Faculty Bibliography

Purpose: The presentation of Coronavirus disease 2019 (COVID-19) ranges from mild illness to severe respiratory failure. Disease progression may differ in immunocompromised patients and immunocompetent hosts. Therefore, we aim to characterize COVID-19 clinical presentation and outcomes in solid organ transplant recipients (SOTRs) to identify initial clinical factors that may predict COVID-19 associated mortality.
Method(s): We prospectively reviewed baseline demographic and clinical characteristics among adult kidney, pancreas, liver, heart and lung transplant recipients diagnosed with COVID-19 between March 1, 2020 and May 5, 2020 at our transplant center in New York City. A series of chi-square and Fisher's exact tests were conducted to investigate the relationship between several predictor variables (baseline characteristics, symptoms at presentation, and baseline immunosuppression regimen) and 30-day mortality.
Result(s): 73 SOTRs (53 kidney, 8 liver, 7 heart, 3 lung, 2 heart/kidney) with SARSCoV-2 PCR-confirmed COVID-19 were included in the final analysis. Median age was 59 years (IQR 54-68) and 34.2% were female. Median time since transplant was 21 months (IQR 13-46.5). All patients were on baseline immunosuppresion as shown in table 1. The majority of patients were diagnosed in the Emergency Department. Most common presenting symptoms were cough (68.5%), gastrointestinal symptoms (54.8%) and dyspnea (45.2%) with median of 5 days from symptom onset to hospitalization. All patients had elevated inflammatory markers at time of diagnosis (median CRP 54 mg/L, median ferritin 704 ng/mL, median procalcitonin 0.11 ng/mL, median D-dimer 311 ng/mL). 84.1% of patients required supplemental oxygen, including intubation in 19.7%. 13 of 63 (21%) hospitalized patients died. Dyspnea on presentation was the only baseline or presenting patient factor found to be predictive of death (p =.004). When stratified by initial chest X-ray findings, dyspnea combined with abnormal chest X-ray predicted mortality (p=.021) while dyspnea with normal chest X-ray did not.
Conclusion(s): Presenting symptoms of dyspnea and radiographic signs of pneumonia on initial imaging predicted mortality among SOTRs with COVID-19 in our cohort. These findings can inform allocation of limited resources in COVID-19 management, including the triage and timing of COVID-19 directed therapies early in the illness course among different patient populations

Purpose: Utilization of HCV viremic donor kidneys for transplant into HCV naive recipients has become more widespread, yet best practices governing the initiation, timing or duration of direct acting antiviral (DAA) therapy are lacking. Most published series describe DAA initiation weeks to months after transplant. However, fibrosing cholestatic hepatitis has been reported with delayed DAA initiation. Herein we report our center practice utilizing donor blood for HCV genotyping to expedite DAA insurance approval and minimize the duration of recipient viremia.
Method(s): Patients received education and DAA insurance benefits were ensured prior to listing for HCV+ organs. At the time of transplant, donor blood accompanying the kidney was used for HCV genotyping. Results were received within one week of transplant. Recipients were screened for HCV RNA by POD#4, and weekly for 12 weeks. Insurance authorization for DAA coverage was sought after both recipient viremia and donor HCV genotyping resulted. In 3 cases, donor viral load was insufficient for genotyping, and these recipients were genotyped once viremic.
Result(s): 80 hepatitis C naive patients received hepatitis C positive donor kidneys between July, 2018 and October, 2020. 17 donors were HCV Ab+/NAT-and 63 donors were HCV Ab+/NAT+. All recipients of NAT+ donor organs became viremic; 89% were genotype 1a or 3. The median time to DAA initiation was 10 days for cases with donor genotyping (IQR 8-13). In contrast, the median time to DAA initiation was 20 days for the 3 cases with recipient genotyping (IQR 18-24). Median time from transplant to clearance of HCV viremia was 38 days (IQR 30-47) (Table 1). SVR12 was achieved in all patients, and no cases of fibrosing cholestatic hepatitis have been observed. There were 2 needlestick exposures of patient family members, though no HCV transmission occurred.
Conclusion(s): Early HCV genotyping using donor blood results in expedited initiation of DAA therapy for recipients of HCV+ kidneys. Compared to published reports, our patients are clearing viremia at the time that most other centers' patients are initiating DAA therapy. Whether duration of viremia or peak viral load are associated with adverse allograft events such as acute rejection is not known. The advantages to a shortened duration of HCV viremia remain to be characterized, but may include a lower risk of fibrosing cholestatic hepatitis and lower risk of HCV exposure to family members and caregivers. Our practice of expedited genotyping using donor blood is immediately implementable at all centers performing these transplants. (Table Presented)

Purpose: Blood type B candidates on the deceased donor kidney waitlist have a lower transplantation rate and longer wait time than candidates of other blood types. The new national kidney allocation system (KAS), implemented in December 2014, prioritizes the allocation of kidneys from blood type A2 and A2B deceased donors to blood type B candidates to mitigate this disparity in access to transplantation. We analyzed our center's data to determine whether blood type A2/A2B to B transplantation is clinically feasible without the need for additional immunosuppression.
Method(s): We conducted a single-center retrospective cohort study to analyze the utilization and outcomes in A2/A2B to B deceased donor renal transplants. Data on adult, kidney-only recipients were extracted with custom reports from the United Network for Organ transplantation (UNOS) portal. We used multivariable Coxproportional hazards models to compare graft and patient survival in blood type A2/A2B to B deceased donor renal transplants to survival in blood type B to B transplants. We estimated Kaplan-Meier (KM) graft and patient survival functions.
Result(s): Since 2015, our center has performed 44 A2/A2B to B and 65 B to B kidney transplants. We followed the patients for a median of 712 days (IQR 343-1143). Recipients of A2/A2B to B and B to B kidney transplants were similar with respect to age, gender, estimated post-transplant survival (EPTS), calculated panel reactive antibody (CPRA), HLA ABDR mismatch, kidney donor profile index (KDPI), and the incidence of delayed graft function (DGF). A higher percentage of A2/A2B to B transplant recipients were Black/African American (22/44, 50%) than B to B transplant recipients (14/65, 21.5%). Blood type A2/A2B to B and B to B transplant recipients had similar 1-year graft (97.7% vs. 93.8%, p=0.34) and 1-year patient survival (97.7% vs. 98.5%, p=0.78) rates. Multivariable models adjusted for race/ ethnicity showed that death censored graft survival (adjusted HR=1.45, p=0.70, 95% CI=0.21 to 9.82) and patient survival (4.22, p=0.14, 95% CI=0.64 to 27.92) in A2/A2B to B transplant recipients were similar to the traditionally ABO blood type compatible B to B transplants.
Conclusion(s): The NYU Langone blood type A2/A2B to B transplantation adds to the body of evidence suggesting that blood type A2/A2B to B transplantation is clinically feasible. This provision of the KAS appears to be having its intended effect of increasing access to transplantation in blood type B candidates with no attendant compromise in overall patient or death censored graft survival

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter wait list times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated to receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+R- had excellent graft function with a mean follow up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, re-operation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV negative pancreas allografts were transplanted, compared to only 5% of ideal HCV positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV positive pancreata for HCV naïve recipients and advocates for increased utilization of ideal HCV positive pancreas allografts.

Background/UNASSIGNED:Patients on maintenance hemodialysis are particularly vulnerable to infection and hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to immunocompromised patients and the clustering that occurs in outpatient dialysis units, the seroprevalence of COVID-19 antibodies in this population is unknown and has significant implications for public health. Also, little is known about their risk factors for hospitalization. Methods/UNASSIGNED:nasopharyngeal, real-time, reverse-transcriptase PCR (RT-PCR); SARS-CoV-2 IgG seropositivity; hospitalization; and mortality. Results/UNASSIGNED:<0.001) compared with those who tested negative. Higher positivity rates were also observed among those who took taxis and ambulettes to and from dialysis, compared with those who used personal transportation. Antibodies were detected in all of the patients with a positive PCR result who underwent serologic testing. Of those that were seropositive, 32% were asymptomatic. The hospitalization rate on the basis of either antibody or PCR positivity was 35%, with a hospital mortality rate of 33%. Aside from COPD, no other variables were more prevalent in patients who were hospitalized. Conclusions/UNASSIGNED:We observed significant differences in rates of COVID-19 infection within three outpatient dialysis units, with universal seroconversion. Among patients with ESKD, rates of asymptomatic infection appear to be high, as do hospitalization and mortality rates.

The COVID-19 pandemic affected transplant center activity in areas with high number of cases such as New York City and prompted reevaluation of patients awaiting organ transplant diagnosed with SARS-CoV-2 infection. To resume safe transplantation at our center, we found it necessary to (1) identify transplant candidates with possible exposure to or history of COVID-19 infection, (2) outline a clinical and laboratory assessment to determine adequate clinical recovery from COVID-19 for transplantation, and (3) determine whether the possibility of perioperative COVID-19 transmission from the patient to staff would pose unacceptable risk. Here, we describe our center's approach to proceeding with transplantation in a SARS-CoV-2 seropositive living donor kidney transplant recipient and describe early posttransplant outcomes.

Background: Studies to date indicate that most adults develop IgG antibody to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 6 weeks of COVID-19 symptom onset. The seroconversion rate of solid organ transplant recipients (SOTR) following COVID-19 is unknown. Elucidation of humoral immune responses following COVID-19 in SOTR may inform risk of reinfection and the development of safe and effective vaccines for immunocompromised hosts.
Method(s): We assessed the frequency of SARS-CoV-2 IgG detection among adult SOTR diagnosed with COVID-19 by nasopharyngeal PCR assays between 3/1/2020 and 6/5/2020. SARS-CoV-2 IgG was detected in serum using the Abbott IgG assay at the manufacturer's recommended cut-off. Our primary objective was the frequency of SARS-CoV-2 IgG seropositivity after COVID-19. A secondary objective was to identify clinical factors associated with seroconversion. The mean age and nadir absolute lymphocyte count (ALC) were calculated between seropositive and negative SOTR and compared by Student's t-test.
Result(s): Among 93 SOTR diagnosed with COVID-19, 19 died before SARSCoV- 2 IgG testing could be performed, and 18 had testing pending as of abstract submission. 56 SOTR (44 kidney, 5 heart, 4 liver, 1 lung, and 1 heart-kidney recipients) completed testing and were included in the analysis. Median age was 58 years (IQR 49.5-67), and all received maintenance immunosuppression at the time of COVID-19 diagnosis with median nadir ALC during illness of 400 (IQR 200-600). SARS-CoV-2 IgG testing was performed at a median of 60 days (IQR 50-70) from symptom onset, the shortest interval being 16 days. 47 out of 56 SOTR tested positive for SARS-CoV-2 IgG. The likelihood of seroconversion was not different between those who were tested at < or >= 60 days from symptom onset (p=0.26), nor did it vary significantly by age (p =0.59), gender (p=0.53) or nadir ALC (p =0.28).
Conclusion(s): 83% of evaluated SOTR with COVID-19 disease had detectable SARS-CoV-2 IgG in serum at a median of 60 days after symptom onset. Studies are ongoing to identify variables associated with poor antibody response among the nearly 20% of SOTR in this cohort who failed to seroconvert. The significance of seroconversion on risk of reinfection and vaccine immunogenicity remains to be determined

Data describing the clinical progression of coronavirus disease 2019 (COVID-19) in transplant recipients are limited. In New York City during the surge in COVID-19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID-19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID-19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID-19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID-19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID-19 outcomes among transplant recipients.

Background: Clinical trials have demonstrated the safety of utilizing hepatitis C viremic donors (HCV+) to expand the donor pool through transplantation into hepatitis C naive recipients (HCV-). However, there has been a lack of enthusiasm to of er HCV+ pancreas grafts to HCV- recipients. We of ered HCV- pancreas patients the option to list for HCV+ donor organs.
Material(s) and Method(s): Patients undergoing pancreas transplant evaluation had informed consent by a transplant physician to receive HCV+ donor organs. We ensured patients had pharmacy coverage for post-transplant HCV anti-retroviral therapy prior to listing. In our early experience, 4 of our 8 transplant recipients elected to list for HCV+ donor organs.
Result(s): In the first 8 months, the average time to transplant from listing was 41 days for patients with standard listing and 21 days for patients listing for HCV+ organs (p<0.05). Of note, 2 of the 4 HCV- recipients were blood type AB and had shorter match time due to their blood type. For all HCV+ donors, COD was anoxia/drug OD, all were HCV antibody and NAT positive, PHS IR, and national imports, with average rank of 3 on the match run. All HCV- donors were local donors with average rank of 21 on the match run. HCV+ donors were younger (28 years) in contrast to HCV- donors (35 years). All recipients have excellent graft function with no signif cant dif erences in complications, LOS, or readmissions.
Conclusion(s): Utilization of HCV+ pancreas donors has allowed our patients increased access to high quality pancreas donors with signif cantly shorter wait times