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177 lines
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<title>19 September, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients</strong> -
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Background: COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. Methods: Based on prospective mortality outcome, 102 critically ill-hospitalized COVID-19 patients were divided into two groups: ICU-Survivors (ICU-S, n=36) and ICU-Non-survivors (ICU-NS, n=66). Blood samples were collected from patients and control subjects to explore correlations between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils for glycolytic activities and for apoptosis using high-throughput fluorescence imaging complemented with transcriptomic analyses. Stratified survival analyses were conducted to estimate mortality risk associated with higher lactate among predefined subgroups. Results: Neutrophil counts were consistently higher in critically ill patients while exhibiting remarkably lower apoptosis. Transcriptomic analysis revealed miRNAs associated with downregulation of genes involved in neutrophils apoptosis. Both CT lung damage scores and neutrophil counts predicted mortality. Severinghaus fitting of hemoglobin oxygen saturation curve revealed a right-shift indicating lower oxygen capacity in non-survivors, which is consistent with lower blood-pH observed in the same group. Levels of blood lactate were increased in patients but significantly more in the ICU-NS relative to the control group. ROC analysis followed by Kaplan-Meyer survival analysis stratified to the obtained cut-off values showed that CT damage scores, neutrophil counts, and lactate levels are predictors of mortality within 15 days following blood collection. Conclusion: The current results implicate neutrophilia as a potential player in metabolic acidosis and deranged oxygen delivery associating SARS-CoV-2 infection thus contributing to mortality outcome.
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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/10.1101/2023.09.17.558185v1" target="_blank">Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients</a>
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</div></li>
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<li><strong>Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming</strong> -
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<div>
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Background: Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We here examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Methods: Healthy adults who received primary BNT162b2 (mRNA) (n=18) or ChAdOx1 (vector) (n=25) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Results: Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5-20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. Conclusion: A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.
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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/10.1101/2023.09.15.557929v1" target="_blank">Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming</a>
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</div></li>
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<li><strong>Moving Beyond the Gradient: Social Classes as Group Contexts Defined by Multiple Forms of Capital</strong> -
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<div>
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Social class is a complex multidimensional phenomenon. Yet social psychologists have typically used indicators of SES or “social rank” to proxy class. Informed by sociology and cultural psychology, we treat social classes as group contexts characterized by the interplay of material, social, and cultural capital. Subjecting three datasets to latent profile analysis (LPA; N = 30,332), we uncover qualitatively distinct class groupings within the U.S. population—each characterized by a unique pattern of capital (Studies 1–3). Consistent with theory in cultural psychology, class formation is guided by a reciprocal relationship between material capital (income and assets) and social capital (interpersonal ties). Across studies, we predict and observe one profile (the “middle/upper class”) that exhibits high material capital but low levels of social capital, and another profile (the “vulnerable workers”) that displays modest material capital but very high social capital. Studies 2 and 3 illuminate the adaptive value of vulnerable workers’ high social capital, with this group reporting similar mental and physical health outcomes to the middle/upper class (Studies 2 and 3) and leveraging their social networks to protect against health impacts of the Covid-19 pandemic (Study 3). Our work reveals that tradeoffs between material and social capital occur most reliably at the group (not individual) level; that class effects are not monotonic, but reflect higher-order interactions between forms of capital; and that LPA can be a fruitful analytic approach when combined with careful theorization, validation of profiles against appropriate covariates, and preregistration.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/ph3ze/" target="_blank">Moving Beyond the Gradient: Social Classes as Group Contexts Defined by Multiple Forms of Capital</a>
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<li><strong>Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society</strong> -
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<div>
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The surge in preprint server use, especially during the Covid-19 pandemic, necessitates a reex-amination of their significance in the realm of science communication. This study rigorously investigates discussions surrounding preprints, framing them within the contexts of systems theory and boundary objects in scholarly communication. An analysis of a curated selection of COVID-19-related preprints from bioRxiv and medRxiv was conducted, emphasizing those that transitioned to journal publications, alongside the associated commentary and Twitter activity. The dataset was bifurcated into comments by biomedical experts versus those by non-experts, encompassing both academic and general public perspectives. Findings revealed that while peers dominated nearly half the preprint discussions, their presence in Twitter dia-logues was markedly diminished. Yet, intriguingly, the themes explored by these two groups diverged considerably. Preprints emerged as potent boundary objects, reinforcing, rather than obscuring, the delineation between scientific and non-scientific discourse. They serve as cru-cial conduits for knowledge dissemination and foster inter-disciplinary engagements. None-theless, the interplay between scientists and the wider public remains nuanced, necessitating strategies to incorporate these diverse discussions into the peer review continuum without compromising academic integrity and to cultivate sustained engagement from both experts and the broader community.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/75gs6/" target="_blank">Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society</a>
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<li><strong>Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study)</strong> -
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Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD]=5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches. This work has received support from the Princely House of the Principality of Liechtenstein, the government of the Principality of Liechtenstein, the Hanela Foundation in Switzerland, and the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 101005177. This Joint Undertaking receives support from the European Union9s Horizon 2020 research and innovation programme and EFPIA.
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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/10.1101/2023.09.17.23295693v1" target="_blank">Sex-specific differences in physiological parameters related to SARS-CoV-2 infections among a national cohort (COVI-GAPP study)</a>
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</div></li>
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<li><strong>Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids</strong> -
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<div>
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The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation is retained for later variants like BA.5 and XBB remains controversial. We show that BA.5 and XBB isolates were significantly more pathogenic in K18-hACE2 mice than a BA.1 isolate, showing increased neuroinvasiveness, resulting in fulminant brain infection and mortality, similar to that seen for original ancestral isolates. BA.5 also infected human cortical brain organoids to a greater extent than the BA.1 and original ancestral isolates. In the brains of mice, neurons were the main target of infection, and in human organoids neuronal progenitor cells and immature neurons were infected. Although fulminant brain infection is not a feature of COVID-19, evidence for brain infection and brain damage in some COVID-19 patients with severe disease is becoming compelling, with the results herein suggesting that evolving omicron variants may have increasing intrinsic neuropathogenic 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/10.1101/2022.12.22.521696v2" target="_blank">Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids</a>
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<li><strong>Adherence Behaviors to Prevent COVID: The Role of Anxiety and Prosocial Behaviors</strong> -
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In situations of acute stress, individuals may engage in prosocial behaviors or alternatively, individuals may engage in risk taking self-oriented behaviors. The COVID-19 pandemic created large stress-promoting conditions that impacted individuals9decisions to adhere to COVID-19 preventative behaviors. The aim of this study is to examine the relationship between anxiety during the pandemic and adherence behaviors to prevent the spread of COVID-19, and the moderating influence prosocial behaviors. Method: 54 undergraduate students completed online questionnaires during the second wave of the pandemic: prosocial behaviors, anxiety, and COVID-19 preventive behaviors. Moderation analyses were conducted using Process in SPSS. Results: Results demonstrated a statistically significant interaction of public prosocial behavior with state anxiety([beta]= -.17, p=.01) predicting engagement in COVID-19 preventative behaviors. At low levels of anxiety, low levels of prosocial public behaviors were associated with higher engagement in COVID-19 preventative behaviors. In contrast, high levels of public prosocial behavior were associated with lower engagement in COVID-19 preventative behaviors at low levels of anxiety. Conclusion: Results provide information that can aid at in the creation of anxiety reducing interventions that could increase adherence to COVID-19 preventative behaviors.
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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/10.1101/2023.09.18.23295630v1" target="_blank">Adherence Behaviors to Prevent COVID: The Role of Anxiety and Prosocial Behaviors</a>
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<li><strong>Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging</strong> -
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Background: Accurately predicting short-term mortality is important for optimizing healthcare resource allocation, developing risk-reducing interventions, and improving end-of-life care. Moreover, short-term mortality risk reflects individual frailty and can serve as digital aging marker. Previous studies have focused on specific, high-risk populations. Predicting all-cause mortality in an unselected population incorporating both health and socioeconomic factors has direct public health relevance but requires careful fairness considerations. Methods: We developed a deep learning model to predict 1-year mortality using nationwide longitudinal data from the Finnish population (N = 5.4 million), including >8,000 features and spanning back up to 50 years. We used the area under the receiver operating characteristic curve (AUC) as a primary metric to assess model performance and fairness. Findings: The model achieved an AUC of 0.944 with strong calibration, outperforming a baseline model that only included age and sex (AUC = 0.897). The model generalized well to different causes of death (AUC > 0.800 for 45 out of 50 causes), including COVID-19 which was not present in the training data. The model performed best among young females and worst in older males (AUC = 0.910 vs. AUC = 0.718). Extensive fairness analyses revealed that individuals belonging to multiple disadvantaged groups had the worst model performance, not explained by age and sex differences, reduced healthcare contact, or smaller training set sizes within these groups. Conclusion: A deep learning model based on nationwide longitudinal multi-modal data accurately identified short-term mortality risk holding the potential for developing a population-wide in-silico aging marker. Unfairness in model predictions represents a major challenge to the equitable integration of these approaches in public health interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.18.23295726v1" target="_blank">Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging</a>
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<li><strong>Сan we start to ignore the SARS-CoV-2 disease?</strong> -
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Current WHO reports claim a decline in COVID-19 testing. Many countries are reporting no new infections. In particular, USA, China and Japan have registered no cases and COVID-19 related deaths since May 15, 2023. To discuss consequences of ignoring SARS-CoV-2 infection, we compare endemic characteristics of the disease in 2023 with ones estimated before using 2022 datasets. The accumulated numbers of cases and deaths reported to WHO by 10 most infected countries and global figures were used to calculate the average daily numbers of cases and deaths per capita (DCC and DDC) and case fatality rates (CFR) for two periods in 2023. The average values of daily deaths per million still vary between 0.12 and 0.41. It means that annual global number of COVID-19 related deaths is still approximately twice higher than the seasonal influenza mortality. Increase of CFR values in 2023 show that SARS-CoV-2 infection is still dangerous despite of increasing the vaccination level. Very low CFR figures in South Korea and very high ones in the UK 4 need further investigations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.18.23295709v1" target="_blank">Сan we start to ignore the SARS-CoV-2 disease?</a>
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<li><strong>Detecting episodic evolution through Bayesian inference of molecular clock models</strong> -
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Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However, formal model testing has the advantage of accommodating a wide range molecular clock models. We also assessed the ability of an automated approach, known as the random local clock, where branches under episodic evolution may be detected without their a priori definition. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find `very strong’ evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.17.545443v2" target="_blank">Detecting episodic evolution through Bayesian inference of molecular clock models</a>
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<li><strong>A highly divergent SARS-CoV-2 lineage B.1.1 sample in a patient with long-term COVID-19</strong> -
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We report the genomic analysis of a highly divergent SARS-CoV-2 sample obtained in October 2022 from an HIV+ patient with presumably long-term COVID-19 infection. Phylogenetic analysis indicates that the sample is characterized by a gain of 89 mutations since divergence from its nearest sequenced neighbor, which had been collected in September 2020 and belongs to the B.1.1 lineage, largely extinct in 2022. 33 of these mutations were coding and occurred in the Spike protein. Of these, 17 are lineage-defining in some of the variants of concern (VOCs) or are in sites where another mutation is lineage-defining in a variant of concern, and/or shown to be involved in antibody evasion, and/or detected in other cases of persistent COVID-19; these include some “usual suspects,” such as Spike:L452R, E484Q, K417T, Y453F, and N460K. Molecular clock analysis indicates that mutations in this lineage accumulated at an increased rate compared to the ancestral B.1.1 strain. This increase is driven by the accumulation of nonsynonymous mutations, for an average dN/dS value of 2.2, indicating strong positive selection during within-patient evolution. Additionally, there is reason to believe that the virus had persisted for at least some time in the gastrointestinal tract, as evidenced by the presence of mutations that are rare in the general population samples but common in samples from wastewater. Our analysis adds to the growing body of research on evolution of SARS-CoV-2 in chronically infected patients and its relationship to the emergence of variants of concern.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.14.23295379v1" target="_blank">A highly divergent SARS-CoV-2 lineage B.1.1 sample in a patient with long-term COVID-19</a>
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<li><strong>Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</strong> -
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Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1m{Psi}), reduce the interferon response and enhance expression levels. Multiple attempts to use modNTPs in saRNA have been unsuccessful, leading to the conclusion that modNTPs are incompatible with saRNA, thus hindering further development. Here, contrary to the common dogma in the field, we identify multiple modNTPs that when incorporated into saRNA at 100% substitution confer immune evasion and enhance expression potency. Transfection efficiency enhances by roughly an order of magnitude in difficult to transfect cell types compared to unmodified saRNA, and interferon production reduces by >8 fold compared to unmodified saRNA in human peripheral blood mononuclear cells (PBMCs). Furthermore, we demonstrate expression of viral antigens in vitro and observe significant protection against lethal challenge with a mouse-adapted SARS-CoV-2 strain in vivo. A modified saRNA vaccine, at 100-fold lower dose than a modified mRNA vaccine, results in a statistically improved performance to unmodified saRNA and statistically equivalent performance to modified mRNA. This discovery considerably broadens the potential scope of self-amplifying RNA, enabling entry into previously impossible cell types, as well as the potential to apply saRNA technology to non-vaccine modalities such as cell therapy and protein replacement.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.557994v1" target="_blank">Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</a>
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<li><strong>Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody</strong> -
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The COVID-19 pandemic has led to over 760 million cases and 6.9 million deaths worldwide. To mitigate the loss of lives, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with susceptible variants. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response anti-viral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.14.557679v1" target="_blank">Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody</a>
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<li><strong>Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge</strong> -
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Adaptive immunity is generated in lymphoid organs, but how these structures defend themselves during infection in humans is unknown. The nasal epithelium is a major site of viral entry, with adenoid nasal-associated lymphoid tissue (NALT) generating early adaptive responses. Here, using a nasopharyngeal biopsy, we examined longitudinal immune responses in NALT following viral challenge, using SARS-CoV-2 infection as a natural experimental model. In acute infection, infiltrating monocytes formed a subepithelial and peri-follicular shield, recruiting NET-forming neutrophils, whilst tissue macrophages expressed pro-repair molecules during convalescence to promote the restoration of tissue integrity. Germinal centre B cells expressed anti-viral transcripts that inversely correlated with fate-defining transcription factors. Among T cells, tissue-resident memory CD8 T cells alone showed clonal expansion and maintained cytotoxic transcriptional programmes into convalescence. Together our study provides a unique insight into how human nasal adaptive immune responses are generated and sustained in the face of viral challenge.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.558006v1" target="_blank">Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge</a>
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<li><strong>VirEvol platform:accurate prediction and visualization of SARS-CoV-2 evolutionary trajectory based on protein language model, structural information and immunological recognition mechanism</strong> -
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Predicting the mutation direction of SARS-CoV-2 using exploratory computational methods presents a challenging, yet prospective, research avenue. However, existing research methods often ignore the effects of protein structure and multi-source viral information on mutation prediction, making it difficult to accurately predict the evolutionary trend of the SARS-CoV-2 S protein receptor-binding domain (RBD). To overcome this limitation, we proposed an interpretable language model combining structural, sequence and immune information. The dual utility of this model lies in its ability to predict SARS-CoV-2's affinity for the ACE2 receptor, and to assess its potential for immune evasion. Additionally, it explores the mutation trend of SARS-CoV-2 via a genetic algorithm-directed evolution. The model exhibits high accuracy in both regards and has displayed promising early warning capabilities, effectively identifying 13 out of 14 high-risk strains, marking a success rate of 93%.". This study provides a novel method for discerning the molecular evolutionary pattern, as well as predicting the evolutionary trend of SARS-CoV-2 which is of great significance for vaccine design and drug development of new coronaviruses. We further developed VirEvol, a unique platform designed to visualize the evolutionary trajectories of novel SARS-CoV- 2 strains, thereby facilitating real-time predictive analysis for researchers. The methodologies adopted in this work may inspire new strategies and offer technical support for addressing challenges posed by other highly mutable viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.15.557978v1" target="_blank">VirEvol platform:accurate prediction and visualization of SARS-CoV-2 evolutionary trajectory based on protein language model, structural information and immunological recognition mechanism</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>A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120; Drug: placebo<br/><b>Sponsor</b>: Huahui Health<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 Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: VYD222; Drug: Normal saline<br/><b>Sponsor</b>: Invivyd, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; Novavax<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 COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration<br/><b>Interventions</b>: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention<br/><b>Sponsors</b>: Arizona State University; 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>Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203)</strong> - <b>Conditions</b>: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: LEM-mR203; Biological: Placebo<br/><b>Sponsor</b>: Lemonex<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: LMN-301<br/><b>Sponsor</b>: Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children</strong> - <b>Conditions</b>: Fever After Vaccination; Fever; Seizures Fever<br/><b>Interventions</b>: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations<br/><b>Sponsors</b>: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention<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>The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students</strong> - <b>Condition</b>: Trauma and Stressor Related Disorders<br/><b>Intervention</b>: Other: Cognitive Behavioral Therapy Group<br/><b>Sponsor</b>: Necmettin Erbakan University<br/><b>Active, not 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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery</strong> - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…</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>Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection</strong> - TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to…</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>Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation</strong> - SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering,…</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>Prostaglandin E<sub>2</sub> and myocarditis; friend or foe?</strong> - This review article summarizes the role of prostaglandin E(2) (PGE(2)) and its receptors (EP1-EP4) as it relates to the inflammatory cardiomyopathy, myocarditis. During the COVID-19 pandemic, the onset of myocarditis in a subset of patients prompted a debate on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, which act to inhibit the actions of prostaglandins. This review aims to further understanding of the role of PGE(2) in the pathogenesis or protection of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SADS-CoV nsp1 inhibits the IFN-β production by preventing TBK1 phosphorylation and inducing CBP degradation</strong> - Swine acute diarrhea syndrome (SADS) is first reported in January 2017 in Southern China. It subsequently causes widespread outbreaks in multiple pig farms, leading to economic losses. Therefore, it is an urgent to understand the molecular mechanisms underlying the pathogenesis and immune evasion of Swine acute diarrhea syndrome coronavirus (SADS-CoV). Our research discovered that SADS-CoV inhibited the production of interferon-β (IFN-β) during viral infection. The nonstructural protein 1 (nsp1)…</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>Bioprospecting the potential of metabolites from a Saharan saline soil strain Nocardiopsis dassonvillei GSBS4</strong> - Saharan soil samples collected in El-Oued province have been investigated for actinobacteria as a valuable source for the production of bioactive metabolites. A total of 273 isolates were obtained and subjected to antagonistic activity tests against human pathogenic germs. A strain with a broad-spectrum antimicrobial activity was selected and identified as Nocardiopsis dassonvillei GSBS4, with high sequence similarities to N. dassonvillei subsp. dassonvillei^(T) X97886.1 (99%) based on…</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>Cholesterol and Ceramide Facilitate Membrane Fusion Mediated by the Fusion Peptide of the SARS-CoV-2 Spike Protein</strong> - SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together and its fusion peptide (FP) that interacts with and perturbs the membrane structure to trigger fusion….</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>Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread</strong> - SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, 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>Exploring the medicinal potential of Dark Chemical Matters (DCM) to design promising inhibitors for PLpro of SARS-CoV-2 using molecular screening and simulation approaches</strong> - The growing concerns and cases of COVID-19 with the appearance of novel variants i.e., BA.2.75. BA.5 and XBB have prompted demand for more effective treatment options that could overcome the risk of immune evasion. For this purpose, discovering novel small molecules to inhibit druggable proteins such as PLpro required for viral pathogenesis, replication, survival, and spread is the best choice. Compounds from the Dark chemical matter (DCM) database is consistently active in various screening…</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 adaptation in Omicron SARS-CoV-2/hACE2: Biophysical origins of evolutionary driving forces</strong> - Since its emergence, the COVID-19 threat has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the host cell receptor (human angiotensin-converting enzyme 2: hACE2) arising from 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>Occurrence, formation, and proteins perturbation of disinfection byproducts in indoor air resulting from chlorine disinfection</strong> - Increased amounts of chlorine disinfectant have been sprayed to inactivate viruses in the environment since the COVID-19 pandemic, and the health risk from chemicals, especially disinfection byproducts (DBPs), has unintentionally increased. In this study, we characterized the occurrence of haloacetic acids (HAAs) and trihalomethanes (THMs) in indoor air and evaluated their formation potential from typical indoor ingredients. Subsequently, the adverse effect of chloroacetic acid on A549 cells was…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans</strong> - CONCLUSIONS: We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies.</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 increases mtDNA copy number causing mild alterations to oxidative phosphorylation</strong> - SARS-CoV-2 causes the severe respiratory disease COVID-19. Remdesivir (RDV) was the first fast-tracked FDA approved treatment drug for COVID-19. RDV acts as an antiviral ribonucleoside (adenosine) analogue that becomes active once it accumulates intracellularly. It then diffuses into the host cell and terminates viral RNA transcription. Previous studies have shown that certain nucleoside analogues unintentionally inhibit mitochondrial RNA or DNA polymerases or cause mutational changes to…</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>Outcomes of a social media campaign to promote COVID-19 vaccination in Nigeria</strong> - The COVID-19 pandemic has been an historic challenge to public health and behavior change programs. In low -and middle-income countries (LMICs) such as Nigeria, there have been challenges in promoting vaccination. Vaccine hesitancy and social norms related to vaccination may be important factors in promoting or inhibiting not only COVID vaccination, but other routine vaccinations as well. The aim of this study was to conduct a national-level quasi-experimental evaluation of a social media based…</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>Phytoconstituents as potential therapeutic agents against COVID-19: a computational study on inhibition of SARS-CoV-2 main protease</strong> - The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has become a global health crisis, and the urgent need for effective treatments is evident. One potential target for COVID-19 therapeutics is the main protease (Mpro) of SARS‑CoV‑2, an essential enzyme for viral replication. Natural compounds have been explored as a source of potential inhibitors for Mpro due to their safety and availability. In this study, we employed a…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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