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<title>24 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research</strong> -
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Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale. Study Design: Quasi-experimental. Setting: Virtual. Methods: CompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform's flexibility in experimental design and its wide range of applications in sound processing research. Results: Performance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com). Conclusion: The CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.22.573126v1" target="_blank">CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research</a>
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</div></li>
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<li><strong>Long Covid Perspectives: history, paradigm shifts, global challenges</strong> -
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The Covid-19 pandemic is one of the most devastating health disasters in recorded history. In addition to the significant death toll, the pandemic is leaving behind a long tail of prolonged disease and disability. The long-term symptoms, clinical signs and sequelae of SARS-CoV-2 infection are collectively known as Long Covid – a patient-made term that was created and gained consistency in just a few months in Spring to Summer 2020. Long Covid was openly recognized by the World Health Organization (WHO) in August 2020, following intense advocacy by Covid-19 survivors. Long Covid has been described as the first illness identified, named and defined by patients finding one other on social media such as Twitter. As a disease entity named and defined collectively by patients, Long Covid has the potential to change knowledge building in medicine, while centring patient expertise within the biomedical community. This paper will, first, explore the rise of Long Covid as patient-made term, clinical entity and collective, grassroots, international advocacy–research movement in early 2020 and beyond. This happened while people with Covid-19 suffered abandonment and lack of care in the pandemic’s disaster context. Second, I will discuss some key paradigm shifts triggered by this ground-breaking patient-driven, collective advocacy–research, while sketching links with earlier patient movements, such as around HIV/AIDS. Then, I will explore the role of Long Covid advocacy–research in our digital era. This advocacy took place during a pandemic when digital spaces such as Twitter and Facebook were often the only arenas available to Covid-19 survivors. Moreover, I will raise some pressing issues around epistemic injustice in relation to the use of patient-produced data and the recognition of patient contributions to knowledge. Finally, I will address the need to fully acknowledge the nature, scope, and severity of Long Covid, which are detailed in thousands of scientific publications, including in relation to the ongoing spread of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u3bfy/" target="_blank">Long Covid Perspectives: history, paradigm shifts, global challenges</a>
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</div></li>
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<li><strong>Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic</strong> -
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Genomic analyses of bacterial isolates are necessary to monitor the prevalence of antibiotic resistance genes and virulence determinants. Herein, we provide a comprehensive genomic description of a collection of 339 Staphylococcus aureus strains isolated from patients with bacteremia between 2014 and 2022. Nosocomial acquisition accounted for 56.6% of episodes, with vascular catheters being the predominant source of infection (31.8%). Cases of fatality (27.4%), persistent bacteremia (19.5%) and diagnosis of septic emboli (24.2%) were documented. During the COVID-19 pandemic, we observed a 140% increase of the episodes of S. aureus bacteremia per year, with a concomitant increase of the cases from nosocomial origin. This prompted us to investigate the existence of genetic features associated with S. aureus isolates from the COVID-19 pandemic. While genes conferring resistance to {beta}-lactams (blaI-blaR-blaZ), macrolides (ermA, ermC, ermT, mphC, msrA) and aminoglycosides (ant(4')-Ia, ant(9)-Ia, aph(3')-IIIa, aph(2'')-Ih) were prevalent in our collection, detection of the msrA and mphC genes increased significantly in pandemic S. aureus isolates. Similarly, we observed a higher prevalence of isolates carrying the genes encoding the Clumping Factors A and B, involved in fibrinogen binding. Of note, macrolides were extensively used as accessory therapy for COVID-19 and fibrinogen levels were usually elevated upon SARS-CoV-2 infection. Therefore, our results reveal a remarkable adaptation of the S. aureus isolates to the COVID-19 pandemic context and demonstrates the potential of whole-genome sequencing to conduct molecular epidemiology studies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.22.572975v1" target="_blank">Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants</strong> -
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The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S.
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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/10.1101/2023.12.21.572824v1" target="_blank">Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022)</strong> -
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Background-COVID-19 pandemic increased the risk of CVD (cardiovascular disease). There is lack of comparative assessment on the incidence of sudden death due to MI during and before COVID-19. This study aimed to quantify this assessment. Another quest to start this study is that several studies have reported COVID-19 vaccine-associated myocarditis/cardiomyopathy. Methods and results-This study was based on NCRB data from all states and UTs of India who died suddenly due to MI between 1 January 2018 and 31 December 2022. 5 coastal states of India accounts for about 70 % of all MI cases related sudden death. The base year 2018 is having least whereas the last year 2022 is having the largest number of total new MI cases related mortality detected in one individual year. The largest and noteworthy percent change in sudden death due to MI in males is found in 2022 when it increased by 14.26% (is it due to delayed cardiomyopathy due to COVID-19 or its due to Vaccine? This will be a matter of research in coming era). This study revealed that there is 25.80 percent increase in total number of new MI cases related mortality in 2022 in comparison to pre-COVID-19 year of 2018. There is an overall increase of 11.24 percent in sudden death due to MI cases in males during the COVID-19 period. The Male-Sudden death due to Myocardial Infarction increased during COVID-19 year 2022 by 26.71 percent in comparison to 2018 pre- COVID-19 year. Conclusion-Sudden death due to MI increased during COVID-19.
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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/dcr9a/" target="_blank">The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022)</a>
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<li><strong>MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity.</strong> -
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BackgroundDespite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics. MethodsIn this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi- omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients. ResultsAs COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods. ConclusionsThis approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.14.557558v2" target="_blank">MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity.</a>
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<li><strong>Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data</strong> -
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Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic novel lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572426v1" target="_blank">Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data</a>
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</div></li>
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<li><strong>Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics</strong> -
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Introduction: The transcriptional heterogeneity of activated platelets, play a significant role in contributing to negative outcomes in sepsis, COVID-19, and autoimmune diseases such as systemic lupus erythematosus (SLE). Despite this, our understanding of these heterogeneous platelet responses remains limited. In this study, we aim to investigate the diverse transcriptional profiles of activated platelets in these diseases, with the goal of deciphering this platelet heterogeneity for new therapeutic strategies to target abnormal and pathogenic platelet subtypes. Materials and methods: We obtained the single cell transcriptional profiles of blood platelets from patients with COVID-19, sepsis, and SLE. Utilizing machine learning algorithms, Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB), we discerned the distinct transcriptomic signatures indicative of fatal versus survival clinical outcomes. Our methodological framework incorporated source data annotations and platelet markers and used SingleR and Seurat for detailed profiling. Additionally, we implemented Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization, aiding in the detection of various platelet subtypes and their correlation with disease status and patient outcomes. Results: Our study identified distinct platelet subpopulations that are associated with disease severity. We demonstrated that alterations in platelet transcription patterns can exacerbate endotheliopathy, potentially heightening the risk of coagulation in fatal patients. Moreover, these changes can also influence lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. Conclusions: Enhanced transcriptional heterogeneity in activated platelets is linked to adverse outcomes in conditions such as sepsis, COVID-19, and autoimmune diseases. The discovery of these unique platelet subpopulations paves the way for innovative therapeutic strategies targeting platelet activation, which could potentially improve patient outcomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572680v1" target="_blank">Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics</a>
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<li><strong>Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro</strong> -
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Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ~20% of the treated cases. The persistence of an intermediary form of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious intermediate decayed slowly with a half-life of ~1 day, suggesting that its persistence could outlive the treatment course to re-ignited SARS-CoV-2 infection as the drug is eliminated. Additional studies are needed to define the nature of this viral intermediate, but our findings point to a particular direction for future investigation and offer a specific treatment recommendation that should be tested clinically.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572655v1" target="_blank">Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro</a>
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<li><strong>Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster</strong> -
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Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characterize the antibody responses following vaccination, particularly in the elderly. Here, we show that the monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a panel of variants, including BA.2.86, in an older population with four or more previous vaccine doses. Furthermore, neutralizing antibody titers to XBB.1.5 and BA.2.86 were boosted more strongly than titers to historical variants were. Our findings thereby suggest increased vaccine induced protection against both antigenically matched variants, as well as the more distant BA.2.86 variant, and support current vaccine policies recommending a monovalent XBB.1.5 booster dose to older individuals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.21.572575v1" target="_blank">Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster</a>
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<li><strong>Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol</strong> -
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Responses to COVID-19 in Canadian postsecondary education have overhauled usual norms and practices, with policies of unclear rationale implemented under the pressure of a public health emergency. However, despite the unprecedented nature of these policies and their dramatic impact on millions of lives, the decision-making process leading to them has not been documented or appraised. Drawing from macro and micro theories of public policy, specifically the critical tradition in policy studies exemplified by Carol Bacchi’s approach “What is the problem represented to be” (WPR), we will conduct a scoping review of COVID-19 policies in Canadian postsecondary education, guided by Arksey and O’Malley’s framework for scoping reviews and by the team-based approach of Levan and colleagues. Data will include diverse and publicly available documents to capture multiple stakeholders’ perspectives on the phenomenon of interest, and will be retrieved from university, newsletter, and legal websites through combinations of search terms adapted to specific data types. Two reviewers will independently screen, chart, analyse and synthesize the data and disagreements will be resolved through full team discussion. By identifying, summarizing, and appraising the evidence, our review should inform practices that can contribute to effective and equitable public health policies in postsecondary institutions moving forward.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u3e28/" target="_blank">Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol</a>
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<li><strong>Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating</strong> -
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The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.24.553565v2" target="_blank">Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating</a>
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<li><strong>Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19</strong> -
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The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.20.572494v1" target="_blank">Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19</a>
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<li><strong>Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages</strong> -
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A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86- B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73- CD24lo) exhibited phenotypical similarities with CD86- IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.19.572339v1" target="_blank">Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages</a>
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<li><strong>Predicting the Trend of SARS-CoV-2 Mutation Frequencies Using Historical Data</strong> -
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As the SARS-CoV-2 virus rapidly evolves, predicting the trajectory of viral variations has become a critical yet complex task. A deep understanding of future mutation patterns, in particular the mutations that will prevail in the near future, is vital in steering diagnostics, therapeutics, and vaccine strategies in the coming months. In this study, we developed a model to forecast future SARS-CoV-2 mutation surges in real-time, using historical mutation frequency data from the USA. To improve upon the accuracy of traditional time-series models, we transformed the prediction problem into a supervised learning framework using a sliding window approach. This involved breaking the time series of mutation frequencies into very short segments. Considering the time-dependent nature of the data, we focused on modeling the first-order derivative of the mutation frequency. We predicted the final derivative in each segment based on the preceding derivatives, employing various machine learning methods including random forest, XGBoost, support vector machine, and neural network models, in this supervised learning setting. Empowered by the novel transformation strategy and the high capacity of machine learning models, we witnessed low prediction error that is confined within 0.1% and 1% when making predictions for future 30 and 80 days respectively. In addition, the method also led to a notable increase in prediction accuracy compared to traditional time-series models, as evidenced by lower MAE, and MSE for predictions made within different time horizons. To further assess the method's effectiveness and robustness in predicting mutation patterns for unforeseen mutations, we categorized all mutations into three major patterns. The model demonstrated its robustness by accurately predicting unseen mutation patterns when training on data from two pattern categories while testing on the third pattern category, showcasing its potential in forecasting a variety of mutation trajectories. To enhance accessibility and utility, we built our methodology into an R-shiny app (https://swdatpredicts.shinyapps.io/rshiny_predict/), a tool with potential applicability in studying other infectious diseases, thus extending its relevance beyond the current pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.19.572480v1" target="_blank">Predicting the Trend of SARS-CoV-2 Mutation Frequencies Using Historical Data</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza.</strong> - <b>Conditions</b>: Influenza; COVID-19 <br/><b>Interventions</b>: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo <br/><b>Sponsors</b>: BioNTech SE; Pfizer <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transcranial Pulse Stimulation (TPS) in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue <br/><b>Interventions</b>: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham <br/><b>Sponsors</b>: Medical University of Vienna; Campus Bio-Medico University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of “Formosa 1-Breath Free (NRICM101)” in Subjects With the Symptoms of COVID-19 or Influenza-like Disease</strong> - <b>Conditions</b>: Influenza Viral Infections; COVID-19 <br/><b>Interventions</b>: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug <br/><b>Sponsors</b>: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo <br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Exercise Intolerance, Riboflavin-Responsive <br/><b>Interventions</b>: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises <br/><b>Sponsors</b>: Columbia University; New York University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues</strong> - <b>Conditions</b>: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission <br/><b>Interventions</b>: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary <br/><b>Sponsors</b>: University of Chicago <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>EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise; Behavioral: Control <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>A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination</strong> - <b>Conditions</b>: SARS-CoV-2; COVID-19 Vaccine <br/><b>Interventions</b>: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo <br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research</strong> - <b>Conditions</b>: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor <br/><b>Interventions</b>: Biological: Any Chinese government-recommended COVID-19 booster vaccine <br/><b>Sponsors</b>: Peking Union Medical College Hospital <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>IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS.</strong> - <b>Conditions</b>: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation <br/><b>Interventions</b>: Dietary Supplement: Nutritional blend (ImmuneRecov). <br/><b>Sponsors</b>: Federal University of São Paulo <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>Physical Activity Coaching in Patients With Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active <br/><b>Sponsors</b>: University of Alcala; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid <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 Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training</strong> - <b>Conditions</b>: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer <br/><b>Interventions</b>: Device: breathing training <br/><b>Sponsors</b>: Tri-Service General Hospital <br/><b>Active, not recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants</strong> - Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition…</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 Antiviral Activity of the Lectin Griffithsin against SARS-CoV-2 Is Enhanced by the Presence of Structural Proteins</strong> - Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptor…</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 25-Hydroxylase Suppresses Swine Acute Diarrhea Syndrome Coronavirus Infection by Blocking Spike Protein-Mediated Membrane Fusion</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine intestinal coronavirus that can cause acute diarrhea, vomiting, rapid weight loss, and high mortality in newborn piglets. Cholesterol 25-hydroxylase (CH25H) is a molecular mediator of innate antiviral immunity and converts cholesterol to 25-hydroxycholesterol (25HC). Previous studies have reported that CH25H and 25HC have an antiviral effect against multiple viruses. However, the interplay between SADS-CoV infection 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>Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists</strong> - Coronavirus infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S), inducing lysosomal degradation of Tetherin, and ORF7a, altering its glycosylation. Similarly, SARS-CoV-2 has also been shown to use ORF7a and Spike to enhance virion release in the presence of Tetherin. Here, we…</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 Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic</strong> - CONCLUSIONS: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.</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 Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation</strong> - Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-β production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-β signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme…</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>Antiviral Potential of Azelastine against Major Respiratory Viruses</strong> - The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced…</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 Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses</strong> - Coronaviruses represent a significant threat to both human and animal health, encompassing a range of pathogenic strains responsible for illnesses, from the common cold to more severe diseases. VV116 is a deuterated derivative of Remdesivir with oral bioavailability that was found to potently inhibit SARS-CoV-2. In this work, we investigated the broad-spectrum antiviral activity of VV116 against a variety of human and animal coronaviruses. We examined the inhibitory effects of VV116 on 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>COVID-19 Vaccination and Immunosuppressive Therapy in Immune-Mediated Inflammatory Diseases</strong> - The COVID-19 vaccination program has probably been the most complex and extensive project in history until now, which has been a challenge for all the people involved in the planning and management of this program. Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy have required special attention, not only because of the particular haste in carrying out the process but also because of the uncertainty regarding their response to the vaccines. We now have…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody Response to SARS-CoV-2 Vaccination in Patients with End-Stage Kidney Disease on Hemodialysis</strong> - Patients with end-stage kidney disease on hemodialysis (ESKD-HD) have a high risk of contracting severe COVID-19. Vaccination can help reduce disease severity, but the immune dysregulation observed in these patients may result in an inadequate antibody response. Therefore, we aimed to evaluate the immune response postvaccination in ESKD-HD patients. This prospective cohort study was conducted in two hemodialysis centers in Indonesia. We enrolled ESKD-HD patients (n = 143) pre- 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>SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection</strong> - Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at finding…</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>Combating Black Fungus: Using Allicin as a Potent Antifungal Agent against Mucorales</strong> - Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated….</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>Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients</strong> - T cell depletion and functional impairment are characteristics of sepsis. CD137 is a costimulatory receptor on activated T cells, while soluble CD137 (sCD137) inhibits CD137 signaling. This study found elevated sCD137 levels in the plasma of patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock compared to healthy controls. The sCD137 levels negatively correlated with the C-reactive protein and positively with procalcitonin and interleukin-6. There was no…</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>De Novo Potent Peptide Nucleic Acid Antisense Oligomer Inhibitors Targeting SARS-CoV-2 RNA-Dependent RNA Polymerase via Structure-Guided Drug Design</strong> - Global reports of novel SARS-CoV-2 variants and recurrence cases continue despite substantial vaccination campaigns, raising severe concerns about COVID-19. While repurposed drugs offer some treatment options for COVID-19, notably, nucleoside inhibitors like Remdesivir stand out as curative therapies for COVID-19 that are approved by the US Food and Drug Administration (FDA). The emergence of highly contagious SARS-CoV-2 variants underscores the imperative for antiviral drugs adaptable 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>Amphiphilic Sialic Acid Derivatives as Potential Dual-Specific Inhibitors of Influenza Hemagglutinin and Neuraminidase</strong> - In the shadow of SARS-CoV-2, influenza seems to be an innocent virus, although new zoonotic influenza viruses evolved by mutations may lead to severe pandemics. According to WHO, there is an urgent need for better antiviral drugs. Blocking viral hemagglutinin with multivalent N-acetylneuraminic acid derivatives is a promising approach to prevent influenza infection. Moreover, dual inhibition of both hemagglutinin and neuraminidase may result in a more powerful effect. Since both viral…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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