Background The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. Methods We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p<0.001], congestive heart failure [aOR 3.2, 95%CI 1.4-7.0, p=0.004], chronic lung disease [aOR 2.5, 95%CI 1.2-5.2, p=0.018], obesity [aOR 1.9, 95% CI 1.0-3.4, p=0.039]) and presenting findings (lymphopenia [aOR 1.9, 95%CI 1.1-3.5, p=0.033], abnormal chest imaging [aOR 2.9, 95%CI 1.1-7.5, p=0.027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. Conclusions Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL-2 and CD28-CD80/CD86 signaling are critical for CD4+CD25+FOXP3+ Treg survival in mice. Yet, both belatacept (a second-generation CTLA-4Ig) and basiliximab (an anti-CD25 monoclonal antibody) are among the arsenal of current immunotherapies being used in kidney transplant patients. In this study, we explored the direct effect of basiliximab and belatacept on the Tregs in peripheral blood both in the short term and long term and in kidney biopsies of patients with acute rejection. We report that the combined belatacept/basiliximab therapy has no long-term effect on circulating Tregs when compared to a calcineurin inhibitor (CNI)-treated group. Moreover, belatacept-treated patients had a significantly greater number of FOXP3+ T cells in graft biopsies during acute rejection as compared to CNI-treated patients. Finally, it appears that the basiliximab caused a transient loss of both FOXP3+ and FOXP3− CD25+ T cells in the circulation in both treatment groups raising important questions about the use of this therapy in tolerance promoting therapeutic protocols.
Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss.
Mortality among patients hospitalized for COVID‐19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID‐19, we compared 28‐day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity‐adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 ( p < .001). Crude 28‐day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL‐6/IL‐6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID‐19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
Focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients with FSGS receiving a first renal transplant and in over 80% of patients receiving a second transplant after a recurrence. Recurrence often leads to graft failure. The pathogenesis remains unknown and may involve a circulating permeability factor that initiates injury to the glomerular capillary. There are anecdotal reports of pediatric patients with posttransplant lymphoproliferative disorder (PTLD) and recurrent FSGS who have had remission of proteinuria after treatment with rituximab. These observations have prompted speculation that B cells may play a role in the pathogenesis of recurrent FSGS. We report four consecutive adult patients with early recurrent FSGS refractory or dependent on plasmapheresis who received rituximab (total dose 2000-4200 mg). None of the patients treated with rituximab achieved remission in proteinuria, and one patient experienced early graft loss. In these four adult renal transplant patients with recurrent FSGS, rituximab failed to diminish proteinuria.
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