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Background: Little is known about de novo human luekocyte antigen (HLA) antibody development with Impella 5.5 temporary mechanical circulatory assist support and downstream effects following heart transplantation in the new heart allocation system. Methods: Thirteen Impella and 17 control patients without device support were prospectively enrolled between December 2020 and June 2022. HLA antibodies with calculated panel reactive antibodies (cPRA) were assessed pre and postdevice implantation and within 1-year postheart transplantation. Results: Baseline prevalence of HLA antibodies and median cPRA were similar between groups. Patients in the study arm were on Impella support for a median of 7 days. No significant differences in HLA antibodies were observed postdevice or postheart transplant. One patient in the Impella arm developed rejection and required treatment. One Impella patient died due to infection and 1 control patient died due to primary graft dysfunction. Conclusions: Short-term use of Impella 5.5 in the new heart allocation system does not appear to increase risk of de novo HLA antibody development. Further studies are needed to validate these preliminary findings.

Summary: Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in PNPLA3 (rs738409 C>G, p.I148M) and HSD17B13 (rs72613567 T>TA; rs80182459, p.A192Lfs∗8) influences post-LT survival. Methods: In this retrospective cohort study, data on 2346 adults who underwent first-time LT between January 1, 1999 and June 30, 2020 and who had donor DNA samples available at five large Transplant Immunology Laboratories in Texas, USA, were obtained from the United Network for Organ Sharing (UNOS). Duplicates, patients with insufficient donor DNA for genotyping, those who were

Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively. Virology sample collection was optional in the study protocols. Sequencing and related viral load data were obtained retrospectively from participants at a subset of study sites with local sequencing capabilities (10 of 183 sites) at timepoints with detectable viral load. Among participants with both baseline and post-baseline sequencing data treated with RDV, emergent Nsp12 substitutions were observed in 4 of 19 (21%) participants in the severe study and none of the 2 participants in the moderate study. The following 5 substitutions emerged: T76I, A526V, A554V, E665K, and C697F. The substitutions T76I, A526V, A554V, and C697F had an EC50 fold change of ≤1.5 relative to the wildtype reference using a SARS-CoV-2 subgenomic replicon system, indicating no significant change in the susceptibility to RDV. The phenotyping of E665K could not be determined due to a lack of replication. These data reveal no evidence of relevant resistance emergence and further confirm the established efficacy profile of RDV with a high resistance barrier in COVID-19 patients.