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176 lines
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<title>09 July, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Carbohydrate-Binding Protein from Stinging Nettle as Fusion Inhibitor for SARS-CoV-2 Variants of Concern</strong> -
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<div>
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Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks entry of pseudotyped SARS-CoV-2 in A549.ACE2+-TMPRSS2 cells, with IC50 values ranging from 0.32 to 1.22 microM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC50 = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC50 ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2+ cells (IC50 values are 1.6 and 0.9 microM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent and broad-spectrum fusion inhibitor for SARS-CoV-2.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.08.499297v1" target="_blank">Carbohydrate-Binding Protein from Stinging Nettle as Fusion Inhibitor for SARS-CoV-2 Variants of Concern</a>
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</div></li>
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<li><strong>Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations</strong> -
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<div>
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Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies that enables reconstructing the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (BASTA and MASCOT). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for CTMC. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for CTMC, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.07.498932v1" target="_blank">Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations</a>
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</div></li>
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<li><strong>Correlation of Alpha-1 Antitrypsin Levels and Exosome Associated Neutrophil Elastase Endothelial Injury in Subjects with SARS-CoV2 Infection</strong> -
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<div>
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Background: Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation. Objectives: Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin. Method: 31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control. Results: We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, was positively correlated with the endothelial damage in those patients. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro. Conclusions: Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.07.499204v1" target="_blank">Correlation of Alpha-1 Antitrypsin Levels and Exosome Associated Neutrophil Elastase Endothelial Injury in Subjects with SARS-CoV2 Infection</a>
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</div></li>
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<li><strong>Chronumental: time tree estimation from very large phylogenies</strong> -
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<div>
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Phylogenetic trees are an important tool for interpreting sequenced genomes, and their interrelationships. Estimating the date associated with each node of such a phylogeny creates a “time tree”, which can be especially useful for visualising and analysing evolution of organisms such as viruses. Several tools have been developed for time-tree estimation, but the sequencing explosion in response to the SARS-CoV-2 pandemic has created phylogenies so large as to prevent the application of these previous approaches to full datasets. Here we introduce Chronumental, a tool that can rapidly infer time trees from phylogenies featuring large numbers of nodes. Chronumental uses stochastic gradient descent to identify lengths of time for tree branches which maximise the evidence lower bound under a probabilistic model, implemented in a framework which can be compiled into XLA for rapid computation. We show that Chronumental scales to phylogenies featuring millions of nodes, with chronological predictions made in minutes, and is able to accurately predict the dates of nodes for which it is not provided with metadata.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.27.465994v2" target="_blank">Chronumental: time tree estimation from very large phylogenies</a>
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</div></li>
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<li><strong>Building Emotion Awareness and Mental Health (BEAM): Study protocol for a randomized controlled trial of the BEAM App-based program for mothers of children 18-36 months.</strong> -
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<div>
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Background: The prevalence of maternal depression and anxiety has increased during the COVID-19 pandemic and pregnant individuals are experiencing concerningly elevated levels of mental health symptoms worldwide. Many individuals may now be at heightened risk of postpartum mental health disorders. Recent evidence suggests that the cognitive development of children born during the pandemic has been impacted. There are significant concerns that a cohort of children may be at-risk for impaired self-regulation and mental illness due to elevated exposure to perinatal maternal mental illness. The intergenerational effects of maternal mental illness are most pronounced when depression persists. With both an increased prevalence of depression and limited availability of services due to the pandemic, there is an urgent need for accessible eHealth interventions for mothers of young children. The aims of this trial are to evaluate the efficacy of the Building Emotion Awareness and Mental Health (BEAM) app-based program for reducing maternal depression symptoms (primary outcome) as well as for improving anxiety symptoms, family relationships, parenting, mother and child functioning (secondary outcomes) compared to treatment as usual (TAU). Methods: A two-arm randomized controlled trial (RCT) with repeated measures will be used to evalute the efficacy of the BEAM intervention compared to TAU among a sample of 140 mothers with children aged 18 to 36 months, who self-report moderate-to-severe symptoms of depression and/or anxiety. Individuals will be recruited online and those randomized to the treatment group will participate in 10 weeks of modules on mental health and parenting, an online social support forum, and weekly group teletherapy sessions. Assessment of depression (primary outcome), family relationship quality, anxiety, parenting, and mother and child functioning will occur at 18-36 months postpartum (pre-test, T1), immediately after the last week of the BEAM intervention (post-test, T2), and at 3 months after the intervention (follow-up, T3). Primary outcomes will also be assessed weekly throughout the 10 week intervention. Discussion: eHealth interventions have the potential to address elevated maternal mental health symptoms, parenting stress, and child funtioning concerns during and after the COVID-19 pandemic and provide accessible programming to mothers who are in need of support. This RCT will build on an open pilot trial of the BEAM program and provide further evaluation of this evidence-based intervention for mothers experiencing depression. Findings will increase understanding of depression and parenting stress in mothers with young children and reveal the potential for long-term improvements in maternal and child health and family well-being.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hfdmq/" target="_blank">Building Emotion Awareness and Mental Health (BEAM): Study protocol for a randomized controlled trial of the BEAM App-based program for mothers of children 18-36 months.</a>
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</div></li>
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<li><strong>Short-Term Effects of Short-Term Work: Dynamics in Fatigue across Two National Lockdowns</strong> -
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<div>
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Objective: Anecdotal evidence suggests work fatigue has increased during the COVID-19 pandemic, and work interventions to offset stresses have been effective. Our study sought to test these propositions, documenting and describing the complexity of worker well-being around two lockdown periods. Methods: Using 17 waves of data from a longitudinal study in Germany (December 2019 to June 2021, n = 1,053 employees), we model discontinuous changes in work fatigue and how participation in a government-sponsored short-term work program (Kurzarbeit) affected change trajectories. Results: The COVID-19 pandemic has not invariably resulted in work fatigue, and individuals with Kurzarbeit at the first lockdown (but not the second) showed significantly larger decreases in each form of fatigue at this transition. Conclusions: Future policy interventions will require more contextual nuance to effectively support worker well-being during public health crises.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/bqxg7/" target="_blank">Short-Term Effects of Short-Term Work: Dynamics in Fatigue across Two National Lockdowns</a>
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</div></li>
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<li><strong>Coping During Covid 19 Facilitator Manual</strong> -
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<div>
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This manual has been created to assist mental health professionals in delivering and facilitating the two hour evidence-based online CBT program “Coping during COVID-19”. It overviews the eight module course, designed to support those who are struggling with symptoms of anxiety and depression due theCOVID-19 crisis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/65spv/" target="_blank">Coping During Covid 19 Facilitator Manual</a>
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</div></li>
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<li><strong>Attitudes towards science during the COVID-19 pandemic: A psychological network approach</strong> -
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<div>
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A better understanding of the public attitude towards science could be crucial to tackle the spread of mis- and disinformation related to the COVID-19 pandemic and beyond. We here contribute to this understanding by conceptualizing and analyzing the attitude toward science as a psychological network. For this analysis, we utilized data from a German probability sample (N = 1,009), the “Science Barometer”, collected during the first wave of the COVID-19 pandemic. Overall, our network analysis revealed that especially the perceived value of science for curbing the pandemic is central to the attitude towards science. Beliefs about this value are related to trust in science and trust in scientific information and to positive and negative evaluations of scientific controversy and complexity. Further, valuing common sense over science was related to seeking less scientific information on official websites, suggesting that this belief, in particular, may drive mis- and disinformation and could be a promising target for interventions. Finally, we found no evidence that seeking scientific information on social media had detrimental consequences for the attitude towards science. Implications for health communication and science communication, limitations, and future directions are discussed.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/zrwy9/" target="_blank">Attitudes towards science during the COVID-19 pandemic: A psychological network approach</a>
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</div></li>
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<li><strong>Machine learning-based predictive modeling of resilience to stressors in pregnant women during COVID-19: a prospective cohort study</strong> -
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<div>
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During the COVID-19 pandemic, pregnant women have been at high risk for psychological distress. Lifestyle factors may be modifiable elements to help reduce and promote resilience to prenatal stress. We used Machine-Learning (ML) algorithms applied to questionnaire data obtained from an international cohort of 804 pregnant women to determine whether physical activity and diet were resilience factors against prenatal stress, and whether stress levels were in turn predictive of sleep classes. A support vector machine accurately classified perceived stress levels in pregnant women based on physical activity behaviours and dietary behaviours. In turn, we classified hours of sleep based on perceived stress levels. This research adds to a developing consensus concerning physical activity and diet, and the association with prenatal stress and sleep in pregnant women. Predictive modeling using ML approaches may be used as a screening tool and to promote positive health behaviours for pregnant women.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/9n8uv/" target="_blank">Machine learning-based predictive modeling of resilience to stressors in pregnant women during COVID-19: a prospective cohort study</a>
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</div></li>
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<li><strong>Homeostatic regulation of energetic arousal during acute social isolation-converging evidence from the lab and the field</strong> -
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<div>
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It has been theorised that social contact is a basic need governed by a dedicated ‘social homeostatic’ system. In contrast to other homeostatic systems, such as food intake regulation, little is known about human psychology and physiology under conditions of altered social homeostasis. Here, we investigated the effects of eight hours of social isolation and compared this to eight hours of food deprivation in a tightly controlled laboratory experiment. Social isolation led to lowered self-reported energetic arousal and heightened fatigue, comparable to food deprivation. To test whether these findings extend from the lab to a real-life setting, we used ecological momentary assessment in a field study performed during COVID-19 lockdown. The drop in energetic arousal after social isolation observed in the lab replicated in the field study, suggesting that lowered energy could be part of a homeostatic response to the extended lack of social contact. These findings provide laboratory and real-life insights into the mechanisms underlying the detrimental effects of longer-term social isolation.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/3z74g/" target="_blank">Homeostatic regulation of energetic arousal during acute social isolation-converging evidence from the lab and the field</a>
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</div></li>
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<li><strong>Digitalization impacts the COVID-19 pandemic and the stringency of government measures</strong> -
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COVID-19 poses a significant burden to populations worldwide. Although the pandemic has accelerated digital transformation, little is known about the influence of digitalization on pandemic developments. Therefore, this country-level study aims to explore the impact of digital adoption on COVID-19 outcomes and government measures. Using the Digital Adoption Index (DAI), we examined the association between countries9 digital preparedness levels and COVID-19 cases, deaths, and stringency indices (SI) of government measures during the early phase of the pandemic. Gradient Tree Boosting pinpointed essential features related to COVID-19 trends, such as digital adoption, populations9 smoker fraction, age, and poverty. Subsequently, regression analyses indicated that higher DAI was associated with significant declines in new cases ( β =-362.25/pm; p<0.001) and attributed deaths ( β =-5.53/pm; p<0.001) months after the peak. When plotting DAI against the SI normalized for the starting day, countries with higher DAI adopted slightly more stringent government measures ( β =4.86; p<0.01). Finally, a scoping review identified 70 publications providing valuable arguments for our findings. Digital adoption shows a positive trend in handling the current pandemic and facilitates the implementation of more decisive governmental measures. Improving the distribution of digital adoption may have the potential to attenuate the impact of COVID-19 cases and deaths.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276377v2" target="_blank">Digitalization impacts the COVID-19 pandemic and the stringency of government measures</a>
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</div></li>
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<li><strong>Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background and Aims: The incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients. Methods: We identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients. Results: We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. Conclusions: In this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.02.25.22271490v2" target="_blank">Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study</a>
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<li><strong>Genomic Surveillance Identifies SARS-CoV-2 Transmission Patterns in Local University Populations, Wisconsin, USA, 2020-2022</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge as the current coronavirus disease 2019 (COVID-19) pandemic extends into its third year. Understanding SARS-CoV-2 circulation in university populations is vital for effective interventions in a higher education setting that will inform pubic health policy during pandemics. In this study, we performed whole-genome sequencing of 537 of 1,717 SARS-CoV-2 positive nasopharyngeal/nasal swab samples collected for nearly 20 months from the two university populations in Wisconsin, United States. We observed that the viral sequences were distributed into 57 lineages/sub-lineages belonging to 15 clades of which the majority were from 21K (Omicron, 36.13%) and 21J (Delta, 30.91%). Nearly 40% (213) of the sequences were Omicron of which BA.1 and its eight descendent lineages account for 91%, while the remaining belong to BA.2 and its six descendent lineages. The independent analysis of these two universities sequences revealed significant differences in circulating the SARS-CoV-2 variants. The genome-based analysis of closely-related strains along with phylogenetic clusters had identified that potential virus transmission occurred within as well as between universities, and between the university and local community. Although this study improves our understanding of distinct transmission patterns of circulating variants in local universities, expanding the genomic surveillance capacity will aid local jurisdictions in identifying emerging SARS-CoV-2 variants like BA.4 and BA.5, and improve data-driven public health mitigation and policy efforts.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277014v1" target="_blank">Genomic Surveillance Identifies SARS-CoV-2 Transmission Patterns in Local University Populations, Wisconsin, USA, 2020-2022</a>
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</div></li>
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<li><strong>Behavioural Insights and the evolving COVID-19 pandemic</strong> -
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<div>
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Behavioural sciences have complemented medical and epidemiological sciences in the response to the SARS-CoV-2 pandemic. As vaccination uptake increases across the EU/EEA – including booster vaccinations - behavioural science research will remain important for both pandemic policy and communication. From a behavioural science perspective, the following four areas are key as the pandemic progresses: 1) Attaining and maintaining high levels of vaccination including booster doses in all groups in society, including in socially vulnerable populations, 2) Informing sustainable pandemic policies and ensuring continued adherence to basic prevention measures, 3) Minimising risk of COVID-19 during travels and holidays, and 4) Facilitating population preparedness and willingness to support and adhere to the reimposition of restrictions locally or regionally whenever outbreaks may occur. Based on mixed-methods research, expert consultations and engagement with communities, behavioural scientists advising on pandemic policies and communication thus have important contributions to make to prevent and effectively respond to local or regional outbreaks, and to minimize socio-economic and health disparities. In this Perspective we briefly outline these topics from a European perspective, while recognizing the importance of considering the specific context in individual countries.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/kun3j/" target="_blank">Behavioural Insights and the evolving COVID-19 pandemic</a>
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<li><strong>Curiosity as a Function of Confidence and Importance in Knowing Information</strong> -
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Curiosity appears to be the driving force for humans to find new information, but despite its general relevance, only few studies investigated the underlying mechanisms of curiosity. Kang et al. (2009) reported that curiosity follows an inverted U-shaped function of confidence, with highest curiosity on moderate confidence levels of knowing information. In addition, they found that the willingness to spend resources to reveal information increased with increasing curiosity. Given that replications of findings on curiosity are rare, this study sought to replicate these previous findings in two experiments, with the same stimulus material (Experiment 1) and new stimulus material using COVID-19-related information (Experiment 2). In addition, we extended previous findings by assessing the effect of the importance of information for the participant on the relationship between curiosity and confidence. Our findings replicated previous results in both experiments with (a) highest curiosity regarding information about which participants were moderately confident in knowing and (b) the level of curiosity affecting the decision to spend more time to reveal the answer. We also found that importance ratings positively scaled the level of curiosity. However, importance also interacted with confidence, showing that low-to-moderate confidence ratings, combined with high importance ratings, led to highest curiosity in both experiments – associated with an increased willingness to close this information-gap. Together, these results emphasize the modulatory effect of perceived importance on the interplay between curiosity and confidence in knowing information.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/dzanq/" target="_blank">Curiosity as a Function of Confidence and Importance in Knowing Information</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immuno-bridging Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 Protein Subunit Recombinant Vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; Faculty of Medicine Universitas Diponegoro; Faculty of Medicine Universitas Andalas; Faculty of Medicine Universitas Hassanudin<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Abbott Panbio rapid antigen self-tests; Other: COVIDSmart CARE! app<br/><b>Sponsors</b>: McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Cape Town Lung Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: Sinovac Biotech (Colombia) S.A.S.; Sinovac Life Sciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Full Intervention; Other: Enhanced Usual Care<br/><b>Sponsors</b>: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Topical Antibacterial Agents for Prevention of COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV2 Infection<br/><b>Interventions</b>: Drug: Neosporin; Other: Vaseline<br/><b>Sponsors</b>: Yale University; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Rehabilitation<br/><b>Intervention</b>: Other: resistance respiratory training with the use of respiratory muscle trainer<br/><b>Sponsor</b>: Medical University of Bialystok<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: ABO1009-DP<br/><b>Sponsor</b>: Suzhou Abogen Biosciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ABO1009-DP; Biological: ABO-CoV.617.2; Other: Placebo<br/><b>Sponsor</b>: Suzhou Abogen Biosciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Dysglycemia<br/><b>Interventions</b>: Drug: Insulin; Drug: Subcutaneous Insulin<br/><b>Sponsor</b>: Benha University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later</strong> - CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Modelling the response to vaccine in non-human primates to define SARS-CoV-2 mechanistic correlates of protection</strong> - The definition of correlates of protection is critical for the development of next generation SARS-CoV-2 vaccine platforms. Here, we propose a model-based approach for identifying mechanistic correlates of protection based on mathematical modelling of viral dynamics and data mining of immunological markers. The application to three different studies in non-human primates evaluating SARS-CoV-2 vaccines based on CD40-targeting, two-component spike nanoparticle and mRNA 1273 identifies and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides</strong> - Suppressors of Cytokine Signaling (SOCS) are intracellular proteins that negatively regulate the induction of cytokines. Amongst these, SOCS1 and SOCS3 are particularly involved in inhibition of various interferons. Several viruses have hijacked this regulatory pathway: by inducing SOCS1and 3 early in infection, they suppress the host immune response. Within the cell, SOCS1/3 binds and inhibits tyrosine kinases, such as JAK2 and TYK2. We have developed a cell penetrating peptide from the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology</strong> - CONCLUSION: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines</strong> - COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Reproducible Are QM/MM Simulations? Lessons from Computational Studies of the Covalent Inhibition of the SARS-CoV-2 Main Protease by Carmofur</strong> - This work explores the level of transparency in reporting the details of computational protocols that is required for practical reproducibility of quantum mechanics/molecular mechanics (QM/MM) simulations. Using the reaction of an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as a test case of chemical reactions in biomolecules, we carried out QM/MM calculations to determine the structures and energies of the reactants, the product, and the transition…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp</strong> - CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Specificity and Confirmation of SARS-CoV-2 Serological Test Methods in Emergency Department Populations across the United States</strong> - CONCLUSIONS: The specificity of the serological assays evaluated in a large, diverse emergency department population was >99% and did not vary by geographical site. A confirmatory algorithm with an automated pseudo-neutralization assay allowed testing on the same specimen while reducing the false positivity rate and increasing the value of serology screening methods.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases</strong> - INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals</strong> - Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections</strong> - Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Title: Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry</strong> - Saliva contributes to the innate immune system, which suggests that it can prevent SARS-CoV-2 entry. We studied the ability of healthy salivary proteins to bind to angiotensin-converting enzyme 2 (ACE2) using biolayer interferometry and pull-down assays. Their effects on binding between the receptor-binding domain of the SARS-CoV-2 spike protein S1 (S1) and ACE2 were determined using an enzyme-linked immunosorbent assay. Saliva bound to ACE2 and disrupted the binding of S1 to ACE2 and four…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Current status and prospects of IL-6-targeting therapy</strong> - INTRODUCTION: Persistent and excess IL-6 production often contributes to a variety of immune diseases. IL-6-targeting therapy was first approved for Castleman disease, then rheumatoid arthritis, and now it is broadly used. Furthermore, it has been approved not only for chronic and acute inflammatory diseases but also for autoantibody-induced diseases such as neuromyelitis optica spectrum disorder and interstitial lung disease due to systemic sclerosis.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro evaluation of antiviral activity of Sisybrium irio (Khaksi) against SARS-COV-2</strong> - SARS-CoV-2 pandemic, drawn attention to the need of virus culture. In vitro SARS-COV-2 culture was performed to carry out therapeutic, environmental and virus genome studies. Isolation of virus from nasopharyngeal swab was performed by inoculating virus positive samples in available cell lines. SARS-CoV-2 topography was observed by using Scanning Electron Microscopy (SEM). Virus specificity was defined by serological confirmation through neutralization assay with COVID 19 convalescent sera. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An outlook on potential protein targets of COVID-19 as a druggable site</strong> - CONCLUSION: Using cryo-electron microscopy or X-ray diffraction, hundreds of crystallographic data of SARS-CoV-2 proteins have been published including structural and non-structural proteins. These proteins have a significant role at different aspects in the viral machinery and presented themselves as potential target for drug designing and therapeutic interventions. Also, there are few host cell proteins which helps in SARS-CoV-2 entry and proteolytic cleavage required for viral infection.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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