Syndromic Surveillance-Based Estimates of Vaccine Efficacy Against COVID-Like Illness from Emerging Omicron and COVID-19 Variants

New infections from the omicron variant of SARS-CoV-2 have been increasing dramatically in South Africa since first identification in November 2021. Despite increasing uptake of COVID-19 vaccine, there are concerns vaccine protection against omicron may be reduced compared to other variants. We sought to characterize a surrogate measure of vaccine efficacy in Gauteng, South Africa by leveraging real-time syndromic surveillance data. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS) is an online, cross-sectional survey conducted among users sampled from the Facebook active user base. We derived three COVID-like illness (CLI) definitions (stringent, classic, and broad) using combinations of self-reported symptoms (present or not in the prior 24 hours) that broadly tracked with reported COVID-19 cases during June 18, 2021 - December 14, 2021 (inclusive of the delta wave and up-trend of the omicron wave). We used syndromic-surveillance-based CLI prevalence measures among the vaccinated (PV) and unvaccinated (PU) respondents to estimate VECLIP = 1 - (PV/PU), a proxy for vaccine efficacy, during the delta (June 18-July 18, N= 9,387 surveys) and omicron (December 4-14, N= 2,389 surveys) wave periods. We assume no waning immunity, CLI prevalence approximates incident infection with each variant, and vaccinated and unvaccinated survey respondents in the two variant wave periods are exchangeable. The vaccine appears to have consistently lower VECLIP against omicron, compared to delta, regardless of the CLI definition used. Stringent CLI (i.e. anosmia plus fever, cough and/or myalgias) yielded a delta VECLIP = 0.85 [0.54, 0.95] higher than omicron VECLIP = 0.62 [0.46, 0.72]. Classic CLI (cough plus anosmia, fever, and/or myalgias) gave lower estimates (delta VECLIP = 0.76 [0.54, 0.87], omicron VECLIP = 0.51 [0.42, 0.59]), but omicron was still lower than delta. We acknowledge the potential for measurement, confounding, and selection bias, as well as limitations for generalizability for these self-reported, syndromic surveillance-based VECLIP measures. Thus VECLIP as estimates of true, population-level vaccine efficacy should therefore be taken with caution. Nevertheless, these preliminary findings demonstrating declining VECLIP raise concern for a true decline in vaccine efficacy versus waning immunity as a potential contributor to the omicron variant taking hold in Gauteng and elsewhere.

A REVIEW OF METHODS FOR HYDRO-ACOUSTIC ANALYSIS OF NON-CAVITATING MARINE PROPELLERS

Underwater Radiated Noise (URN) emanating from surface and underwater marine platforms has become a significant concern for all the Nations in view of the global requirement to minimise the increasing adverse impact on marine mammals and fishes and maintain ecological balance in the ‘Silent’ ocean environment. Ambient noise level in the sea, in 10 to 300 Hz frequency band, has increased by 20 to 30 dB due to shipping (Wittekind, 2009). Marine propeller (in non- cavitating and cavitating regime) is a potential contributor to the ships noise and a lot of scientific research has been undertaken and considerable progress has been achieved in estimating the hydro-acoustic performance of marine propellers. In light of this, the scope of this paper is to review and critically examine the various methods used for estimating the hydro-acoustic performance of marine propellers, particularly in the non-cavitating regime, over the past many years. This review paper brings out the details, applicability, merits and demerits of various methods, extrapolation laws to obtain full scale results, scientific conclusion of all the know-how on this subject and the scope of further research as perceived by the authors. This paper also presents a numerical methodology to estimate the noise radiated by a DTMB 4119 model propeller in the non-cavitating regime in open water condition. The hydrodynamic analysis of the propeller was performed using commercial CFD software STARCCM+, closure was achieved using standard k-ε turbulence model and hydro-acoustic predictions have been performed using FWH acoustic analogy. The results compare very well with the published literature.

The Relationship Between Psychological Stress and Anxiety with Gastrointestinal Symptoms Before and During a 56 km Ultramarathon Running Race

Background This study assessed relationships and sex differences between psychological state (recovery, stress, anxiety, and self-confidence) and gastrointestinal symptoms (GIS) prior to and during a 56 km ultramarathon running race and identified predictive factors of race GIS. Forty-four (26 males, 18 females) ultramarathon competitors completed anxiety, recovery, stress and GIS questionnaires for three days prior to the race and immediately pre-race. Race GIS were assessed immediately post-race. Spearman’s rank order, Mann–Whitney U tests and regression analyses were used to determine correlations and identify sex differences between psychological state and GIS and determine predictors of race GIS. Results Race GIS were significantly correlated with recovery (rs = − 0.381, p = 0.011), stress (rs = 0.500, p = 0.001) and anxiety (rs = 0.408, p = 0.006), calculated as the mean of the three days preceding the race and on race morning. The correlation between anxiety and GIS was strongest in the 24 h immediately prior to the race (all rs > 0.400, and all p < 0.05), but unclear patterns were identified for stress and recovery. Regression analyses showed 36% and 40% of variation in the severity and number of race GIS was accounted for by body mass and measures of stress, anxiety, and GIS over the three days preceding the race and on race morning (both p < 0.001). There were no sex differences in the number and severity of GIS leading up to or during the race (all p > 0.05), however, females reported greater state anxiety (p = 0.018) and lower self-confidence than males (p = 0.006) over the three days preceding the race and on race morning. Conclusion Endurance athletes that experience GIS during competition should investigate elevated stress and/or anxiety as a potential contributor and identify if management strategies can reduce the occurrence and severity of GIS.

Abstract 11269: Recombinant Soluble Thrombomodulin in Prolonged Porcine Cardiac Arrest

Introduction: Sudden Cardiac Arrest (CA) affects more than 400,000 people per year in the United States. Although a third of these patients survive to hospital admission, another 60-70% go on to die due to failed recovery of vital organ function. Microvascular thrombosis has been suggested as a potential contributor to prolonged organ dysfunction, but no antithrombotic therapies have been shown to be beneficial and coagulofibrinolytic abnormalities in prolonged CA remain poorly understood. Objectives: To establish key biomarkers of porcine coagulation and fibrinolysis in the setting of prolonged CA and cardiopulmonary resuscitation (CPR) and test the ability of ART-123 (recombinant human thrombomodulin alpha) to reverse these abnormalities. Methods: 15 pigs (n=5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR. Animals were randomized to receive saline or ART-123 (~1mg/kg) pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Results: Robust and ongoing activation of coagulation and fibrinolysis were detected throughout the resuscitation. After 50 minutes of CPR, plasma tests suggested consumptive coagulopathy, while whole blood testing (thromboelastography) indicated a persistent hypercoagulable state. ART-123 had a clear anticoagulant effect irrespective of timing (TAT complexes 381±25 vs. 238±18 vs. 226±12, p<0.01, and d-dimer 4.86±0.54 vs. 2.39±0.2 vs. 2.46±0.21 for vehicle, pre-arrest, post-arrest, p = 0.05). A pro-fibrinolytic effect was also observed, but only when the drug was given before no-flow, with a significant increase in levels of free endogenous tPA (1.2±0.12 vs. 3.29±0.29 vs. 1.72±0.3, p < 0.001) and corresponding suppression of free PAI-1 (0.59±0.15 vs. 0.14±0.01 vs. 0.41±0.09, p < 0.001). Conclusion: Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration.

Temporary Nature-based Carbon Removal Can Lower Peak Warming in a Well-below 2°C Scenario

There is growing recognition that meeting the climate objectives of the Paris Agreement will require the world to achieve net-zero carbon dioxide emissions around or before mid-century1–4. Natural climate solutions (NCS), which aim to preserve and enhance carbon storage in terrestrial or aquatic ecosystems5,6, are increasingly being evoked as a potential contributor to net-zero emissions targets7,8. However, there is a risk that any carbon that we succeed in storing in land-based systems could be subsequently lost back to the atmosphere as a result of either climate-related or human-caused disturbances such as wildfire or deforestation9–12. Here, we show that temporary NCS-based carbon sequestration has the potential to decrease the peak temperature increase, but only if implemented alongside an ambitious mitigation scenario where fossil fuel CO2 emissions were decreased to net-zero during the time that NCS-sequestered carbon remained stored. We also demonstrate the importance of non-CO2 climate effects of NCS implementation, which have the potential to counter a substantial portion of the climate effect of carbon sequestration. Our results suggest that there is some climate benefit associated with temporary NCS, but only if implemented as a complement (and not an alternative) to ambitious fossil fuel CO2 emissions reductions.

CXCL13 Neutralization Attenuates Neuropsychiatric Manifestations in Lupus-Prone Mice

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target.

Overcoming the Prokaryote/Eukaryote Barrier in Tuberculosis Treatment: A Prospect for the Repurposing and Use of Antiparasitic Drugs

Antimicrobial resistance, the so-called silent pandemic, is pushing industry and academia to find novel antimicrobial agents with new mechanisms of action in order to be active against susceptible and drug-resistant microorganisms. In the case of tuberculosis, the need of novel anti-tuberculosis drugs is specially challenging because of the intricate biology of its causative agent, Mycobacterium tuberculosis. The repurposing of medicines has arisen in recent years as a fast, low-cost, and efficient strategy to identify novel biomedical applications for already approved drugs. This review is focused on anti-parasitic drugs that have additionally demonstrated certain levels of anti-tuberculosis activity; along with this, natural products with a dual activity against parasites and against M. tuberculosis are discussed. A few clinical trials have tested antiparasitic drugs in tuberculosis patients, and have revealed effective dose and toxicity issues, which is consistent with the natural differences between tuberculosis and parasitic infections. However, through medicinal chemistry approaches, derivatives of drugs with anti-parasitic activity have become successful drugs for use in tuberculosis therapy. In summary, even when the repurposing of anti-parasitic drugs for tuberculosis treatment does not seem to be an easy job, it deserves attention as a potential contributor to fuel the anti-tuberculosis drug pipeline.

Spatiotemporal Expression and Functional Analysis of miRNA-22 in the Developing Secondary Palate

Objective Normal development of the embryonic orofacial region requires precise spatiotemporal coordination between numerous genes. MicroRNAs represent small, single-stranded, non-coding molecules that regulate gene expression. This study examines the role of microRNA-22 (miR-22) in murine orofacial ontogeny. Methods Spatiotemporal and differential expression of miR-22 (mmu-miR-22-3p) within the developing secondary palate was determined by in situ hybridization and quantitative real-time PCR, respectively. Bioinformatic approaches were used to predict potential mRNA targets of miR-22 and analyze their association with cellular functions indispensable for normal orofacial ontogeny. An in vitro palate organ culture system was used to assess the role of miR-22 in secondary palate development. Results There was a progressive increase in miR-22 expression from GD12.5 to GD14.5 in palatal processes. On GD12.5 and GD13.5, miR-22 was expressed in the future oral, nasal, and medial edge epithelia. On GD14.5, miR-22 expression was observed in the residual midline epithelial seam (MES), the nasal epithelium and the mesenchyme, but not in the oral epithelium. Inhibition of miR-22 activity in palate organ cultures resulted in failure of MES removal. Bioinformatic analyses revealed potential mRNA targets of miR-22 that may play significant roles in regulating apoptosis, migration, and/or convergence/extrusion, developmental processes that modulate MES removal during palatogenesis. Conclusions Results from the current study suggest a key role for miR-22 in the removal of the MES during palatogenesis and that miR-22 may represent a potential contributor to the etiology of cleft palate.