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.

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.

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.

Non-simultaneous kidney exchange cycles in resource-restricted countries without non-directed donation - a prospective single-center cohort study.

Recent reports suggest that bridge-donor reneging is rare (1.5%) in non-simultaneous kidney exchange chains. However, in developing countries, the non-directed donors who would be needed to initiate chains are unavailable, and furthermore, limited surgical space and resources restrain the feasibility of simultaneous kidney exchange cycles. Therefore, the aim of this study was to evaluate the bridge-donor reneging rate during non-simultaneous kidney exchange cycles (NSKEC) in a prospective single-center cohort study (n = 67). We describe the protocol used to prepare co-registered donor-recipient pairs for non-simultaneous surgeries, in an effort to minimize the reneging rate. In addition, in order to protect any recipients who might be left vulnerable by this arrangement, we proposed the use of standard criteria deceased-donor kidneys to rectify the injustice in the event of any bridge-donor reneging. We report 17 successful NSKEC resulting in 67 living-donor kidney transplants (LDKT) using 23 bridge-donors without donor renege and no intervening pairs became unavailable. We propose that NSKEC could increase LDKT, especially for difficult-to-match sensitized pairs (25 of our 67 pairs) in countries with limited transplantation resources. Our study confirms that NSKEC can be safely performed with careful patient-donor selection and non-anonymous kidney exchanges.

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.

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.

Invasive fungal infections in renal transplant patients: a single center study.

BACKGROUND: Timely diagnosis of invasive fungal infections (IFI) in renal transplant (RT) patients on immunosuppression is often difficult, jeopardizing their life and graft. We reported IFI and their causative fungal agents in post-RT patients. MATERIALS AND METHODS: This was a retrospective 6-year clinical study carried out from 2010 to 2015 on 1900 RT patients. Clinical data included patient-donor demographics, time to onset of infection, risk factors and graft function in terms of serum creatinine (SCr). To identify IFI, we examined bronchoalveolar lavage (BAL), blood, tissue, and wound swab samples by conventional mycological methods. RESULTS: IFI were diagnosed in 30 (1.56%) patients on triple immunosuppression, mainly males (n = 25) with mean age of 36.57 ± 11.9 years at 13.12 ± 18.35 months post-RT. Aspergillus species was identified in 11 BAL, one tissue, and one wound specimen each, 30.76% of these were fatal and 15.38% caused graft loss; Candida albicans was in nine BAL, four blood, two wound swab, and one tissue specimens, 25% of these were fatal and 25% had graft loss and one mucor in BAL which was fatal. Seven patients were diabetic, 10 had superadded cytomegalovirus infection, and 15 were anti-rejected. CONCLUSION: IFI are associated with increased morbidity and mortality in RT patients. Triple immunosuppression, broad spectrum antibiotics for ≥ two weeks, diabetes and superadded infection are added risks for these patients. Prevention, early diagnosis, and appropriate management are necessary to improve their prognosis.