A Randomized Phase 2 Study of MAU868 vs. Placebo to Treat BK Viremia in Kidney Transplant Recipients

Background: Reactivation of BK virus (BKV) infection can cause significant kidney disease in immunocompromised patients. BKV nephropathy is a leading cause of allograft loss in kidney transplant recipients. There are currently no effective or BKV-specific therapies. MAU868 is a novel monoclonal human IgG1 that binds to the BKV major capsid protein with potent in vitro neutralizing activity against the 4 major BKV genotypes. Method(s): This is a Phase 2, randomized, placebo-controlled, double-blind study in patients (pts) who received a kidney transplant within one year. Pts had BK viremia;either >=104 copies/ml within 10 days of randomization or >=103 copies/ml in 2 consecutive samples 1-3 wks apart with most recent value measured within 10 days of randomization. Pts were randomized (2:1) to MAU868 or placebo intravenously (IV) every 28 days for 12 wks, with 24 wks follow-up. This analysis reports efficacy results at 16 and 36 wks for 2 cohorts: Cohort 1: MAU868 1350 mg IV X4 doses, and Cohort 2: MAU868 6750 mg IV followed by 1350 mg IV X3 doses. The primary endpoint was safety;BKV viral load (VL) response to treatment was assessed as secondary endpoints and post-hoc analyses. Result(s): 20 pts received MAU868 and 8 pts received placebo;all completed 12 wks of treatment and 24 wks of follow-up. Baseline characteristics were comparable between groups. Median baseline VL was 16,700 log10 BKV DNA copies/ml (range 1,200-1,800,000). MAU868 was well tolerated, with a comparable frequency of adverse events and serious adverse events between groups through wk 36. There were 2 deaths in the MAU868 group due to COVID-19 infection deemed unrelated to study drug. The antiviral effect was greater in the MAU868 group than in the placebo group at wk 16 and sustained through wk 36 (Table). Conclusion(s): MAU868 was well tolerated and demonstrated clinically meaningful BK antiviral activity in kidney transplant recipients with BK viremia. These results support the further development of MAU868 as a therapy for BK viremia. (Table Presented).

Post-Acute Sequelae of Sars-Cov-2 Infection in Solid Organ Transplant Recipients

Purpose: Post-acute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon manifested by long lasting cognitive, mental, and physical symptoms. We aimed to estimate the prevalence of PASC symptoms in solid organ transplant recipients (SOTRs) in the short (1- 6 months) and long-term (> 6 months) periods after SARS-CoV-2 infection. We also compared the prevalence of these symptoms between those with SARS-CoV-2 infection requiring hospitalization and those not requiring hospitalization. Method(s): We surveyed 111 SOTRs with self-reported SARS-CoV-2 infection diagnosed more than 4 weeks prior to survey administration. The survey consisted of 7 validated questionnaires ("Quick Dementia Rating System (QDRS)", "Patient Health Questionnaire (PHQ9)", "Generalized Anxiety Disorder 7 (GAD-7)", "Impact of Events Scale (IES-6)", "EuroQol- 5 Dimension (EQ-5D)", "PROMIS global physical health scale (GHS) "and "Breathlessness, Cough and Sputum Scale (BCSS)"). Result(s): Of the 111 survey participants, 32 (33%) had been hospitalized and 35 (36%) had SARS-CoV-2 infection >6 months ago. Median (IQR) age was 58 years (46, 65). Median time from SARS-CoV-2 diagnosis was 167 days (138, 221). Cognitive impairment, anxiety, depression, insomnia, feeling of trauma, fatigue, pain, breathing problems, cough, abnormal smell, abnormal taste, and diarrhea were reported by 40%, 23%, 36%, 55%, 53%, 41%, 19%, 33%, 33%, 21%, 22%, and 32% of patients respectively. Hospitalized patients had poorer scores in cognition (QDRS survey score of 2 versus 0.75, p=0.048) (Figure 1), quality of life (EQ-5D survey score of 2 versus 1, p=0.043), physical health (PROMIS GHS survey score of 10 versus 11, p=0.013), respiratory status (BCSS survey score of 1 versus 0, p=0.056), and pain (Pain score of 3 versus 0, p 0.006). Among patients who had SARS-CoV-2 infection >6 months ago, abnormal breathing, cough, abnormal smell, abnormal taste, and diarrhea continued to be reported by 31%, 31%, 29%, 32%, and 32% of patients respectively. Conclusion(s): After SARS-CoV-2 infection, SOTRs had a high prevalence of PASC symptoms. Some of the symptoms are more severe in patients who had required hospitalization and persist beyond 6 months. Further studies are needed to understand the long term sequalae of SARS-CoV-2 infection in SOTRs and to develop an evidence-based multidisciplinary approach for caring for these patients beyond the acute phase. (Table Presented).

Identifying scenarios of benefit or harm from kidney transplantation during the COVID-19 pandemic: A simulation study

Background: Clinical decision-making in kidney transplantation (KT) during the COVID-19 pandemic is a challenge: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. Methods: To quantify the benefit/harm of KT in this context, we conducted a Markov simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios (Figure 1), simulating expected life-months gained from transplant over 5 years. A calculator was implemented (http://www.transplantmodels.com/covid-sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Results: Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority for DDKT) had greatest influence on benefit/ harm (Figure 2). In most scenarios of COVID-19 dynamics and patient characteristics, immediate-KT provided survival benefit;KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (e.g. ≥50% fatality) than for waitlist registrants. Conclusions: Our simulations suggest that KT remains beneficial under COVID-19 in many scenarios. Our calculator can help identify patients who would benefit most. As the pandemic evolves, our calculator can update these predictions.

Telemedicine in the care of kidney transplant recipients with COVID-19

Introduction: Kidney transplant (KT) recipients with COVID-19 symptoms are bringing challenges to providers given the risk of COVID-19 exposure to health care workers, patients, and the public. Case Description: Three KT recipients with COVID-19 were managed using telemedicine via synchronous video visits integrated with an electronic medical records system, from home to inpatient settings (Figure 1-2). Patient 1 is a 53-year-old male s/p KT in 2012;Patient 2 is a 56-year-old female s/p KT in 2019;and Patient 3 is a 53-yearold female s/p simultaneous liver-kidney transplant in 2014. Patients 1 and 3 had followup COVID-19 NAT testing: Patient 1 converted to be negative at 24 & 28 days, whereas Patient 2 converted to be negative at 45 & 48 days. Discussion: Telemedicine helped assess, diagnose, triage, and treat patients with COVID-19 while avoiding an ER or outpatient clinic visit. We highlight the value of telemedicine in the maintenance of uninterrupted follow-up care for immunosupressed patients with prolong viral shedding.