Competing Risks Analysis of Kidney Transplant Waitlist Outcomes: Two Important Statistical Perspectives.

Modern competing risks analysis has 2 primary goals in clinical epidemiology as follows: (i) to maximize the clinician's knowledge of etiologic associations existing between potential predictor variables and various cause-specific outcomes via cause-specific hazard models, and (ii) to maximize the clinician's knowledge of noteworthy differences existing in cause-specific patient risk via cause-specific subdistribution hazard models (cumulative incidence functions [CIFs]). A perfect application exists in analyzing the following 4 distinct outcomes after listing for a deceased donor kidney transplant (DDKT): (i) receiving a DDKT, (ii) receiving a living donor kidney transplant (LDKT), (iii) waitlist removal due to patient mortality or a deteriorating medical condition, and (iv) waitlist removal due to other reasons. It is important to realize that obtaining a complete understanding of subdistribution hazard ratios (HRs) is simply not possible without first having knowledge of the multivariable relationships existing between the potential predictor variables and the cause-specific hazards (perspective #1), because the cause-specific hazards form the "building blocks" of CIFs. In addition, though we believe that a worthy and practical alternative to estimating the median waiting-time-to DDKT is to ask, "what is the conditional probability of the patient receiving a DDKT, given that he or she would not previously experience one of the competing events (known as the cause-specific conditional failure probability)," only an appropriate estimator of this conditional type of cumulative incidence should be used (perspective #2). One suggested estimator, the well-known "one minus Kaplan-Meier" approach (censoring competing events), simply does not represent any probability in the presence of competing risks and will almost always produce biased estimates (thus, it should never be used).

Nocardiosis in Solid Organ Transplant Recipients: 10-Year Single Center Experience and Review of Literature.

Solid organ transplant recipients (SOTRs) are at an increased risk of nocardiosis, a rare but life-threatening opportunistic infection. Universal PCP prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is used at our center, which is active in vitro against most species of the Nocardia genus and may have a role in preventing early infections. This is a single-center retrospective cohort study of nocardiosis in adult SOTRs at a large transplant center between January 2012 and June 2022, with comprehensive review of literature. Out of 6179 consecutive cases, 13 (0.2%) were diagnosed with nocardiosis. The patients were predominantly male (76.9%) and kidney transplant recipients (62%). Infection was diagnosed at median of 8.8 months (range, 3.7-98) after transplant. Patients were followed for a median of 457 days (range 8-3367). Overall mortality within one year after diagnosis was 46% (6/13), of which 17% (1/6) of deaths was attributable to Nocardia infection. No recurrence was reported. Nocardia infections were noted in a small proportion of our SOTRs and carried significant morbidity and mortality. TMP-SMX prophylaxis may be protective in some cases given low incidence of cases.

Optimizing the kidney donor pool: transplanting donor kidneys after partial nephrectomy of masses or cysts.

Background: A limiting factor in expanding the kidney donor pool is donor kidneys with renal tumors or cysts. Partial nephrectomy (PN) to remove these lesions prior to transplantation may help optimize organ usage without recurrence of malignancy or increased risk of complications. Methods: We retrospectively analyzed all recipients of a living or deceased donor graft between February 2009 and October 2022 in which a PN was performed prior to transplant due to the presence of one or more concerning growths. Donor and recipient demographics, perioperative data, donor allograft pathology, and recipient outcomes were obtained. Results: Thirty-six recipients received a graft in which a PN was performed to remove suspicious masses or cysts prior to transplant. Majority of pathologies turned out to be a simple renal cyst (65%), followed by renal cell carcinoma (15%), benign multilocular cystic renal neoplasm (7.5%), angiomyolipoma (5%), benign renal tissue (5%), and papillary adenoma (2.5%). No renal malignancy recurrences were observed during the study period (median follow-up: 67.2 months). Fourteen complications occurred among 11 patients (30.6% overall) during the first 6mo post-transplant. Mean eGFR (± standard error) at 36 months post-transplant was 51.9 ± 4.2 ml/min/1.73 m2 (N = 23). Three death-censored graft losses and four deaths with a functioning graft and were observed. Conclusion: PN of renal grafts with suspicious looking masses or cysts is a safe option to optimize organ usage and decrease the kidney non-use rate, with no observed recurrence of malignancy or increased risk of complications.

The Impact of Ethnicity on Research Authorization at the Time of Organ Donation: A Single-Center Experience Among Deceased Donor Kidney Transplantation.

Objective: Research on deceased organ donors is needed to expand the donor organ supply. Little is known about the rate of research authorization among various groups. We aimed to determine the percentage of research authorization by the deceased donor family across different donor characteristics. Materials and Methods: We performed a retrospective review of deceased donors referred to one U.S. institution for kidney transplantation over a 12-month period. Organs were offered from multiple organ procurement organizations (OPO) across the United States. Stepwise logistic regression was performed to determine the predictors of research authorization. Results: From 10/2018 to 10/2019, 437 deceased donors were accepted for transplantation. 81.5% came from OPOs outside our donor service area and 18.5% from our local OPO. Overall, research authorization was declined in 24.0% of donors. Declined authorization was highest among Black donors (42.0%) compared to Whites (16.3%) and Hispanics (26.9%); p=0.000006. Donors <35 years had highest declined research authorization at 42.9% compared to older donors. There were no significant differences between individual OPOs. Conclusion: Deceased donor research authorization declined at the time of organ donation is higher among Black and younger donors. There is an immediate need for the transplant and donor community to develop best-practices to eliminate barriers to research in organ transplantation.

Long-term effects of average calcineurin inhibitor trough levels (over time) on renal function in a prospectively followed cohort of 150 kidney transplant recipients.

More favorable clinical outcomes with medium-term follow-up have been reported among kidney transplant recipients receiving maintenance therapy consisting of "reduced-tacrolimus (TAC) dosing," mycophenolate mofetil (MMF), and low-dose corticosteroids. However, it is not clear whether long-term maintenance therapy with reduced-calcineurin inhibitor (CNI) dosing still leads to reduced renal function. A prospectively followed cohort of 150 kidney transplant recipients randomized to receive TAC/sirolimus (SRL) versus TAC/MMF versus cyclosporine microemulsion (CSA)/SRL, plus low-dose maintenance corticosteroids, now has 20 years of post-transplant follow-up. Average CNI trough levels over time among patients who were still alive with functioning grafts at 60, 120, and 180 months post-transplant were determined and ranked from smallest-to-largest for both TAC and CSA. Stepwise linear regression was used to determine whether these ranked average trough levels were associated with the patient's estimated glomerular filtration rate (eGFR) at those times, particularly after controlling for other significant multivariable predictors. Experiencing biopsy-proven acute rejection (BPAR) and older donor age were the two most significant multivariable predictors of poorer eGFR at 60, 120, and 180 months post-transplant (p < 000001 and 0.000003 for older donor age at 60 and 120 months; p = 0.00008 and <0.000001 for previous BPAR at 60 and 120 months). Assignment to CSA also implied a significantly poorer eGFR (but with less magnitudes of effect) in multivariable analysis at 60 and 120 months (p = 0.01 and 0.002). Higher ranked average CNI trough levels had no association with eGFR at any timepoint in either univariable or multivariable analysis (p > 0.70). Long-term maintenance therapy with reduced-CNI dosing does not appear to cause reduced renal function.

Past, Current, and Future Perspectives on Transplanting Acute Kidney Injury Kidneys.

(1) Background: Acute kidney injury (AKI) kidneys have high non-utilization rates due to concerns regarding unfavorable outcomes. In this paper, we aimed to review the past, present, and future opinions on AKI kidneys. (2) Methods: A PubMed search was conducted for topics relevant to AKI kidney transplantation. (3) Results: Current short- and long-term data on AKI kidneys have demonstrated good outcomes including favorable graft function and survival. The role of procurement biopsies is controversial, but they have been shown to be beneficial in AKI kidneys by allowing clinicians to differentiate between reversible tubular injury and irreversible cortical necrosis. Machine perfusion has also been applied to AKI kidneys and has been shown to reduce delayed graft function (DGF). The incidence of DGF increases with AKI severity and its management can be challenging. Strategies employed to counteract this have included early initiation of dialysis after kidney transplantation, early targeting of adequate immunosuppression levels to minimize rejection risk, and establishment of outpatient dialysis. (4) Conclusions: Despite good outcomes, there continue to be barriers that impact AKI kidney utilization. Successful strategies have included use of procurement biopsies or machine perfusion and expectant management of DGF. With increasing experience, better use of AKI kidneys can result in additional opportunities to expand the donor pool.

Should VV ECMO be considered as treatment option in COVID-19 infection after kidney transplant? A word of caution.

Several reports have shown that hospitalized kidney transplant recipients (KTR) had high mortality rates when infected with COVID-19. Extracorporeal Membrane Oxygenation (ECMO) has been shown to be an option for refractory respiratory failure in COVID-19 patients with variable rates of recovery. The outcome of ECMO in respiratory failure is highly related to cohort investigated and patient selection. Over a 10-month period in the height of COVID-19 pandemic 5 KTR patients were placed on ECMO with none of the patients surviving to discharge. All patients experienced multisystem organ failure (MSOF) and hematologic pathology while on ECMO. We concluded that COVID-19 in KTR patients presents with a refractory MSOF that is not well supported with ECMO in a traditional approach. Future work is needed to determine how to best support refractory respiratory failure in KTR patients with COVID-19.

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

Percutaneous Ultrasound-Guided Kidney Transplant Biopsy Outcomes: From the Nephrologist to the Radiologist Standpoint.

Background: Kidney transplant biopsies are the gold standard for evaluating allograft dysfunction. These biopsies are performed by nephrologists and radiologists under real-time ultrasound guidance. A few studies have examined the outcomes of ultrasound-guided kidney transplant biopsy in transplant recipients; however, none have compared these outcomes between both specialties. Methods: We retrospectively analyzed a cohort of 678 biopsies performed in a single center during a 44-month study period. Biopsies were stratified into two groups based upon the specialist performing the procedure: interventional radiology (IR; N=447) and transplant nephrology (TN; N=231). Results: There were 55 (8%) complications related to biopsies in the entire cohort: 37 (8.2%) in the IR group and 18 (7.7%) in the TN group, without statistical difference between the groups (P=0.94). Blood pressure control and prior use of anticoagulation were significant predictors of complicated biopsies (P=0.004 and 0.02, respectively). Being a woman and prior use of anticoagulation were significant predictors of transfusion of blood products (P=0.01 and 0.01, respectively). Being a woman and blood pressure control were significant predictors of overall perinephric hematoma (P=0.01 and 0.01, respectively), and Black race was a significant predictor of perinephric hematoma without worsening of renal function (P=0.005). The specialist team performing the procedure was not a statistically significant predictor of biopsy complications, transfusion of blood products, or perinephric hematoma with comparable sample yield. Conclusions: Percutaneous ultrasound-guided kidney transplant biopsy performed by transplant nephrologists have similar complication rates when compared with interventional radiologists in an academic center.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

Creating a Single Inflow Orifice From Living Donor Kidney Allografts With Multiple Renal Arteries.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow. Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant. Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20-42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed-death-censored graft survival was 98.6%. Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Reinfection with SARS-CoV-2 in solid-organ transplant recipients: Incidence density and convalescent immunity prior to reinfection.

BACKGROUND: Long-term protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains poorly characterized, particularly in solid organ transplant (SOT) patients. METHOD: We determined the incidence density of SARS-CoV-2 reinfection in a cohort of adult SOT recipients initially infected between March 1st, 2020 and March 30th, 2021 and included those with initial infection before or after transplantation. Incidence density was the total cases divided by total days after initial diagnosis with active graft. RESULTS: Of 210 infected recipients, five (2.4%) developed reinfection, including two who had received full mRNA vaccination, but none developed hypoxia. The incidence density for reinfection was 9.4 (95% confidence interval [CI] 3.9-22.6) and for primary infection the density was 9.1 (95% CI 7.9-10.5) cases/100,000 patient days. Two recipients had immunity evaluated in the weeks prior to reinfection, by measuring immunoglobulin-G (IgG) antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools. Both mounted virus specific CD4 T-cell responses prior to reinfection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). CONCLUSIONS: This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for reinfection even after generating cellular and humoral immune responses.

Graft Failure Due to Nonadherence among 150 Prospectively-Followed Kidney Transplant Recipients at 18 Years Post-transplant: Our Results and Review of the Literature.

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients' overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients <50 years of age-at-transplant (20/56 experienced GFNA), with estimated percentages of such patients ever developing GFNA ranging between 36.9 and 41.5%. These patients were also at a higher risk of developing Other GF. For the remaining patients (2/94 experienced GFNA), estimated percentages of ever-developing GFNA were much lower (range: 0.0−6.7%). The major cause of graft loss among recipients ≥50 years of age was DWFG; GFNA rarely occurred among older recipients. In 21/22 GFNA patients, NA behavior lasted continuously from the time of developing NA until GFNA. In total, 28/150 patients became NA, and 67.9% (19/28) occurred beyond 36 months post-transplant. A total of 25 of 28 NA patients (89.3%) developed biopsy-proven acute rejection and/or chronic rejection that was directly attributed to the NA behavior. Lastly, 25/28 admitted to NA behavior, with financial and psychological components documented in 71.4% (20/28) and 96.4% (27/28) of NA cases, respectively. Conclusions: These results highlight the importance of performing serial monitoring of patients for overt NA behavior throughout their post-transplant follow-up. Financial and psychological components to NA behavior need to be simultaneously addressed with the goal of achieving complete avoidance/elimination of NA behavior among higher risk patients.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

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.