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.

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.

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.

Feasibility of Convalescent Plasma Therapy in Kidney Transplant Recipients With Severe COVID-19: A Single-Center Prospective Cohort Study.

OBJECTIVES: There are limited clinical data on feasibility and safety of convalescent plasma therapy in kidney transplant recipients with severe COVID-19. The present study was conducted to explore the feasibility of convalescent plasma treatment in 10 kidney transplant recipients with severe COVID-19. MATERIALS AND METHODS: The prospective observational cohort study was conducted at the Institute of Kidney Disease and Research Centre, Ahmedabad, India. All patients were admitted to the intensive care unit and received antiviral therapy, glucocorticoids, and other supportive care. Two doses of 200 mL each of convalescent plasma with neutralization activity of >1:640 were transfused into patients 24 hours apart following the World Health Organization blood transfusion protocol. The endpoints were the improvement of clinical symptoms and laboratory parameters within 1 day and 7 days after convalescent plasma transfusion. RESULTS: The patients showed resolution of clinical symptoms, and there was a significant decrease in inflammatory markers (P < .05) within 7 days of convalescent plasma transfusion. Of the 10 patients, 9 patients had full recovery and 1 patient died. CONCLUSIONS: Convalescent plasma therapy is highly safe and clinically feasible and reduces mortality in kidney transplant recipients with severe COVID-19. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical outcomes associated with convalescent plasma use in kidney transplant recipients with severe COVID-19.

Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India.

BACKGROUND: There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS: Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS: COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS: Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.

Clinical Profile and Outcome of COVID-19 in 250 Kidney Transplant Recipients: A Multicenter Cohort Study From India.

BACKGROUND: There is a scarcity of data on the consequences of coronavirus disease-19 (COVID-19) infections in kidney transplant recipients (KTRs) from emerging countries. METHODS: Here, we present a cohort study of 13 transplant centers in India including 250 KTR (226 living and 24 deceased donors) with polymerase chain reaction-confirmed COVID-19 positivity from March 23, 2020, until September 15, 2020. We detailed demographics, immunosuppression regimen, clinical profile, treatment, and outcomes. RESULTS: Median age of transplant recipients was 43 years, and recipients presented at a median of 3.5 years after transplant. Most common comorbidities (94%) included arterial hypertension (84%) and diabetes (32%); presenting symptoms at the time of COVID-19 included fever (88%), cough (72%), and sputum production (52%). Clinical severity ranged from asymptomatic (6%), mild (60%), and moderate (20%) to severe (14%). Strategies to modify immunosuppressants included discontinuation of antimetabolites without changes in calcineurin inhibitors and steroids (60%). Risk factors for mortality included older age; dyspnea; severe disease; obesity; allograft dysfunction before COVID-19 infection; acute kidney injury; higher levels of inflammatory markers including C-reactive protein, interleukin-6 level, and procalcitonin; chest X-ray abnormality, and intensive care unit/ventilator requirements. Overall patient mortality was 11.6% (29 of 250), 14.5% (29 of 200) in hospitalized patients, 47% (25 of 53) in intensive care unit patients, and 96.7% (29 of 30) in patients requiring ventilation. KTRs with mild COVID-19 symptoms (n = 50) were managed as outpatients to optimize the utilization of scarce resources during the COVID-19 pandemic. CONCLUSIONS: Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients, and high mortality was noted among those requiring intensive care and those on ventilator.

Benefit to Few Versus Risk to Many: An Ethical Dilemma During Coronavirus Disease 2019 Pandemic for Deceased-Donor Organ Transplant in a Resource-Limited Developing Country.

The tools in our armamentarium to prevent the transmission of coronavirus disease 2019, known as COVID-19, are social distancing; frequent handwashing; use of facial masks; preventing nonessential contacts/travel; nationwide lockdown; and testing, isolation, and contact tracing. However, the World Health Organization's suggestions to isolate, test, treat, and trace contacts are difficult to implement in the resourcelimited developing world. The points to weigh before performing deceased-donor organ transplant in developing countries are as follows: limitations in standard personal protective equipment (as approved by the World Health Organization), testing kits, asymptomatic infections, negative-pressure isolation rooms, intensive care unit beds, ventilator support, telehealth, availability of trained health care workers, hospital beds, the changing dynamic of this pandemic, the unwillingness of recipients, education updates, and additional burdens on the existing health care system. This pandemic has created ethical dilemmas on how to prioritize the use of our facilities, equipment, and supplies in the cash-strapped developing world. We believe that, at the present time, we should aim to resolve the COVID-19 pandemic that is affecting a large sector of the population by diverting efforts from deceased-donor organ transplant. Transplant units should conduct case-bycase evaluations when assessing the convenience of carrying out lifesaving deceased-donor organ transplant, appropriately balanced with the resources needed to address the current pandemic.

"Infodemic" COVID 19: More Pandemic than the Virus.

Coronavirus disease (COVID 19), which was started in Wuhan, China in December 2019 has become a pandemic, leading to unprecedented risk to the human race. However, fear wave accelerating ahead of pandemic worldwide is driven by prejudice or erroneous information. This has been termed as "infodemics" by WHO considering its fake nature, which triggered discrimination and stigma of disease along with the failure of rapid response policies. Additionally, the lack of adequate pandemic preparedness plans identified in many countries may be responsible for infodemics. NonCOVID medical illnesses have taken a back seat at many places while implementing COVID 19 control strategies and patients are diverted to COVID 19 screening hospitals leading to a potential health crisis. Now, we also have to focus on mitigating infodemics and its implications at the social front while strategic planning to control current and future pandemics.