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<title>01 February, 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>The Dark Side of Nurse Superhuman Narrative: Perspective from a Developing Country</strong> -
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<div>
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Throughout human history, many people believed that there is a power beyond the normal realm that falls into either physical or super strength, spiritual and mental powers. Since then, people have always been captivated by the idea of having someone different from the normal one, which is indicated by their skills and abilities. A superhuman abilities perspective is characterized by having superior cognitive and perceptual capacities that are above normal humans, especially useful during times of crises and situations wherein life and death are the core subject of the occurrence. Angels and heroes are the common figures associated with having special superpowers that are beyond the usual, ordinary, and typical attributes of a person. Nurses are often associated with these superhuman traits and this narrative was magnified during the height of Covid-19 pandemic. This paper argues that this narrative is detrimental to both the discipline and profession of nursing.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/3vew2/" target="_blank">The Dark Side of Nurse Superhuman Narrative: Perspective from a Developing Country</a>
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</div></li>
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<li><strong>Caring-Based Curriculum Design in Helping & Healing Profession and Discipline: Theoretical Integration and Pedagogical Innovation in an Undergraduate Nursing Curriculum</strong> -
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<div>
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The pandemic experience has brought up issues and concerns about the competencies of healthcare workers, especially those working in hospitals, especially nurses. The importance of caring, creating caring moments, and being a caring healthcare provider has been essential to all persons during the pandemic, whether Covid-19 afflicts them or not. Post-pandemic, the central question of, “are we educating nurses to be caring professionals or to be mere technicians?” needs more reflection as the realities of another pandemic emerging is well within the horizon. If caring is considered by many nurses as the essence of nursing and is fundamental to the nursing discipline and profession, how is it reflected in the current curriculum for an undergraduate degree in nursing? If it is not fully articulated as one of the basic requirements for the undergraduate curriculum in nursing, how do we functionally integrate it into our respective curriculum? These fundamental questions guide the flow and discussion of this paper as educating the next generation of nursing to explicitly express caring attributes in their professional practice rest upon the institution’s curricular development and innovations. As Smith & McCarthy (2010) greatly emphasized, the preparation of the next generations of nurses in the knowledge of the discipline of nursing will determine the potential for advancing the health of society through nursing’s unique contributions at a time of national healthcare crisis when they are most needed. This paper is composed of three distinct parts; first, the discourse of the philosophical and theoretical assumptions that serve as the grounding for curriculum innovation. Second is the exploration of the current context of caring in nursing education, emphasizing the need for the infusion of caring in the undergraduate nursing curriculum. Lastly, the presentation of the process by which caring is functionally integrated and fully articulated in the current BSN curriculum of San Beda University College of Nursing.
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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/543wr/" target="_blank">Caring-Based Curriculum Design in Helping & Healing Profession and Discipline: Theoretical Integration and Pedagogical Innovation in an Undergraduate Nursing Curriculum</a>
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</div></li>
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<li><strong>Scalable neighbour search and alignment with uvaia</strong> -
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<div>
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Despite millions of SARS-CoV-2 genomes being sequenced and shared globally, manipulating such data sets is still challenging, especially selecting sequences for focused phylogenetic analysis. We present a novel method, uvaia, which is based on partial and exact sequence similarity for quickly extracting database sequences similar to query sequences of interest. Many SARS-CoV-2 phylogenetic analyses rely on very low numbers of ambiguous sites as a measure of quality since ambiguous sites do not contribute to single nucleotide polymorphism (SNP) differences, which uvaia alleviates by using measures of sequence similarity that consider partially ambiguous sites. Such fine-grained definition of similarity allows not only for better phylogenetic analyses, but also for improved classification and biogeographical inferences. Uvaia works natively with compressed files, can use multiple cores and efficiently utilises memory, being able to analyse large data sets on a standard desktop.
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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/10.1101/2023.01.31.526458v1" target="_blank">Scalable neighbour search and alignment with uvaia</a>
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</div></li>
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<li><strong>Coinfection with Strongyloides and SARS-CoV-2: protocol for a systematic review</strong> -
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Rationale for the review: COVID-19 treatment can worsen parasitic disease in patients with coinfection. Consequently, there is a need to investigate the infection with SARS CoV 2 and Strongyloides. We aim to systematically review clinical and laboratory features of COVID 19 and Strongyloides coinfection, to investigate possible interventions and outcomes in this pathology. Also, we aim to identify difficulties in managing the parasitic disease manifestations in this context and to emphasize research gaps requiring further attention. Methods: We will search two electronic databases (LitCOVID, and WHO COVID 19) and will include studies on SARS CoV 2 and Strongyloides coinfection. We will adapt the WHO UMC system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID 19 patients determined acute strongyloidiasis manifestations. Expected results: We will present the evidence in three distinct packages: study description, methodological quality assessment and data extracted. We will summarize the evidence and will draw conclusions as to the quality of the evidence.
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</p>
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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.medrxiv.org/content/10.1101/2023.01.30.23285219v1" target="_blank">Coinfection with Strongyloides and SARS-CoV-2: protocol for a systematic review</a>
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</div></li>
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<li><strong>Current Status and Emerging Trends of COVID-19-related Studies in Seven ″Tropical Medicine″-entitled Journals</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created enormous medical and economic burdens on human society. However, the co-existence of COVID-19 and diseases in tropical regions is not taken seriously. To improve the understanding of the current status and trends on crosstalk of COVID-19 and tropical diseases, this paper provided an analysis, from a bibliometric perspective, of the COVID-19-related publications in ″Tropical Medicine″-entitled journals. Methods: We used Clarivate Analytics and VOSviewer to analyze 783 publications in seven ″ Tropical Medicine″-entitled journals. Document overview, basic bibliometric characteristics, citation performance, co-authorship, co-citation, bibliographic coupling, and co-occurrence of keywords and terms were summarized in this article. Results: Document overview revealed that 76.12% of the related publications were published in open access mode, and basic bibliometric characteristics indicated that the year 2021 was the peak of the number of publications, the documents in the seven journals were unevenly distributed, and ″ article″ was the main publication type. The citation performance analysis elucidated that the documents of interest were frequently cited. The co-authorship analysis showed cooperation networks on the level of region, organization and author. General knowledge of COVID-19 was the overlap of co-citation and bibliographic coupling behavior. Finally, the co-occurrence of keywords and terms revealed the current and emerging hotspots. Conclusions: The main current research focuses in ″Tropical Medicine″-entitled journals are the clinical features of COVID-19 patients, and the emerging trends are the hesitancy in making vaccines against SARS-CoV-2 and the circumstance where COVID-19 coexisted with tropical diseases. In summary, this bibliometric analysis of COVID-19-related studies in seven ″Tropical Medicine″-entitled journals highlights the current research focuses of this field to inspire future studies.
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</p>
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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.medrxiv.org/content/10.1101/2023.01.30.23285173v1" target="_blank">Current Status and Emerging Trends of COVID-19-related Studies in Seven ″Tropical Medicine″-entitled Journals</a>
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</div></li>
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<li><strong>Quantitative Annotations of T-Cell Repertoire Specificity</strong> -
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<div>
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The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modelled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. Applying TCRanno to 4,195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, indicating their past abortive infections instead of non-exposure to the virus. TCRanno discovered age-accumulated SARS-CoV2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of COVID-19. TCRanno also identified the encounter of Hepatitis B antigens as a trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.
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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/10.1101/2023.01.29.526145v1" target="_blank">Quantitative Annotations of T-Cell Repertoire Specificity</a>
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</div></li>
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<li><strong>Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures</strong> -
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<div>
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The advent of single-cell multi-omics sequencing technology makes it possible for researchers to leverage multiple modalities for individual cells and explore cell heterogeneity. However, the high dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Most of the existing computational methods for single-cell data analysis are either limited to single modality or lack flexibility and interpretability. In this study, we propose an interpretable deep learning method called multi-omic embedded topic model (moETM) to effectively perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder for efficient variational inference and then employs multiple linear decoders to learn the multi-omic signatures of the gene regulatory programs. Through comprehensive experiments on public single-cell transcriptome and chromatin accessibility data (i.e., scRNA+scATAC), as well as scRNA and proteomic data (i.e., CITE-seq), moETM demonstrates superior performance compared with six state-of-the-art single-cell data analysis methods on seven publicly available datasets. By applying moETM to the scRNA+scATAC data in human peripheral blood mononuclear cells (PBMCs), we identified sequence motifs corresponding to the transcription factors that regulate immune gene signatures. Applying moETM analysis to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omic biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.
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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/10.1101/2023.01.31.526312v1" target="_blank">Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures</a>
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</div></li>
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<li><strong>A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic</strong> -
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<div>
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Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all coronaviruses represented in the NCBI Virus database. Cognate substrates of these representative proteases were inferred from their polyprotein sequences. We clustered MPro sequences based on sequence identity and AlphaFold2-predicted structures, showing approximate correspondence with known viral subspecies. Predicted structures of five representative MPros bound to their inferred cognate substrates showed high conservation in protease:substrate interaction modes, with some notable differences. Yeast-based proteolysis assays of the five representatives were able to confirm activity of three on inferred cognate substrates, and demonstrated that of the three, only one was effectively inhibited by nirmatrelvir. Our findings suggest that comprehensive preparedness against future potential coronaviral threats will require continued inhibitor development. Our methods may be applied to candidate coronaviral MPro inhibitors to evaluate in advance the breadth of their inhibition and identify target coronaviruses potentially meriting advanced development of alternative countermeasures.
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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/10.1101/2023.01.30.526101v1" target="_blank">A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic</a>
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</div></li>
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<li><strong>Fitness effects of mutations to SARS-CoV-2 proteins</strong> -
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<div>
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Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino-acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.
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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/10.1101/2023.01.30.526314v1" target="_blank">Fitness effects of mutations to SARS-CoV-2 proteins</a>
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</div></li>
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<li><strong>A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection</strong> -
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While the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population, delayed administration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection. Optimizing vaccine dosing schedules could thus make the difference between periodic occurrence of breakthrough infections or effective control of the pandemic. To this end, we have developed a mechanistic mathematical model of adaptive immune response to vaccines and demonstrated its applicability to COVID-19 mRNA vaccines as a proof-of-concept for future outbreaks. The model was thoroughly calibrated against multiple clinical datasets involving immune response to SARS-CoV-2 infection and mRNA vaccines in healthy and immunocompromised subjects (cancer patients undergoing therapy); the model showed robust clinical validation by accurately predicting neutralizing antibody kinetics, a correlate of vaccine-induced protection, in response to multiple doses of mRNA vaccines. Importantly, we estimated population vulnerability to breakthrough infections and predicted tailored vaccination dosing schedules to maximize protection and thus minimize breakthrough infections, based on the immune status of a sub-population. We have identified a critical waiting window for cancer patients (or, immunocompromised subjects) to allow recovery of the immune system (particularly CD4+ T-cells) for effective differentiation of B-cells to produce neutralizing antibodies and thus achieve optimal vaccine efficacy against variants of concern, especially between the first and second doses. Also, we have obtained optimized dosing schedules for subsequent doses in healthy and immunocompromised subjects, which vary from the CDC-recommended schedules, to minimize breakthrough infections. The developed modeling tool is based on generalized adaptive immune response to antigens and can thus be leveraged to guide vaccine dosing schedules during future outbreaks.
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</p>
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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.medrxiv.org/content/10.1101/2022.09.14.22279959v2" target="_blank">A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection</a>
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</div></li>
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<li><strong>Probable transmission of SARS-CoV-2 from an African lion to zoo employees</strong> -
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Animal to human transmission of SARS-CoV-2 has not previously been reported in a zoo setting. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after development of respiratory signs. Zoo employees were screened, monitored prospectively for development of symptoms, then re-screened as indicated, with confirmation by RT-PCR and whole-genome virus sequencing when possible. Trace-back investigation narrowed the source of infection to one of five people. Three exposed employees subsequently developed symptoms, two with viral genomes identical to the lion9s. Forward contact tracing investigation confirmed probable lion-to-human transmission. Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods in big cats and other susceptible animals should be developed and validated to facilitate timely implementation of One Health investigations.
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</p>
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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.medrxiv.org/content/10.1101/2023.01.29.23285159v1" target="_blank">Probable transmission of SARS-CoV-2 from an African lion to zoo employees</a>
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<li><strong>Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life</strong> -
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The dynamics of innate and adaptive immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to SARS-CoV-2 infection in infants and young children in the first weeks and months of life by analyzing blood samples collected before, during, and after infection with Omicron and Non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, were stably maintained for >300 days. Antigen-specific memory B cell (MCB) responses were durable for 150 days but waned thereafter. Somatic hypermutation of V-genes in MCB accumulated progressively over 9 months. The innate response was characterized by upregulation of activation markers on blood innate cells, and a plasma cytokine profile distinct from that seen in adults, with no inflammatory cytokines, but an early and transient accumulation of chemokines (CXCL10, IL8, IL-18R1, CSF-1, CX3CL1), and type I IFN. The latter was strongly correlated with viral load, and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell transcriptomics. Consistent with this, single-cell ATAC-seq revealed enhanced accessibility of chromatic loci targeted by interferon regulatory factors (IRFs) and reduced accessibility of AP-1 targeted loci, as well as traces of epigenetic imprinting in monocytes, during convalescence. Together, these data provide the first snapshot of immunity to infection during the initial weeks and months of life.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.28.23285133v1" target="_blank">Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life</a>
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<li><strong>A PUBLIC HEALTH HACKATHON FOR MEDICAL STUDENTS IN AFRICA: PROCESS, OUTCOME AND RECOMMENDATIONS</strong> -
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Africa has a dual burden of disease, which causes preventable morbidities and fatalities. This is a result of our healthcare system9s deficiencies, which has suffered a serious decline since the COVID-19 pandemic. However, this opened up the possibilities for digital health interventions, which innovators could utilize to provide solutions to these public health issues. Health hackathons, which offer an environment for innovators to brainstorm and collaborate, are rare in Africa. This paper outlines the planning and execution of a virtual hackathon and explores its implications for the promotion of public health in Africa. Over the course of a month, we collaborated with innovation hubs in Africa to hold an open call, a training session, a design sprint, as well as a 48-hour virtual hackathon. We received 68 submissions from 13 African nations. Following the selection of 10 teams, design thinking was employed to develop solutions to a public health problem in Africa. The theme for the hackathon was 9Promoting Health Equity with Digital Technology in Africa9 and areas of focus were non-communicable diseases; infectious disease epidemiology and surveillance; and health information and data management. All ten teams developed prototypes, the top three teams were offered the opportunity to continue on to the startup accelerator program, while the winning team also received a cash prize. In conclusion, the public health hackathon challenged African medical students to develop innovations to healthcare problems. There is need for further study to evaluate the solutions developed.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.28.23284802v1" target="_blank">A PUBLIC HEALTH HACKATHON FOR MEDICAL STUDENTS IN AFRICA: PROCESS, OUTCOME AND RECOMMENDATIONS</a>
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<li><strong>Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range</strong> -
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<div>
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Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors.[3,4] Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein to enable the binding to the mouse ACE2 receptor.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.12.27.474250v2" target="_blank">Cryo-EM structures and binding of mouse and human ACE2 to SARS-CoV-2 variants of concern indicate that mutations enabling immune escape could expand host range</a>
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<li><strong>SARS-CoV-2 spike RBD and nucleocapsid encoding DNA vaccine elicits T cell and neutralising antibody responses that cross react with variants</strong> -
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<div>
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Although the efficacy of vaccines targeting SARS-CoV-2 is apparent now that the approved mRNA and adenovirus vector vaccines are in widespread use, the longevity of the protective immune response and its efficacy against emerging variants remains to be determined. We have therefore designed a DNA vaccine encoding both the SARS-CoV-2 spike receptor-binding domain (RBD) and nucleocapsid proteins, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4+ Th1 and CD8+ T-cell responses to both proteins, with responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain. We have shown that the vaccine also stimulates high titre antibody responses to RBD that efficiently neutralise in pseudotype and live virus neutralisation assays and show cross reactivity with spike proteins from the variants B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). The vaccine also showed good protection in a viral challenge model. This DNA platform can be easily adapted to target variant proteins and we show that a vaccine variant encoding the Beta variant sequence stimulates cross-reactive humoral and T cell responses. These data support the translation of this DNA vaccine platform into the clinic, thereby offering a particular advantage for rapidly targeting emerging SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.18.448932v2" target="_blank">SARS-CoV-2 spike RBD and nucleocapsid encoding DNA vaccine elicits T cell and neutralising antibody responses that cross react with variants</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>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio 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>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Plitidepsin<br/><b>Sponsor</b>: PharmaMar<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 Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Corfluvec component 1 low dose; Biological: Corfluvec component 2 low dose; Biological: Corfluvec component 1 high dose; Biological: Corfluvec component 2 high dose; Biological: Corfluvec low dose; Biological: Corfluvec high dose; Biological: Placebo<br/><b>Sponsors</b>: Tatyana Zubkova; MDP-CRO, LLC; St. Petersburg State Pavlov Medical 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>COVID-19 Self-testing Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: SMARTest mobile app for COVID-19 self-testing<br/><b>Sponsor</b>: Columbia 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 Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>: Shandong Provincial Hospital; Central hospital Affiliated to Shandong First Medical University; The Second Affiliated Hospital of Shandong First Medical University; The Affiliated Hospital Of Southwest Medical University; Gansu Provincial Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Chatbot to Enhance COVID-19 Knowledge</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: chatbot; Other: Printed educational booklet<br/><b>Sponsor</b>: Sun Yat-sen 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>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>: Jiangsu Cancer Institute & Hospital; Nanjing Chest Hospital; The Affiliated BenQ Hospital of Nanjing Medical University; Central South University; Zhongda Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tetrandrine<br/><b>Sponsor</b>: Peking University Third Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo 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>A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<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>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>: Vitamin C; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Vitamin C; Drug: Placebo<br/><b>Sponsor</b>: Zhujiang 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>Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsor</b>: Peking Union Medical College Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: UC-MSCs treatment<br/><b>Sponsors</b>: Shanghai East Hospital; Sir Run Run Shaw 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>The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Non-invasive Ventilation<br/><b>Interventions</b>: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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 and Efficacy of the Therapy With BREINMAX® for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19<br/><b>Interventions</b>: Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 M<sup>pro</sup> with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination</strong> - CONCLUSIONS: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.</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 Potential of Vouacapanes from <em>Pterodon emarginatus</em> Vogel Against COVID-19 Cytokine Storm</strong> - Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In…</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>Bafilomycin A1 inhibits SARS-CoV-2 infection in a human lung xenograft mouse model</strong> - Coronavirus disease 2019 is a global pandemic caused by SARS-CoV-2. The emergence of its variant strains has posed a considerable challenge to clinical treatment. Therefore, drugs capable of inhibiting SARS-CoV-2 infection, regardless of virus variations, are in urgently need. Our results showed that the endosomal acidification inhibitor, Bafilomycin A1 (Baf-A1), had an inhibitory effect on the viral RNA synthesis of SARS-CoV-2, and its Beta and Delta variants at the concentration of 500 nM….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of neutrophil extracellular traps in coronavirus disease - 2019 pathophysiology</strong> - Coronavirus disease 2019 (COVID-19), which is caused by novel coronavirus-2019 (nCoV-2019), is a highly contagious disease with high mortality and morbidity risk. Infected people may suffer from respiratory infections, which may be more progressive in patients with a defective immune system and underlying medical problems. In this regard, the cells involved in the innate immune system, play a decisive role in disease progression and complication development. Pathogen entrapment is the critical…</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>Traditional herbal compounds as candidates to inhibit the SARS-CoV-2 main protease: an <em>in silico</em> study</strong> - COVID-19, a disease caused by the SARS-CoV-2 virus, is responsible for a pandemic since March 2020 and it has no cure. Therefore, herein, different theoretical methods were used to obtain potential candidates from herbal compounds to inhibit the SARS-CoV-2 main protease (M^(pro)). Initially, the 16 best-scored compounds were selected from a library containing 4066 ligands using virtual screening by molecular docking. Among them, six molecules (physalin B 5,6-epoxide (PHY), methyl amentoflavone…</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>Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases</strong> - Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of…</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 Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study</strong> - Given the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Meanwhile, the continuous…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The impact of loneliness on compliance with COVID-19 prevention guidelines</strong> - Many individuals have been reluctant to follow the COVID-19 prevention guidelines (e.g., wearing a mask, physical distancing, and vigilant handwashing) set forth by the U.S. Center for Disease Control to reduce the spread of COVID-19. In this research, we use reciprocal altruism theory to investigate the role of loneliness and its impact on compliance with these guidelines. Our findings indicate that lonely individuals are less willing to comply with COVID-19 prevention guidelines than…</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>B cell response after SARS-CoV-2 mRNA vaccination in people living with HIV</strong> - CONCLUSIONS: The mRNA vaccination against SARS-CoV-2 elicits humoral and B cell responses quantitatively similar between PLWHIV and HCs, but there are important differences in terms of antibody functionality and phenotypes of memory B cells, reinforcing the notion that tailored vaccination policies should be considered for these patients.</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>Design, synthesis, docking, and biochemical characterization of non-nucleoside SARS-CoV-2 RdRp inhibitors</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic. The identification of effective antiviral drugs remains an urgent medical need. In this context, here we report 17 new 1,4-benzopyrone derivatives, which have been designed, synthesized, and characterized for their ability to block the RNA-dependent RNA polymerase (RdRp) enzyme, a promising target for antiviral drug discovery. This compound series represents a good starting point for developing…</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>Broadly neutralizing aptamers to SARS-CoV-2: a diverse panel of modified DNA antiviral agents</strong> - Since its discovery COVID-19 has rapidly spread across the globe with a massive toll on human health with infection mortality rates as high as 10% and a crippling impact on the world economy. Despite numerous advances there remains an urgent need for accurate and rapid point-of-care diagnostic tests, and better therapeutic treatment options. To contribute chemically distinct, non-protein-based affinity reagents, we report here the identification of modified DNA-based aptamers that selectively…</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>Functional nucleic acids as potent therapeutics against SARS-CoV-2 infection</strong> - The COVID-19 pandemic has posed a severe threat to human life and the global economy. Although conventional treatments, including vaccines, antibodies, and small-molecule inhibitors, have been broadly developed, they usually fall behind the constant mutation of SARS-CoV-2, due to the long screening process and high production cost. Functional nucleic acid (FNA)-based therapeutics are a newly emerging promising means against COVID-19, considering their timely adaption to different mutants 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>Protein post-translational modification in SARS-CoV-2 and host interaction</strong> - SARS-CoV-2 can cause lung diseases, such as pneumonia and acute respiratory distress syndrome, and multi-system dysfunction. Post-translational modifications (PTMs) related to SARS-CoV-2 are conservative and pathogenic, and the common PTMs are glycosylation, phosphorylation, and acylation. The glycosylation of SARS-CoV-2 mainly occurs on spike (S) protein, which mediates the entry of the virus into cells through interaction with angiotensin-converting enzyme 2. SARS-CoV-2 utilizes glycans 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>Inhibitory effect of phytochemicals towards SARS-CoV-2 papain like protease (PLpro) proteolytic and deubiquitinase activity</strong> - Recent studies have shown that RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) are necessary for SARS-CoV-2 replication. Among these three enzymes, PLpro exhibits both proteolytic and deubiquitinase (DUB) activity and is responsible for disrupting the host’s innate immune response against SARS-CoV-2. Because of this unique property of PLpro, we investigated the inhibitory effects of phytochemicals on the SARS-CoV-2 PLpro enzyme. Our…</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>Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial</strong> - Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical…</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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