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.

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: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.

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:Solid organ transplant recipients (SOTR) have diminished humoral immune responses to COVID-19 vaccination and higher rates of COVID-19 vaccine breakthrough infection than the general population. Little is known about COVID-19 disease severity in SOTR with COVID-19 vaccine breakthrough infections. METHODS:Between 4/7/21 and 6/21/21 we requested case reports via the Emerging Infections Network (EIN) listserv of SARS-CoV-2 infection following COVID-19 vaccination in SOTR. Online data collection included patient demographics, dates of COVID-19 vaccine administration and clinical data related to COVID-19. We performed a descriptive analysis of patient factors and evaluated variables contributing to critical disease or need for hospitalization. RESULTS:Sixty-six cases of SARS-CoV-2 infection after vaccination in SOTR were collected. COVID-19 occurred after the second vaccine dose in 52 (78.8%) cases of which 43 (82.7%) occurred ≥14 days post-vaccination. There were 6 deaths, 3 occurring in fully vaccinated individuals (7.0%, n = 3/43). There was no difference in the percentage of patients who recovered from COVID-19 (70.7% vs 72.2%, p = 0.90) among fully and partially vaccinated individuals. We did not identify any differences in hospitalization (60.5% vs. 55.6%, p = 0.72) or critical disease (20.9% vs. 33.3%, p = 0.30) among those who were fully vs. partially vaccinated. CONCLUSIONS:SOTR vaccinated against COVID-19 can still develop severe, and even critical, COVID-19 disease. Two doses of mRNA COVID-19 vaccine may be insufficient to protect against severe disease and mortality in SOTR. Future studies to define correlates of protection in SOTR are needed. This article is protected by copyright. All rights reserved.

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.