A Retrospective and Comparative Analysis of Clinical Outcomes of Kidney Transplant Recipients During First and Second COVID-19 Waves in North-West India.

Introduction Kidney transplant recipients (KTRs) are prone to coronavirus disease 2019 (COVID-19) disease secondary to chronic immunosuppressive therapy. There have been differences in mortality and morbidity amongst the general population with different COVID-19 waves. This study is done to understand the effects of different COVID-19 waves amongst KTRs. Methods This was a retrospective single-centre trial from a high-volume transplant centre in North India. The immunosuppression protocol was changed according to national guidelines, and predictors of survival were evaluated. Results A total of 62 patients got infected during the first COVID-19 wave (March 2020 to February 2021) and 50 patients during the second COVID-19 wave (March 2021 to December 2021). Analysis showed a higher incidence of severe COVID-19 disease (79% vs. 50%) in the first wave, while the rest of the baseline parameters were similar in both waves. Mortality was similar in both groups. In both groups, severe COVID-19 disease, the requirement of hospitalisation, invasive oxygen therapy, and CT score findings were significant predictors of survival. There was no change in survival with respect to immunosuppression modification. Allograft dysfunction was more common in the second wave (7 vs. 1). Baseline creatinine was significantly associated with allograft dysfunction in follow-up. Conclusion Patients had severe COVID-19 disease during the first wave; however, poor availability of healthcare services during the second wave led to more patients with allograft dysfunction. Though immunosuppression change is necessary to prevent flare-ups of COVID-19 infection, it is not associated with survival benefits.

Act Together and Act Now to Overcome Gender Disparity in Organ Transplantation.

Gender disparity refers to the unequal treatment or a perception of individuals based on their gender and arises from differences in socially constructed gender roles. In the field of transplantation, gender inequality arises at different stages, affecting access to medical care, donation practices, and posttransplant followup care. Gender disparity in transplantation is not limited to any geographic region but is thought to be more prevalent in developing nations. An unusually high number of female donations with relatively fewer female recipients is not only attributable to the low economy but a congregation of medical, social, cultural, and psychological factors. Gender disparities can also be shown in transplant-related professional societies. This review highlights the complexities of spousal donation and vulnerability of women, especially in the developing world. There is a growing need to further modify transplant policies to tackle gender disparities, especially in living related donation. Systematic research in the context of gender-related concerns in transplantation will further aid in understanding the complexities and formulating policies for eliminating gender disparities. Gender disparity is a global problem and not merely limited to transplantation.

A Multicenter Retrospective Cohort Study on Management Protocols and Clinical Outcomes After ABO-incompatible Kidney Transplantation in India.

BACKGROUND: There is no robust evidence-based data for ABO-incompatible kidney transplantation (ABOiKT) from emerging countries. METHODS: Data from 1759 living donor ABOiKT and 33 157 ABO-compatible kidney transplantations (ABOcKT) performed in India between March 5, 2011, and July 2, 2022, were included in this retrospective, multicenter (n = 25) study. The primary outcomes included management protocols, mortality, graft loss, and biopsy-proven acute rejection (BPAR). RESULTS: Protocol included rituximab 100 (232 [13.18%]), 200 (877 [49.85%]), and 500 mg (569 [32.34%]); immunoadsorption (IA) (145 [8.24%]), IVIG (663 [37.69%]), and no induction 200 (11.37%). Mortality, graft loss, and BPAR were reported in 167 (9.49%), 136 (7.73%), and 228 (12.96%) patients, respectively, over a median follow-up of 36.3 mo. In cox proportional hazard model, mortality was higher with IA (hazard ratio [HR]: 2.53 [1.62-3.97]; P < 0.001), BPAR (HR: 1.83 [1.25-2.69]; P = 0.0020), and graft loss (HR: 1.66 [1.05-2.64]; P = 0.0310); improved graft survival was associated with IVIG (HR: 0.44 [0.26-0.72]; P = 0.0010); higher BPAR was reported with conventional tube method (HR: 3.22 [1.9-5.46]; P < 0.0001) and IA use (HR: 2 [1.37-2.92]; P < 0.0001), whereas lower BPAR was reported in the prepandemic era (HR: 0.61 [0.43-0.88]; P = 0.008). Primary outcomes were not associated with rituximab dosing or high preconditioning/presurgery anti-A/anti-B titers. Incidence of overall infection 306 (17.39%), cytomegalovirus 66 (3.75%), and BK virus polyoma virus 20 (1.13%) was low. In unmatched univariate analysis, the outcomes between ABOiKT and ABOcKT were comparable. CONCLUSIONS: Our largest multicenter study on ABOiKT provides insights into various protocols and management strategies with results comparable to those of ABOcKT.

A Comparative Analysis of Chikungunya in Kidney Transplant Recipients Compared With the General Population: A Multicenter, Retrospective, Cohort Study From India.

OBJECTIVES: Chikungunya is an arboviral illness, with patients presenting with fever, arthralgias, and myalgias. Outbreaks have occurred in tropical regions, and the virus is now endemic to many tropics, including South Asia, with India contributing a large part of the global burden. The presentation and long-term effects on transplant recipients are largely unknown. MATERIALS AND METHODS: In this retrospective analytical study, we compared chikungunya infection in 44 kidney transplant recipients from multiple centers in India and 34 patients from the general population. Data were collected from medical records and patient recall. RESULTS: Differences in presentation were remarkable between the 2 groups, with significantly lower incidence of musculoskeletal symptoms on presentation in transplant recipients compared with the general population. The incidence of acute graft dysfunction was 17.08% in transplant recipients, with return to baseline at the end of 1 month. Acute symptomatology resolved in transplant recipients within 1 month, and insignificant chronic symptoms were reported after 3 months. CONCLUSIONS: Chikungunya in kidney transplant recipients is markedly different from that of the general population, with significantly lower incidence of musculoskeletal symptoms such as arthralgias. The infection caused acute graft dysfunction, but no long-term sequelae were shown at the end of 1 year.

Kidney paired donation in developing countries: A global perspective.

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

Molecular Epidemiology of Rifampicin-Resistant Mycobacterium tuberculosis by GeneXpert MTB/RIF Assay in Renal Transplant Recipients: A Single-Center Experience.

OBJECTIVES: There are scarce data on the incidence and resistance pattern of rifampicin-resistant Mycobacterium tuberculosis among kidney transplant recipients. MATERIALS AND METHODS: This is a retrospective, single- center study of kidney transplantrecipients suspected of M. tuberculosis infection. The GeneXpert assay we used detected mutations in the rpoB gene that confer rifampicin resistance using 5 overlapping probes (A, B, C, D, and E). The probes can detect mutations in the codons 507 to 511 (probe A), 511 to 518 (probe B), 518 to 523 (probe C), 523 to 529 (probe D), and 529 to 533 (probe E).We also detailed the treatment protocol and outcomes of kidney transplantrecipients infected with rifampicin-resistant M. tuberculosis. RESULTS: In total, 2700 samples were processed during the period from October 2018 to February 2022 with successful results in 2640 samples (97.04%). One hundred and ninety (7.19%) samples were positive for M.tuberculosis, and rifampicin resistance was detected in 12 (0.45%) cases (11 pulmonary, 1 genitourinary). The most common rpoB mutation was located in the region of probe E (75.0%), followed by probe A (16.6%) and in 1 combination probe DE (8.33%). The rpoB mutations were not observed in probe B and probe C. Six patients received bedaquiline-based treatmentfor a short course of 11 months, whereas the other 6 patients required a long course of 18 to 20 months. Three patients died, 2 were lost to follow-up, and 7 were cured. During treatment, 4 patients experienced acute rejection, and 1 graft loss was reported. CONCLUSIONS: We report for the first time the incidence and pattern of rifampicin resistance among kidney transplant recipients with tuberculosis infection. Further investigations are required for exploring the molecular and clinical phenotypes.

Outcomes of Living Donor Kidney Transplant After SARS-CoV-2 Infection in Both the Donor and the Recipient: A Multicenter Study.

OBJECTIVES: Evidence on living donor kidney transplant procedures when both the donor and recipient have had a history of COVID-19 infection is scarce. MATERIALS AND METHODS: We retrospectively explored the protocol, outcomes, and follow-up of 64 donors and recipients of living donor kidney transplant who had recovered from COVID-19. This was a multicenter (n = 12) study from India that included transplants between October 29, 2020, and December 1, 2021. Induction and immunosuppression regimens forthose with different severities of COVID-19 were similar to standard practice. RESULTS: COVID-19 clinical severity ranged from asymptomatic/mild (not requiring oxygen therapy) in 49 recipients (77%) and 63 donors (95.4%) and moderate/severe (requiring oxygen therapy) in 15 recipients (23%) and 1 donor (4.6%). Mean wait time±SEM (SD)from firstdocumentednegative reverse transcriptase-polymerase chain reaction testto surgery for recipients and donors was 90.9 ± 9.27 (74.1) and 47 ± 4.5 (29.2) days, respectively. Six episodes (9.3%) of biopsy-proven acute rejection were reported at follow-up of 214 ± 14.8 (119) days and median of 227 (interquartile range, 109-309) days. The locally weighted scatter plot smoothing curve for creatinine during follow-up in donor-recipients pairs showed no trends of increased creatinine in the context of wait time from COVID-19 to transplant surgery. No graft loss, death, reactivation/reinfection, and complications related to surgery or COVID-19 were reported. CONCLUSIONS: Our report showed excellent outcomes and follow-up data of living donor kidney transplant in recovered donor-recipient pairs with the standard immunosuppression protocol. To our knowledge, this is the first and the largest study of donor-recipient living donor kidney transplant pairs when both donors and recipients had prior COVID-19.

COVID-19 Vaccination in Solid-Organ Transplant: A Real-World Multicenter Experience.

OBJECTIVES: India ranks third globally in organ procurement and transplant and has the second highest COVID-19 incidence rate, but data regarding COVID-19 vaccination in solid-organ transplant patients are scarce. MATERIALS AND METHODS: We created a cross-sectional, anonymous, online questionnaire and sentinvitations to several transplant centers in India. We surveyed vaccine mandates, immunization coverage and side effects, administration timing, infection severity among solid-organ transplant recipients, and booster dosage recommendations. RESULTS: The survey results showedthat vaccinepolicy is heterogeneous among centers; vaccination is voluntary at some centers (44.7%), but some centers have established COVID-19 vaccination as a requirement for transplant candidates (44.6%). CoviShield was the most common vaccine administered (89.3%), and more than 50% of transplant recipients and donors were fully vaccinated. Survey results showed that the pretransplant wait time after full vaccination (both doses) is 2 to 4 weeks (48.9%), and the optimal time for vaccination after transplant is 3 to 6 months (59.3%). For vaccinated transplant patients, 89.4% of respondents reported an incidence rate for posttransplant breakthrough infection of less than 25%. For unvaccinated patients, 38.3% ofrespondents reported a 25% to 50% incidence rate of posttransplant COVID- 19 infection. Booster doses are recommended at many transplant centers in India, as reported by 89.4% of survey respondents. CONCLUSIONS: The results of the survey suggested that there are no substantial safety concerns Future targets should include increasing efficacy and increasing booster doses of the COVID-19 vaccine.

A Narrative Review COVID-19 in Solid-Organ Transplantation: Real-World Evidence From India.

Worldwide, India ranks number 2 and 3 for COVID-19 burden and absolute transplant numbers, respectively. Here, we summarized our single and multicenter Indian studies on solid-organ transplant during the COVID-19 pandemic. During the pandemic, solid-organ transplants declined 40% to 50%. The mortality rate in COVID-19-positive kidney transplant recipients (11.6%) was lower in India compared with the developed world during the first wave and lower compared with maintenance hemodialysis patients (13% to 38%) but significantly higher compared with the nonimmunosuppressed general population (1% to 3%) in India. We contributed to National Organ and Tissue Transplant Organization transplant-related guidelines to increase safety and access to solid-organ transplant. We reported the safety and feasibility of remdesivir (n = 57) and convalescent plasma therapy (n = 10) in kidney transplant recipients. We reported 100% patient and graft survival without any complications related to COVID-19 in a large cohort of kidney transplant recipients who recovered from COVID-19 (n = 372) and a large cohort of kidney transplant recipients of living donors (n = 31) who recovered from COVID-19 without any change in induction and maintenance immunosuppression. COVID-19 disease severity and mortality in the second episode (reoccurring infection) was higher (46%) compared with the first episode (11.6%). There was 4.4% incidence of COVID-19-associated mucormycosis in kidney transplant recipients with mortality of 46% in the second wave. We reported COVID-19 vaccine safety with suboptimal efficacy in kidney transplant recipients and dialysis patients compared with the general population. Our report suggested that transplant with carefully selected COVID-19-recovered donors and patients may be feasible and safe, at least over the short term. Continued research is needed on vaccine efficacy, booster doses, and long-term follow up sequelae.

A Multicenter Cohort Study From India of ABO-Incompatible Kidney Transplantation in Post-COVID-19 Patients.

BACKGROUND: There is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post-COVID-19 candidates. METHODS: The study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post-COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections. RESULTS: A total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post-COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL. CONCLUSIONS: Our report implies that ABOiKTx in post-COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol.

Humoral and cellular response of COVID-19 vaccine among solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUND: We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response. METHODS: We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547. RESULTS: Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]). INTERPRETATION: Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.

COVID-19 Pandemic Research Opportunities in India: What the Pandemic Is Teaching Us About Transplantation.

Coronavirus disease (COVID-19) has engulfed the whole world, and India has been the second worst-hit nation. Organ transplant services were halted in both the public and private care sectors of India, with public care sectors more adversely affected. Deceased donations were disproportionately more affected, with unfavorable rates at the peak of the pandemic. Mortality outcomes of COVID-19 among different organ transplant recipients in India have been lower compared with the Western world, with younger age and less comorbidities among Indian populations partly responsible for the lower mortality. Mortality and graft loss were mostly associated with older age and those with chronic graft dysfunction. During the pandemic, invasive fungal infections, like mucormycosis, have been reported, illustrating the need for multidisciplinary management. The Indian transplant societies have formulated and timely revised guidelines for transplantation in the COVID-19 era. Living donor transplants (both liver and kidney) after recovery from COVID-19 were both first described in India, providing a guiding tool for the world. Follow-up reports of recovered solid-organ transplant recipients have also been reported in Indian studies, showing reassuring long-term outcomes. Data of breakthrough COVID-19 cases after vaccination among both transplant recipients and waitlist candidates and research in vaccine efficacy for solid-organ transplant recipients is still underway. We suggest continuing and intensifying research activities for a better plan and strategy in case of a future pandemic.

Solid Organ Transplantation in SARS-CoV-2 Recovered Transplant Candidates: a Comprehensive Review of Recent Literature.

Purpose of Review: As the coronavirus disease 2019 (COVID-19) pandemic continues to surge, determining the safety and timing of proceeding with solid organ transplantation (SOT) in transplant candidates who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and who are otherwise transplant eligible is an important concern. We reviewed the current status of protocols and the outcomes of SOT in SARS-CoV-2 recovered patients. Recent Findings: We identified 44 published reports up through 7 September 2021, comprising 183 SOT [kidney = 115; lung = 27; liver = 36; heart = 3; simultaneous pancreas-kidney (SPK) = 1, small bowel = 1] transplants in SARS-CoV-2 recovered patients. The majority of these were living donor transplants. A positive SARS-CoV-2 antibody test, although not obligatory in most reports, was a useful tool to strengthen the decision to proceed with transplant. Two consecutive real-time polymerase chain test (RT-PCR) negative tests was one of the main prerequisites for transplant in many reports. However, some reports suggest that life-saving transplantation can proceed in select circumstances without waiting for a negative RT-PCR. In general, the standard immunosuppression regimen was not changed. Summary: In select cases, SOT in COVID-19 recovered patients appears successful in short-term follow-up. Emergency SOT can be performed with active SARS-CoV-2 infection in some cases. In general, continuing standard immunosuppression regimen may be reasonable, except in cases of inadvertent transplantation with active SARS-CoV-2. Available reports are predominantly in kidney transplant recipients, and more data for other organ transplants are needed.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

Global Impact of the COVID-19 Pandemic on Solid Organ Transplant.

BACKGROUND: COVID-19 has drastically affected transplant services, but there is limited understanding of the discrepancy of COVID-19 effects on various regions of the world. METHODS: We have explored the Global Observatory for Organ Donation and Transplantation data for assessing the transplant number changes between the calendar year 2019 (n = 157,301) and 2020 (129,681). RESULTS: There was a disproportionate impact of COVID-19 on different areas of the world. Globally, there was a decline of 17.5%, in which deceased donation, kidney (20.9%), pancreas (16.2%), lung (12.7%), liver (11.3%), and heart (8%) transplant declined disproportionally in different regions of the world. The pandemic affected almost all geographic regions and nations, but China and the United States were mostly able to recover from the initial halt of the transplant practices by the pandemic so that there was a cumulative increase in transplant numbers. CONCLUSIONS: Our data show that developing nations lagged behind, whereas developed nations have been able to recover their transplantation programs during the pandemic. Further policy making and preparedness is required to safeguard the most vulnerable areas of the world to minimize the impact of any future pandemic on transplantation practices.