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.

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.

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 in Hemodialysis Patients: Experience from a Western Indian Center.

Introduction: Chronic kidney disease patients on hemodialysis (CKD-5D) are among the worst hit by the coronavirus disease 2019 (COVID-19) pandemic. Need to travel for dialysis, comorbidities, and immunosuppressive state put them at risk of severe disease and poor outcomes. We report our experience of COVID-19 in a cohort of CKD-5D from a public sector tertiary-care center from western India. Material and Methods: We retrospectively analyzed the records of 58 CKD-5D patients with confirmed COVID-19 admitted to our COVID-19 hospital. Suspected COVID-19, acute kidney injury (AKI), or AKI on CKD were excluded. We studied the clinical, demographic, radiological, and laboratory profiles; treatment; and outcomes of the patients. We assessed the potential clinical and laboratory parameters to predict mortality. Results: The mean age of the patients was 48.7 ± 16.9 years, with 55% males. Comorbidities included hypertension (65%), diabetes (19%), and cardiovascular disease (15.5%). The presenting features included fever (69%), respiratory distress (50%), upper respiratory symptoms (36%), and diarrhea (13%). Five (8.6%) were asymptomatic. Bilateral infiltrates on chest imaging were the commonest radiological pattern. The patients were managed with oxygenation, hydroxychloroquine, steroids, anticoagulation, remdesivir, and favipiravir. Twenty-two (37.9%) patients died, predominantly due to respiratory failure. Disease severity and C-reactive protein (CRP) above 175 mg/L at admission were the only parameters predictive of mortality. Conclusion: CKD-5D patients with COVID-19 were less likely to present with the classical syndrome of fever and respiratory distress compared with reports from the general population and had higher mortality. Only disease severity and high CRP (>175 mg/L) were predictive of mortality in our cohort.

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.

Cytomegalovirus and Severe Acute Respiratory Syndrome Coronavirus 2 Co-infection in Renal Transplants: A Retrospective Study from a Single Center.

There is a scarcity of data regarding the impact of cytomegalovirus (CMV) infection complicating the coronavirus disease-2019 (COVID-19) course. The objective of the study was to explore the clinical profile and outcome of CMV co-infection with COVID-19. This is a single-center retrospective study of COVID-19 cases with concomitant CMV infection. A total of 18 cases were diagnosed with CMV infection during the study period May 2020 to December 2020. The median age (Interquartile range) of the study was 45 (53-38) years with predominant male sex (n = 14, 77%). The baseline donor-recipient status for CMV included D+/R+ (10, 55%), D-/R+(6, 33%), and D+/R- (2, 12%). COVID-19 severity in the study included mild (1, 7%), moderate (5, 28%), severe (8, 44%), and critical (4, 22%) cases. Criteria for hyperinflammatory state was met by 77% (n = 14) of cases. The most common therapeutic modality for COVID-19 given was remdesivir (n = 13), tocilizumab (n = 4), and convalescent plasma (n = 4). The median CMV titer at diagnosis was 1200 (1800-1000) copies/mL. The median duration of hospital stay was 12.5 (14-11). Mortality observed in the study was four (22%). The management of CMV co-infection with COVID-19 is associated with high morbidity and mortality, and we suggest screening for CMV infection in all posttransplant COVID-19 cases.

A Propensity-Matched Analysis of COVID-19 in Kidney Transplant Recipients Compared With Non-Kidney Transplant Patients: A Single-Center Report From India.

OBJECTIVES: Comparisons of COVID-19 incidence between kidney transplant recipients and patients who did not receive kidney transplant are underexplored in various geographic regions. MATERIALS AND METHODS: This Indian, single-center, retrospective study analyzed COVID-19 data of patients hospitalized between May 12, 2020, and January 11, 2021. A propensity matching score was used to compare outcomes between the 2 groups. We also used multivariable Cox proportional hazard analyses to assess association of kidney transplantation with mortality. RESULTS: Of the 1627 COVID-19 cases, 179 were kidney transplant recipients and 1448 were not kidney transplant patients (control group). Ofthe 436 reported in-hospital deaths, 20 (11.1%) were in the kidney transplant group and 416 (28.7%) were in the control group. Propensity matching identified 98 kidney transplantrecipients and167 controlpatients. InKaplanMeier survival plots for these patients, there was no statistical difference in mortality (log-rank, Mantel Cox test; P = .07) or severity (log-rank, Mantel Cox test; P = .07) with regard to COVID-19. In Cox analysis, age groups from 61 to 70 years (hazard ratio = 1.5; 95% CI, 1.0-2.2; P = .04), 71 to 80 years (hazard ratio = 1.64; 95% CI, 1.0-2.5; P = .02), and >80 years (hazard ratio = 1.91; 95% CI, 1.1-3.1; P = .01)were associatedwith statistically significant greater mortality.Having a kidney transplant (hazard ratio = 0.43; 95% CI, 0.3-0.7; P = 0.001) was not associated with mortality. CONCLUSIONS: In our analysis, age was the most important predictor of mortality. Kidney transplant status was not found to have an independent association with mortality and severity.

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.

Clinical Profiles and Outcomes of COVID-19 in Kidney Transplant Recipients: Experience From a High-Volume Public Sector Transplant Center in India.

OBJECTIVES: Data are so far limited on outcomes of kidney transplant recipients with COVID-19 seen at public sector hospitals in developing countries with limited resources. MATERIALS AND METHODS: We retrospectively investigated a cohort of 157 kidney transplant recipients (75% living and 25% deceased donors) seen at a public sector transplant hospital in India from March to December 2020 who had reverse-transcriptase polymerase chain reaction tests that confirmed COVID-19. Demographic data, immunosuppression regimens, clinical profiles, treatments, and outcomes were analyzed. In our center, maintenance immunosuppression was reduced according to disease severity and case-by-case evaluations. There were also 53 patients with asymptomatic or mild COVID-19 symptoms who received home care to optimize the utilization of scarce resources during travel restrictions. RESULTS: In our kidney transplant recipient group, median age was 43 years (133 male; 24 female patients); recipients presented at a median of 4 years after transplant. The most common comorbidities included arterial hypertension (73%) and diabetes (24%); presenting symptoms at the time of COVID-19 positivity included cough (49%), fever (58%), and sputum production (32%). Clinical severity ranged from asymptomatic (4%), mild (45%), moderate (31%), and severe (20%) disease. Statistically significant risk factors for mortality included older age, dyspnea, severe disease, obesity, allograft dysfunction prior to COVID-19, acute kidney injury, higher levels of inflammatory markers (C-reactive protein, interleukin 6, procalcitonin), abnormality in chest radiography, and intensive care/ventilator requirements (P < .05). Overall patient mortality was 9.5% (15/157) in hospitalized patients, 21% (15/71) in patients in the intensive care unit, 100% (15/15) in patients who required ventilation, and 0% among those in home treatment. CONCLUSIONS: The mortality rate in kidney transplant recipients with COVID-19 was higher than in the nonimmunosuppressed general population (1.2%) in India. To our knowledge, this is a largest single-center study of kidney transplant recipients with COVID-19 so far.

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.

The Impact of COVID-19 Pandemic on Nephrology and Transplant Services and Clinical Training in India.

OBJECTIVES: COVID-19 has emerged as a global pandemic with significant impacts on health care systems. The present study was conducted to analyze the effects of the COVID-19 pandemic on nephrology and transplant services and clinical training at our center. MATERIALS AND METHODS: This observational study was conducted at the Institute of Kidney Disease and Research Centre (Ahmedabad, India). Our institute is one of the largest tertiary care centers of its kind in India with around 400 total inpatient beds for nephrology, urology, and transplant patients. In 2019, our center had annual outpatient and inpatient numbers of 132 181 and 7471, respectively, and conducted 412 renal transplant procedures. For this study, monthly data on number of outpatients, inpatients, and patients undergoing renal transplant, as well as various nonelective procedures, conducted in 2019 and 2020 were collected and analyzed. We investigated the impact of the COVID-19 pandemic on various non-COVID-19-related health care facilities and on clinical training and research activities at our institute. RESULTS: During the 2020 COVID-19 period, the number of outpatients and inpatients was greatly reduced compared with data from 2019. A similar decrease was seen in patients undergoing hemodialysis, renal transplant, and nonelective procedures at our center. The COVID-19 period also greatly affected clinical training of residents enrolled at our institute and research activities, as a result of focus on COVID-19 as a priority. CONCLUSIONS: The effects of reduced numbers of outpatients and inpatients on workflow, as well as reduced numbers of renal transplants and nonelective procedures on the health of our patients, are unknown. Hence, a strategic scheme is needed to develop new health care models that can help manage the COVID-19 pandemic at present and any further waves arising in the future.

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.

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.