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191 lines
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<title>16 October, 2021</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>Japanese Dictionary for Sentiment Analysis of Counselling Text</strong> -
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Chat-based counselling has become increasingly popular in the era of telecommunication. The need for accessible therapy has been exacerbated by the COVID-19 pandemic. Given its text-based nature, chat-based counselling provides an opportunity for machine-based analysis. It even has the potential to provide machine-based counselling services. However, the informational resources for machine-based analysis and interaction are rather scarce especially in a Japanese-language context. We created a Japanese dictionary for sentiment analysis, using a technique via machine-based text analysis, tailored for counselling related text. It includes 2389 words that were frequently used in chat-based counselling corpora. The following attributes were included for each word: (1) valence rating by the general public, (2) valence rating by clinical psychologists, (3) emotionality, and (4) body-relatedness.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2g6jt/" target="_blank">Japanese Dictionary for Sentiment Analysis of Counselling Text</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally to cause the COVID-19 pandemic. Despite the constant accumulation of genetic variation in the SARS-CoV-2 population, there was little evidence for the emergence of significantly more transmissible lineages in the first half of 2020. Starting around November 2020, several more contagious and possibly more virulent Variants of Concern (VoCs) were reported in various regions of the world. These VoCs share some mutations and deletions that haven arisen recurrently in distinct genetic backgrounds. Here, we build on our previous work modelling the association of mutations to SARS-CoV-2 transmissibility and characterise the contribution of individual recurrent mutations and deletions to estimated viral transmissibility. We then assess how patterns of estimated transmissibility in all SARS-CoV-2 clades have varied over the course of the COVID-19 pandemic by summing transmissibility estimates for all individual mutations carried by any sequenced genome analysed. Such an approach recovers the Delta variant (21A) as the most transmissible clade currently in circulation, followed by the Alpha variant (20I). By assessing transmissibility over the time of sampling, we observe a tendency for estimated transmissibility within clades to slightly decrease over time in most clades. Although subtle, this pattern is consistent with the expectation of a decay in transmissibility in mainly non-recombining lineages caused by the accumulation of weakly deleterious mutations. SARS-CoV-2 remains a highly transmissible pathogen, though such a trend could conceivably play a role in the turnover of different global viral clades observed over the pandemic so far.
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</div></li>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.05.06.442903v2" target="_blank">A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2</a>
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</div>
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<li><strong>Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity</strong> -
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Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in COVID-19 patients. Lower plasma ATP and adenosine levels were identified in mild and severe COVID-19 patients associated with proinflammatory cytokine profiles compared to healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory Treg) and CD4+CD25+CD39+CD73+ T cells, and increased frequencies of high differentiated (CD27-CD28-) CD8+T cells compared to health controls. Severe COVID-19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25-CD39+ (memory T effector cell), high differentiated CD8+ T cells (CD27-CD28-) and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg, CD4+CD25+CD39+CD73+, CD8+CD73+ and low-differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+Annexin-V+ and CD8+Annexin-V+ T cells, showing increased T cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of PBMC from severe COVID-19 patients with adenosine reduced the NF-kB activation in T cells and monocytes. Together, these data add new knowledge regarding the immunopathology of COVID-19 through purinergic regulation, especially concerning adenosine deficiency.
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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/10.1101/2021.09.18.21263782v2" target="_blank">Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity</a>
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<li><strong>COVID-19 Underreporting and its Impact on Vaccination Strategies</strong> -
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We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease- transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.11.21253404v2" target="_blank">COVID-19 Underreporting and its Impact on Vaccination Strategies</a>
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<li><strong>COVID-19 Risk Factors and Mortality among Native Americans</strong> -
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BACKGROUND: Academic research on the disproportionate impact of COVID-19 among Native Americans has largely been restricted to particular indigenous groups or reservations. OBJECTIVE: We estimate COVID-19 mortality for Native Americans relative to other racial/ethnic groups and explore how state-level mortality is associated with known risk factors. METHODS: We use the Standard Mortality Ratio (SMR), adjusted for age and county, to estimate COVID-19 mortality by racial/ethnic groups for the U.S. and 10 selected states. The prevalence of risk factors is derived from the American Community Survey and the Behavioral Risk Factor Surveillance System. RESULTS: The SMR for Native Americans greatly exceeds those for Black and Latino populations and varies enormously across states. There is a strong correlation between the share of Native Americans living on a reservation and the SMR. The SMR for Native Americans is also highly correlated with the income-poverty ratio and the prevalence of multigenerational families, crowded housing, frontline worker status, and health insurance (excluding the Indian Health Service). Risk factors associated with socioeconomic status and co-morbidities are generally more prevalent for Native Americans living on homelands, a proxy for reservation status, than for those living elsewhere. CONCLUSIONS: Most risk factors for COVID-19 are disproportionately high among Native Americans, particularly for those living on homelands. Reservation life appears to increase the risk of COVID-19 mortality. CONTRIBUTION: We assemble and analyze a broader set of COVID-19-related risk factors for Native Americans than previous studies, a critical step toward understanding the exceptionally high COVID-19 death rates in this population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.13.21253515v2" target="_blank">COVID-19 Risk Factors and Mortality among Native Americans</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficient incorporation and template-dependent polymerase inhibition are major determinants for the broad-spectrum antiviral activity of remdesivir</strong> -
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Remdesivir (RDV) is a direct antiviral agent that is approved in several countries for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RDV exhibits broad- spectrum antiviral activity against positive-sense RNA viruses, e.g., SARS-CoV-2 and hepatitis C virus (HCV) and non- segmented negative-sense RNA viruses, e.g., Nipah virus (NiV), while several segmented negative-sense RNA viruses such as influenza (Flu) virus or Crimean-Congo hemorrhagic fever virus (CCHFV) are not sensitive to the drug. The reasons for this apparent pattern are unknown. Here, we expressed and purified representative RNA-dependent RNA polymerases (RdRp) and studied three biochemical parameters that have been associated with the inhibitory effects of RDV-triphosphate (TP):</div></li>
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<ol type="i">
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<li>selective incorporation of the nucleotide substrate RDV-TP, (ii) the effect of the incorporated RDV-monophosphate (MP) on primer extension, and (iii) the effect of RDV-MP in the template during incorporation of the complementary UTP. The results of this study revealed a strong correlation between antiviral effects and efficient incorporation of RDV-TP. Delayed chain-termination is heterogeneous and usually inefficient at higher NTP concentrations. In contrast, template- dependent inhibition of UTP incorporation opposite the embedded RDV-MP is seen with all polymerases. Molecular modeling suggests a steric conflict between the 1’-cyano group of RDV-MP and conserved residues of RdRp motif F. We conclude that future efforts in the development of nucleotide analogues with a broader spectrum of antiviral activities should focus on improving rates of incorporation while capitalizing on the inhibitory effects of a bulky 1’-modification.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.14.464416v1" target="_blank">Efficient incorporation and template- dependent polymerase inhibition are major determinants for the broad-spectrum antiviral activity of remdesivir</a>
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<li><strong>Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis.</strong> -
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While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203-205 in SARS-CoV-2 nucleocapsid protein. Recreating the alpha variant mutation in an early pandemic (WA-1) background, we found that the R203K-G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. Importantly, the R203K-G204R mutation increases nucleocapsid phosphorylation, providing a molecular basis for these phenotypes. Notably, an analogous alanine substitution mutant also increases SARS-CoV-2 fitness and phosphorylation, suggesting that infection is enhanced through ablation of the ancestral RG motif. Overall, these results demonstrate that variant mutations outside spike are also key components in SARS-CoV-2 continued adaptation to human infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.14.464390v1" target="_blank">Nucleocapsid mutations in SARS-CoV-2 augment replication and pathogenesis.</a>
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<li><strong>Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis</strong> -
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Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike- bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike- dependent modulation of opsonization seems to affect the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.14.464464v1" target="_blank">Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis</a>
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<li><strong>Deep learning based on stacked sparse autoencoder applied to viral genome classification of SARS-CoV-2 virus</strong> -
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Since December 2019, the world has been intensely affected by the COVID-19 pandemic, caused by the SARS-CoV-2 virus, first identified in Wuhan, China. In the case of a novel virus identification, the early elucidation of taxonomic classification and origin of the virus genomic sequence is essential for strategic planning, containment, and treatments. Deep learning techniques have been successfully used in many viral classification problems associated with viral infections diagnosis, metagenomics, phylogenetic, and analysis. This work proposes to generate an efficient viral genome classifier for the SARS-CoV-2 virus using the deep neural network (DNN) based on the stacked sparse autoencoder (SSAE) technique. We performed four different experiments to provide different levels of taxonomic classification of the SARS-CoV-2 virus. The confusion matrix presented the validation and test sets and the ROC curve for the validation set. In all experiments, the SSAE technique provided great performance results. In this work, we explored the utilization of image representations of the complete genome sequences as the SSAE input to provide a viral classification of the SARS- CoV-2. For that, a dataset based on k-mers image representation, with k=6, was applied. The results indicated the applicability of using this deep learning technique in genome classification problems.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.10.14.464414v1" target="_blank">Deep learning based on stacked sparse autoencoder applied to viral genome classification of SARS-CoV-2 virus</a>
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<li><strong>Recombination in Sarbecovirus lineage and mutations/insertions in spike protein linked to the emergence and adaptation of SARS-CoV-2</strong> -
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The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Researchers across the world are involved in finding the origin and evolution of SARS-CoV-2, its transmission route, molecular mechanism of interaction between SARS-CoV-2 and host cells, and the cause of pathogenicity etc. In this paper, we shed light on the origin, evolution and adaptation of SARS-CoV-2 into human systems. Our phylogenetic/evolutionary analysis supported that bat-CoV-RaTG13 is the closest relative of human SARS-CoV-2, outbreak of SARS-CoV-2 took place via inter-intra species mode of transmission, and host-specific adaptation occurred in SARS-CoV-2. Furthermore, genome recombination analysis found that Sarbecoviruses, the subgenus containing SARS-CoV and SARS-CoV-2, undergo frequent recombination. Multiple sequence alignment (MSA) of spike proteins revealed the insertion of four amino acid residues PRRA (Proline- Arginine-Arginine-Alanine) into the SARS-CoV-2 human strains. Structural modeling of spike protein of bat-CoV-RaTG13 also shows a high number of mutations at one of the receptor binding domains (RBD). Overall, this study finds that the probable origin of SARS-CoV-2 is the results of intra-species recombination events between bat coronaviruses belonging to Sarbecovirus subgenus and the insertion of amino acid residues PRRA and mutations in the RBD in spike protein are probably responsible for the adaptation of SARS-CoV-2 into human systems. Thus, our findings add strength to the existing knowledge on the origin and adaptation of SARS-CoV-2, and can be useful for understanding the molecular mechanisms of interaction between SARS-CoV-2 and host cells which is crucial for vaccine design and predicting future pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.05.12.091199v2" target="_blank">Recombination in Sarbecovirus lineage and mutations/insertions in spike protein linked to the emergence and adaptation of SARS-CoV-2</a>
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<li><strong>Social media as a dissemination and knowledge translation strategy among health professions educators: A scoping review protocol</strong> -
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COVID-19 has arguably affected health professions education. Educators have rapidly transitioned to delivering educational sessions remotely while clinical training opportunities have been canceled, postponed or modified. Recent commentaries and reports have recommended leveraging existing online educational resources like pre-recorded lectures, blogs, and podcasts to facilitate health professions remote learning. However, the feasibility of doing so remains uncertain and the impacts thereof are also a matter for concern. In this work, we present our critical scoping review protocol. We aim to explore whether and how health professions educators have used social media as a mechanism of dissemination and knowledge translation to support evidence informed HPE approaches in the peer-reviewed and grey literature, drawing on Engeström’s Activity Theory as a guiding theoretical framework.
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🖺 Full Text HTML: <a href="https://osf.io/te3h5/" target="_blank">Social media as a dissemination and knowledge translation strategy among health professions educators: A scoping review protocol</a>
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<li><strong>Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV-1</strong> -
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Background It has been proven that inactivated COVID-19 vaccines are safe and effective in general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). Methods 42 HIV-1 infected individuals who were stable on cART and 28 healthy individuals were enrolled in this study. Two doses of an inactivated COVID-19 vaccine (BIBP-CorV) were given 4 weeks apart. The safety and reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. Findings All the HIV-1 infected participants had a CD4+ T cell count of above 200 cells/μL both at baseline and 4 weeks after vaccination. No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. Further analyses showed that PLWH with low baseline CD4+/CD8+ T cell ratios (<0.6) generated lower antibody responses after vaccination than PLWH with medium (0.6~1.0) or high (≥1.0) baseline CD4+/CD8+ T cell ratios (P<0.01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination, but it did not lead to any adverse clinical manifestation. Moreover, we found that the general burden of HIV-1 among the PLWH cohort decreased significantly (P=0.0192) after vaccination. And the alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation. Interpretation Our data demonstrate that the inactivated COVID-19 vaccine is safe and immunogenic in PLWH who are stable on cART with unsuppressed CD4 counts. Funding This work was funded by the National Natural Science Foundation of China (Grant No. 81971559, 82041010).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.14.21263556v2" target="_blank">Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV-1</a>
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<li><strong>Association between obesity and hospitalization in mild COVID-19 young adult outpatients in Brazil: a prospective cohort study</strong> -
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Background/Objectives The aim of this study was to evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects/Methods Adults with signs and symptoms suggestive of acute SARS- CoV-2 infection who sought two hospitals (one public and one private) emergency department were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at day (D) D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results A total of 1,050 participants were screened, 310 were diagnosed with COVID-19 by RT-PCR. Median age was 37.4 (IQR 29.8-45.0) years, and 186 (60.0%) were female. Duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. A total of 98 (31.6%) were obese, and 243 (78.4%) had no previous medical conditions. Twenty three participants (23/310, 7.4%) required hospitalization during the period. After adjusting, obesity (BMI≥30.0 kg/m2) (OR=2.69, 95%CI 1.63-4.83, P<0.001) and older age (OR=1.05, 95%CI 1.01-1.09, P<0.001), were significantly associated with higher risks of hospitalization. Conclusions Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low- middle income country. Our findings highlighted the need for actions to promote additional protection for obese population, such as vaccination, and to encourage lifestyle changes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.04.21261538v2" target="_blank">Association between obesity and hospitalization in mild COVID-19 young adult outpatients in Brazil: a prospective cohort study</a>
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<li><strong>Low uptake of COVID-19 lateral flow testing among university students: a mixed methods evaluation</strong> -
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Objective: To evaluate COVID-19 lateral flow testing (LFT) among asymptomatic university students. Study design: Mixed methods evaluation of LFT among University of Bristol students. Methods: i) An analysis of testing uptake and exploration of demographic variations in uptake using logistic regression; ii) an online student survey about views on university testing; and iii) qualitative interviews to explore participants9 experiences of testing and subsequent behaviour, analysed using a thematic approach. Results: 12,391 LFTs were conducted on 8025/36,054 (22.3%) students. Only one in 10 students had the recommended two tests. There were striking demographic disparities in uptake with those from ethnic minority groups having lower uptake (e.g. 3% of Chinese students were tested vs. 30.7% of White students), and variations by level and year of study (ranging from 5.3% to 33.7%), place of residence (29.0% to 35.6%) and faculty (15.2% to 32.8%). Differences persisted in multivariable analyses. A total of 436 students completed the online survey, and twenty in-depth interviews were conducted. Barriers to engagement with testing included a lack of awareness, knowledge and understanding, and concerns about the accuracy and safety. Students understood limitations of LFTs but requested further information about test accuracy. Tests were used to inform behavioural decisions, often in combination with other information, such as the potential for exposure to the virus and perceptions of vulnerability. Conclusions: The low uptake of testing brings into question the role of mass LFT in university settings. Innovative strategies may be needed to increase LFT uptake among students.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.20.21260836v2" target="_blank">Low uptake of COVID-19 lateral flow testing among university students: a mixed methods evaluation</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Who are the Masked Unvaccinated and the Unmasked Vaccinated? Concern, Trust, and Demographic Features relating to Mask-wearing and Vaccination Status</strong> -
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In mid-August 2021, the Centers for Disease Control and Prevention (C.D.C.) issued a recommendation for both vaccinated and unvaccinated Americans to begin wearing masks in public again, particularly in places experiencing outbreaks of COVID-19, driven by the Delta variant. Further compounding this concern is the lower propensity of unvaccinated individuals to wear masks. For example, a report from July 2021 found that unvaccinated Americans, on average, tended to wear masks less than vaccinated Americans by a margin of 25 percentage points. Given the link between mask-wearing and vaccination, discussions of behaviors relating to COVID-19 often lump people into two categories: those who behave in ways that prevent the spread of COVID-19 and those who do not. However, doing so misses the complexity of who engages or doesn’t engage in behaviors that stem the spread of COVID-19, or why they do so. Vaccination and mask-wearing are two different means to the same end: preventing infection. They are, in part, driven by the same factor, concern over infection. But they are also partial substitutes, aimed at the same target, preventing infection. In our data, we find that 30% of the population is either vaccinated and unmasked; or unvaccinated and masked. Indeed, most unvaccinated individuals report wearing masks. Understanding this complexity is significant in getting people vaccinated, and in getting people to wear masks - particularly those who are unvaccinated. In this report, we divide Americans into four categories and investigate the tendencies of each group: (1) those who report wearing masks and who are unvaccinated (“the masked unvaccinated”), (2) those who report wearing masks and who are vaccinated (“the masked vaccinated”), (3) those who report not wearing masks and who are unvaccinated (“the unmasked unvaccinated”), and (4) those who report not wearing masks and who are vaccinated (“the unmasked vaccinated”).
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🖺 Full Text HTML: <a href="https://osf.io/4cr7a/" target="_blank">Who are the Masked Unvaccinated and the Unmasked Vaccinated? Concern, Trust, and Demographic Features relating to Mask-wearing and Vaccination Status</a>
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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>Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVI-DROPS; Drug: Placebo<br/><b>Sponsor</b>: Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: AD17002; Biological: Placebo (Formulation buffer)<br/><b>Sponsor</b>: Advagene Biopharma 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>Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Lymphatic OMM; Other: Light Touch<br/><b>Sponsor</b>: Rowan 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>Efficacy and Safety of Ergoferon for COVID-19 Prevention During Vaccination Against SARS-CoV-2</strong> - <b>Condition</b>: Immunization Against COVID-19<br/><b>Interventions</b>: Drug: Ergoferon; Drug: Placebo<br/><b>Sponsor</b>: Materia Medica Holding<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 Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Device: Inspiratory muscle training<br/><b>Sponsor</b>: <br/>
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Universidade Federal do Rio Grande do Norte<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 Ph 2 Trial With an Oral Tableted COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VXA-CoV2-1.1-S; Other: Placebo Tablets<br/><b>Sponsor</b>: Vaxart<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>Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Self-Benefit/Social Norm; Behavioral: Self- Benefit/No Social Norm; Behavioral: Other Benefit/Social Norm; Behavioral: Other Benefit/No Social Norm<br/><b>Sponsors</b>: University of Pennsylvania; Pennsylvania Department of Health<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine; Biological: SARS-CoV-2 Inactivated Vaccine<br/><b>Sponsors</b>: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; National Institute of Health Research and Development, Ministry of Health Republic of Indonesia<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 Safety and Tolerability Study of BDB-001 in Mild, Moderate COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: BDB-001 injection<br/><b>Sponsors</b>: <br/>
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Staidson (Beijing) Biopharmaceuticals Co., Ltd; Beijing Defengrui Biotechnology Co. Ltd<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Acetylsalicylic Acid in COVID-19 (ASA-SARS)</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Covid19<br/><b>Interventions</b>: Drug: Low-dose acetylsalicylic acid; Drug: Placebo<br/><b>Sponsors</b>: Barcelona Institute for Global Health; Hospital Universitario de Torrejón,Madrid; Hospital Universitario Infanta Leonor; Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau; Hospital del Mar; Hopsital Central de Maputo, Mozambique<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>Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: diaphragm ultrasonography<br/><b>Sponsor</b>: University Hospital, Limoges<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 Immunogenicity Study of Booster Vaccination With Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine for Prevention of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: High-dosage SARS-CoV-2 vaccine; Biological: Medium-dosage SARS-CoV-2 vaccine<br/><b>Sponsor</b>: Sinovac 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>Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Dietary Supplement: Probiotics; Dietary Supplement: Placebo<br/><b>Sponsors</b>: Centre de recherche du Centre hospitalier universitaire de Sherbrooke; Lallemand Health Solutions<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>Telerehabilitation in COVID-19 Survivors</strong> - <b>Conditions</b>: COVID-19; Telerehabilitation<br/><b>Interventions</b>: Other: telerehabilitation; Other: home exercise program; Other: informed program<br/><b>Sponsor</b>: Bandırma Onyedi Eylül 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>Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Coronavirus Infections<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08); Biological: COVID-19 vaccine (Vero cells); Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of Traditional Chinese Medicine in COVID-19: Theory, Initial Clinical Evidence, Potential Mechanisms, and Implications</strong> - CONCLUSION: While there is initial support for the use of Traditional Chinese Medicine for COVID-19, conclusions cannot be drawn to support its use as a replacement for conventional COVID-19 treatment, given the lack of high-quality evidence from strictly-designed randomized controlled trials. However, there is initial evidence suggesting that TCM may serve as an effective adjunct to conventional treatments in alleviating COVID-19 symptoms. More research is needed to confirm the efficacy 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>Structure and Dynamics of RNA Guanine Quadruplexes in SARS-CoV-2 Genome. Original Strategies against Emerging Viruses</strong> - Guanine quadruplex (G4) structures in the viral genome have a key role in modulating viruses’ biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modeling and corroborated by the excellent agreement between the corresponding calculated and experimental…</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>Acetylation of H3K27 activated lncRNA NEAT1 and promoted hepatic lipid accumulation in non-alcoholic fatty liver disease via regulating miR-212-5p/GRIA3</strong> - Non-alcoholic fatty liver disease (NAFLD) was a world-wide health burden. H3K27 acetylation, long non-coding RNA (lncRNA), and miRNA were all implicated in NAFLD regulation, yet the detailed regulatory mechanism was not well understood. LncRNA NEAT1, miR-212-5p, and GRIA3 expression were detected both in high fatty acid-treated hepatocytes cells and NAFLD patients. Lipid droplets were stained and analyzed by oil red O staining. Expression of fatty acid synthase (FASN), acetyl-CoA carboxylase…</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>Sweet Drugs for Bad Bugs: A Glycomimetic Strategy against the DC-SIGN-Mediated Dissemination of SARS-CoV-2</strong> - The C-type lectin receptor DC-SIGN is a pattern recognition receptor expressed on macrophages and dendritic cells. It has been identified as a promiscuous entry receptor for many pathogens, including epidemic and pandemic viruses such as SARS-CoV-2, Ebola virus, and HIV-1. In the context of the recent SARS-CoV-2 pandemic, DC-SIGN-mediated virus dissemination and stimulation of innate immune responses has been implicated as a potential factor in the development of severe COVID-19. Inhibition 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>Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells</strong> - An unprecedented global health crisis has been caused by a new virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed experiments to test if a hypertonic saline solution was capable of inhibiting virus replication. Our data show that 1.2% NaCl inhibited virus replication by 90%, achieving 100% of inhibition at 1.5% in the nonhuman primate kidney cell line Vero, and 1.1% of NaCl was sufficient to inhibit the virus replication by 88% in human epithelial lung cell…</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>Characterization of Phytochemicals in Ulva intestinalis L. and Their Action Against SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain</strong> - Coronavirus disease-2019 (COVID-19) has caused a severe impact on almost all aspects of human life and economic development. Numerous studies are being conducted to find novel therapeutic strategies to overcome COVID-19 pandemic in a much effective way. Ulva intestinalis L. (Ui), a marine microalga, known for its antiviral property, was considered for this study to determine the antiviral efficacy against severe acute respiratory syndrome-associated Coronavirus-2 (SARS-CoV-2). The algal sample…</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>Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine</strong> - SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cell generation and long-term persistence. Here, we investigated spike-specific memory B cells and humoral responses in 145 subjects, up to 6 months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibodies peaked 7 days after the second dose and significant antibody titers and ACE2/RBD binding inhibiting activity were still observed after…</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>ORF3a Protein of Severe Acute Respiratory Syndrome Coronavirus 2 Inhibits Interferon-Activated Janus Kinase/Signal Transducer and Activator of Transcription Signaling via Elevating Suppressor of Cytokine Signaling 1</strong> - Coronavirus disease 2019 (COVID-19) has caused a crisis to global public health since its outbreak at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, appears to efficiently evade the host immune responses, including interferon (IFN) signaling. Several SARS-CoV-2 viral proteins are believed to involve in the inhibition of IFN signaling. In this study, we discovered that ORF3a, an accessory protein of SARS-CoV-2, inhibited IFN-activated…</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>Integrin activation is an essential component of SARS-CoV-2 infection</strong> - SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS- CoV-2^(R18) particles engage…</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>Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review</strong> - Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a…</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>Possible Benefits of Zinc supplement in CVD and COVID-19 Comorbidity</strong> - As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead…</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>Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life- threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited…</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>Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19</strong> - [Figure: see text].</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>Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins</strong> - SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin’s help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface…</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>Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition</strong> - Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles (“cellular nanosponges”) mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that…</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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