Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.

The impact of active cytomegalovirus infection on donor-derived cell-free DNA testing in heart transplant recipients.

BACKGROUND: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. METHODS: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. RESULTS: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75% vs. 8%, p < .001) and ≥.20% (58% vs. 8%, p = .002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p = .002). CONCLUSION: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.

Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors.

BACKGROUND: Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). METHODS: We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS: Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20% versus 28.8% at 2 years, and 33.3% versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p = 0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p = 0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. CONCLUSION: Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry.

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.

Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era.

BACKGROUND: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described. METHODS: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival. RESULTS: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43. CONCLUSIONS: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Diagnostic and management roles of FDG PET/CT imaging in post-transplant lympho-proliferation in pediatric heart transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of pediatric heart transplant (PHTx). 18F-FDG PET/CT has been used to differentiate early lympho-proliferation from more advanced PTLD. We report our experience with PET/CT in the management of PTLD following PHTx. METHODS: This was a retrospective study of 100 consecutive PHTx recipients at our institution between 2004 and 2018. Patients who underwent PET/CT or conventional CT scans to evaluate for PTLD or high Epstein-Barr viral load were included. RESULTS: Males, eight females. Median age at transplant was 3.5 months (IQR = 1.5-27.5). Median age at PTLD diagnosis was 13.3 years (IQR = 9.2-16.1). Median time between transplant and PTLD diagnosis was 9.5 (IQR = 4.5-15) years. Induction agents were used in 12 patients (50%): Thymoglobulin (N = 9), anti-IL2 (N = 2), and Rituximab (N = 1). Eighteen patients (75%) had PET/CT, of whom 14 had 18FDG-avid PTLD. Six had conventional CT. Nineteen patients (79.2%) had diagnostic biopsy confirmation of PTLD, and 5 (20.8%) had excisional biopsies. Two patients had Hodgkin's lymphoma; nine had monomorphic PTLD; eight had polymorphic PTLD; five were classified as other. Nine patients had monomorphic PTLD, including seven with diffuse large cell lymphoma (DLBC) and one with T cell lymphoma. The majority (16/24) had multi-site involvement at PTLD diagnosis, and PET/CT showed that 31.3% (5/16) had easily accessible subcutaneous nodes. Seventeen patients (overall survival 71%) underwent successful treatment without recurrence of PTLD. Of seven deaths (7/24, 29%), five had DLBC lymphoma, one had polymorphic PTLD and one had T-cell lymphoma. CONCLUSION: PET-CT allowed simultaneous anatomical and functional assessment of PTLD lesions, while guiding biopsy. In patients with multiple lesions, PET/CT revealed the most prominent and active lesions, improving diagnostic accuracy.

Impact of Omicron BA.1 infection on BA.4/5 immunity in transplant recipients.

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.

Early initiation of glecaprevir/pibrentasvir after transplantation of HCV-viremic kidneys into HCV-negative recipients is associated with normalization in the altered inflammatory milieu.

Our previous Multicenter Trial to Transplant HCV-infected Kidneys (MYTHIC) observed that 100% of hepatitis C virus (HCV)-uninfected patients who received a kidney from an HCV-infected deceased donor were cured of HCV with an 8-week regimen of glecaprevir and pibrentasvir (G/P) initiated 2-5 days after transplantation. Following acute and chronic infection with HCV, immune system perturbations have been reported to persist even after viral clearance. The aim of this study was to determine whether HCV viremic kidney recipients in the MYTHIC study experience sustained changes in the soluble inflammatory milieu associated with HCV infection. Among nine patients with HCV viremia at day 3 post-kidney transplant (post-KT D3), IP-10, IL-10, MIP-1ß, and IL-8 were significantly elevated from baseline. However, over the subsequent visits, there was a rapid, dramatic reduction back to baseline levels. Among seven patients who were not HCV viremic at post-KT D3, the cytokine levels did not significantly change. HCV-uninfected patients who received a kidney from an HCV-viremic deceased donor and were treated with early G/P experienced only transient alterations in the soluble inflammatory milieu. These data provide reassuring evidence that there appear to be no persistent cytokine disturbances with transient HCV viremia accompanying HCV donor positive/recipient negative kidney transplant.

Infection and clinical xenotransplantation: Guidance from the Infectious Disease Community of Practice of the American Society of Transplantation.

This guidance was developed to summarize current approaches to the potential transmission of swine-derived organisms to xenograft recipients, health care providers, or the public in clinical xenotransplantation. Limited specific data are available on the zoonotic potential of pig pathogens. It is anticipated that the risk of zoonotic infection in xenograft recipients will be determined by organisms present in source animals and relate to the nature and intensity of the immunosuppression used to maintain xenograft function. Based on experience in allotransplantation and with preclinical models, viral infections are of greatest concern, including porcine cytomegalovirus, porcine lymphotropic herpesvirus, and porcine endogenous retroviruses. Sensitive and specific microbiological assays are required for routine microbiological surveillance of source animals and xenograft recipients. Archiving of blood samples from recipients, contacts, and hospital staff may provide a basis for microbiological investigations if infectious syndromes develop. Carefully implemented infection control practices are required to prevent zoonotic pathogen exposures by clinical care providers. Informed consent practices for recipients and their close contacts must convey the lack of specific data for infectious risk assessment. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with carefully developed protocols for pretransplant assessment, syndrome evaluation, and microbiological monitoring.

Seasonal variation of cytomegalovirus disease in kidney transplant recipients.

PURPOSE: Studies conducted in the northern United States found cytomegalovirus (CMV) disease after liver transplantation follows a seasonal pattern, with increased incidence in fall and winter. This has not been evaluated in kidney transplant recipients. Improved understanding of CMV seasonality may help guide use of preventative therapies. METHODS: We evaluated adult patients receiving a kidney transplant at our center in Wisconsin from January 1, 1995 to December 31, 2018. CMV event was defined as quantifiable viral replication with clinical signs or symptoms suspicious for CMV per current consensus recommendations. Seasons were divided as follows: winter (December-February), spring (March-May), summer (June-August), and fall (September-November). The primary objective was to evaluate the annual distribution of CMV disease and determine whether this differed by season. RESULTS: There were 6151 kidney transplants in the study period. A total of 913 patients had 1492 episodes of CMV. Median time from transplant to first detection was 5.51 months (interquartile range [IQR] 2.87-11.7). The observed overall incidence exceeded the expected incidence in winter (+.7%), spring (+5.5%), and fall (+3.4%) and was less than expected in summer (-9.5%) (p = .18). The incidence of CMV during summer, however, was 21% less than expected (p = .001) in recipients who were CMV positive (R+) at the time of transplantation. No such difference was observed in CMV negative recipients (R-; p = .58). CONCLUSION: CMV after kidney transplant appears to be less common during the summer season in patients who were R+ at transplant but does not follow seasonal variation in R-. Reasons for this are unclear but are likely related to CMV-specific cell-mediated immunity. These findings may have clinical implications, particularly the use of non-pharmacologic strategies to improve response to antiviral therapy.

Serologic follow-up of solid organ transplant recipients who received organs from donors with reactive syphilis tests: A retrospective cohort study.

The increased procurement of organs from donors with risk factors for blood-borne diseases and the expanding syphilis epidemic have resulted in a growing number of organs transplanted from donors with reactive syphilis serology in our center. Based on guidelines, recipients typically receive therapy shortly after the transplant, but data on outcomes are limited. The primary objective of this study was to determine syphilis seroconversion rates at three months post-transplant in recipients of solid organs procured from donors with reactive syphilis serology. Organ donors and recipients were tested for syphilis antibody; positive results were confirmed with Treponema pallidum Particle Agglutination (TPPA). Eleven donors with reactive syphilis antibody donated organs to 25 syphilis negative recipients. Three recipients seroconverted at post-transplant month 3. All of them had received therapy shortly after transplant. TPPA was negative in all 3. Despite post-transplant treatment, 3 of 25 (12%) syphilis negative recipients of organs from syphilis positive donors seroconverted at 3 months. All remained TPPA negative possibly reflecting passive antibody transfer or differing test sensitivity to low level treponemal antibodies. Further studies are needed to assess optimal syphilis transmission prevention strategies and follow up recipient testing in organ transplantation.

Impact of belatacept and tacrolimus on cytomegalovirus viral load control and relapse in moderate and high-risk cytomegalovirus serostatus kidney transplant recipients.

BACKGROUND: Belatacept improves long-term graft survival, but control of some primary viral infections may be impaired. We evaluated the impact of belatacept and tacrolimus on cytomegalovirus (CMV) viral control, remission and relapse in CMV high-risk and moderate-risk recipients. METHODS: Using a multistate Markov model, we evaluated viral load state transitions of 173 kidney transplant recipients with at least one episode of viremia within 1 year after transplant: state 1, undetectable/low viral load; state 2, moderate viremia; and state 3, severe viremia. RESULTS: Among high-risk recipients, belatacept-treated recipients exhibited a significantly higher probability of entering moderate viremia (.36; 95% CI = .31, .41) than tacrolimus-treated recipients (.20; 95% CI = .13, .29). The expected number of days in viremic states differed. High-risk belatacept-treated recipients persisted in moderate viremia for significantly longer (128 days, 95% CI = 110, 146) than did tacrolimus-treated recipients (70.0 days, 95% CI = 45.2, 100) and showed a trend of shorter duration in low/undetectable viral load state (172 days, 95% CI = 148, 195) than did tacrolimus-treated recipients (239 days, 95% CI = 195, 277). Moderate-risk recipients showed better viral load control and with no differences by immunosuppression. CONCLUSION: High-risk belatacept-treated recipients showed defects in sustaining viral control relative to tacrolimus-treated recipients. Avoidance of initial use belatacept in high-risk recipients or development of modified management protocols should be considered.

Epidemiology of surgical site infections after solid organ transplants in the period 2015-2019: A single-center retrospective cohort study.

Surgical site infections (SSI) are severe complications of solid organ transplant (SOT). This retrospective study assessed the epidemiology of and outcomes associated with invasive primary SSI (IP-SSI) occurring within 3 months of transplantation in adult SOT recipients at Duke University over a 5-year period (2015-2019). Among 2073 consecutive SOT recipients, 198 IP-SSI were identified. The IP-SSI rate declined over the period (14.4% in 2015 vs. 8.3% in 2019) and was higher among multi-organ compared with single-organ transplants (33.9% vs. 8.1%, p < .01). SOT recipients with IP-SSI had longer hospital stays than patients without SSI (30.0 vs. 17.0 days, p < .01). Transplant hospitalization (9.6% vs. 2.2%, p < .01), 6-month (11.6% vs. 3.3%, p < .01), and 1-year mortality (15.7% vs. 5.8%, p < .01) were higher in SOT recipients with IP-SSI than in those without. While Gram-positive bacteria were the most common pathogens, urogenital Mollicute and atypical Mycobacteria were identified as an unexpected cause of IP-SSI, particularly among lung transplant recipients. The median time to IP-SSI was 24.0 (IQR 13.8-48.3) days, although the time to IP-SSI varied based on organ transplanted and the causative pathogen. IP-SSI is an important and potentially modifiable complication of SOT, associated with prolonged hospitalizations and reduced survival, particularly in the lung transplant population.

Long-term follow-up of acute and chronic rejection in heart transplant recipients from hepatitis C viremic (NAT+) donors.

The long-term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center from January 2018 through August 2020. Routine testing was performed to assess for donor-derived cell-free DNA, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy-five NAT- recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post-transplant. Patients who underwent NAT testing starting on post-operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post-operative day 1 (NAT+ Group 2). Through 3.5 years of follow-up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT- cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT- group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.

Pediatric solid organ transplant recipients demonstrate robust cell-mediated and humoral responses to three doses of mRNA SARS-CoV-2 vaccine.

Pediatric solid organ transplant recipients (pSOTR) often demonstrate suboptimal vaccine responses and are not included in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy trials. This population has shown variable humoral immunity following SARS-CoV-2 vaccination, and no studies have assessed cell-mediated responses after SARS-CoV-2 vaccination in pSOTR. SARS-CoV-2-specific interferon-gamma release assay (IGRA), immunoglobulin G (IgG), and receptor-binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) blocking antibody (Ab) were measured in pSOTR aged 5-17 years after 2-3 doses of SARS-CoV-2 mRNA vaccine. In all, 33 subjects were included, with 25 tested after the second dose of mRNA vaccine (V2) and 21 tested after the third dose of mRNA vaccine (V3). Of the 19 subjects who had IgG testing after V3, 100.0% (19/19) had a positive IgG response. Of the 17 subjects who had IGRA testing after V3, 94.1% (16/17) had a positive IGRA response. RBD-ACE2 blocking antibody increased significantly from V2 to V3 (p = .007). Subjects <1 year from transplant demonstrated a significantly larger increase in RBD-ACE2 blocking Ab from V2 to V3 than did those >1 year from transplant (p = .05). SARS-CoV-2 vaccination induces humoral and cell-mediated responses in the majority of pSOTR, with improved quantitative humoral response after three doses.

Comparative outcomes for over 100 deceased donor kidney transplants from SARS-CoV-2 positive donors: A single-center experience.

Emerging data support the safety of transplantation of extra-pulmonary organs from donors with SARS-CoV-2-detection. Our center offered kidney transplantation (KT) from deceased donors (DD) with SARS-CoV-2 with and without COVID-19 as a cause of death (CoV + COD and CoV+) to consenting candidates. No pre-emptive antiviral therapies were given. We retrospectively compared outcomes to contemporaneous DDKTs with negative SARS-CoV-2 testing (CoVneg). From February 1, 2021 to January 31, 2022, there were 220 adult KTs, including 115 (52%) from 35 CoV+ and 33 CoV + COD donors. Compared to CoVneg and CoV+, CoV + COD were more often DCD (100% vs. 40% and 46%, p < .01) with longer cold ischemia times (25.2 h vs. 22.9 h and 22.2 h, p = .02). At median follow-up of 5.7 months, recipients of CoV+, CoV + COD and CoVneg kidneys had similar rates of delayed graft function (10.3%, 21.8% and 21.9%, p = .16), rejection (5.1%, 0% and 8.5%, p = .07), graft failure (1.7%, 0% and 0%, p = .35), mortality (0.9%, 0% and 3.7%; p = .29), and COVID-19 diagnoses (13.6%, 7.1%, and 15.2%, p = .33). Though follow-up was shorter, CoV + COD was associated with lower but acceptable eGFR on multivariable analysis. KT from DDs at various stages of SARS-CoV-2 infection appears safe and successful. Extended follow-up is required to assess the impact of CoV + COD donors on longer term graft function.