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.

Simultaneous heart‐kidney transplant (sHK) has enabled the successful transplantation of patients with end‐stage heart disease and concomitant kidney disease, with non‐inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi‐organ transplantation were also debated. The findings and consensus statements are presented.

With the continuing coronavirus disease 2019 (COVID-19) pandemic coupled with phased reopening, it is critical to identify risk factors associated with susceptibility and severity of disease in a diverse population to help shape government policies, guide clinical decision making, and prioritize future COVID-19 research. In this retrospective case-control study, we used de-identified electronic health records (EHR) from the University of California Los Angeles (UCLA) Health System between March 9th, 2020 and June 14th, 2020 to identify risk factors for COVID-19 susceptibility (severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) PCR test positive), inpatient admission, and severe outcomes (treatment in an intensive care unit or intubation). Of the 26,602 individuals tested by PCR for SARS-CoV-2, 992 were COVID-19 positive (3.7% of Tested), 220 were admitted in the hospital (22% of COVID-19 positive), and 77 had a severe outcome (35% of Inpatient). Consistent with previous studies, males and individuals older than 65 years old had increased risk of inpatient admission. Notably, individuals self-identifying as Hispanic or Latino constituted an increasing percentage of COVID-19 patients as disease severity escalated, comprising 24% of those testing positive, but 40% of those with a severe outcome, a disparity that remained after correcting for medical co-morbidities. Cardiovascular disease, hypertension, and renal disease were premorbid risk factors present before SARS-CoV-2 PCR testing associated with COVID-19 susceptibility. Less well-established risk factors for COVID-19 susceptibility included pre-existing dementia (odds ratio (OR) 5.2 [3.2-8.3], p=2.6 x 10-10), mental health conditions (depression OR 2.1 [1.6-2.8], p=1.1 x 10-6) and vitamin D deficiency (OR 1.8 [1.4-2.2], p=5.7 x 10-6). Renal diseases including end-stage renal disease and anemia due to chronic renal disease were the predominant premorbid risk factors for COVID-19 inpatient admission. Other less established risk factors for COVID-19 inpatient admission included previous renal transplant (OR 9.7 [2.8-39], p=3.2x10-4) and disorders of the immune system (OR 6.0 [2.3, 16], p=2.7x10-4). Prior use of oral steroid medications was associated with decreased COVID-19 positive testing risk (OR 0.61 [0.45, 0.81], p=4.3x10-4), but increased inpatient admission risk (OR 4.5 [2.3, 8.9], p=1.8x10-5). We did not observe that prior use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers increased the risk of testing positive for SARS-CoV-2, being admitted to the hospital, or having a severe outcome. This study involving direct EHR extraction identified known and less well-established demographics, and prior diagnoses and medications as risk factors for COVID-19 susceptibility and inpatient admission. Knowledge of these risk factors including marked ethnic disparities observed in disease severity should guide government policies, identify at-risk populations, inform clinical decision making, and prioritize future COVID-19 research.

Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.