Impact of Covid-19 Pandemic on Epidemiology of Infections in Pre- and Post-Covid-19 Pandemic a Single Centre Study

Introduction: Infections are the leading cause of death in kidney transplant recipients (KTR) at all time intervals. The non-pharmaceutical interventions (NPIs) taken during the COVID-19 pandemic have reduced almost all kinds of infections in the general population, as shown in the Chunmei Su et al. study. The aim of this study was to investigate the impact of NPIs for the COVID-19 pandemic on infections in KTR patients. Method(s): This was a single-center retrospective observational study conducted at Mumbai's Jaslok Hospital and Research Centre.Samples from symptomatic KTR patients were taken and those who had positive cultures were thought to be infected. The data were analysed and compared between the years 2021 (during the COVID-19 pandemic) and 2019 (before the COVID-19 pandemic). Result(s): A total of 224 patients were enrolled, including 117 patients in 2019 and 107 patients in 2021. In 2019 and 2021, the prevalence of nosocomial infection and community-acquired infection in KTR patients remains unchanged.In 2021, both the number of protective gloves and level 2 PPE kits used per individual, as well as the number of healthcare professionals per patient, have increased dramatically. Regarding the source of infections, no significant change in major infections was observed in respiratory tract infections (12% vs. 10.3%, p = 0.8985), gastrointestinal infections (1.8% vs. 6.5%, p = 0.0786), catheter related blood stream infections (CRBSI) (4.5% vs. 3.7%, p = 0.776), and blood stream infections (11.7% vs. 10.3%, p = 0.73), However, there were increases in urinary tract infections (23% vs. 42.1%;p = 0.0006). The microorganism analysis of respiratory infections shows declines in nocardia and tuberculosis. Gastrointestinal infections show increased Clostridium difficile cases in 2021 compared to 2019, which can be attributed to the overuse of antibiotics. Regarding urinary tract infection, a decline in mixed infection cases and an increase in Enterobacter faecalis and Enterobacter cloacae cases were observed. There were no significant variations in catheter-related nosocomial infections between 2019 and 2021. In comparison to an older study done in the general population by Chunmei Su et al, our study shows no significant change in respiratory, gastrointestinal, and catheter-related blood infections in 2021 compared to 2019 in KTR, despite restrictions being relaxed in general populations beginning in June 2020.Also, there was no significant increase in community acquired pneumonia in 2021, even after reopening public places. Conclusion(s): Our institutional NPIs for KTR patients in the pre-COVID-19 era were shown to be as effective as NPIs for the COVID-19 pandemic in reducing the prevalence of common infections like respiratory, gastrointestinal, blood stream, and catheter-related infections in KTR patients. No conflict of interestCopyright © 2023

Single Center Comparative Analysis of Abo Compatible Versus Abo Incompatible Kidney Transplant with Short Term 1 Year Follow Up

Introduction: Kidney transplantation is the best treatment option for patients with end-stage kidney diseases. Quality and longevity of life are better with kidney transplant than chronic dialysis. Kidney paired donation and ABO incompatible kidney transplant (ABOiKT) are among the strategies to expand the living donor pool to overcome shortage of organs. Although first ABOiKT done in 1951 by Hume et al. was an unsuccessful attempt;Alexander et al. in 1987, proposed desensitization protocol with successful ABOiKT. Advancements in desensitization protocols have resulted in increasing success with ABOiKT. In developing countries like India, numbers of ABOiKT are steadily increasing. Aim of this study was to assess short term outcome of ABOiKT and their comparison with ABO compatible kidney transplant (ABOcKT). Method(s): This was a single center prospective observational study done over a period of 2 years. All the living donor kidney transplants including both ABOcKT and ABOiKT done between September 2020 to August 2021 at Jaslok Hospital and Research Center, Mumbai were included in this study. All ABOiKT recipients underwent pre-transplantation desensitization with injection rituximab and plasmapheresis. Pretransplant isoagglutinin titer of <= 1 : 8 was considered acceptable. Inj. Antithymocyte globulin (ATG) (1mg/kg), Inj. Anti-T lymphocyte globulin (ATLG) (3 to 5 mg/kg) or Inj. Basiliximab (20mg 2 doses 4 days apart) was used as induction agent. Triple immunosuppression regimen of prednisolone, tacrolimus and mycofenolate mofetil was started 7 days prior to transplant in ABOiKT and 2 days prior to transplant in ABOcKT and continued in post-transplant period. Valganciclovir was given to all patients for Cytomegalovirus (CMV) infection prophylaxis for 6 months. All the transplant recipients were followed up at 0, 3, 6, 9 and 12 months after transplant and in between when clinically indicated. Data collected was analyzed at the end of 1 year for outcomes of rejection episodes, graft dysfunction, graft loss, infections and death. Result(s): Total 95 patients were included in study, 29 (30.5%) out of them were ABOiKT recipients. Mean (SD) age of study population was 37.8 (+/- 10.5) years. Blood group B to B was the most common ABOcKT and B to O was the most common ABOiKT. Highest baseline isoagglutinin titer was 1:1024.There was no significant difference for rejection episodes, graft dysfunction, graft loss and death in ABOiKT and ABOcKT groups. Urinary tract infection was the most common infection in post-transplant period. COVID-19 was most common viral infection followed by CMV infection. Bacterial infections and overall infections were significantly higher in ABOiKT recipients (p value 0.001 and 0.006 respectively) but severe infections requiring hospitalizations and ICU care were not significantly higher. Two deaths occurred during our study, one in each group. One death was related to COVID-19 infection and second was because of pulmonary mucormycosis. Conclusion(s): Contrary to belief, ABOiKT has non inferior short term outcomes when compared with ABOcKT. Though in our study, bacterial infections were significantly higher in ABOiKT recipients, severe infections requiring hospitalization and ICU care were not increased. ABO incompatible kidney transplantation is an effective modality to increase donor pool and can be applied more widely. No conflict of interestCopyright © 2023

Immunosuppression Minimization Strategy for Abo Incompatible Kidney Transplant Recipients during Covid-19 Pandemic

BACKGROUND: In the presence of COVID-19 illness immunosuppressed patients such as kidney transplant recipients (KTRs) have a higher mortality risk. ABO incompatible KTRs (ABOi - KTRs) are high-risk transplants and the use of lowdose maintenance immunosuppression during the COVID-19 pandemic is unknown. AIM OF THE STUDY: To study effect of low dose maintenance immunosuppressive therapy on graft function and immunologic events in patients following ABOi-KTRs during COVID-19 pandemic. METHOD(S): We present the results of a follow-up study of eight ABOi-KTRs done in Kidney Transplant Unit at Jaslok Hospital during COVID-19 pandemic. RESULT(S): Seven (87%) of the eight patients were male, while one was female. The median age was 49 years. Prior to transplant, all patients received rituximab (500 mg) and plasmapheresis. Six (75%) patients received antithymocyte globulin (1 mg/kg) induction, while two (25%) received basiliximab. Dose of one immunosuppressive agent tacrolimus was decreased to trough level of 6 to 8 ng/ mL instead of 8 to 12 as compared to our institutional protocol in pre-covid era. Antimetabolites and steroids were used in usual doses. Although immunosuppression was decreased, no rejection episodes or infection observed up at 10 days, 1 and 3 month after discharge, and no significant changes occurred in creatinine level during same period. Acute graft dysfunction was seen in 1 patient and the severity was related to tacrolimus trough levels, which were higher. All patients recovered baseline kidney function with no mortality during follow-up. CONCLUSION(S): Our observational study suggests that the reduction of tacrolimus dose in ABOi KTRs performed during COVID-19 appears to be safe, since no patient experienced rejection episodes.

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.

Is Early COVID-19 in Kidney Transplant Recipients Concerning Enough to Halt Transplantation? A Multicenter Comparative Analysis from India.

BACKGROUND: Limited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR). METHODS: A retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID-19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19. RESULTS: The incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D-dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID-19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR. CONCLUSIONS: We report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.

SARS-COV-2 infection in the early post-transplant period after a living donor kidney transplant

Introduction: Coronavirus disease 2019 (COVID-19) pandemic presented multiple challenges for living and deceased donor kidney transplant programs with the likelihood of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the course of COVID-19 and immunosuppression within 3 months of living donor kidney transplant (LDKT) which has not been described previously. Case Description: Three LDKT recipients developed COVID-19 in the early posttransplant period and were detected positive for SARS-CoV-2 at day 7, day 19 and 2 months post-transplant. Patients 1 and 2 had received 1 mg/kg of anti-thymocyte globulin (ATG) as induction and patient 3 had received no induction at the time of transplant. Patients 1 and 2 had minimal symptoms at diagnosis, whereas patient 3 had high grade fever, cough and shortness of breath. All 3 patients had lymphopenia at diagnosis and none required supplemental oxygen or intensive care unit monitoring. All 3 patients received azithromycin and hydroxychloroquine. Mycophenolate mofetil dose was reduced in patient 1 and was stopped in patients 2 and 3. Patient 3 developed acute kidney injury with a peak serum creatinine of 2.4 mg/dL, whereas other 2 patients did not develop kidney allograft dysfunction. All 3 patients recovered from SARS-CoV-2 infection with normal renal function at discharge. Discussion: Limited experience of SARS-CoV-2 infection in early post-transplant period is available in deceased donor kidney transplant (DDKT) with serious morbidity and mortality implications. Lymphopenia described in patients with severe illness due to SARS-CoV-2 can be aggravated by recently used higher dose of lymphocyte depleting agent, especially to cover for delayed graft function in DDKT. As compared to previously reported cases of DDKT, our relatively young recipients of LDKT had a milder course, minimal complications and recovered from SARS-CoV-2 infection. We suggest consideration of recipient age, pretransplant isolation and using induction agent basiliximab or lower dose of ATG for a LDKT program during COVID-19 pandemic.

Pragmatic approach toward nephrology practice in the COVID-19 era: Shared learnings and experiences toward consensus through a virtual educational platform involving 404 nephrologists

Background: COVID19 rapidly spread globally, imposing the need for change in nephrology practices guided by the recommendations, issued by scientific associations Methods: We conducted a nationwide virtual educational initiative with an inbuilt technological platform to enable live sharing of experiences of new modes for nephrology practice during COVID 19 pandemic, based on the adoption of current recommendations and evidences to enable indigenous, adaptive experiences of 404 nephrologists with approximately 8,000-man hours of cumulative clinical experience. The four zones across the country were represented by an individual educational task force member Results: There was a uniform consensus that suspected patients need to be treated similar to a COVID 19 positive patient, with dialysis facility provided in isolation area, to mitigate direct risk to both healthcare providers and patients and indirect risk of contamination of the hospital system. Multiple screening procedures and prohibition of eatables in dialysis area is the new mandate. Role and importance of CRRT, PIRRT and peritoneal dialysis was highlighted. Femoral catheterization is the preferred route. The experience of Tenckhoff catheter technique in peritoneal dialysis in 38 patients was discussed. Higher dose of anticoagulants is being utilised for extracorporeal procedures to reduce risk of enhanced risk of thrombus formation in COVID 19. The varied, emerging clinical presentation, including asymptomatic cases has made COVID 19 testing compulsory at most of the institutions. The nephrologists were informed about the emerging evidence for the need to continue the ongoing ARBs or ACE inhibitors. Renal transplantation with careful precautionary practice is being performed with modulation of dose of immunosuppressive agents in COVID 19 positive patients Conclusions: Safe and efficient delivery of nephrology care practices needs a uniform acceptance. Even minor liberties and deviations from established safe practice protocols could compromise the safety of the health care workers.

Study of COVID-19 Pandemic in Representative Dialysis Population Across Mumbai, India: An Observational Multicentric Analysis.

COVID-19 has emerged as a pandemic of significance with potential to cause significant morbidity and mortality worldwide. Elderly with or without following comorbidities i.e Diabetes, hypertension, cardiac disease, chronic respiratory illnesses, chronic liver disease, CKD, malignancy and immunocompromised hosts are at increased risk of developing complicated course. Hemodialysis population hence are at increased risk for contracting the infection due to patient characteristics, environmental characteristics and procedural lapses. The current study was aimed at describing prevalence and characteristics of COVID19 in hemodialysis population across different HD centers across Mumbai. We found a prevalence rate of COVID19 in 6.4%, with 9 patients (12%) died during the study period. A fair proportion of Non covid HD patients (1.5%) also died due to lack of access to dialysis. At baseline, mean age of presentation was 54.5 years. On routine test 80% were asymptomatic at presentation. Patients with COPD, requiring ICU care and those on ventilation faired poorly. Contrary to assumption patients with underlying cardiovascular disease didn't show poor outcome. Total of 4.1% health care workers turned positive during the study period with mean age of 31 years and median of 28years. Out of them 5 (45.4%) were symptomatic. All recovered from the illness without any sequelae. Seventy two percent of healthcare workers were on Hydroxy-chloroquine chemoprophylaxis didn't reach statistical significance in preventing the infection. In our study elderly age with comorbidities had poor prognosis. We proposed extra healthcare measures to be taken in the dialysis unit presuming all as COVID suspect in the resource limited settings.