Phase 3 Study of Safety and Immunogenicity of Gbp510 Vaccine Adjuvanted with As03 in Adults

Intro: GBP510 contains the self-assembling recombinant nanoparticle displaying SARS-CoV-2 Spike protein receptor binding domain and is adjuvanted with AS03. We report interim Phase 3 study (NCT05007951) results up to 4 weeks post-dose 2 (Data-cut: March-18-2022), where immunogenicity to the D614G ancestral strain and safety of 25mug GBP510/AS03 candidate was compared to ChAdOx1-S (Vaxzevria). Method(s): This Phase 3 randomized, active-controlled, observer-blind, parallel- group study in adults was conducted in 6 countries. Cohort1: 1,895 subjects (naive to COVID-19 vaccination and infection) randomized at 2:1 ratio (GBP510/AS03:ChAdOx1-S) to assess immunogenicity and safety;Cohort 2: 2,141 subjects at 5:1 ratio, regardless of their serostatus at screening for safety assessment. Subjects were vaccinated twice at a 4-week interval with 0.5 mL of the test vaccine (GBP510/AS03) or active control (ChAdOx1-S) in deltoid muscle. The primary objective was to demonstrate the superiority of geometric mean titer (GMT) and non-inferiority in seroconversion rate (SCR: >=4-fold rise from baseline) of neutralizing antibodies over ChAdOx1-S by live-virus neutralization assay (FRNT). Finding(s): At 2 weeks post-dose 2, GMT ratio of the two groups (Test vaccine/Active control) was 2.93 [95% CI: 2.63, 3.27], satisfying the hypothesis of superiority (95% CI lower limit> 1). The SCR difference (Test vaccine - Active control) was 10.76% [95% CI: 7.68, 14.32], satisfying the hypothesis of non- inferiority (95% CI lower limit> -5%). Good cell-mediated immune responses for Th1 cytokines were also observed with the test vaccine (FluoroSpot). The AE incidence rate for the test vaccine was higher than the active control for solicited local AEs (56.69% vs 49.20%), and comparable for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.34% vs 14.66%) after any vaccination. Conclusion(s): Higher immune responses were observed with GBP510/AS03 compared to ChAdOx1-S against D614G strain after 2 weeks post-dose 2. GBP510/AS03 showed a clinically acceptable safety profile;no safety concerns were identified during the study period.Copyright © 2023

Initial five and ten-minute regional cerebral oxygen saturation as a predictor of the futility of resuscitation for out-of-hospital cardiac arrest

This study aimed to investigate the usefulness of cerebral regional oxygen saturation (rSO2) during the initial 5 and 10 minutes of cardiopulmonary resuscitation (CPR) compared with an initial rSO2 and mean rSO2 during entire CPR to predict the futility of resuscitation for patients without of-hospital-cardiac arrest (OHCA). This was a prospective study involving 52 adult patients presenting in OHCA and whose cerebral rSO2 values were measured until either CPR was terminated or sustained return of spontaneous circulation (ROSC) was achieved. Receiver operating characteristics analyses were used to evaluate which time and type of measurement is better to predict non-ROSC. The area under the curve (AUC) of each rSO2 value according to measurement time (overall, initial 5 minutes and 10 minutes) were the highest value of 0.743, 0.724, and 0.739, mean values of 0.724, 0.677 and 0.701 and rSO2 (Changes in values of regional cerebral oxygen) value of 0.722, 0.734 and 0.724, respectively, while all of the initial values had a poor AUC (<0.7) and also were not statistically significant. The optimal cut-off value of each rSO2 values during overall, initial 5 minutes and 10 minutes were the highest value of 26% (sensitivity, 53.9% specificity, 92.3%), 24% (sensitivity, 56.4% specificity, 92.3%), and 30% (sensitivity, 61.5% specificity, 84.6%), mean value of 15.2%, 15.3% and 16%, respectively. None of the patients with a persistent rSO2 <=18% during the overall period achieved ROSC. Initial 5 minutes and 10 minutes cerebral rSO2 values an out-of-hospital-cardiac arrest (OHCA) are a better predictor in deciding the futility of CPR, compared to initial and overall measurements.Copyright © 2023 The Author(s). Published by MRE Press.

Effect of Mask Mandates on the Intraocular Pressure Measured via Goldmann Applanation Tonometry

Purpose: The corona virus disease-19 (COVID-19) pandemic has resulted in mandatory masking of patients and physicians during outpatient visits. This study evaluated the changes in intraocular pressure (IOP) according to mask use. Methods: This prospective study enrolled 30 healthy volunteers (60 eyes). IOP was measured via Goldmann applanation tonometry (GAT) for the subjects wearing one of four commonly used masks: dental, bi-folding Korean Filter (KF)94, tri-folding KF94, and dust masks. Subjects with IOP measurement errors of more than 5 mmHg were rechecked with another GAT type. Results: The mean IOP measured via GAT before mask wearing was 13.7 +/- 1.7 mmHg. It was 13.5 +/- 2.1, 14.0 +/- 2.3, 14.3 +/- 2.5, and 13.8 +/- 1.6 mmHg with the dental, bi-folding KF94, tri-folding KF94, and dust masks, respectively. There were no significant differences in IOP according to mask type (p = 0.635). IOP errors above 5 mmHg were detected in three subjects who had contact between the GAT feeler arm and tri-folding KF94 mask during IOP measurement. Conclusions: The IOP as measured via GAT is artificially elevated by mechanical interference from the tri-fold KF94 mask. To minimize such mask-induced artifacts in GAT measurements, compress the patient's mask or change the mask type to prevent any contact during measurement.

Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea

Background: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. Materials and Methods: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. Results: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. Conclusion: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes. FAU - Choi, Won Suk