Perspectives on AI-based recommendations for mask-wearing and COVID-19 vaccination for transplant recipients in the post-COVID-19 era.

In the aftermath of the COVID-19 pandemic, the ongoing necessity for preventive measures such as mask-wearing and vaccination remains particularly critical for organ transplant recipients, a group highly susceptible to infections due to immunosuppressive therapy. Given that many individuals nowadays increasingly utilize Artificial Intelligence (AI), understanding AI perspectives is important. Thus, this study utilizes AI, specifically ChatGPT 4.0, to assess its perspectives in offering precise health recommendations for mask-wearing and COVID-19 vaccination tailored to this vulnerable population. Through a series of scenarios reflecting diverse environmental settings and health statuses in December 2023, we evaluated the AI's responses to gauge its precision, adaptability, and potential biases in advising high-risk patient groups. Our findings reveal that ChatGPT 4.0 consistently recommends mask-wearing in crowded and indoor environments for transplant recipients, underscoring their elevated risk. In contrast, for settings with fewer transmission risks, such as outdoor areas where social distancing is possible, the AI suggests that mask-wearing might be less imperative. Regarding vaccination guidance, the AI strongly advocates for the COVID-19 vaccine across most scenarios for kidney transplant recipients. However, it recommends a personalized consultation with healthcare providers in cases where patients express concerns about vaccine-related side effects, demonstrating an ability to adapt recommendations based on individual health considerations. While this study provides valuable insights into the current AI perspective on these important topics, it is crucial to note that the findings do not directly reflect or influence health policy. Nevertheless, given the increasing utilization of AI in various domains, understanding AI's viewpoints on such critical matters is essential for informed decision-making and future research.

Successful treatment of Rhodococcus lung abscess and empyema thoracis in a heart transplant recipient.

Rhodococcosis is an uncommon cause of pulmonary infection in thoracic organ transplant recipients. We describe a heart transplant recipient diagnosed with Rhodococcus equi left upper lung abscess with empyema thoracis complicated by bacteremia. The patient was successfully treated with appropriate antibiotics, adequate surgical resection, and optimization of immunosuppressants.

Clinical and immunological characteristics for BK polyomavirus-associated nephropathy after kidney transplantation.

INTRODUCTION: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV-specific immunity is associated with viral containment. This study investigated BKPyV-specific immunological factors among KT recipients. METHODS: This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV-cell-specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon-gamma (IFN-γ)-producing CD4+  T, CD8+  T, natural killer (NK), and natural killer T (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). RESULTS: In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1-year cumulative incidence of high-level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre-KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077-1.469; p = .004) and %VP1-specific NK cells (HR, 1.209; 95% CI, 1.055-1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1-specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). CONCLUSION: Individuals with nonspecific and VP1-specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high-level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV-specific innate immune surveillance in predicting the occurrence of BKPyVAN.

A Prospective Immunogenicity Study of a Quadrivalent Inactivated Influenza Vaccine Among Persons With HIV With Different Levels of CD4 Cell Count.

INTRODUCTION: Data regarding the immunogenicity of a quadrivalent inactivated influenza vaccine (IIV4) among persons with HIV with different levels of CD4 cell count are limited. Here, we report the immunogenicity of IIV4 in persons with HIV with different CD4 cell count levels by determining seroprotection (SP) and seroconversion rate after vaccination. METHOD: Persons with HIV were prospectively recruited to receive IIV4 (season 2021) between November 2021 and January 2022. Hemagglutination inhibition titers were assessed before and at 28 days after vaccination and classified as SP or seroconversion with comparison of characteristic between CD4 cell count >350 cells/mm 3 group and CD4 cell count ≤350 cells/mm 3 . RESULT: A total of 70 persons with HIV received the IIV4. The mean (SD) age was 48 (9) years, and 64% were men. Most of them (74%) were maintained on a nonnucleoside reverse transcriptase inhibitor-based regimen with an undetectable HIV viral load (100%). There was a significantly greater proportion of persons with HIV who achieved SP against A/Hong Kong/2571/2019-like virus (H3N2) variant in those with CD4 cell count >350 cells/mm 3 compared with those with CD4 cell count ≤350 cells/mm 3 (98.3% vs. 72.3%), relative risk 1.35 (95% confidence interval: 1.13 to 1.61, P = 0.011). Furthermore, the participants with CD4 cell count >350 cells/mm 3 were significantly more likely to achieve SP against B/Phuket/287/2013 strain (98.3% vs. 72.3%, relative risk 1.35; 95% confidence interval: 1.13 to 1.61, P = 0.011). CONCLUSION: Persons with HIV with greater CD4 cell count could achieve a higher chance of SP against B/Phuket/287/2013 and A/Hong Kong/2571/2019-like virus (H3N2) strains after IIV4 vaccination. Therefore, new strategies should be investigated and offered to those with low CD4 cell counts.

Lung abscess and empyema in a heart transplant recipient from Thailand.

The case discussed involves a 69-year-old Thai woman who underwent orthotopic heart transplantation 9 months before this event. She presented with fever without localizing signs or symptoms. However, her chest images revealed mass-like consolidation in the left upper lobe. Blood culture and lung tissue identified Rhodococcus equi. She was successfully treated with a combination of antimicrobial therapy, optimization of immunosuppressants, and surgical resection.

Utility of the Interferon-Gamma Enzyme-Linked Immunosorbent Spot Assay to Predict Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

Non-specific interferon-gamma (IFN-γ) enzyme-linked immunosorbent (ELISpot) responses after solid organ transplant (SOT) and their relationship with cytomegalovirus (CMV) reactivation have hardly been investigated. Adult kidney transplant (KT) recipients underwent measurement of IFN-γ-producing T cells using the ELISpot assay before and 1 month after transplantation. Data for CMV infection episodes were collected. Risk factors for post-transplant CMV infection, based on IFN-γ responses, were analyzed using a Cox proportional hazards model. A total of 93 KT recipients were enrolled in the study and 84 evaluable participants remained at 1 month post KT. Thirty-three (39%) recipients developed subsequent CMV infection within 6 months post-transplant. At 1-month post-transplant, IFN-γ-producing T cells with <250 spot-forming units (SFUs)/2.5 × 105 peripheral blood mononuclear cells (PBMCs) were significantly associated with CMV infection (HR 3.1, 95% CI 1.4-7.1, p = 0.007). On multivariable analysis, posttransplant IFN-γ-producing T cells with <250 SFUs/2.5 × 105 PBMCs remained independently associated with CMV infection (HR 3.1, 95% CI 1.2-7.8, p = 0.019). Conclusions: KT recipients with low IFN-γ-producing T cells measured by the ELISpot assay are more likely to develop CMV infection after transplantation. Therefore, measurement of nonspecific cell-mediated immunity ELISpot responses could potentially stratify recipients at risk of CMV infection (Thai Clinical Trials Registry, TCTR20210216004).

Interferon-gamma release assays for diagnosis of latent TB infection in chronic kidney diseases and dialysis patients.

Introduction: Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). The prevalence and predictors of LTBI assessed by a high-sensitivity, high-specificity test such as an interferon-gamma release assay (IGRA) has not been thoroughly explored. Methods: All patients with CKD were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. The prevalence of LTBI was determined using IGRA by CKD stage and dialysis type. Predictors of LTBI were assessed by logistic regression analysis. Results: In total, 199 patients with CKD were enrolled (102 prospectively, 97 retrospectively). Of these, 173 patients were evaluable (mean age, 53 ± 16 years; 44% male). Ninety-five (55%) patients had ESKD and were maintained on renal replacement therapy. Overall, 39 (22.5%) patients had LTBI with a prevalence of 25.0%, 12.5%, 25.0%, 25.0%, and 24.2% among patients with CKD stage 1, 2, 3a, 3b, and ESKD, respectively (p=0.89). Among patients with ESKD, the prevalence of LTBI was higher in those on hemodialysis than in those on peritoneal dialysis (28.9% vs. 5.3%, p=0.03). In the multivariable analysis of patients with ESKD, drinking alcohol was significantly associated with LTBI (odds ratio, 8.51; 95% confidence interval, 1.24-58.38; p=0.029), and hemodialysis was marginally associated with LTBI (odds ratio, 8.14; 95% confidence interval, 0.95-69.91; p=0.056). Conclusion: In TB-endemic settings, 20% of patients with CKD and 25% of patients with ESKD may have LTBI. Alcohol consumption and hemodialysis can help to identify high-risk patients with ESKD and potentially screen for LBTI.

Clinical outcome of rapid diagnosis and antibiotic stewardship in patients with bloodstream infection in Lampang Hospital.

Bloodstream infection is a significant cause of morbidity and mortality. Early diagnosis and appropriate antibiotic treatment contribute to a favorable prognosis. We demonstrate a reduction of time to proper antibiotics and reduced mortality utilizing prompt diagnosis and antibiotic stewardship by infectious diseases physicians at a general hospital in Thailand.

Current state of antimicrobial stewardship and organ transplantation in Thailand.

BACKGROUND: Antimicrobial stewardship (AMS) is a coherent set of actions to optimize antimicrobial use, improve patient outcomes, and reduce antimicrobial resistance (AMR). Thailand's national strategic plan has included AMS since 2017. Due to an increased risk of infection and AMR, solid organ transplant (SOT) recipients can benefit from antimicrobial stewardship programs (ASPs). However, the AMS in SOT has not been well defined. Balancing ASPs with the need for early and frequent antimicrobial treatment in this population is challenging. This review assesses the barriers and potential strategies of AMS in SOT in the setting of Thailand. METHODS: We used PubMed to identify published articles on AMS in organ transplantation in Thailand from January 2013 to January 2022. We also searched local literature and local data from Google Scholar and Google. Finally, we described the AMS experience at Ramathibodi hospital as a proxy for transplant centers in Thailand. RESULTS: There was no specific article on AMS in SOT in Thailand. At our hospital, ASPs have been part of the hospital's routine patient care, including the practice in the transplant unit. Modifiable challenges to AMS in SOT include prescriber opposition, diagnosis uncertainty, and lack of high quality. Both systems and individualized approaches should be implemented to overcome these barriers. The potential interventions include shortening antibiotic time-out, updating clinical guidelines, continuing education, handshake ASP, adopting new technology, and further research. CONCLUSIONS: There are limited data on AMS in organ transplantation in Thailand. Strategic priorities should focus on modifiable barriers tailored to organ transplantation. Quality improvement should be ensured by process and outcome measures.

Clinical Course and Outcomes among COVID-19 Patients at the Hospitel in Bangkok: A Retrospective Study.

A hospitel is a hotel that has been designated as an extension of the healthcare facilities during the COVID-19 pandemic in resource-limited settings. However, the clinical course and outcomes of patients with COVID-19 admitted to this unique type of facility have never been studied. We retrospectively reviewed the medical records of adult patients with COVID-19 who were admitted to a single hospitel in Bangkok, Thailand. Risk factors with respect to chest X-ray progression and clinical progression were analyzed using a logistic regression. A total of 514 patients were recruited, with a mean (standard deviation) age of 35.6 (13.4) years, and 58.6% were women. Patients were admitted after a median (interquartile range) of 3 (2−6) days of illness and were classified with mild (12.3%), moderate (86.6%), and severe (1.1%) conditions. Favipiravir and corticosteroids were prescribed in 26.3% and 14.9% of patients, respectively. Chest X-ray progression was found in 7.6% of patients, and hospital transfer occurred in 2.9%, with no deaths. Favipiravir use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4−7.5, p = 0.005), nausea/vomiting after admission (OR 32.3, 95% CI 1.5−700.8, p = 0.03), and higher oxygen saturation on admission (OR 1.99; 95% CI 1.22−3.23, p = 0.005) were factors associated with chest X-ray progression. Additionally, an oxygen requirement on admission was an independent risk factor for hospital transfer (OR 904, 95% CI 113−7242, p < 0.001). In a setting where the hospitel has been proposed as an extension facility for patients with relatively non-severe COVID-19, most patients could achieve a favorable clinical outcome. However, patients who require oxygen supplementation should be closely monitored for disease progression and promptly transferred to a hospital if necessary.

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

A Prospective Study of Plasma and Bronchoalveolar Lavage Fluid CMV DNA Load Quantification for the Diagnosis and Outcome of CMV Pneumonitis in Immunocompromised Hosts.

BACKGROUND: Molecular testing has been utilized for cytomegalovirus (CMV) pneumonitis (CMVP) diagnosis, although its validity and optimal cut-off values remain limited. METHODS: A prospective study of CMVP diagnosis among immunocompromised patients was conducted by measuring quantitative CMV DNA polymerase chain reaction in plasma and bronchoalveolar lavage fluid (BALF). RESULTS: Forty-five adult immunocompromised patients were investigated. Thirty-two patients (71%) received immunosuppressive therapy. Eleven patients (24%) were confirmed to have CMVP. Of those, three and eight patients were classified as proven and probable CMVP, respectively. Median (IQR) plasma CMV DNA loads in CMVP and non-CMVP were 41,939 (4,424-122,608) and 0 (0-44) IU/mL, respectively (p<0.001). Median (IQR) BALF CMV DNA loads in CMVP and non-CMVP were 379,652 (163,800-1,254,000) and 0 (0-1,348) IU/mL, respectively (p<0.001). A significant correlation was observed between plasma and BALF CMV DNA loads (r=0.887, p<0.001). Plasma CMV DNA load of 831 IU/mL was established as a cut-off value for diagnosing CMVP (AUC 0.9987, sensitivity 100%, specificity 94.1%, positive predictive value 84.5%, negative predictive value 100%). CONCLUSIONS: A strongly positive correlation was observed between CMV DNA loads measured in plasma and BALF. CMV DNA load quantification could potentially assist in diagnosing CMVP in immunocompromised patients, although bronchoscopy remains encouraged for a definitive diagnosis.

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3).

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136−3083) BAU/mL vs. 373 (188−607) BAU/mL) and PD (1093 (617−1911) BAU/mL vs. 180 (126−320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

Coronavirus Disease 2019 Vaccinations in Patients With Chronic Liver Disease and Liver Transplant Recipients: An Update.

Coronavirus disease 2019 (COVID-19) is a current global pandemic associated with an increased mortality, particularly in patients with comorbidities. Patients with chronic liver disease (CLD) and liver transplant (LT) recipients are at higher risk of morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Many liver societies have recommended that these patients should receive COVID-19 vaccinations, although there are limited studies assessing risks and benefits in this population. In addition, two doses of mRNA vaccines may not provide sufficient immune response, and booster dose(s) may be necessary, especially in LT recipients. Notably, variants of concern have recently emerged, and it remains unclear whether currently available vaccines provide adequate and durable protective immunity against these novel variants. This review focuses on the role of COVID-19 vaccinations in CLD and LT recipients.

Impact of Carbapenem Peri-Transplant Prophylaxis and Risk of Extended-Spectrum Cephalosporin-Resistant Enterobacterales Early Urinary Tract Infection in Kidney Transplant Recipients: A Propensity Score-Matched Analysis.

Background: Urinary tract infection (UTI) is the most common bacterial infection after kidney transplantation (KT), leading to unfavorable clinical and allograft outcomes. Gram-negative uropathogenic bacteria are frequently encountered especially extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (EB), causing UTI early after KT. Methods: A retrospective single transplant study was conducted between January 2016 and December 2019. We performed 1:1 nearest-neighbor propensity score matching without replacement using recipient age, recipient sex, induction, transplant year, human leukocyte antigen, cold ischemia time, and panel-reactive antibody before analyses. Cumulative incidence of ESC-R EB early (within 14 days after KT) UTI was estimated by the Kaplan-Meier method. Risk factors for ESC-R EB early UTI were analyzed by a Cox proportional hazards model. Variables measured after transplantation were considered time-dependent covariates. Results: We included 620 KT recipients (37% women; mean age ± SD, 43 ± 11 years). Overall, 64% and 76% received deceased-donor allograft and induction therapy. Sixty-five (10%) and 555 (90%) received carbapenems and cefuroxime peri-transplant prophylaxis, respectively. Early UTI occurred in 183 (30%) patients, 52% caused by ESC-R EB. Propensity score matching produced 65 well-balanced pairs. During a 14-day follow-up, the cumulative incidence of ESC-R EB early UTI was 5 and 28% in the carbapenems and cefuroxime groups, respectively (log-rank test = 0.003). Peri-transplant carbapenems prophylaxis was a protective factor against ESC-R EB after KT (hazard ratio, 0.19; 95% confidence interval, 0.05-0.64; p = 0.008). Clinical and allograft outcomes did not differ significantly between the groups. Conclusions: In the setting where ESC-R EB UTI is common among KT recipients, carbapenems peri-transplant prophylaxis could protect against the occurrence of early ESC-R EB UTI after KT. Further prospective studies should focus on this specific infection prevention strategy.

Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes.

Importance: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. Objective: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. Design, Setting, and Participants: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster's key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. Exposure: Machine learning consensus clustering approach. Main Outcomes and Measures: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. Results: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. Conclusions and Relevance: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

Short-Term Immunogenicity Profiles and Predictors for Suboptimal Immune Responses in Patients with End-Stage Kidney Disease Immunized with Inactivated SARS-CoV-2 Vaccine.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored. METHODS: We conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls. RESULTS: After two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses. CONCLUSIONS: Patients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

Feature Importance of Acute Rejection among Black Kidney Transplant Recipients by Utilizing Random Forest Analysis: An Analysis of the UNOS Database.

Background: Black kidney transplant recipients have worse allograft outcomes compared to White recipients. The feature importance and feature interaction network analysis framework of machine learning random forest (RF) analysis may provide an understanding of RF structures to design strategies to prevent acute rejection among Black recipients. Methods: We conducted tree-based RF feature importance of Black kidney transplant recipients in United States from 2015 to 2019 in the UNOS database using the number of nodes, accuracy decrease, gini decrease, times_a_root, p value, and mean minimal depth. Feature interaction analysis was also performed to evaluate the most frequent occurrences in the RF classification run between correlated and uncorrelated pairs. Results: A total of 22,687 Black kidney transplant recipients were eligible for analysis. Of these, 1330 (6%) had acute rejection within 1 year after kidney transplant. Important variables in the RF models for acute rejection among Black kidney transplant recipients included recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration. The three most frequent interactions consisted of two numerical variables, including recipient age:donor age, recipient age:serum albumin, and recipient age:BMI, respectively. Conclusions: The application of tree-based RF feature importance and feature interaction network analysis framework identified recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration as important variables in the RF models for acute rejection among Black kidney transplant recipients in the United States.