Additional Dose of SARS-CoV-2 Vaccine Increases Neutralization Capacity in Solid Organ Transplant Recipients

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

Outcomes After Covid-19 Infection in Transplant Recipients

Purpose: The purpose of this study is to evaluate outcomes of readmission, rejection, graft dysfunction, graft failure, and death in SOT recipients (SOTR) after COVID-19 infection. Method(s): We conducted a retrospective cohort study of SOTR diagnosed with COVID-19 infection before 5/1/2021. COVID-19 disease severity was assigned retrospectively by NIH criteria and grouped into asymptomatic/mild and moderate/ severe/critical infection. Data collected included demographics, clinical features, treatment, and outcomes. Bivariate comparisons to evaluate characteristics associated with outcomes were performed with independent group t-tests for continuous variables and Fisher's exact tests for categorical variables. Result(s): 138 SOTR were diagnosed with COVID-19 at a median of 5 (IQR 3-8) years post-transplant with a mean age of 57+/-12 years at diagnosis. Most were kidney or liver recipients (Table 1);49 (36%) had asymptomatic or mild infection. 29 (21%) of SOTR had moderate, 26 (19%) severe, and 31 (22%) critical infection. Disease severity, treatment with steroids or remdesivir did not correlate with rejection. Most graft failures occurred in SOTR with critical (n=12) disease (Table 2). 102 (74%) SOTR were admitted to the hospital for COVID-19 infection, of which 27 (26%) were readmitted more than 2 months after their index hospitalization. Of the readmissions, 5 were for renal complications, 5 infectious, and 7 pulmonary. Among those hospitalized, 13 (13%) SOTR died during the index admission. Among the 27 SOTR who were readmitted, 3 (11%) SOTR died during readmission. The mean time from initial infection to death was 121+/-176 days. Conclusion(s): In this cohort, disease severity was associated with graft failure. Readmissions were frequent more than 2 months after the index admission. Mortality in those who were readmitted remained high. Rejection was relatively infrequent.

Differences in Acceptance to the Kidney Transplant List

Purpose: During the COVID-19 pandemic, kidney transplant (KT) evaluations shifted from in-person evaluation (IPE) to telemedicine evaluation (TME). Given differences in access to electronics and internet, we thought that TME may advantage some social groups' access to the KT list. We evaluated if differences in acceptance to KT listing exist between pre- and post-pandemic eras, or between IPE and TME. We identified associations between other socioeconomic factors and KT listing. Method(s): Demographic and social data were collected from charts of patients evaluated for KT in the pre- (3/13/2019-3/13/2020) and post-pandemic era (3/14/2020- 3/14/2021). Categorical data are presented in proportions and frequencies;continuous data in means+/-SDEV. Independent group t-tests and Fisher's exact tests were used for bivariate comparisons. Result(s): Of 1061 charts, 1015 included data on race/ethnicity: 608 (59.1%) Black, 335 (33.6%) White, 40 (3.9%) Hispanic, 29 (2.8%) Asian, and 3 (0.3%) other. Overall, 629 (59%) evaluations were pre- and 430 (41%) post-pandemic. 734 (72%) were IPE and 288 (28%) TME. 553 (54%) candidates were denied for medical (310, 56%) and social (184, 33%) reasons;469 (46%) were accepted for listing. Employment status was known in 979 candidates: 278 (28%) employed, 368 (38%) disabled, 66 (7%) unemployed, and 267 (27%) retired. Evaluation in the post-pandemic era (p=0.002) was associated with acceptance for listing. TME was also associated with acceptance for listing (p<0.001). Pre-pandemic, there were 604 IPE and 1 TME of whom 253 (42%) were accepted, including the TME (p=0.238). Post-pandemic 130 evaluations were IPE and 287 TME, of whom 215 (52%) were accepted, including 58 (45%) IPE and 157 (55%) TME (p=0.061). Employment status (p<0.001) and mental health status (p=0.009) were associated with acceptance for listing. There was no association between race/ethnicity (p=0.809) or distance from home to the transplant center (p=0.693) and acceptance for listing. There were no differences in race/ ethnicity (p=0.951), employment status (p=0.202), or mental health status (p=0.742) between pre- and post-pandemic eras. Assessment of social support (p=0.002) and overall social work assessment (p<0.001) were associated with acceptance for listing. The level of social support (rated on a 1-5 scale) was associated with being accepted for listing pre-pandemic (p=0.001) but not post-pandemic (p=0.769). Conclusion(s): KT evaluations decreased by about one third during the post-pandemic era. Evaluation in the post-pandemic era, evaluation by TME, employment status, mental health status, assessment of social support and overall social work assessment were all associated with being listed for KT. There were no differences in race/ethnicity, employment status, or mental health status between eras, which is unexpected given the additional stressors of the pandemic on employment and mental health.

One-year monitoring of changes to kidney-pancreas waiting time criteria: An OPTN analysis

Purpose: In 2018, the OPTN board approved changes to kidney-pancreas (KP) waiting time criteria. KP candidates accrued waiting time if they were (1) on insulin and had a C-peptide <=2ng/mL or (2) on insulin and had a C-peptide >=2ng/ mL and had a BMI <=30kg/m∧2 which was the maximum allowable BMI. Since 7/11/2019 candidates must be on insulin, registered for a KP, and meeting kidney waiting time criteria. Methods: Registrations added to the waitlist and transplants between 7/11/2018- 7/10/2019 (pre-implementation) or 7/11/2019-7/10/2020 (post-implementation) were compared. Data originated from OPTN waitlist, Transplant Candidate Registration forms and Transplant Recipient Registration forms as of 10/16/2020. Results: 1,389 registrations were added to KP and 42,229 to kidney alone (KI) waitlists (pre-implementation);854 KP and 19,196 KI transplants performed. 1,401 registrations were added to KP and 19,493 KI waitlists (post-implementation);814 KP and 19,493 KI transplants performed. The proportion of type 2 diabetes (T2DM) KP candidates and recipients increased from 23.29% to 27.45% and 21.41% to 27%, respectively (Table 1). Candidate mean BMI increased from 25.7 to 26.3. KP recipients with T2DM and C-peptide >2ng/mL had higher median BMIs than those with lower C-peptide. KP post-transplant outcomes stratified by ethnicity, BMI, and diabetes status remained similar. The proportion of KI candidates and recipients remained roughly unchanged. Pediatric KI organ offers increased (527 to 592 offers per 100 active patient-years) but transplants remained unchanged. Conclusions: Changes in KP waiting time criteria did not adversely affect KI or pediatric KI candidates. Removing the BMI cutoff for obese patients with T2DM resulted in higher BMI KP transplants with equivalent post-transplant outcomes compared to lower BMI recipients. Although total KP transplants were slightly less in the post-implementation period, registrations were more and the transplant volumes were likely adversely affected by the COVID-19 pandemic.