170 lines
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HTML
170 lines
46 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>10 February, 2024</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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity</strong> -
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<div>
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Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.08.579463v1" target="_blank">Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity</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/JN.1 lineages combining increased fitness and antibody evasion</strong> -
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<div>
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The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary 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/10.1101/2023.11.20.567873v3" target="_blank">Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion</a>
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</div></li>
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<li><strong>Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders</strong> -
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<div>
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The coronavirus disease of 2019 (COVID-19) pandemic is characterized by sequential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and lineages outcompeting previously circulating ones because of, among other factors, increased transmissibility and immune escape. We devised an unsupervised deep learning AutoEncoder for viral genomes anomaly detection to predict future dominant lineages (FDLs), i.e., lineages or sublineages comprising >= 10% of viral sequences added to the GISAID database on a given week. The algorithm was trained and validated by assembling global and country specific data sets from 16,187,950 Spike protein sequences sampled between December 24th, 2019, and November 8th, 2023. The AutoEncoder flags low frequency FDLs (0.01% - 3%), with median lead times of 4-16 weeks. Over time, positive predictive values oscillate, decreasing linearly with the number of unique sequences per data set, showing average performance up to 30 times better than baseline approaches. The B.1.617.2 vaccine reference strain was flagged as FDL when its frequency was only 0.01%, more than one year earlier of being considered for an updated COVID-19 vaccine. Our AutoEncoder, applicable in principle to any pathogen, also pinpoints specific mutations potentially linked to increased fitness, and may provide significant insights for the optimization of public health pre-emptive intervention 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/10.1101/2023.10.24.563721v2" target="_blank">Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders</a>
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</div></li>
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<li><strong>The Importance of Cause-of-Death Certification for the COVID-19 Burden Assessment: the Case of Central Europe</strong> -
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<div>
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Background: In Central Europe, the increase in mortality during the COVID-19 pandemic exceeded the number of deaths registered due to coronavirus disease. Miscertification of COVID-19 has been suggested as one of the possible explanations. Analysis of all mentions from death certificates allows us to identify cases where COVID-19 was reported as a contributing rather than the underlying cause of death (UCoD). Methods: Analysis of 187,000 death certificates with a COVID-19 mention from Austria, Bavaria, Czechia, Lithuania and Poland, 2020–2021. Cause of Death Association Indicators (CDAIs) and Contributing CDAIs were calculated to identify and measure the strength of associations between COVID-19, reported as UCoD or not, and all other medical mentions. Results: Death certificates reporting COVID-19 included on average more medical information than other death certificates. In 171,600 deaths with COVID-19 as the UCoD, ten groups of comorbidities and ten types of complications revealed significant and strong association with COVID-19. Further 15,700 deaths were certified with COVID-19 only as a contributing condition, of which almost 20% were assigned to typical coronavirus complications, such as cerebral infarction, Acute Myocardial Infarction, renal failure. In Austria, Bavaria, Czechia and Lithuania the reported scale of COVID-19 mortality would have been 18-27% higher had COVID-19 been coded as the UCoD in all the cases. Conclusions: Complete death certificate information allows us to assess the scale of COVID-19 miscertification and the burden of COVID-19. Deaths registered with a coronavirus comorbidity were equivalent to the total estimated excess mortality in Austria and Czech Republic, and a large proportion of in Lithuania and Bavaria.
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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/hy9zn/" target="_blank">The Importance of Cause-of-Death Certification for the COVID-19 Burden Assessment: the Case of Central Europe</a>
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<li><strong>Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals</strong> -
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<div>
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Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
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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/10.1101/2024.02.08.576722v1" target="_blank">Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals</a>
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</div></li>
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<li><strong>Use of substances to cope predicts PTSD symptom persistence: Investigating patterns of interactions between PTSD symptoms and its maintaining mechanisms</strong> -
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<div>
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Objective. Post-traumatic stress disorder (PTSD) remains a growing public health challenge across the globe and is associated with negative and persistent long-term consequences. The last decades of research identified different mechanisms associated with the development and persistence of PTSD, including maladaptive coping strategies, cognitive and experiential avoidance, positive, and negative metacognitions. Despite these advances, little is known about how these different processes interact with specific PTSD symptoms, and how they influence each other over time at the within-person level. Method. Leveraging a large (N > 1,800) longitudinal dataset representative of the Norwegian population during the COVID-19 pandemic, this pre-registered study investigated these symptom-process interactions over an eight-month period. Results. Our panel graphical vector autoregressive (GVAR) network model revealed the dominating role of substance use to cope in predicting higher levels of PTSD symptoms over time and increases in PTSD symptomatology within more proximal time-windows (i.e., within six weeks). Threat monitoring was associated with increased suicidal ideation, while threat monitoring itself was increasing upon decreased avoidance behavior, greater presence of negative metacognitions, and higher use of substances to cope. Conclusions. Our findings speak to the importance of attending to different coping strategies, particularly the use of substances as a coping behavior in efforts to prevent PTSD chronicity upon symptom onset. We outline future directions for research efforts to better understand the complex interactions and temporal pathways leading up to the development and maintenance of PTSD symptomatology.
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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/7r9e6/" target="_blank">Use of substances to cope predicts PTSD symptom persistence: Investigating patterns of interactions between PTSD symptoms and its maintaining mechanisms</a>
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<li><strong>Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2</strong> -
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<div>
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Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis (PCA), multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection (UMAP) to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS maintained the strongest correlation between pairwise genetic and Euclidean distances between sequences and best captured the intermediate placement of recombinant lineages between parental lineages. Clusters from t-SNE most accurately recapitulated known phylogenetic clades and recombinant lineages. Both MDS and t-SNE accurately identified reassortment groups. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.
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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/10.1101/2024.02.07.579374v1" target="_blank">Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2</a>
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</div></li>
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<li><strong>Identification of B cell subsets based on antigen receptor sequences using deep learning</strong> -
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<div>
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B cell receptors (BCRs) denote antigen specificity, while corresponding cell subsets indicate B cell functionality. Since each B cell uniquely encodes this combination, physical isolation and subsequent processing of individual B cells become indispensable to identify both attributes. However, this approach accompanies high costs and inevitable information loss, hindering high-throughput investigation of B cell populations. Here, we present BCR-SORT, a deep learning model that predicts cell subsets from their corresponding BCR sequences by leveraging B cell activation and maturation signatures encoded within BCR sequences. Subsequently, BCR-SORT is demonstrated to improve reconstruction of BCR phylogenetic trees, and reproduce results consistent with those verified using physical isolation-based methods or prior knowledge. Notably, when applied to BCR sequences from COVID-19 vaccine recipients, it revealed inter-individual heterogeneity of evolutionary trajectories towards Omicron-binding memory B cells. Overall, BCR-SORT offers great potential to improve our understanding of B cell responses.
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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/10.1101/2024.02.06.579098v1" target="_blank">Identification of B cell subsets based on antigen receptor sequences using deep learning</a>
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<li><strong>BootCellNet, a resampling-based procedure, promotes unsupervised identification of cell populations via robust inference of gene regulatory networks.</strong> -
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<div>
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Recent advances in measurement technologies, particularly single-cell RNA sequencing (scRNA-seq), have revolutionized our ability to acquire large amounts of omics-level data on cellular states. As measurement techniques evolve, there has been an increasing need for data analysis methodologies, especially those focused on cell-type identification and inference of gene regulatory networks (GRNs). We have developed a new method named BootCellNet, which employs smoothing and resampling to infer GRNs. Using the inferred GRNs, BootCellNet further infers the minimum dominating set (MDS), a set of genes that determines the dynamics of the entire network. We have demonstrated that BootCellNet robustly infers GRNs and their MDSs from scRNA-seq data and facilitates unsupervised cell labeling using scRNA-seq datasets of peripheral blood mononuclear cells and hematopoiesis. It has also identified COVID-19 patient-specific cells and their potential regulatory transcription factors. BootCellNet not only identifies cell types in an unsupervised and explainable way but also provides insights into the characteristics of identified cell types through the inference of GRNs and MDS.
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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/10.1101/2024.02.06.579236v1" target="_blank">BootCellNet, a resampling-based procedure, promotes unsupervised identification of cell populations via robust inference of gene regulatory networks.</a>
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<li><strong>Social Sharing of Emotion During the Collective Crisis of COVID-19</strong> -
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We collected data from two sources — social media and online questionnaires — to investigate the emotional consequences of social sharing during the COVID-19 pandemic. Study 1 tracked and analysed sentiment of tweets posted over the course of a month in the crisis period and found that users who tweeted more frequently about COVID-19 expressed decreasing negative sentiment and increasing positive sentiment over time. Granger-causality tests confirmed that this association was better interpreted in the forward direction (sharing levels predicting sentiment) than in the reverse direction (sentiment predicting sharing levels). Study 2 focused on immediate emotional consequences of sharing COVID-related events and found that participants reported improved overall affect about an event to after sharing it, especially when that event was a personal experience rather than a news story. Reported positive feelings about both kinds of event were also significantly higher after sharing. Taken together, both studies suggested that social sharing is linked with emotional relief and may therefore help people to deal with their negative experiences during a persistent collective crisis.
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🖺 Full Text HTML: <a href="https://osf.io/9p3wh/" target="_blank">Social Sharing of Emotion During the Collective Crisis of COVID-19</a>
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<li><strong>Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</strong> -
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The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, the usage of S2 as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of S2 trimer opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Moreover, a corroborating set of experiments indicate that the engineered S2 immunogen exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.563841v2" target="_blank">Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</a>
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<li><strong>Trait Intolerance of Uncertainty Is Associated with Decreased Reappraisal Capacity and Increased Suppression Tendency</strong> -
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The COVID-19 pandemic has been a time of great uncertainty for the general population and highlights the need to understand how attitudes towards uncertainty may affect well-being. Intolerance of uncertainty is a trait associated with worry, anxiety, and mood disorders. As adaptive emotion regulation supports well-being and mental health, it is possible that intolerance of uncertainty is also associated with the ability and tendency to regulate emotions. However, the relationships between intolerance of uncertainty and widely studied cognitive emotion regulation strategies — such as reappraisal and suppression — have received little attention. In two studies that recruited participants online from the United States, we tested the hypotheses that higher trait intolerance of uncertainty would be associated with greater worry, decreased capacity and tendency to use reappraisal, and increased tendency to use suppression in daily life. Study 1 provided an initial test of our hypotheses. Study 2 was a confirmatory, preregistered study that replicated findings in a young adult sample, demonstrating that scores on the Intolerance of Uncertainty Scale (IUS) were associated with greater COVID-related worry, decreased capacity to regulate negative emotions on a task that manipulated the use of reappraisal, and greater self-reported use of suppression in daily life. Together, these results indicate that intolerance of uncertainty is associated with the capacity and tendency to use emotion regulation strategies important for well-being.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/fsnvy/" target="_blank">Trait Intolerance of Uncertainty Is Associated with Decreased Reappraisal Capacity and Increased Suppression Tendency</a>
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<li><strong>Boosting Positive Mood During Stress: A Daily Coping Toolkit Replication in College Undergraduates</strong> -
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College students today face significant challenges. Evidence suggests mental-health burdens are substantial and resources limited. We sought to replicate prior evidence supporting a one-time daily ambulatory intervention to facilitate adaptive regulation of negative emotion and increase generation of positive emotions. The Daily Coping Toolkit (DCT) was developed at the outset of the COVID-19 Pandemic and was effective in boosting mood in front-line medical personnel (Coifman et al., 2021). This investigation aimed to replicate against a valid control condition in college students returning to campus in 2021. N = 125 college students were randomized to one of two experimental conditions (high v. low dose) or the control condition. Data analyses was pre-registered. Results indicated students in experimental groups experienced significant decreases in negative and increases in positive emotion when compared to controls, providing evidence of efficacy. This was notable because a high proportion of participants reported prior mental illness. Although, there was no difference by dose (high v. low) on emotional reports, there was preliminary evidence that low-dose condition was associated with greater adaptive coping (e.g., exercise, social support seeking). Overall, the results suggest the DCT is an efficacious emotion-regulation intervention that can boost mood during high stress.
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🖺 Full Text HTML: <a href="https://osf.io/ah43p/" target="_blank">Boosting Positive Mood During Stress: A Daily Coping Toolkit Replication in College Undergraduates</a>
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<li><strong>copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling</strong> -
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T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce copepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity. copepodTCR implements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for “deorphaning” TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.28.569052v2" target="_blank">copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling</a>
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<li><strong>Can Worries about COVID-19 Enhance Well-Being? Evidence from a Cross-National Study</strong> -
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Can worrying about COVID-19 have positive consequences for well-being? In a preregistered study, we examined the effect of worries about COVID-19 on well-being through divergent associations with social interaction and depression. In August 2020, participants from high and low prevalence regions in the United States and Italy (N = 857) completed assessments of COVID-19 worry, social interaction, depression, and well-being. Worries about COVID-19 predicted both more social interaction and more depression. In mediational analyses, an adaptive pathway of COVID-19 worry through social interaction was associated with higher well-being, whereas a maladaptive pathway through depression was associated with lower well-being. Further, a comparison of high and low COVID-19 prevalence regions replicated the mediational findings for social interaction, providing evidence against reverse causation and common method variance. Findings suggest that normative worries about acute stressors can both benefit and undermine well-being, depending on their impact on social behavior or depression.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h8y4c/" target="_blank">Can Worries about COVID-19 Enhance Well-Being? Evidence from a Cross-National Study</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>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <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>Effects of Physiotherapy Via Video Calls on Cardiopulmonary Functions, Physical Function, Cognitive Function, Activity Daily Livings, and Quality of Life in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <br/><b>Enrolling by invitation</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>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <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>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <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>SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19</strong> - <b>Conditions</b>: Anxiety; COVID-19 Pandemic <br/><b>Interventions</b>: Behavioral: Mindfulness <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International <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 Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults</strong> - <b>Conditions</b>: Influenza, Human; SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo <br/><b>Sponsors</b>: Pfizer <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 Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus</strong> - <b>Conditions</b>: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus <br/><b>Interventions</b>: Behavioral: Nutritional Intervention <br/><b>Sponsors</b>: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo <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>The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management</strong> - <b>Conditions</b>: Trauma; COVID-19 Pandemic <br/><b>Interventions</b>: Other: epidemyolojical <br/><b>Sponsors</b>: Bakirkoy Dr. Sadi Konuk Research and Training Hospital <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>Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age.</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: BIMERVAX <br/><b>Sponsors</b>: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion <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 of Amantadine for Cognitive Dysfunction in Patients With Long-Covid</strong> - <b>Conditions</b>: Long COVID; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management <br/><b>Sponsors</b>: University of Texas Southwestern Medical Center <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>Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19</strong> - <b>Conditions</b>: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID <br/><b>Interventions</b>: Behavioral: Incentive Spirometer respiratory training <br/><b>Sponsors</b>: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital <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>Balance Acceptance and Commitment Therapy for Long COVID</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long COVID <br/><b>Interventions</b>: Behavioral: Balance Acceptance and Commitment Therapy <br/><b>Sponsors</b>: King’s College London <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>Predict + Protect Study: Exploring the Effectiveness of a Predictive Health Education Intervention on the Adoption of Protective Behaviors Related to ILI</strong> - <b>Conditions</b>: Influenza; Influenza A; Influenza B; COVID-19; Respiratory Syncytial Virus (RSV) <br/><b>Interventions</b>: Behavioral: ILI Predictive Alerts, Reactive Content, and Proactive Content; Behavioral: ILI Predictive Alerts, Reactive Content; Behavioral: Proactive Content; Behavioral: No Intervention <br/><b>Sponsors</b>: Evidation Health; Biomedical Advanced Research and Development Authority <br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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>SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA</strong> - A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We identify specific…</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>Application of a Biomimetic Nanoparticle-Based Mock Virus to Determine SARS-CoV-2 Neutralizing Antibody Levels in Blood Samples Using a Lateral Flow Assay</strong> - The presence of neutralizing antibodies against SARS-CoV-2 in blood, acquired through previous infection or vaccination, is known to prevent the (re)occurrence of outbreaks unless the virus mutates. Therefore, the measurement of neutralizing antibodies constitutes an indispensable tool in assessing an individual’s and a population’s immunity against SARS-CoV-2. For this reason, we have developed an innovative lateral flow assay (LFA) capable of detecting blood-derived neutralizing antibodies…</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>Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection</strong> - With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets kidney cells to directly impact renal function, or whether renal damage is primarily an indirect outcome. To date, several studies have utilized kidney organoids to understand the pathogenesis of COVID-19, revealing the ability for SARS-CoV-2 to predominantly infect cells of the proximal tubule (PT), with reduced infectivity…</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>Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review</strong> - The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9…</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>Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases</strong> - Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib…</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>TMPRSS2 inhibitors for the treatment of COVID-19 in adults: a systematic review and meta-analysis of nafamostat and camostat mesylate randomised clinical trials</strong> - CONCLUSION: The RCT evidence is inconclusive to determine whether there is a mortality reduction and safety with either nafamostat or camostat for the treatment of adults with COVID-19. There were high risk-of-bias, small sample size, and high heterogeneity between RCTs.</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 rationally designed antimicrobial peptide from structural and functional insights of <em>Clostridioides difficile</em> translation initiation factor 1</strong> - A significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem. Clostridioides difficile is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of C. difficile infection and antibiotic resistance in C. difficile has led to an unmet need for the discovery of new compounds distinctly different from present antimicrobials, while antimicrobial peptides…</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>BRD4354 Is a Potent Covalent Inhibitor against the SARS-CoV-2 Main Protease</strong> - Numerous organic molecules are known to inhibit the main protease (M^(Pro)) of SARS-CoV-2, the pathogen of Coronavirus Disease 2019 (COVID-19). Guided by previous research on zinc-ligand inhibitors of M^(Pro) and zinc-dependent histone deacetylases (HDACs), we identified BRD4354 as a potent inhibitor of M^(Pro). The in vitro protease activity assays show that BRD4354 displays time-dependent inhibition against M^(Pro) with an IC(50) (concentration that inhibits activity by 50%) of 0.72 ± 0.04 μM…</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>Assessing the mitochondrial safety profile of the molnupiravir active metabolite, β-d-N4-hydroxycytidine (NHC), in the physiologically relevant HepaRG model</strong> - CONCLUSIONS: Overall, NHC does not cause direct mitochondrial toxicity in HepaRG cells at clinically relevant concentrations, but may induce minor cellular perturbations. As HepaRG cells have increased physiological relevance, these findings provide additional assurance of the mitochondrial safety profile of NHC.</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>Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series</strong> - CONCLUSIONS: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an…</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>Arbidol attenuates liver fibrosis and activation of hepatic stellate cells by blocking TGF-β1 signaling</strong> - Chronic liver diseases (CLD) impact over 800 million people globally, causing about 2 million deaths annually. Arbidol (ARB), an indole-derivative used to treat influenza virus infection, was extensively used during COVID-19 pandemic in China. In recent years, studies have shown that ARB, compared to other antiviral drugs, exhibits greater liver-protective efficacy, indicating a potential hepatoprotective effect beyond its antiviral activity. However, the mechanism remains unclear. In 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>Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds with spike protein and inhibits the entry of SARS-CoV-2 into host cells</strong> - CONCLUSIONS: Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells.</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>TREG cells and CXCR3+ circulating TFH cells concordantly shape the neutralizing antibody responses in individuals who have recovered from mild COVID-19</strong> - Regulatory T (TREG) cells are involved in the antiviral immune response in patients with COVID-19; however, whether TREG cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of TREG cells and lower frequencies of CXCR3+ circulating TFH (cTFH) cells than healthy controls. Furthermore, TREG and CXCR3+ cTFH cells were negatively and positively correlated…</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>Influenza vaccine compatibility among hospitalized patients during and after the COVID-19 pandemic</strong> - INTRODUCTION: Following the significant decrease in SARS-CoV-2 cases worldwide, Israel, as well as other countries, have again been faced with a rise in seasonal influenza. This study compared circulating influenza A and B in hospitalized patients in Israel with the influenza strains in the vaccine following the 2021-2022 winter season which was dominated by the omicron variant.</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 as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity</strong> - Recently, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, caused > 6 million deaths. Symptoms included respiratory strain and complications, leading to severe pneumonia. SARS-CoV-2 attaches to the ACE-2 receptor of the host cell membrane to enter. Targeting the SARS-CoV-2 entry may effectively inhibit infection. Acid sphingomyelinase (ASMase) is a lysosomal protein that catalyzes the conversion of sphingolipid (sphingomyelin) to ceramide….</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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