the greatest improvements. CONCLUSIONS:Among candidates, very high symptom burden was associated with waitlist mortality, but for those surviving and undergoing kidney transplantation, symptoms improved.

Background/UNASSIGNED:Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes. Methods/UNASSIGNED:This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data. Results/UNASSIGNED: = 0.06). Conclusions/UNASSIGNED:Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival.

The coronavirus disease 2019 (COVID-19) pandemic has had a variable course across the United States. Understanding its evolving impact on heart and lung transplantation (HT and LT) will help with planning for next phases of this pandemic as well as future ones.

Background/UNASSIGNED:Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits. Methods/UNASSIGNED:Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010-2016). We estimated the length of stay (LOS), acute rejection (AR), graft failure, and death by induction type using logistic and Cox regression weighted by propensity score to adjust for confounders. We tested whether these estimates differed by age (65+ versus 18-64 y) using a Wald test. Results/UNASSIGNED: = 0.03 and 0.003) differed by recipient age. Discharge was on average 11% shorter in rATG among younger recipients (relative time = 0.89; 95% confidence interval [CI], 0.81-0.99) but not among older recipients (relative time = 1.01; 95% CI, 0.95-1.08). rATG was not associated with mortality among older (hazard ratio = 1.05; 95% CI, 0.96-1.15), but among younger recipients (hazard ratio = 0.87; 95% CI, 0.80-0.95), it was associated with reduced mortality risk. Conclusions/UNASSIGNED:rATG should be considered to prevent AR, especially among recipients with high-immunologic risk regardless of age; however, choice of induction should be tailored to reduce LOS and risk of mortality, particularly among younger recipients.

Organ procurement organizations (OPOs) evaluate referrals for deceased organ donation in the United States. Efforts to expand the donor pool, such as the HIV organ policy equity (HOPE) Act that permits transplants from HIV-positive donors to HIV-positive recipients, can only succeed if OPOs pursue referrals. However, relatively little is known about how OPO staff evaluate referrals. To better understand this process, OPO staff completed a discrete choice experiment to quantify the relative importance of seven donor characteristics on the decision to pursue a theoretical donor. Relative importance was defined by Partworth utility using a hierarchical Bayesian conditional logit model. There were 51 respondents from 36 of 58 OPOs in the United States. Of the seven attributes, organ and tissue potential were the most influential, followed by age, type of death, HIV status, donor registration, and Hepatitis C status. To be preferred to an HIV-negative donor, an HIV-positive donor needed to have the potential to donate two additional organs. These data provide insight into the preferences of OPO referral staff and may help explain the lower than expected number of HIV-positive transplants performed since the passage of the HOPE Act.

BACKGROUND:While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. METHODS:US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. RESULTS:Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. CONCLUSIONS:HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

BACKGROUND:Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. METHODS:To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8). RESULTS:Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%). CONCLUSION/CONCLUSIONS:Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.