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Background: Incidence of COVID-19 Omicron infection in SOTR is high, but there are few data on interventions after BA.1. Tixagevimab- cilgavimab (TC) was available for pre-exposure prophylaxis (ppx) as of 1/2022: and bebtelovimab (BEB) as treatment in 4/2022 with the rise of BA.2. Aims: We aimed to describe Omicron outcomes in SOTR at a single US center through 7/9/22, focusing on TC (ppx) and BEB (treatment). Methods: Candidates for TC were identified by electronic medical record (EMR), referrals, and RN outreach. EMR eports of positive SARS-COV-2 tests in SOTR were generated daily. NPs and RNs helped arrange BEB for those who met criteria. Results: 213 SOTR received TC (197 got 300/300mg), and 22(10.3%) developed COVID-19;3 were hospitalized, 1 required mechanical ventilation (MV), 2 died (one with BA-1). 4 (18.2%) cases were <14 days after TC. 7 (3.3%) patients had cardiac events, with median time of 13 weeks post TC. 212 SOTR were diagnosed with COVID-19 from 4/4/22-7/9/22 (127 kidney, 30 liver, 18 lung, 27 heart, 10 dual). 145 (68.4%) were treated with BEB;of those, 18 (12.4%) were hospitalized, 1 required MV, and 1 (0.7%) died. Conclusions: Despite large numbers of Omicron cases, almost 90% of SOTR who received TC did not contract COVID-19;of the 10.3% who did, most had mild disease and 2 died. 7 cardiac events were reported after TC, but relationship to TC is unclear. SOTR with COVID-19 who received BEB had low rates of hospitalization and 1 death. These favorable outcomes underscore the value of an RN-led program for rapid referral for monoclonal antibody ppx or treatment.
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The potential shortage of ventilators during the COVID-19 crisis has resulted in guidelines being published denying any moral difference between withholding and withdrawing medical treatment. This reflects some ethicists' support for ‘the equivalence thesis’, the idea that wherever it is permissible to withhold treatment, it is permissible to withdraw it, and vice versa. Some ethicists claim that doctors' opposition to the equivalence thesis discourages treatment withdrawal, leading to unnecessary loss of life amid pronounced scarcity. But first we need to ascertain whether the equivalence thesis is true. If it is, then we can work out what to do about the negative impacts of doctors opposing it. In this article, we argue that the equivalence thesis is false. There is a difference between withholding and withdrawing in that there can be instances in which an act of one type would be permissible while an act of the other type would be wrong, even though all other things are equal. We use Heidi Malm's distinction between comparison and conflict cases to show that equivalence proponents and opponents may be talking past one another, with proponents focussing on comparison cases and opponents rightly thinking of conflict cases as well. © 2021 Society for Applied Philosophy.
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Purpose: Monoclonal antibody (mAB) infusion (bamlanivimab or casirivimab/ imdevimab) for symptomatic, non-hypoxemic, high-risk outpatients with COVID-19 infection, is an available early intervention for COVID-19+ SOT recipients. We aimed to assess efficiency in time from diagnosis to treatment, and outcomes in a retrospective cohort of SOT recipients with COVID-19 who received mAB. Methods: We developed a Nurse Coordinator-led initiative to screen, refer, and facilitate mAB infusion for COVID-19+ SOT recipients within 10 days of symptom onset. SOT recipients received electronic messaging to promptly report potential COVID-19 symptoms to the transplant team. Data were collected on time from symptom onset to diagnosis, mAB infusion, and follow-up > 21 days, and hospital admissions, disease severity, mortality, and rejection. Results: 34 out of 36 referred SOT recipients with symptomatic COVID-19 disease without hypoxia received mAB therapy (3 heart, 8 lung, 16 kidney, 2 Liver-Kidney, 2 Pancreas-Kidney, 3 Kidney-Heart). Median time from symptom onset to diagnosis was 2 days and from date of diagnosis to mAB infusion was 4 days. Of those 34, 88% did not require hospitalization and recovered uneventfully. 12% required hospitalization for COVID disease progression, two on the same day as mAB infusion, and the other 2, more than 26 days post infusion. Of these, 2 patients had mild-moderate hypoxia, and 2 had critical disease. Only 1 patient died from COVID-19 complications and no episodes of rejection or graft loss were observed. Conclusions: The Nurse Coordinator-led initiative efficiently facilitated mAB therapy for COVID-19+ SOT recipients and was associated with excellent outcomes. Compared to prior published COVID-19 outcomes in SOT recipients, patients who received mAB may have reduce hospitalization and low mortality. As mAB therapy may be underutilized in the general population, these results support efforts to educate transplant centers to implement efficient interventions for the screening and referral of COVID+ SOT recipients for mAB therapy.
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Nanoparticles are playing an increasingly powerful role in vaccine development. Here, we report the repurposing of nonstructural proteins 10 and 11 (hereafter NSP10) from the replicase polyprotein 1a (pp1a) of the human SARS coronavirus (severe acute respiratory syndrome) as a novel self-assembling platform for bioengineered nanoparticles for a variety of applications including vaccines. NSP10 represents a 152 amino acid, 17 kD zinc finger transcription/regulatory protein which self-assembles to form a spherical 84 Å diameter nanoparticle with dodecahedral trigonal 32 point symmetry. As a self-assembling nanoparticle, NSP10 possesses numerous advantages in vaccine development and antigen display, including the unusual particle surface disposition of both the N- and C-termini. Each set of N- or C-termini is spatially disposed in a tetrahedral arrangement and positioned at optimal distances from the 3-fold axes (8-10 Å) to nucleate and stabilize the correct folding of complex helical or fibrous trimeric receptors, such as those responsible for viral tropism and cell infection. An application example in the exploratory development of a therapeutic vaccine for idiopathic pulmonary fibrosis (IPF), including preliminary analysis and immunogenic properties, is presented. The use of this system could accelerate the discovery and development of vaccines for a number of human, livestock, and veterinary applications. © 2020 Daniel C. Carter et al.
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STATEMENT: The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight.