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.

Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre.

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.

Successful management of dengue in renal transplant recipients: A retrospective cohort from a single center.

INTRODUCTION: The literature on dengue infection in renal transplant recipients has shown wide diversity in clinical presentation and outcome. The objective of this study was to report the clinical profile, short-term and long-term outcomes of dengue among renal transplant recipients. METHODS: A total of 59 post-transplant dengue suspected cases were admitted from July 2019 to April 2020 of which 31 had confirmed dengue infection. The clinical and laboratory profile of the confirmed dengue cases (n = 31) were compared with non-dengue cases (n = 28). RESULTS: Among the clinical and laboratory features retro-orbital pain, conjunctival redness, thrombocytopenia on admission, and absence of arthralgia were significantly associated with dengue compared to non-dengue cases. No mortality was observed in the dengue cases. Allograft dysfunction, acute rejection and graft losses were identified in 64.5% (n = 20), 6.4% (n = 2) and 6.4% (n = 2) dengue cases respectively. No rejection or graft losses were observed in 1-year follow-up. CONCLUSIONS: We report a differential clinical profile for dengue in transplant settings which will aid in the diagnosis. We also report successful management of dengue infection in renal transplant recipients with the majority having allograft dysfunction. A long-term follow-up of the cohort was uneventful.

Long-term follow-up of SARS-CoV-2 recovered renal transplant recipients: A single-center experience from India.

INTRODUCTION: Follow-up studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in kidney transplant recipients (KTR) are scarcely reported. METHODS: We studied 142 hospitalized KTR for a median (interquartile range) follow-up of 9 (8-11) months who recovered from SARS-CoV-2 during May 2020 to Dec 2020. The outcomes were to assess persistent symptoms post-discharge; EuroQoL visual analogue score (EQ-VAS); EuroQoL 5-dimension score (E5-QD-5L) score and modified medical research dyspnea score (mMRC) at 1 month, 3-month, and beyond 6 months. Graft outcome was also analyzed. RESULTS: The age of the cohort was 43 (34-69) years and COVID-19 severity ranged from asymptomatic (4%), mild (50%), moderate (35%) to severe (12%). The most common persistent symptom was fatigue which significantly decreased in the follow-up (n = 45 [32.3] vs. 10 [7.4] vs. 4 [2.9]; p-value = 0.001) at 1-month, 3-month, and beyond 6 months respectively. Decrement in the mean (standard deviation) EQ-VAS score from baseline was also improved (28.6 [13] vs. 10.4 [12.5] vs. 7.5 [12.0]; p-value = 0.012). There was significant improvement in all EQ-5D-5L scores in follow-up. There was no deterioration in mMRC scores during the follow-up (n = 4, 3% vs. 7, 5% vs. 3, 2%; p-value = 0.86). Cases requiring oxygen had significantly poorer overall scores initially, but there was no difference at 6 months. All 10 graft losses had oxygen requirement and chronic graft dysfunction at baseline. CONCLUSION: Our initial assessment reports significant improvement in the quality of life in follow-up. The majority recovered from allograft dysfunction. Further research is warranted to study the full spectrum of follow-up.

Feasibility and safety of remdesivir in SARS-CoV2 infected renal transplant recipients: A retrospective cohort from a developing nation.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has drastically impacted the transplant communities. Remdesivir (RDV) has shown some promising results in coronavirus disease (COVID-19) albeit with low certainty. Data in kidney transplant recipients (KTR) are still lacking. METHODS: This was a retrospective cohort of 57 moderate to severe COVID-19 positive KTR in a single center who received RDV as a part of COVID-19 management. No dose adjustments were done. The outcomes were measured as acute kidney injury (AKI) recovery; liver function tests abnormalities; other side effects; graft loss and death. RESULTS: The median (inter-quartile range) age of presentation was 44 (31-51) years. The duration from onset of symptoms to RDV initiation was 6 (5-7) days. Thirty-two (56%) cases received RDV on the day of admission. Forty-six (81%) cases were on oxygen support upon initiation of RDV. Thirty-eight (66.6%) cases had acute kidney injury on admission. The median baseline, admission, and 28-day follow-up serum creatinine of the cohort were 1.59 (1.1-2.1), 2.13 (1.3-3.1), and 1.58 (1.05-2.1) mg/dl, respectively. A total of 8(14%) cases died in the study with 1 (1.7%) graft loss. All those cases that died were on oxygen therapy at the time of initiation of RDV. No liver function derangements or any other major adverse events with the drug were reported. CONCLUSION: RDV therapy is safe and clinically feasible in renal transplant recipients as seen in our cohort. Larger clinical registries and randomized clinical trials should be conducted to further explore the efficacy in transplant recipients.

Expanding donor pool by utilizing deceased donors with snake envenoming.

In India, the deceased kidney transplant program is still in its preliminary stage, and accepting deceased donors with snakebite is just a forward step to expand the donor pool. We report here the outcome of 8 successful renal transplantations from brain-dead donors who died from a neurotoxic snakebite. We accepted them as donors as they had no evidence of hemotoxic snakebite. 7 recipients did well. 1 died due to sepsis with a functioning graft. 1 required renal biopsy that showed acute tubular necrosis. 1 required re-exploration due to graft collection due to a surgical issue. Patient and graft survival in follow-up were similar to other matched deceased donors in our center. According to our experience, utilizing brain-dead donors who died from a neurotoxic snakebite is safe and may dramatically expand the donor pool especially in countries where death due to snakebite is high in numbers.

Status of adult immunity to hepatitis A virus in healthcare workers from a tertiary care hospital in north India.

Background & objectives: Humans are considered to be the principal host for hepatitis A virus (HAV) infection. In India, heterogeneous groups of susceptible individuals coexist in different regions. There has been a decline in antibody titres to HAV among young adults which may pose a major public health problem. The objective of this study was to assess the IgG anti-HAV level among healthcare workers (HCWs) in the age group of 20-60 yr and its association with the socio-demographic variables. Methods: Blood sample (2 ml) was collected under aseptic conditions from each participant followed by the preparation of serum and storing at -20°C. ELISA-based kits were used for the determination of IgG antibodies to HAV in the human serum samples. Results: Two hundred and fifty four HCWs were enrolled. IgG anti-HAV antibodies were detected in 97.2 per cent of the samples analyzed. No differences were observed in the levels of IgG anti-HAV antibody and education, income, occupation and socio-economic classes of the HCWs. A seropositivity rate of over 90 per cent was seen amongst all the socio-economic classes. Interpretation & conclusions: High levels of IgG protective antibodies were seen among the studied HCWs, hence HAV vaccination may not be required. It will be advisable to do a cost-benefit analysis of vaccination for HAV.

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.

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.

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.

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.

Mucormycosis as SARS-CoV2 sequelae in kidney transplant recipients: a single-center experience from India.

PURPOSE: Coronavirus disease (COVID-19) sequelae in the transplant population are scarcely reported. Post-COVID-19 mucormycosis is one of such sequelae, which is a dreadful and rare entity. The purpose of this report was to study the full spectrum of this dual infection in kidney transplant recipients (KTR). METHODS: We did a comprehensive analysis of 11 mucormycosis cases in KTR who recovered from COVID-19 in IKDRC, Ahmedabad, Gujarat, India during the study period from Nov 2020 to May 2021. We also looked for the risk factors for mucormycosis with a historical cohort of 157 KTR who did not develop mucormycosis. RESULTS: The median age (interquartile range, range) of the cohort was 42 (33.5-50, 26-60) years with 54.5% diabetes. COVID-19 severity ranged from mild (n = 10) to severe cases (n = 1). The duration from COVID-19 recovery to presentation was 7 (7-7, 4-14) days. Ten cases were Rhino-orbital-cerebral-mucormycosis (ROCM) and one had pulmonary mucormycosis. Functional endoscopic sinus surgery (FESS) was performed in all cases of ROCM. The duration of antifungal therapy was 28 (24-30, 21-62) days. The mortality rate reported was 27%. The risk factors for post-transplant mucormycosis were diabetes (18% vs 54.5%; p-value = 0.01), lymphopenia [12 (10-18) vs 20 (12-26) %; p-value = 0.15] and a higher neutrophil-lymphocyte ratio [7 (4.6-8.3) vs 3.85 (3.3-5.8); p-value = 0.5]. CONCLUSION: The morbidity and mortality with post-COVID-19 mucormycosis are high. Post-transplant patients with diabetes are more prone to this dual infection. Preparedness and early identification is the key to improve the outcomes.

Current Scenarios of Pediatric Transplants of Kidney, Liver, Heart, and Lung in India: Systematic Review and Meta-Analysis.

OBJECTIVES: There is no systematic review and meta- analysis for pediatric solid-organ transplants in India. The objective of the study was to collect high-evidence data in this regard. MATERIALS AND METHODS: A systematic review and meta- analysis was performed for pediatric solid-organ transplants in India. We used the search engines of PubMed, Google Scholar, PubMed Central, Embase, and MEDLINE from beginning of data availability until April 26, 2022. Data from 2 participating centers were also used. Analyses were performed by the DerSimonian random model. RESULTS: Of 50 000 primary searches, only 31 studies were included for analysis. In total, data for pediatric kidney (n = 1057), liver (n = 914), and heart (n = 117) were reported. For the pediatric kidney, the 1-year, 5-year, and 10-year patient survival rates were 96% (range, 93%-99%; I² = 91.17%, H² = 11.33, P < .01), 90% (range, 85%-94%; I² = 93.54%, H² = 15.47, P < .01), and 75% (range, 62%-88%; I² = 97.36%, H² = 37.82, P < .01), respectively. The 1-year, 5-year, and 10-year renal graft survival rates were 93% (range, 90%-96%; I² = 63.82, H² = 2.76, P < .01), 83% (range, 76%-89%; I² = 86.39%, H² = 7.35, P < .01), and 66% (range, 57%-75%; I² = 81.68%, H² = 5.46, P < .01), respectively. The acute rejection rate was 23% (range, 20%-27%; I² = 5.44%, H² = 1.06, P = .39). For the pediatric liver transplant, the 1-year and 5-year survival rates were 92% (range, 89%-95%; I² = 49.96%, H² = 2, P < .04) and 88% (range, 85%-90%; I² = 0; H² = 1, P = .72), respectively. CONCLUSIONS: The outcomes of pediatric solid-organ transplants in India are comparable to those of the Western world. However, cause of graft loss and patient death is largely attributed to infections, unlike the experiences reported in the West. An effective registry is a primary pillar to expand pediatric solid- organ transplants in India.

Comparative Analysis of Kidney Transplant Recipients with Severe Acute Respiratory Syndrome Coronavirus 2 Compared with Nonkidney Transplant Recipients: A Largest Single-center Report from the Second Wave of Coronavirus Disease 2019 Pandemic in South East Asia.

Outcomes of severe acute respiratory syndrome coronavirus 2 in kidney transplant recipients (KTR) compared with matched cohort are certainly lacking for different pandemic waves and geographic regions. In this single-center retrospective study of coronavirus disease-2019 (COVID-19) cases admitted during March 26, 2021 to June 7, 2021, a propensity-matched analysis in a 1:1 ratio was performed to compare the clinical profile and outcomes between KTR and non-KTR. A Cox proportional hazard model from the whole study population to analyze risk factors for severe disease and mortality was calculated. We identified 1052 COVID-19 cases, of which 107 (10.1%) were KTR. In propensity-matched analysis, KTR had higher fever (81.6 % vs. 60%; P = 0.01), lymphopenia (30% vs. 11.7%; P = 0.02), higher neutrophil-to-lymphocyte ratio (43.3% vs. 25%; P = 0.05), and acute kidney injury (66.6% vs. 36.7%; P = 0.001). In Kaplan-Meier survival analysis, there was no difference in mortality or severity of COVID-19. In Cox hazard proportional analysis, the European cooperative oncology group (ECOG) score of 1 to 2 [Hazard ratio (HR) 95% lower confidence interval (CI), upper CI = 4.9 (1.8-13.5); P <0.01], ECOG of >2 [HR = 20 (7.5, 54.7); P <0.01] and waitlisted status [HR = 1.9 (1.1-3.3); P = 0.02] was associated with significant mortality. Kidney transplantation [HR = 0.8 (0.47-1.44); P = 0.5] was not associated with mortality in the analysis. In our report, kidney transplantation status had a different spectrum but was not found to be independently associated with COVID-19 severity or mortality.