Expecting the unexpected: COVID-19 in Kidney Transplant Recipients within United Network for Organ Sharing Region 1

There are numerous case reports and a handful of single center studies reporting on COVID‐19 in kidney transplant recipients. Most reports arise from the epicenters of where the SARS‐CoV‐2 virus was first detected such as New York City and Europe3. We in UNOS Region 1 experienced COVID‐19 weeks to a month later and questioned whether our experience was different. The programs within UNOS Region 1 have had a long history of sharing information in an attempt to mitigate the effect of viruses on our patients

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Antibodies, boosters and optimizing SARS-CoV-2 vaccine for transplantation: A call for more research

Despite emerging data suggesting reduced antibody responses among SOT recipients following SARS-CoV-2 vaccine, critical unanswered questions remain. The clinical implications of the reduced humoral response need to be assessed through prospective studies. Studies are likewise needed to inform which vaccine dosing strategies result in improved immunity and if such approaches maximize protection against severe infection in the vulnerable transplant population

Antibodies, boosters, and optimizing SARS‐CoV‐2 vaccines for transplantation: A call for more research

Despite emerging data suggesting reduced antibody responses among solid organ transplant recipients following SARS‐CoV‐2 vaccine, critical unanswered questions remain. The clinical implications of the reduced humoral response need to be assessed through prospective studies. Studies are likewise needed to inform which vaccine dosing strategies result in improved immunity and if such approaches maximize protection against severe infection in the vulnerable transplant population.In this Viewpoint, the authors review the existing data on SARS‐CoV‐2 vaccine in transplant recipients and outline next steps in understanding how to optimize immunologic responses to the vaccine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171219/1/ajt16758.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171219/2/ajt16758_am.pd

SARS-CoV-2 Vaccination and Solid Organ Transplant Patients: Data Needed to Inform Safety and Efficacy

Solid organ transplant (SOT) recipients appear to have higher rates of mortality from COVID-19 when compared to other populations, attributed to underlying immunosuppression and concomitant co-morbidities.1 Such findings are consistent with other respiratory viral infections that are associated with an increased risk of morbidity and mortality in immunocompromised hosts.2 Further, these patients experience prolonged SARS-CoV-2 shedding which has been linked to emergence of viral mutants. Prolonged shedding also poses a risk of transmission and requires prolonged isolation, potentially leading to delays in medical care

476. A Global Survey of Countermeasures Against the COVID-19 Pandemic Among Solid Organ Transplant Centers

AbstractBackgroundSolid organ transplantation (SOT) profoundly impacts vulnerable recipients with chronic end organ diseases. The COVID-19 pandemic disrupted healthcare systems, including organ transplants. We aimed to evaluate the responses of SOT centers to COVID-19 at the beginning of the pandemic around the world.MethodsWe conducted a web-based survey amongst transplant centers, sent to members of The American Society of Transplantation Infectious Diseases Community of Practice Group, between April and May 2020. The survey included basic information of each transplant center (number and types of transplants in 2019), the countermeasures employed against COVID-19 such as timing of postponing of transplantation, and management of outpatient clinics including implementation of telemedicine and screening for in-person visits.ResultsA total of 65 centers from 19 countries responded (Table 1). Regarding the percentage of hospitalized patients with COVID-19 at the time of the survey, 39 (60%) centers reported 80%. All centers reduced their services to some extent as shown in Table 2. Centers reported postponing living donor kidney transplant (50/58, 86%), deceased donor kidney transplant (20/57, 35%), living donor liver transplant (32/42, 80%), deceased donor liver transplant (17/41, 41%), lung transplant (20/31, 65%), heart transplant for LVAD (18/33, 55%) and non-LVAD patients (18/33, 55%). In March and April 2020, cancellation of pre- and post- transplant clinics were reported by 36/64 (56%) and 17/65 (26%) centers. Postponing clinic appointments were reported by 56/65 (86%) centers. Most institutions (54/64, 85%) used telemedicine. Screening for COVID-19 for clinic visits was done by telephone, in-person questionnaires and/or temperature checks.ConclusionDuring the early phase of the pandemic, when management strategies were highly uncertain, non-urgent and living donor transplants were frequently postponed. Emergent liver transplants continued regardless. These findings could help us navigate SOT in future epidemics. Limitations included a small sample and lack of assessment of clinical outcomes from postponing SOT.DisclosuresDeepali Kumar, MD, MSc, FRCPC, Astellas (Individual(s) Involved: Self): Speakers’ bureau; Atara Biotherapeutics (Individual(s) Involved: Self): Grant/Research Support; GSK (Individual(s) Involved: Self): Consultant, Grant/Research Support; Merck (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support; Oxford immunotec (Individual(s) Involved: Self): Consultant, Grant/Research Support; Pfizer (Individual(s) Involved: Self): Speakers’ bureau; Roche (Individual(s) Involved: Self): Consultant, Grant/Research Support; Sanofi (Individual(s) Involved: Self): Advisor or Review Panel member; Shire/Takeda (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support Lara Danziger-Isakov, MD, MPH, Ansun (Individual(s) Involved: Self): Scientific Research Study Investigator; Astellas (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Pfizer (Individual(s) Involved: Self): Scientific Research Study Investigator; Shire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Viracor: Grant/Research Suppor

Randomized phase 3 trial of ruxolitinib for COVID-19-associated acute respiratory distress syndrome

Objectives: Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19-associated acute respiratory distress syndrome requiring mechanical ventilation. Design: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19-Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620). Setting: Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites). Patients: Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pao2/Fio2 of less than or equal to 300 mm Hg within 6 hours of randomization. Interventions: Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy. Measurements and main results: The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p \u3c 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24-87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39-62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42-64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55-83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201-1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171-1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments. Conclusions: The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19-associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination

SARS-CoV-2 Reinfection in a Liver Transplant Recipient

We present a case of a liver transplant recipient with 2 distinct SARS-CoV-2 infections, separated by 111 days without symptoms and 2 negative test results for SARS-CoV-2 infection. The clinical course suggested reinfection, and viral genomic sequencing was used to distinguish whether the later positive samples were due to SARS-CoV-2 relapse or reinfection