ABSTRACT
Purpose: Lymphocyte depleting induction is associated with increased risk of infection. Our institution adopted a stratified induction protocol with the intent to decrease risk for recipients exposed to SARS-CoV-2. Baseline protocol was 6-7.5 mg/ kg thymoglobulin with a 3 dose steroid taper. This was modified to a protocol based on immunologic risk. Low risk group included KTA (PRA <20%) was basiliximab 40 mg and 4 week steroid taper;intermediate group was KTA (PRA 20-80%) or SPK (PRA <80%) and consisted of thymo 2 mg/kg and basiliximab 40 mg with 4 week steroid taper;high risk group included any recipient with PRA >80%, PTA, positive DSA and induction was unchanged from the pre-SARS-CoV-2 protocol. All recipients received tacrolimus/MMF maintenance. The primary objective was to evaluate the effect of adjusting induction immunosuppression on acute cellular rejection (AR) and infection rates. Methods: Outcomes of all adult transplants performed between March 24-October 18, 2020 were reviewed. Time to first infection and AR was analyzed using Kaplan- Meier curves. Patients were censored at the earliest of death, graft failure or 10/22/20. Results: 81 patients were assessed: 61 KTA, 2 PTA, 18 SPK. Demographics: 69.1% Caucasian, 59.3% male, 84.0% primary transplant and 76.5% deceased donor. 2 grafts were lost: one due to thrombosis on POD 0 and the other due to primary non function. There were 2 deaths: one due to CVA/MDR TB and another due to NSTEMI. Populations of the 3 risk groups: low (16), intermediate (33) and high (32). In the low risk group there were 2 (12.5%) AR within 6 weeks of transplant. One of these patients developed AMR, BK and CMV. The intermediate group included 6 (18.2%) recipients who developed AR. 2 of these recipients developed 2 AR episodes, the first episodes were within 4 weeks of transplant. The first had Banff 1A in addition to AMR followed by borderline AR a month after initial biopsy. The second had 2 episodes of borderline AR and that graft ultimately failed due to primary non function. Of note the pathology of the other 4 recipients was consistent with borderline AR. There were 2 (6.3%) AR in the high risk group. The first was 1A within 6 weeks of transplant, this patient also developed EBV and CMV. The second was IIA within 3 weeks of transplant. There was no significant difference in AR rates among these groups (log rank p-value 0.396). No significant difference in overall infection rate (p-value 0.482), bacterial (p-value 0.906), fungal (p-value 0.553) or viral (p-value 0.494). An asymptomatic recipient tested positive for SARS-CoV-2 in the high risk group 2 months following KTA. Conclusions: Optimal induction regimens for pancreas and kidney transplant in the SARS-CoV-2 era remain unclear. Although rejection rates in the abbreviated induction groups were slightly higher, most were borderline. Short-term infection rate did not seem to be impacted. Tailored induction regimens stratified by risk may be safe and effective during this pandemic era and beyond. (Table Presented).
ABSTRACT
Purpose: The current pandemic has created uncertainty surrounding the transmission of COVID-19. It was recently published that in the general population, household contacts have a 53% rate of secondary infection from index patient (Grijalva et al. (2020). MMWR, 69(44), 1631.). Our experience was reviewed in an effort to understand transmission in the immunosuppressed population. The primary objective was to evaluate the effect of recent induction upon COVID-19 transmission to contacts. Methods: A retrospective review of adult recipients with COVID-19 detected by PCR within one year of pancreas and kidney transplant was conducted. These patients were interviewed regarding the timeline of their symptoms and the symptoms and testing of household and close contacts. Results: 9 patients were identified: 8 Kidney and 1 Kidney/panc. All were primary transplants, except one with a prior lung transplant 2 years earlier, 33.3% were Caucasian, 33.3% Black, 22.2% Asian, 11.1% Hispanic, 55.6% female, 66.7% deceased donor, BMI ranged from 23.1-31.9 and age ranged from 46-68. 66.6% were tested due to symptoms. There were no recipient deaths, graft loss, rejection or decreased graft function resulting from COVID-19. Induction immunosuppression consisted of thymoglobulin (5.2-6.4mg/kg) and 3 dose methylprednisolone. The kidney after lung received 2 mg/kg thymoglobulin. All recipients had tacrolimus/ MMF maintenance. Of these recipients, 5 had a history of infection post-transplant, 2 others had concurrent infections with COVID-19. 22.2% had a history of steroid treated rejection prior to diagnosis. The time to diagnosis of COVID-19 ranged from 2 to 12 months post-transplant. All 9 recipients were the index case in their household as far as could be determined, as there were no household contacts reporting symptoms or positive tests prior to the recipient. The recipients had a total of 20 household contacts, 3 (15%) tested positive, 8 (40%) asymptomatic and tested negative, 1 (5%) developed cough but tested negative and 8 (40%) asymptomatic and not tested. In addition to household contacts there were 7 people identified as close contacts;1 close contact was the likely source of COVID-19 to a recipient, 2 that did contract COVID-19 after recipient exposure and 4 tested negative. One recipient appeared to transmit COVID-19 to 3 contacts, 1 of whom he lived with and 2 other close contacts. There was no indication that the asymptomatic recipients transmitted COVID-19 to any contacts. Conclusions: We found no evidence that pancreas and kidney recipients contracting COVID-19 within the first year after transplant had a higher rate of household/close contact transmission than the general population. The recipients were encouraged to wear masks and minimize contact with others. This study suggests that in a very limited sample size, the risk to family members of COVID-19 PCR positive recipients does not appear greater than the general population. Precautionary distancing and barrier measures should be used.
ABSTRACT
Purpose: The current pandemic has created uncertainty of induction regimen impact upon severity of COVID-19 disease. Our experience with COVID-19 infection was reviewed to stratify outcomes of infection occurring before or after one year from transplant. Methods: All COVID-19 PCR positive pancreas and/or kidney transplant recipients were reviewed for demographics and outcomes. Results: 65 recipients were identified: 9 <1 year and 56 >1year post-transplant. There were clinically relevant differences between groups. In the <1 year group 100% received thymoglobulin induction and 2 (22.2%) received steroid rejection treatment 2 and 10 months prior to COVID-19 diagnosis. Of recipients > 1 year from transplant there were no rejection treatments within the year prior. Maintenance immunosuppression was CNI/MMF in 66.1%. Infection <1 year post-transplant resulted in no mortality nor worse outcomes. In fact 3 recipients were asymptomatic (tested for upcoming procedure, known exposure or admission). Mild-moderate symptoms (cough, fever) were the cause for testing in 4, but symptoms were of insufficient severity to warrant admission. All non-hospitalized patients recovered without sequala. 2 patients were hospitalized for COVID-19 disease. One recipient had a prior lung transplant and developed fever and hypoxia. Treatment with MMF reduction, dexamethasone and remdesivir permitted avoidance of intubation and discharge within a week. The other hospitalized patient was asymptomatic at positive test, but developed diarrhea and weight loss 2 weeks after initial diagnosis. Other causes of diarrhea were ruled out and it was concluded that symptoms were COVID-19 related, as PCR remained positive. There were no respiratory symptoms. Infections diagnosed >1 year after transplantation were diagnosed because of symptoms, had a higher rate of hospitalization and death. Due to small sample size, statistical significance of increased severity was not feasible. Conclusions: With a limited experience, COVID-19 infection within the first year after transplantation does not appear to have a greater mortality or need for hospitalization after lymphocyte depletion induction contrasted to recipients acquiring COVID-19 greater than a year after transplantation. (Table Presented).