Comparison of Six-Month Outcomes in Patients with Cardiac Amyloidosis before and after the UNOS Allocation System Change

Advanced amyloid cardiomyopathy (ACM) patients have high waitlist (WL) mortality. Given the greater emphasis and clarity for status exceptions for ACM patients in the new allocation system, we sought to assess whether this change in the allocation policy would affect the WL and post-transplant outcomes in ACM pts. Thirty-five patients were identified in the UNOS database that underwent heart transplant (HT) with a prior diagnosis of ACM during a 6-month period immediately before and after the policy change. Comparisons between patient characteristics in the pre (n=24) and post (n=11) policy-change cohorts are reported using standard statistical methods; survival analysis was performed using Cox proportional hazards modeling. The WL statuses of the pre patients were 1A (n=15), 1B (n=5), 2 (n=4) while the WL statuses of the post patients were 2 (n=7), 3 (n=2), 4 (n=2). The recipient age, donor age, gender, ethnicity, diabetes status, and ischemic time were similar for both groups. Total days on WL for pre and post were similar (26.0 days vs 29.0 days, p=0.82). The use of IABP was greater following the policy change (55% post vs 4% pre, p<0.001). Pre-transplant hemodynamic parameters and serum creatinine were similar before and after the policy change. Additionally, there was no difference in 6-month survival between the groups (p=0.58). The heart allocation policy change did not significantly decrease wait list times in ACM patients awaiting heart transplant, however there was significant greater utilization of pre-transplant IABP use. There were overall fewer patients that underwent HT in the 6 months following implementation of the new system, and there was no observed difference in 6-month post-HT survival for patients with ACM in the new allocation system

Characterization of SARS-CoV-2 spike mutations important for infection of mice and escape from human immune sera

Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in "mouse-adapted" SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera