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176 lines
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<title>22 November, 2023</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>Serodynamics: a review of methods for epidemiological inference using serological data</strong> -
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<div>
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The availability and diversity of serological data measuring antibody responses to infectious pathogens, accelerated in response to the SARS-CoV-2 pandemic, has enabled key insights into infectious disease dynamics and population health. Here, we present a review of analytical approaches and considerations for inference using serological data, highlighting the range of epidemiological and biological insights that are possible using appropriate mathematical and statistical models. This in-depth review focuses on methods to understand transmission dynamics and infer past exposures from serological data, referred to as serodynamics, though we note that such analyses often address complementary immunological questions. We first discuss key considerations for data processing and interpretation of raw serological data which are prerequisite for fitting serodynamical models. We then review a range of approaches for estimating epidemiological trends, ranging from classical serocatalytic models applied to binary serostatus data, to contemporary methods using full quantitative antibody measurements and immunological understanding to estimate if and when individuals have been previously infected. Here, we collate and synthesize these approaches within the context of a unifying framework for the overall data-generation process, consisting of key concepts including antibody kinetics, quantitative models to represent within-host and epidemic processes, and considerations for linking observed serological data to models. We close with a discussion of the types of methodological developments needed to meet the increasingly complex serological data becoming available that provide new avenues for scientific discovery and public health insights.
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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/kqdsn/" target="_blank">Serodynamics: a review of methods for epidemiological inference using serological data</a>
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</div></li>
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<li><strong>Rapid increase in depression within the first month of the Shanghai Covid lockdown in 2022</strong> -
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<div>
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In the global efforts to combat Covid-19, researchers have increasingly recognized the profound impacts of society lockdown on population mental health. However, the fine temporal evolution of negative psychological consequences induced by lockdowns remains poorly understood. Here we report a rapid and systematic increase in depression due to the Shanghai Covid lockdown in March 2022. Measured by Beck Depression Inventory-2, 10% of the participants experienced at least mild depression before the official citywide lockdown started, and two and four weeks later this number increased to 21% and 36 %, respectively. Regression analyses show that lockdown duration and physical restriction jointly contribute to worsening depression. Furthermore, the time of sleep and social communication during the lockdown are associated with the severity of depression symptoms. These results highlight the fast development of depression during lockdowns and call for special attention to early psychological interventions once a lockdown is initiated.
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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/preprints/psyarxiv/mwge8/" target="_blank">Rapid increase in depression within the first month of the Shanghai Covid lockdown in 2022</a>
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</div></li>
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<li><strong>Accurate Characterization of Conformational Ensembles and Binding Mechanisms of the SARS-CoV-2 Omicron BA.2 and BA.2.86 Spike Protein with the Host Receptor and Distinct Classes of Antibodies Using AlphaFold2-Augmented Integrative Computational Modeling</strong> -
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<div>
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The latest wave SARS-CoV-2 Omicron variants displayed a growth advantage and the increased viral fitness through convergent evolution of functional hotspots that work synchronously to balance fitness requirements for productive receptor binding and efficient immune evasion. In this study, we combined AlphaFold2-based structural modeling approaches with all-atom MD simulations and mutational profiling of binding energetics and stability for prediction and comprehensive analysis of the structure, dynamics, and binding of the SARS-CoV-2 Omicron BA.2.86 spike variant with ACE2 host receptor and distinct classes of antibodies. We adapted several AlphaFold2 approaches to predict both structure and conformational ensembles of the Omicron BA.2.86 spike protein in the complex with the host receptor. The results showed that AlphaFold2-predicted conformational ensemble of the BA.2.86 spike protein complex can accurately capture the main dynamics signatures obtained from microscond molecular dynamics simulations. The ensemble-based dynamic mutational scanning of the receptor binding domain residues in the BA.2 and BA.2.86 spike complexes with ACE2 dissected the role of the BA.2 and BA.2.86 backgrounds in modulating binding free energy changes revealing a group of conserved hydrophobic hotspots and critical variant-specific contributions of the BA.2.86 mutational sites R403K, F486P and R493Q. To examine immune evasion properties of BA.2.86 in atomistic detail, we performed large scale structure-based mutational profiling of the S protein binding interfaces with distinct classes of antibodies that displayed significantly reduced neutralization against BA.2.86 variant. The results quantified specific function of the BA.2.86 mutations to ensure broad resistance against different classes of RBD antibodies. This study revealed the molecular basis of compensatory functional effects of the binding hotspots, showing that BA.2.86 lineage may have primarily evolved to improve immune escape while modulating binding affinity with ACE2 through cooperative effect of R403K, F486P and R493Q mutations. The study supports a hypothesis that the impact of the increased ACE2 binding affinity on viral fitness is more universal and is mediated through cross-talk between convergent mutational hotspots, while the effect of immune evasion could be more variant-dependent.
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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/10.1101/2023.11.18.567697v1" target="_blank">Accurate Characterization of Conformational Ensembles and Binding Mechanisms of the SARS-CoV-2 Omicron BA.2 and BA.2.86 Spike Protein with the Host Receptor and Distinct Classes of Antibodies Using AlphaFold2-Augmented Integrative Computational Modeling</a>
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</div></li>
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<li><strong>Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung</strong> -
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<div>
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Global microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis. Herein we described the effects of azide-free, 1 um polystyrene MP beads co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum using a mouse model of mild COVID-19. Lung virus titres and viral RNA levels were not significantly affected by MPs, with overt clinical or histopathological changes also not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 days post infection (dpi) and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the cytokine release syndrome signature seen in some severe COVID-19 patients. This study adds to a growing body of literature suggesting that MPs can dysregulate inflammation in specific disease settings.
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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/10.1101/2023.11.19.567745v1" target="_blank">Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung</a>
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</div></li>
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<li><strong>Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86 lineages combining increased fitness and antibody evasion</strong> -
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<div>
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The unceasing SARS-CoV-2 circulation in an immune population led to the continuous emergence of new viral sublineages. Here, we isolated and characterized XBF, XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3 and BA.2.86.1 variants, that represented >80% of circulating strains as of November 2023. These XBB subvariants carry few recurrent mutations in the spike, whereas BA.2.86.1 harbors >30 additional mutations. We compared their fitness in culture, sensitivity to antivirals and sera from vaccinees. These variants replicated in IGROV-1 and no longer in VeroE6 cells. They were not markedly fusogenic. BA.2.86.1 displayed the strongest binding to ACE2. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Nirmatrelvir, Remdesivir and Molnupiravir remained active, whereas Sotrovimab lost efficacy against BA.2.86.1. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were 7 to 21-fold lower compared to BA.1, without major differences between variants. A breakthrough XBB infection enhanced NAb responses, particularly against XBB variants. Thus, while distinct, the evolution trajectory of these variants combines increased fitness and antibody evasion.
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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/10.1101/2023.11.20.567873v1" target="_blank">Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86 lineages combining increased fitness and antibody evasion</a>
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</div></li>
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<li><strong>Comprehensive contact tracing during an outbreak of alpha-variant SARS-CoV-2 in a rural community reveals less viral genomic diversity and higher household secondary attack rates than expected</strong> -
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<div>
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Sequencing of SARS-CoV-2 genomes throughout the COVID-19 pandemic has generated a wealth of data on viral evolution across populations, but only a few studies have so far explored SARS-CoV-2 evolution across transmission networks of tens to hundreds of persons. Here, we couple data from SARS-CoV-2 sequencing with contact tracing data from an outbreak with a single origin in a rural Norwegian community where samples from all exposed persons were collected prospectively. A total of 134 nasopharyngeal samples were positive by PCR. Among the 121 retrievable genomes, 81 were identical to the genome of the introductor, thus demonstrating that genomics offers limited additional value to manual contact-tracing. In the cases where mutations were discovered, five small genetic clusters were identified. We observed a household secondary attack rate of 67%, with 92% of household members infected among households with secondary transmission, suggesting that SARS-CoV-2 introduction into large families are likely to affect all household members.
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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/10.1101/2023.11.17.567570v1" target="_blank">Comprehensive contact tracing during an outbreak of alpha-variant SARS-CoV-2 in a rural community reveals less viral genomic diversity and higher household secondary attack rates than expected</a>
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</div></li>
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<li><strong>Dysregulated Platelet Function in Patients with Post-Acute Sequelae of COVID-19</strong> -
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<div>
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Objective: Post-acute sequelae of COVID-19 (PASC, also referred as Long-COVID) sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, and especially to activate platelets acutely, less is known about the thrombosis risk in PASC. Approach and Results: PASC patients and age-matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under venous shear stress conditions. While only a mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed platelet activation through the glycoprotein VI (GPVI) receptor was markedly decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under venous shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed using age- and sex-matched platelets from healthy individuals. Conclusions: PASC patients demonstrate dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating plasma-derived molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to 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/10.1101/2023.06.18.545507v2" target="_blank">Dysregulated Platelet Function in Patients with Post-Acute Sequelae of COVID-19</a>
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</div></li>
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<li><strong>War fatalities in Russia in 2022 estimated via excess male mortality</strong> -
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<div>
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In this paper, we used excess deaths among young males to estimate the number of Russian fatalities in the Russo-Ukrainian war in 2022. We based our calculations on the official mortality statistics in 2022, split by age and gender. To separate excess deaths due to war from those due to Covid-19, we relied on the ratio of male to female deaths, and extrapolated the 2015–19 trend to get the baseline value for 2022. We found noticeable excess male mortality in all age groups between 15 and 49, with 20,600±1,000 excess male deaths overall. This estimate was obtained after excluding all HIV deaths that showed complex dynamics unrelated to the war. Depending on the modelling assumptions, the estimated number of deaths varied from about 15,700 to about 23,600, with 20,600 corresponding to our preferred model. Our estimate should be treated as a lower bound on the true number of deaths as the data do not include either the Russian military personnel missing in action and not officially declared dead, or the deaths registered in the Ukrainian territories annexed in 2022.
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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/preprints/socarxiv/xcrme/" target="_blank">War fatalities in Russia in 2022 estimated via excess male mortality</a>
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</div></li>
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<li><strong>Development of a fast feature extraction method for SARS-CoV-2 spike sequences using amino acid physicochemical properties</strong> -
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<div>
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COVID-19 continues to spread today, leading to an accumulation of SARS-CoV-2 virus mutations in databases, and large amounts of genomic datasets are currently available. However, due to these large datasets, utilizing this amount of sequence data without random sampling is challenging. Major difficulties for downstream analyses include the increase in the dimension size along with the conversion of sequences into numerical values when using conventional amino acid representation methods, such as one-hot encoding and k-mer-based approaches that directly reflect sequences. Moreover, these sequences are deficient in physicochemical characteristics, such as structural information and hydrophilicity; hence, they fail to accurately represent the inherent function of the given sequences. In this study, we utilized the physicochemical properties of amino acids to develop a rapid and efficient approach for extracting feature parameters that are suitable for downstream processes of machine learning, such as clustering. A fixed-length feature vector representation of a spike sequence with reduced dimensionality was obtained by converting amino acid residues into physicochemical parameters. Next, t-distributed stochastic neighbor embedding (t-SNE), a method for dimensionality reduction and visualization of high-dimensional data, was performed, followed by density-based spatial clustering of applications with noise (DBSCAN). The results show that by using the physicochemical properties of amino acids rather than conventional methods that directly represent sequences into numerical values, SARS-CoV-2 spike sequences can be clustered with sufficient accuracy and a shorter runtime. Interestingly, the clusters obtained by using amino acid properties include subclusters that are distinct from those produced utilizing the method for the direct representation of amino acid sequences. A more detailed analysis indicated that the contributing parameters of this novel cluster identified exclusively when utilizing the physicochemical properties of amino acids significantly differ from one another. This suggests that representing amino acid sequences by physicochemical properties might enable the identification of clusters with enhanced sensitivity compared to conventional methods.
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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/10.1101/2023.11.18.567675v1" target="_blank">Development of a fast feature extraction method for SARS-CoV-2 spike sequences using amino acid physicochemical properties</a>
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</div></li>
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<li><strong>Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15</strong> -
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<div>
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SARS-CoV-2 non-structural protein 15 (Nsp15) is critical for productive viral replication and evasion of host immunity. The uridine-specific endoribonuclease activity of Nsp15 mediates the cleavage of the polyuridine [poly(U)] tract of the negative-strand coronavirus genome to minimize the formation of dsRNA that activates the host antiviral interferon signaling. However, the molecular basis for the recognition and cleavage of the poly(U) tract by Nsp15 is incompletely understood. Here, we present cryogenic electron microscopy (cryoEM) structures of SARS-CoV-2 Nsp15 bound to viral replication intermediate dsRNA containing poly(U) tract at 2.7-3.3 [A] resolution. The structures reveal one copy of dsRNA binds to the sidewall of an Nsp15 homohexamer, spanning three subunits in two distinct binding states. The target uracil is dislodged from the base-pairing of the dsRNA by amino acid residues W332 and M330 of Nsp15, and the dislodged base is entrapped at the endonuclease active site center. Up to 20 A/U base pairs are anchored on the Nsp15 hexamer, which explains the basis for a substantially shortened poly(U) sequence in the negative strand coronavirus genome compared to the long poly(A) tail in its positive strand. Our results provide mechanistic insights into the unique immune evasion strategy employed by coronavirus Nsp15.
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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/10.1101/2023.11.17.567629v1" target="_blank">Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15</a>
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</div></li>
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<li><strong>Tropism of AAV.CPP.16 in the respiratory tract and its application for a CRISPR-based gene therapy against SARS-CoV-2</strong> -
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<div>
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Efficient gene delivery vectors are essential for developing gene therapies for respiratory diseases. Here, we report that AAV.CPP.16, a novel AAV9-derived adeno-associated virus vector, can efficiently transduce airway epithelium systems and lung parenchyma cells in both mice and non-human primates after intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism to respiratory tract tissues, and can target major cell types in the respiratory tract and the lung. We also report an all-in-one, CRISPR-Cas13d-based AAV gene therapy vector that targets the highly conserved RNA-dependent RNA polymerase (Rdrp) gene in SARS-CoV-2, and show the potential of such gene therapy against a broad range of circulating and emergent SARS-CoV-2 variants. Thus, AAV.CPP.16 could be a useful gene delivery vector for treating genetic respiratory diseases and airborne infections including for developing a potential prophilaxis to 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/10.1101/2023.11.17.567583v1" target="_blank">Tropism of AAV.CPP.16 in the respiratory tract and its application for a CRISPR-based gene therapy against SARS-CoV-2</a>
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</div></li>
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<li><strong>Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine</strong> -
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<div>
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As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN[γ]+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains.
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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/10.1101/2023.11.17.567633v1" target="_blank">Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine</a>
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</div></li>
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<li><strong>Lung inflammation is associated with lipid deposition</strong> -
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<div>
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Lung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.
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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/10.1101/2022.12.30.522299v2" target="_blank">Lung inflammation is associated with lipid deposition</a>
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</div></li>
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<li><strong>Wastewater surveillance pilot at US military installations: a cost model analysis</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for pathogen surveillance systems to augment both early warning and outbreak monitoring/control efforts. Wastewater samples provide a rapid and accurate source of environmental surveillance data to complement direct patient sampling. Due to its global presence and critical missions, the US military is a leader in global pandemic preparedness efforts. Clinical testing for COVID-19 on US Air Force (USAF) bases (AFBs) was effective, but costly with respect to direct costs and indirect costs of lost time. To remain operating at peak capacity such bases sought a more passive surveillance option and piloted wastewater surveillance (WWS) at 17 AFBs to demonstrate feasibility, safety, and utility from May 2021 to January 2022. Objective: Here we model the costs of a wastewater program for pathogens of pandemic potential within the specific context of US military installations using assumptions based on the results of the USAF and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) pilot program. The objective was to determine the cost of deploying WWS to all AFBs, relative to clinical swab testing surveillance regimes. Methods: A simple WWS cost projection model was built based on subject matter expert input and actual costs incurred during a WWS pilot program at USAF AFBs. Several SARS-CoV-2 circulation scenarios were considered and costs of both WWS and clinical swab testing were projected. Break even analysis was conducted to determine how reduction in swab testing could open up space to enable WWS to occur in complement. Results: Our model confirms that wastewater surveillance is complimentary and highly cost-effective when compared to existing alternative forms of biosurveillance. We find that the cost of WWS was between $10.5 - $18.5 million less expensive annually in direct costs as compared to clinical swab testing surveillance. When indirect cost of lost work is incorporated, including assumed lost work required to go obtain a clinical swab test, we estimate that over two thirds of clinical swab testing could be maintained with no additional costs upon implementation of WWS. Conclusions: Our results support adoption of wastewater surveillance across US military installations as part of a more comprehensive and early warning system that will enable adaptive monitoring during disease outbreaks.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.14.23298310v2" target="_blank">Wastewater surveillance pilot at US military installations: a cost model analysis</a>
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<li><strong>Protocol for VIVALDI Social Care: Pilot Study to reduce Infections, Outbreaks and Antimicrobial Resistance in Care Homes for Older Adults</strong> -
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Care home residents are vulnerable to severe outcomes from infections such as COVID-19 and influenza. However, measures to control outbreaks, such as care home closures to visitors and new admissions, have a detrimental impact on their quality of life. Many infections and outbreaks could be prevented but the first step is to measure them reliably. This is challenging in care homes due to the lack of data and research infrastructure. During the pandemic, the VIVALDI study measured COVID-19 infections in residents and staff by partnering with care providers and using routinely collected data. This study aims to establish sentinel surveillance and a research database to enable observational and future interventional studies in care homes. The project has been co-produced with care providers, staff, residents, relatives, and researchers. The study (October 2023 to March 2025) will explore the feasibility of establishing a network of 500-1500 care homes for older adults in England that is underpinned by a linked data platform. No data will be collected from staff. The cohort will be created by regularly extracting resident identifiers from Digital Social Care Records (DSCR), followed by pseudonymisation and linkage to routinely collected datasets. Following extensive consultation, we decided not to seek informed consent from residents for data collection, but they can opt out of the study. Our goal is to be inclusive, and it is challenging to give every resident the opportunity to opt in due to cognitive impairment and the requirement for consultees. The project, and all requests to use the data will be overseen by relatives, residents, staff, and care providers. The study has been provisionally approved by the Health Research Authority Confidentiality Advisory Group and the South-West Frenchay Research Ethics Committee. It is funded by the UK Health Security Agency.
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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/10.1101/2023.11.20.23298504v1" target="_blank">Protocol for VIVALDI Social Care: Pilot Study to reduce Infections, Outbreaks and Antimicrobial Resistance in Care Homes for Older Adults</a>
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</div></li>
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</ul>
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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>Promoting Engagement and COVID-19 Testing for Health</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging <br/><b>Sponsors</b>: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology <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>Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19</strong> - <b>Conditions</b>: Certain Disorders Involving the Immune Mechanism <br/><b>Interventions</b>: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 <br/><b>Sponsors</b>: University Hospital, Tours <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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19 <br/><b>Interventions</b>: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources <br/><b>Sponsors</b>: Idaho State University <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>Water-based Activity to Enhance Recovery in Long COVID</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Behavioral: WATER+CT; Behavioral: Usual Care <br/><b>Sponsors</b>: VA Office of Research and Development <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>Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID</strong> - <b>Conditions</b>: Persistent COVID-19 <br/><b>Interventions</b>: Other: exercise programe <br/><b>Sponsors</b>: Facultat de ciencies de la Salut Universitat Ramon Llull <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>Performance Evaluation of the Lucira COVID-19 & Flu Test</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Device: Lucira COVID-19 & Flu Test <br/><b>Sponsors</b>: Lucira Health Inc <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>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <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>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <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>Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine <br/><b>Sponsors</b>: Pfizer <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>A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial</strong> - <b>Conditions</b>: Long COVID-19 Syndrome; Chronic Fatigue Syndrome <br/><b>Interventions</b>: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet <br/><b>Sponsors</b>: Cardresearch <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ <br/><b>Sponsors</b>: Abbott Rapid Dx <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>Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes</strong> - <b>Conditions</b>: Normobaric Hypoxia; Hypoventilation; Normoxia <br/><b>Interventions</b>: Other: Repeated sprint <br/><b>Sponsors</b>: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. <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>Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities</strong> - <b>Conditions</b>: COVID-19; Vaccine <br/><b>Interventions</b>: Behavioral: REDES; Behavioral: Control <br/><b>Sponsors</b>: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University <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>The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray</strong> - <b>Conditions</b>: SARS-CoV-2; Prevention <br/><b>Interventions</b>: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient <br/><b>Sponsors</b>: The Second Affiliated Hospital of Chongqing Medical University <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>Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation without maintenance program <br/><b>Sponsors</b>: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design) <br/><b>Not yet recruiting</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>Synthesis, characterization, biological activity and computation-based efficacy of cobalt(II) complexes of biphenyl-2-ol against SARS-CoV-2 virus</strong> - Cobalt(II) complexes of biphenyl-2-ol of composition, CoCl(2-n)(OC(6)H(4)C(6)H(5)-2)(n)(H(2)O)(4) (where n = 1 or 2), were prepared by reacting cobaltous(II) chloride with equi- and bimolar ratios of sodium salt of biphenyl-2-ol. The structural characterization of the synthesized complexes was accomplished by NMR, FTIR, thermogravimetry (TGA), high resolution mass spectroscopy (HRMS), electronic spectroscopic techniques coupled with density functional theory (DFT). The stability of the complexes…</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>Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry</strong> - Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases 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>Chemical Composition of Rosemary (<em>Rosmarinus officinalis</em> L.) Extract and Its Inhibitory Effects on SARS-CoV-2 Spike Protein-ACE2 Interaction and ACE2 Activity and Free Radical Scavenging Capacities</strong> - This study evaluated the chemical composition of rosemary water extract (RWE) and its influence on mechanisms by which the SARS-CoV-2 virus enters into cells as a potential route for reducing the risk of COVID-19 disease. Compounds in RWE were identified using UHPLC-MS/MS. The inhibitory effect of RWE was then evaluated on binding between the SARS-CoV-2 spike protein (S-protein) and ACE2 and separately on ACE2 activity/availability. Additionally, total phenolic content (TPC) and free radical…</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>Minimal impact of IL-17 and IL-12/23 inhibition on SARS-CoV-2/COVID-19 antibody response in psoriasis patients</strong> - No abstract</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>Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection</strong> - An object of the present study was the development of liposomes loaded with the medicine Veklury^(®) (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through the inclusion of an aptamer (oligonucleotide sequence) with specific affinity to the spike protein of the human coronavirus HCoV-OC43. The hydrodynamic size, electrokinetic…</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>Molecular Docking and ADME-TOX Profiling of <em>Moringa oleifera</em> Constituents against SARS-CoV-2</strong> - The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2019) etiological agent, which has a high contagiousness and is to blame for the outbreak of acute viral pneumonia, is the cause of the respiratory disease COVID-19. The use of natural products grew as an alternative treatment for various diseases due to the abundance of organic molecules with pharmacological properties. Many pharmaceutical studies have focused on investigating compounds with therapeutic potential. Therefore, this…</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>SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia</strong> - CONCLUSION: The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.</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 exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects</strong> - CONCLUSIONS: The comparison between the salivary CPC concentration and EC50/CC50 values from in vitro antiviral experiments suggests that CPC buccal tablets may inhibit SARS-CoV-2 activity, and the inhibition may last for approximately 30 min without cytotoxicity.</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>Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions</strong> - Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus…</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>Licochalcone A regulates viral IRES activity to inhibit enterovirus replication</strong> - Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses…</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>AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity</strong> - An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5…</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>SARS-CoV-2 ORF6 protein targets TRIM25 for proteasomal degradation to diminish K63-linked RIG-I ubiquitination and type-I interferon induction</strong> - Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host’s innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction 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>Highly potent dual-targeting angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP1) peptides: A promising broad-spectrum therapeutic strategy against SARS-CoV-2 infection</strong> - The efficacy of approved vaccines has been diminishing due to the increasing advent of SARS-CoV-2 variants with diverse mutations that favor sneak entry. Nonetheless, these variants recognize the conservative host receptors angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) for entry, rendering the dual blockade of ACE2 and NRP1 an advantageous pan-inhibition strategy. Here, we identified a highly potent dual-targeting peptide AP-1 using structure-based virtual screening protocol….</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>Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors</strong> - The COVID-19 pandemic, caused by SARS-CoV-2, has had a huge impact on global health. To respond to rapidly mutating viruses and to prepare for the next pandemic, there is an urgent need to develop small molecule therapies that target critical stages of the SARS-CoV-2 life cycle. Inhibiting the entry process of the virus can effectively control viral infection and play a role in prevention and treatment. Host factors involved in this process, such as ACE2, TMPRSS2, ADAM17, furin, PIKfyve, TPC2,…</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>Lianhua Qingwen protects LPS-induced acute lung injury by promoting M2 macrophage infiltration</strong> - CONCLUSIONS: Taken together, our data demonstrate that LHQW reduces the inflammatory response and ameliorates acute lung injury by promoting anti-inflammatory polarization of macrophages.</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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