GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults.

SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings.

The Physiological Response of Different Brook Willow (Salix acmophylla Boiss.) Ecotypes to Salinity.

Few phytoremediation studies have been conducted under semi-arid conditions where plants are subjected to drought and/or salinity stress. Although the genus Salix is frequently used in phytoremediation, information regarding its tolerance of drought and salinity is limited. In the present study, Salix acmophylla Boiss. cuttings from three sites (Adom, Darom and Mea She'arim) were tested for tolerance to salinity stress by growing them hydroponically under either control or increasing NaCl concentrations corresponding to electrical conductivities of 3 and 6 dS m-1 in a 42-day greenhouse trial. Gas exchange parameters, chlorophyll fluorescence and concentration, and water-use efficiency were measured weekly and biomass was collected at the end of the trial. Root, leaf and stem productivity was significantly reduced in the Adom ecotype, suggesting that Darom and Mea She'arim are the more salt-tolerant of the three ecotypes. Net assimilation and stomatal conductance rates in salt-treated Adom were significantly reduced by the last week of the trial, coinciding with reduced intrinsic water use efficiency and chlorophyll a content and greater stomatal aperture. In contrast, early reductions in stomatal conductance and stomatal aperture in Darom and Mea She'arim stabilized, together with pigment concentrations, especially carotenoids. These results suggest that Darom and Mea She'arim are more tolerant to salt than Adom, and provide further phenotypic support to the recently published data demonstrating their genetic similarities and their usefulness in phytoremediation under saline conditions.

Serial rotational thromboelastography (ROTEM) in mechanically ventilated patients with COVID-19 demonstrates hypercoagulopathy despite therapeutic heparinization.

Background: Clinical hypercoagulopathy in patients with COVID-19 has been anecdotally described, but there is lack of evidence due to the novelty of this disease. Our study reports the results of rotational thromboelastography (ROTEM) in relation to traditional laboratory coagulation tests and acute phase markers among a cohort of severely ill, mechanically ventilated patients with COVID-19. Methods: Patients with COVID-19 (N=21) with respiratory failure requiring mechanical ventilation were included in this prospective case series. ROTEM was serially obtained for all patients on three different days during their intensive care unit (ICU) stay and analyzed using repeated measures analysis. Demographic variables, symptoms at the time of presentation, ROTEM values, laboratory values for traditionally measured coagulation profiles, and acute phase reactants were analyzed, in addition to the use of anticoagulation and clinical hypercoagulopathic complications. Results: The average age of our cohort was 57.9 years old (SD=14.4) and 76.2% were male. The mortality rate was 14.3% (3 of 21). Two patients (12.5%) were identified to have new-onset deep vein thrombosis, two patients (12.5%) were found to have ≥3 episodes of central venous catheter thrombosis, and three patients (18.7%) had confirmed stroke. ROTEM demonstrated elevated EXTEM and INTEM clotting times, including elevated FIBTEM maximum clot firmness (MCFFIB). All patients treated with therapeutic anticoagulation still demonstrated hypercoagulopathy within the MCFFIB tests. Discussion: Repeated measure ROTEMs were able to detect hypercoagulopathy in ICU patients with COVID-19 despite therapeutic anticoagulation with heparin. Level of evidence: III.

Data-independent acquisition mass spectrometry for site-specific glycoproteomics characterization of SARS-CoV-2 spike protein.

The spike protein of SARS-CoV-2, the virus responsible for the global pandemic of COVID-19, is an abundant, heavily glycosylated surface protein that plays a key role in receptor binding and host cell fusion, and is the focus of all current vaccine development efforts. Variants of concern are now circulating worldwide that exhibit mutations in the spike protein. Protein sequence and glycosylation variations of the spike may affect viral fitness, antigenicity, and immune evasion. Global surveillance of the virus currently involves genome sequencing, but tracking emerging variants should include quantitative measurement of changes in site-specific glycosylation as well. In this work, we used data-dependent acquisition (DDA) and data-independent acquisition (DIA) mass spectrometry to quantitatively characterize the five N-linked glycosylation sites of the glycoprotein standard alpha-1-acid glycoprotein (AGP), as well as the 22 sites of the SARS-CoV-2 spike protein. We found that DIA compared favorably to DDA in sensitivity, resulting in more assignments of low-abundance glycopeptides. However, the reproducibility across replicates of DIA-identified glycopeptides was lower than that of DDA, possibly due to the difficulty of reliably assigning low-abundance glycopeptides confidently. The differences in the data acquired between the two methods suggest that DIA outperforms DDA in terms of glycoprotein coverage but that overall performance is a balance of sensitivity, selectivity, and statistical confidence in glycoproteomics. We assert that these analytical and bioinformatics methods for assigning and quantifying glycoforms would benefit the process of tracking viral variants as well as for vaccine development.

Neurohospitalist Practice and Well-Being During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Neurohospitalists play an important role in, and have been variably affected by, the ongoing COVID-19 pandemic. In this study, we survey neurohospitalists to characterize practice changes and the impact of the pandemic on their well-being. METHODS: A 22-item survey was distributed to neurohospitalists through the Neurohospitalist Society and the American Academy of Neurology Neurohospitalist, Stroke & Vascular Neurology, and Critical Care & Emergency Neurology Sections. RESULTS: After 2 weeks of collection, 123 responses were received, with 57% of respondents practicing in academic settings, 23% in private practice, and 7% in community hospitals. A minority of neurohospitalists (8%) were redeployed to care for COVID-19 or non-COVID-19 medicine patients. The most common neurologic diagnoses they reported in COVID-19 patients were delirium (85%), cerebrovascular events (75%), and seizure (35%); however, most neurohospitalists (59%) had evaluated fewer than 10 patients with COVID-19. Respondents observed that fewer patients with unrelated neurological diseases were admitted to the hospital compared to before the pandemic. Neurohospitalists experienced changes in administrative (27%), educational (15%), and research duties (11%), and had overall worse well-being and work-life balance (77%). CONCLUSIONS: The most common neurologic diagnoses seen in COVID-19 patients by neurohospitalists in this sample are delirium, cerebrovascular disease, and seizure. Though the majority of survey respondents reported not being primary frontline providers, they report key clinical and operational roles during the pandemic, and report worse well-being as compared to before the pandemic. Our data suggests that there are opportunities to improve neurohospitalists' experience through flexible work practices and providing family care support.