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190 lines
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<title>14 November, 2022</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>Mortality Classification of Hospitalized COVID-19 Patients in Zambia Using Machine Learning</strong> -
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<div>
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COVID-19 has wreaked havoc globally, it has resulted in millions of cases and deaths. Scientist and public health professionals have used every form of advancing technology to curb the spread, predict the unforeseen adverse events, improve preparedness, and bring the world under control once more. The objective of this study was to predict mortality in hospitalized COVID-19 patients in Zambia using ML methods from factors that have been shown to be predictive of mortality. This research used powerful ML models in predicting COVID-19 mortality in 1,433 hospitalized patients in Zambia. The feature importance analysis helped in identification of important factors. The ML models of GB, RF, SVM, DT, LR, and NB were used and various performance metrics were checked. The feature importance analysis found that hospital length of stay (LOS) and white blood cell count were the most influential, other factors arranged in order of reducing importance included: age, wave, diabetes, hypertension, and sex. The top 3 performing models achieved the following: GB had accuracy of 91.5%, recall of 93.6%, F1 Score of 91.7%, and ROC-AUC of 96.9%. RF had accuracy of 90.9%, recall of 93.8%, F1 Score of 91.2%, and ROC-AUC of 96.8%. SVM had accuracy of 87.8%, recall of 91.2%, F1 Score of 88.2%, and ROC-AUC of 94.1%. Other models showed similar results for the same metrics. The study successfully derived and validated multiple ML models that predicted mortality effectively with reasonably high performance in stated metrics. The GB was the best suited for the data in this study. GB was thus recommended for similar studies with RF as best alternative. Knowledge of underlying health conditions about patients’ LOS, white blood cell count, age, and other factors can help healthcare providers offer lifesaving services on time, improve preparedness and decongest health facilities.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/africarxiv/98wvg/" target="_blank">Mortality Classification of Hospitalized COVID-19 Patients in Zambia Using Machine Learning</a>
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</div></li>
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<li><strong>A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including with SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE (S100A12) gene expression, which was up-regulated in airway and blood myeloid cells from COVID-19 patients. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE+ myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell exhaustion markers, such as PD-1. IL-6 treatment of monocytes in vitro upregulated many of the severity-associated genes in the EN-RAGE gene program, along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to a rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.
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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/10.1101/2022.11.07.22282049v1" target="_blank">A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling</a>
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</div></li>
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<li><strong>Requirements to minimize airborne infections related to virus aerosol contamination at indoor cultural events</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The SARS-CoV-2 pandemic has resulted in many live events being canceled or held without spectator participation. It is therefore necessary to develop strategies to determine the conditions under which cultural activities can be maintained. In this study the results from available literature were combined with findings, guidelines and regulations for other indoor environments and recommendations were derived. In the cultural sector, the number of experimental investigations, surveys and simulations is comparatively small. This is probably due to the complexity of the events in terms of location and visitor flow, so the respective conditions under which they take place can be very different. It is therefore practically impossible to predict the risk of infection for a specific situation with potential virus spreaders attending or to derive general rules that go beyond the known measures of vaccination, testing, masks and distance. Cultural events can be held under pandemic conditions, provided certain conditions are met. Most study results agree on this. However, any recommendations for hygiene, safety and ventilation measures in cultural institutions can only minimize the risk of infection, but cannot completely rule it out. It is also of considerable importance that visitors protect themselves individually and act responsibly.
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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/10.1101/2022.11.07.22281932v1" target="_blank">Requirements to minimize airborne infections related to virus aerosol contamination at indoor cultural events</a>
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</div></li>
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<li><strong>Wastewater as a backdoor to serology?</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease in urban populations, with predictive value for upcoming increases in cases and hospitalizations. The approach primarily used in disease surveillance has been to measure the number of viral copies detected in wastewater for a study area of known population, and systems for wastewater monitoring have been put in place worldwide during the SARS-CoV-2 pandemic. However, the potential to measure other biomarkers such as proteins and metabolites in wastewater has not been fully explored. Here we develop an approach to determine antibody optical density and titer measurements from wastewater. We measured abundance of anti-SARS-CoV-2 spike IgG and IgA from typical fresh samples of community wastewater, and from a collection of frozen samples dating from 2020-22. The assay described can be performed with readily available commercial reagents, at a moderate per-sample cost, facilitating non-invasive population level immune surveillance. Our findings demonstrate the feasibility of indirect serological surveillance through wastewater for population level monitoring, and the protocol described will enable the collection of larger data sets and development of models that can be leveraged to anticipate public health needs.
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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/10.1101/2022.11.11.22282224v1" target="_blank">Wastewater as a backdoor to serology?</a>
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</div></li>
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<li><strong>SIR analytical model applied to 2020 Covid-19 data in Italy</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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A simple analytical Susceptible-Infectious- Recovered (SIR) model without vital dynamics is developed from basic assumptions. Based on the data available for the spread of the Covid 19 virus in Italy in 2020, the characteristic parameters of the model are estimated.
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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/10.1101/2022.11.09.22282122v1" target="_blank">SIR analytical model applied to 2020 Covid-19 data in Italy</a>
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</div></li>
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<li><strong>Transparency in infectious disease research: a meta-research survey of specialty journals</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Introduction: Infectious diseases carry a large global burden and have implications for society at large. Therefore, reproducible, transparent research is extremely important. To assess the current state of transparency in this field, we investigated code sharing, data sharing, protocol registration, conflict of interest and funding disclosures in articles published in the most influential infectious disease journals. Methods: We evaluated transparency indicators in the 5340 PubMed Central Open Access (PMC OA) articles published in 2019 or 2021 in the 9 most-cited specialty journals in infectious disease. We used a previously validated text-mining R package, rtransparent. The approach was manually validated for a random sample of 200 articles for which study characteristics were also extracted in detail. Main comparisons assessed 2019 versus 2021 articles, 2019 versus 2021 non-COVID-19 articles, and 2021 non-COVID-19 articles versus 2021 COVID-19 articles. Results: A total of 5340 articles were evaluated (1860 published in 2019 and 3480 in 2021 (of which 1828 on COVID-19)). Text-mining identified code sharing in 98 (2%) articles, data sharing in 498 (9%), registration in 446 (8%), conflict of interest disclosures in 4209 (79%) and funding disclosures in 4866 (91%). There were substantial differences across the 9 journals in the proportion of articles fulfilling each transparency indicator: 1-9% for code sharing, 5-25% for data sharing, 1-31% for registration, 7-100% for conflicts of interest, and 65-100% for funding disclosures. There were no major differences between articles published in 2019 and non-COVID-19 articles in 2021. In 2021, non-COVID-19 articles had more data sharing (12%) than COVID-19 articles (4%). Validation-corrected imputed estimates were 3% for code sharing, 11% for data sharing, 8% for registrations, 79% for conflict of interest disclosures and 92% for funding disclosures. Conclusion: Data sharing, code sharing, and registration are very uncommon in infectious disease specialty journals. Increased transparency is required.
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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/10.1101/2022.11.11.22282231v1" target="_blank">Transparency in infectious disease research: a meta-research survey of specialty journals</a>
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</div></li>
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<li><strong>Learning from the past: a short term forecast method for the COVID-19 incidence curve</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemy has created a radically new situation where most countries provide raw measurements of their daily incidence and disclose them in real time. This enables new machine learning forecast strategies where the prediction might no longer be based just on the past values of the current incidence curve, but could take advantage of observations in many countries. We present such a simple global machine learning procedure using all past daily incidence trend curves. Each of the 27,418 COVID-19 incidence trend curves in our database contains the values of 56 consecutive days extracted from observed incidence curves across 61 word regions and countries. Given a current incidence trend curve observed over the past four weeks, its forecast in the next four weeks is computed by matching it with the first four weeks of all samples, and ranking them by their similarity to the query curve. Then the 28 days forecast is obtained by a statistical estimation combining the values of the 28 last observed days in those similar samples. Using comparison performed by the European Covid-19 Forecast Hub with the current state of the art forecast methods, we verify that the proposed global learning method, EpiLearn, compares favorably to methods forecasting from a single past curve.
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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/10.1101/2022.11.05.22281904v1" target="_blank">Learning from the past: a short term forecast method for the COVID-19 incidence curve</a>
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</div></li>
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<li><strong>Arrayed Imaging Reflectometry monitoring of anti-viral antibody production throughout vaccination and breakthrough Covid-19</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Immune responses to COVID-19 infection and vaccination are individual and varied. There is a need to understand the timeline of vaccination efficacy against current and yet to be discovered viral mutations. Assessing immunity to SARS-CoV-2 in the context of immunity to other respiratory viruses is also valuable. Here we demonstrate the capability of a fully automated prototype Arrayed Imaging Reflectometry (AIR) system to perform reliable longitudinal serology against a 34-plex respiratory array. The array contains antigens for respiratory syncytial virus, seasonal influenza, common human coronaviruses, MERS, SARS-CoV-1, and SARS-CoV-2. AIR measures a change in reflectivity due to the binding of serum antibodies to the antigens on the array. Samples were collected from convalescent COVID-19 donors and individuals vaccinated with a two-dose mRNA vaccine regimen. Vaccinated samples were collected prior to the first dose, one week after the first dose, one week after the second dose, and monthly thereafter. Information following booster dose and/or breakthrough infection is included for a subset of subjects. Longitudinal samples of vaccinated individuals demonstrate a rise and fall of SARS-CoV-2 spike antibodies in agreement with general knowledge of the adaptive immune response and other studies. Linear Regression analysis was performed to understand the relationship between antibodies binding to different antigens on the array. Our analysis identified strong correlations between closely related influenza virus strains as well as correlations between SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. A small test of using diluted whole blood from a fingerstick provided clean arrays with antibody binding comparable to serum. Potential applications include assessing immunity in the context of exposure to multiple respiratory viruses, clinical serology, population monitoring to facilitate public health recommendations, and vaccine development against new viruses and virus mutations.
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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/10.1101/2022.11.08.22282042v1" target="_blank">Arrayed Imaging Reflectometry monitoring of anti-viral antibody production throughout vaccination and breakthrough Covid-19</a>
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</div></li>
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<li><strong>Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Understanding early innate immune responses to coronavirus disease 2019 (COVID‐19) is crucial to developing targeted therapies to mitigate disease severity. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection elicits interferon expression leading to transcription of IFN-stimulated genes (ISGs) to control viral replication and spread. SARS-CoV-2 infection also elicits NF-κB signaling which regulates inflammatory cytokine expression contributing to viral control and likely disease severity. Few studies have simultaneously characterized these two components of innate immunity to COVID-19. We designed a study to characterize the expression of interferon alpha-2 (IFNA2) and interferon beta-1 (IFNB1), both type-1 interferons (IFN-1), interferon-gamma (IFNG), a type-2 interferon (IFN-2), ISGs, and NF-κB response genes in the upper respiratory tract (URT) of patients with mild (outpatient) versus severe (hospitalized) COVID-19. Further, we characterized the weekly dynamics of these responses in the upper and lower respiratory tracts (LRTs) and blood of severe patients to evaluate for compartmental differences. We observed significantly increased ISG and NF-κB responses in the URT of mild compared with severe patients early during illness. This pattern was associated with increased IFNA2 and IFNG expression in the URT of mild patients, a trend toward increased IFNB1-expression and significantly increased STING/IRF3/cGAS expression in the URT of severe patients. Our by-week across-compartment analysis in severe patients revealed significantly higher ISG responses in the blood compared with the URT and LRT of these patients during the first week of illness, despite significantly lower expression of IFNA2, IFNB1, and IFNG in blood. NF-κB responses, however, were significantly elevated in the LRT compared with the URT and blood of severe patients during peak illness (week 2). Our data support that severe COVID-19 is associated with impaired interferon signaling in the URT during early illness and robust pro-inflammatory responses in the LRT during peak illness.
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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/10.1101/2022.11.08.22281846v1" target="_blank">Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients</a>
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</div></li>
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<li><strong>Pandemic panic? Results of a 6-month longitudinal study on fear of COVID-19</strong> -
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<div>
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Fear is an evolutionary adaptive emotion that serves to protect the organism from harm. Once a threat diminishes, fear should also dissipate as otherwise fear may become chronic and pathological. While threat (i.e., number of infections, hospitalizations and deaths) during the ongoing COVID-19 pandemic has substantially varied over time, it remains unclear whether fear has followed a similar pattern. To examine the development of fear of COVID-19 and investigate potential predictors for chronic fear, we conducted a large online longitudinal study (N = 2000) using the Prolific platform. Participants represented unselected residents of 34 different countries. The Fear of the Coronavirus Questionnaire (FCQ) and several other demographic and psychological measures were completed monthly between March and August 2020. Overall, we find that fear steadily decreased after a peak in April 2020. Additional analyses showed that elevated fear was predicted by region (i.e., North America), anxious traits, and media use.
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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://psyarxiv.com/xtu3f/" target="_blank">Pandemic panic? Results of a 6-month longitudinal study on fear of COVID-19</a>
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</div></li>
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<li><strong>Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</strong> -
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<div>
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Emerging variants of SARS-CoV-2 still threaten the effectiveness of currently deployed vaccines, and antivirals can prove to be an effective therapeutic option for attenuating it. The papain-like protease (PLpro) is an attractive target due to its sequence conservation and critical role in the replication and pathogenesis of SARS-CoV-2. PLpro also plays very important role in modulation of host immune responses by deubiquitinating (DUBs) or deISGylating host proteins. Thus, targeting PLpro serves as a two-pronged approach to abate SARS-CoV-2. Due to its structural and functional similarities with the host DUB enzymes, an in-house library of DUB inhibitors was constituted in this study. Five promising compounds exhibiting high binding affinities with the substrate binding site of PLpro were identified from a library of 81 compounds with in silico screening, docking, and simulation studies. Interestingly, lithocholic acid, linagliptin, teneligliptin, and flupenthixol significantly inhibited the proteolytic activity of PLpro. Each of these compounds abrogated in vitro replication of SARS-CoV-2 with EC50 values in the range of 5-21 micro M. In addition, crystal structure of SARS-CoV-2 PLpro and its complex with inhibitors have been determined that revealed their inhibitory mechanism. The findings of this study provide the proof-of-principle that the DUB inhibitors hold high potential as a new class of therapeutics against SARS-CoV-2. Additionally, this is the first study that has opened a new avenue towards not only targeting PLpro active site but also simultaneously directing towards restoration of antiviral immune response of the host for deterring SARS-CoV-2.
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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/10.1101/2022.11.11.516107v1" target="_blank">Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</a>
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</div></li>
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<li><strong>Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles</strong> -
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<div>
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People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+ T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.
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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/10.1101/2022.11.11.516111v1" target="_blank">Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles</a>
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</div></li>
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<li><strong>A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein</strong> -
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<div>
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The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection and also pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor binding domain and other domains, distal to the ACE2 receptor-interaction site. Collectively, our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that can be targeted by peptides and potentially other drug-like molecules.
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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/10.1101/2022.11.11.516114v1" target="_blank">A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein</a>
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</div></li>
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<li><strong>Selection of long COVID symptoms influences prevalence estimates in a prospective cohort</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Studies on long COVID differ in the selection of symptoms used to define the condition. We aimed to assess to what extent symptom selection impacts prevalence estimates of long COVID. Methods: In a prospective cohort of patients who experienced mild to critical coronavirus disease 2019 (COVID-19), we used longitudinal data on the presence of 20 different symptoms to evaluate changes in the prevalence of long COVID over time when altering symptom selection. Results: Changing symptom selection resulted in wide variation in long COVID prevalence, even within the same study population. Long COVID prevalence at 12 months since illness onset ranged from 39.6% (95%CI=33.4-46.2) when using a limited selection of symptoms to 80.6% (95%CI=74.8-85.4) when considering any reported symptom to be relevant. Conclusions: Comparing the occurrence of long COVID is already complex due to heterogeneity in study design and population. Disparate symptom selection may further hamper comparison of long COVID estimates between populations. Harmonised data collection tools could be one means to achieve greater reproducibility and comparability of results.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.09.22282120v1" target="_blank">Selection of long COVID symptoms influences prevalence estimates in a prospective cohort</a>
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</div></li>
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<li><strong>Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study</strong> -
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A nationwide prospective study showed year-round RSV transmission in the Netherlands after an initial 2021 summer outbreak. The pattern was unprecedented and distinct from neighboring countries. Our dynamic simulation model suggests that this transmission pattern could be associated with waning immunity because of low RSV circulation during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.10.22282132v1" target="_blank">Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<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 Bivalent Booster Megastudy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Assessing Performance of the Testing Done Simple Covid 19 Antigen Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test<br/><b>Sponsors</b>: Testing Done Simple; Nao Medical Urgent Care<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 Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics 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>Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir/ritonavir; Drug: Standard of care<br/><b>Sponsors</b>: Promomed, LLC; Sponsor GmbH<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>Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products 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>A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®<br/><b>Sponsor</b>: GreenLight Biosciences, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo<br/><b>Sponsors</b>: Intravacc B.V.; Novotech (Australia) Pty Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Phase Ⅱ/Ⅲ Trial of LYB001</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB001; Biological: Placebo<br/><b>Sponsor</b>: Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Mild COVID-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: Nitric Oxide<br/><b>Sponsors</b>: Sanotize Research and Development corp.; Glenmark Pharmaceuticals Ltd. India<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1, Randomised, Double-blinded, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Immunogenicity of RH109 as Booster</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: Lyophilized COVID-19 mRNA Vaccine; Drug: Sodium chloride<br/><b>Sponsors</b>: Wuhan Recogen Biotechnology Co., Ltd.; Shenzhen Rhegen Biotechnology Co., Ltd.; Wuhan Rhegen Biotechnology 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>Role of Tele-physical Therapy in Patients With Type 2 Diabetes Mellitus Following COVID-19 Infection.</strong> - <b>Conditions</b>: Type 2 Diabetes Mellitus; COVID-19<br/><b>Interventions</b>: Other: Tele physical therapy; Other: Patient educationa and Conventional exercises<br/><b>Sponsor</b>: Prince Sattam Bin Abdulaziz University<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>Immunogenicity and Safety of ChulaCov19 BNA159 Vaccine as a Booster Dose in Adults</strong> - <b>Condition</b>: COVID-19, SARS CoV 2 Infection<br/><b>Interventions</b>: Biological: ChulaCov19 BNA159 vaccine (50 mcg); Biological: Pfizer/BNT vaccine (30 mcg)<br/><b>Sponsors</b>: Technovalia, Pty Ltd; Chulalongkorn University; Bionet Co., Ltd; Southern Star Research Pty 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 numerical solution of a mathematical model of the Covid-19 pandemic utilizing a meshless local discrete Galerkin method</strong> - It was in early December 2019 that the terrible news of the outbreak of new coronavirus disease (Covid-19) was reported by the world media, which appeared in Wuhan, China, and is rapidly spreading to other parts of China and several overseas countries. In the field of infectious diseases, modeling, evaluating, and predicting the rate of disease transmission are very important for epidemic prevention and control. Several preliminary mathematical models for Covid-19 are formulated by various…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of novel inhibitors of high affinity iron permease (FTR1) through implementing pharmacokinetics index to fight against black fungus: An in silico approach</strong> - Mucormycosis is a life-threatening fungal infection, particularly in immunocompromised patients. Mucormycosis has been reported to show resistance to available antifungal drugs and was recently found in COVID-19 as a co-morbidity that demands new classes of drugs. In an attempt to find novel inhibitors against the high-affinity iron permease (FTR1), a novel target having fundamental importance on the pathogenesis of mucormycosis, 11,000 natural compounds were investigated in this study. Virtual…</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>Chicken interferon-induced transmembrane protein 1 promotes replication of coronavirus infectious bronchitis virus in a cell-specific manner</strong> - Interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit numerous virus infections by impeding viral entry into target cells. However, increasing evidence suggests diverse functions of IFITMs in virus infection, especially with the coronavirus. We analyzed the effect of chicken interferon-induced transmembrane proteins (chIFITMs) on coronavirus infectious bronchitis virus (IBV) infection in vitro. We demonstrated that the antiviral effects of IFITMs…</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, and Biological Evaluation of Novel Ruxolitinib and Baricitinib Analogues for Potential Use Against COVID-19</strong> - The coronavirus pandemic known as COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), threatens public health worldwide. Approval of COVID-19 vaccines and antiviral drugs have greatly reduced the severe cases and mortality rate. However, the continues mutations of viruses are challenging the efficacies of vaccines and antiviral drugs. Drug repurposing campaign has identified two JAK1/2 inhibitors ruxolitinib and baricitinib as potential antiviral drugs. Ruxolitinib…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 at the Human-Animal Interface: Implication for Global Public Health from an African Perspective</strong> - The coronavirus disease 2019 (COVID-19) pandemic has become the most far-reaching public health crisis of modern times. Several efforts are underway to unravel its root cause as well as to proffer adequate preventive or inhibitive measures. Zoonotic spillover of the causative virus from an animal reservoir to the human population is being studied as the most likely event leading to the pandemic. Consequently, it is important to consider viral evolution and the process of spread within zoonotic…</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 Short 5’triphosphate RNA nCoV-L Induces a Broad-Spectrum Antiviral Response by Activating RIG-I</strong> - Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5’triphosphoric acid (5’PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Human coxsackievirus B5 and Influenza A virus) in cells. 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>Canine Coronavirus Activates Aryl Hydrocarbon Receptor during In Vitro Infection</strong> - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that interacts with substrates, including microbial metabolites. Recent advances reveal that AhR is involved in the host response to coronaviruses (CoVs) infection. Particularly, AhR antagonists decrease the expression of angiotensin-converting enzyme 2 (ACE2) via AhR up-regulation, resulting in suppression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mammalian cells. Herein, we report…</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>DNAJA3 Interacts with PEDV S1 Protein and Inhibits Virus Replication by Affecting Virus Adsorption to Host Cells</strong> - Porcine epidemic diarrhea virus (PEDV) infection causes huge economic losses to the pig industry worldwide. DNAJA3, a member of the Hsp40 family proteins, is known to play an important role in the replication of several viruses. However, it remains unknown if it interacts with PEDV. We found that DNAJA3 interacted with PEDV S1, initially with yeast two-hybrid screening and later with Co-IP, GST pull-down, and confocal imaging. Further experiments showed the functional relationship between DNAJA3…</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>An ACE2-Based Decoy Inhibitor Effectively Neutralizes SARS-CoV-2 Omicron BA.5 Variant</strong> - The recently circulating SARS-CoV-2 Omicron BA.5 is rampaging the world with elevated transmissibility compared to the original SARS-CoV-2 strain. Immune escape of BA.5 was observed after treatment with many monoclonal antibodies, calling for broad-spectrum, immune-escape-evading therapeutics. In retrospect, we previously reported Kansetin as an ACE2 mimetic and a protein antagonist against SARS-CoV-2, which proved potent neutralization bioactivity on the Reference, Alpha, Beta, Delta, 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>Immunogenicity of an mRNA-Based COVID-19 Vaccine among Adolescents with Obesity or Liver Transplants</strong> - There are limited data regarding the immunogenicity of mRNA-based SARS-CoV-2 vaccine BNT162b2 among immunosuppressed or obese adolescents. We evaluated the humoral immune response in adolescents with obesity and adolescent liver transplant recipients (LTRs) after receiving two BNT162b2 doses. Sixty-eight participants (44 males; mean age 14.9 ± 1.7 years), comprising 12 LTRs, 24 obese, and 32 healthy adolescents, were enrolled. Immunogenicity was evaluated by anti-SARS-CoV-2 spike protein…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2</strong> - Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Doxorubicin as Repurposing Inhibitory Drug for MERS-CoV PLpro</strong> - Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV…</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 <em>TMPRSS2</em> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2</strong> - As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Homology Modeling and Molecular Dynamics-Driven Search for Natural Inhibitors That Universally Target Receptor-Binding Domain of Spike Glycoprotein in SARS-CoV-2 Variants</strong> - The rapid spread of SARS-CoV-2 required immediate actions to control the transmission of the virus and minimize its impact on humanity. An extensive mutation rate of this viral genome contributes to the virus’ ability to quickly adapt to environmental changes, impacts transmissibility and antigenicity, and may facilitate immune escape. Therefore, it is of great interest for researchers working in vaccine development and drug design to consider the impact of mutations on virus-drug interactions….</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><em>Lentinus edodes</em> Polysaccharides Alleviate Acute Lung Injury by Inhibiting Oxidative Stress and Inflammation</strong> - Acute lung injury (ALI) is a kind of lung disease with acute dyspnea, pulmonary inflammation, respiratory distress, and non-cardiogenic pulmonary edema, accompanied by the mid- and end-stage characteristics of COVID-19, clinically. It is imperative to find non-toxic natural substances on preventing ALI and its complications. The animal experiments demonstrated that Lentinus edodes polysaccharides (PLE) had a potential role in alleviating ALI by inhibiting oxidative stress and inflammation, which…</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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