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<title>20 June, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds</strong> -
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<div>
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Multivalent antigen display is a well-established principle to enhance humoral immunity. Protein based virus-like particles (VLPs) are commonly used to spatially organize antigens. However, protein-based VLPs are limited in their ability to control valency on fixed scaffold geometries and are thymus-dependent antigens that elicit neutralizing B cell memory themselves, which can distract immune responses. Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV-2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo- and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.
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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/10.1101/2022.08.16.504128v3" target="_blank">Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds</a>
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</div></li>
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<li><strong>What drives preventative health behaviors several months into a pandemic: A replication and extension</strong> -
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<div>
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There is continued interest in understanding what leads people to do CDC-recommended COVID-19 prevention behaviors. We tested whether fear and COVID-19 worry would replicate as the primary drivers of six CDC recommend prevention behaviors. We recruited 741 adult participants during the second major peak of the COVID-19 pandemic in the United States (early 2021). Participants completed a 10-day daily diary. Mixed effects models identified the strongest predictors of each individual prevention behavior. At the between-person level, COVID-19 worry, COVID-19 perceived susceptibility, fear, and positive emotions all had positive zero-order associations with the prevention behaviors. However, with all predictors in the same model together, only COVID-19 worry remained significant. At the within-person level, only fear related to assessing oneself for COVID-19 on the same day, but not the next day. Findings replicated worry about yourself or a loved one getting COVID-19 as the strongest predictor of prevention behaviors.
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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/6ds3q/" target="_blank">What drives preventative health behaviors several months into a pandemic: A replication and extension</a>
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</div></li>
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<li><strong>Effective Leadership Strategies in Managing the COVID-19 Pandemic</strong> -
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<div>
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The COVID-19 pandemic has posed unprecedented challenges to governments, organizations, and communities worldwide. Effective leadership has played a critical role in managing the crisis and mitigating its impact. This paper examines the various leadership approaches and strategies employed by leaders across the globe in response to the COVID-19 pandemic. It explores the key attributes and actions demonstrated by effective leaders during this crisis and identifies best practices for future leaders facing similar challenges. The findings highlight the importance of proactive decision-making, clear communication, empathy, and collaboration in effective COVID-19 leadership.
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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/evnxz/" target="_blank">Effective Leadership Strategies in Managing the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Detecting episodic evolution through Bayesian inference of molecular clock models</strong> -
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<div>
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Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However formal model testing has the advantage of accommodating a wide range molecular clock models. In contrast, the random local clock had low power for detecting episodic evolution. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find 'very strong' evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.17.545443v1" target="_blank">Detecting episodic evolution through Bayesian inference of molecular clock models</a>
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</div></li>
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<li><strong>Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up?</strong> -
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<div>
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Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials. Some of the most notable benefits include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The use of medicinal mushrooms (MMs) as extracts in nutraceuticals and other health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.
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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/hd6vz/" target="_blank">Health promoting properties and functions of medicinal and culinary mushrooms for the COVID-19 era. An appraisal: does the “anti” mantra stack up?</a>
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</div></li>
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<li><strong>The public health impact of Paxlovid COVID-19 treatment in the United States</strong> -
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The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario (Re~1.2) treating 20% of symptomatic cases with Paxlovid would be life and cost saving, leading to an estimated 0.26 (95% CrI:0.03, 0.59) million hospitalizations averted, 30.61 (95% CrI:1.69, 71.15) thousand deaths averted, and US$52.16 (95% CrI:2.62, 122.63) billion reduction in the US. Rapid and broad use of the antiviral Paxlovid could substantially reduce COVID-19 morbidity and mortality, while averting socioeconomic hardship.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.16.23288870v1" target="_blank">The public health impact of Paxlovid COVID-19 treatment in the United States</a>
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</div></li>
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<li><strong>Association of Long COVID with housing insecurity in the United States, 2022-2023</strong> -
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Objectives. To assess the association of Long COVID with housing insecurity in the United States. Methods. To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don9t report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to-day life were associated with a higher prevalence of housing insecurity. Results. During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity. Conclusions. Compared with COVID-19 survivors who don9t experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-to-day life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.05.23290930v2" target="_blank">Association of Long COVID with housing insecurity in the United States, 2022-2023</a>
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</div></li>
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<li><strong>BUILDING RESILIENCE AGAINST HOAX: IMPROVING INTERNET MEDIA LITERACY IN THE ERA OF THE PANDEMIC COVID-19</strong> -
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<div>
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In facing the Covid-19 pandemic, the importance of enhancing internet media literacy has become crucial in building resilience against misinformation. The dissemination of false information is increasingly worrisome, despite intensive social campaigns addressing hoaxes. This research aims to enhance internet media literacy in the era of the Covid-19 pandemic. This study adopts a literature research or library research methodology. The data collection method involves two sources: primary data and secondary data. Primary data is obtained from reliable journals, articles, and readings that support this research. Meanwhile, secondary data is obtained from relevant books that pertain to the main issues addressed in the research. The findings of this study include the high prevalence of misinformation, the increase in internet media literacy, and the model for combating hoaxes.
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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/rpxdu/" target="_blank">BUILDING RESILIENCE AGAINST HOAX: IMPROVING INTERNET MEDIA LITERACY IN THE ERA OF THE PANDEMIC COVID-19</a>
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</div></li>
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<li><strong>Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19</strong> -
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<div>
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Objective: Post-acute sequelae of COVID-19 (PASC, also referred as Long-COVID) sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, and especially to activate platelets acutely, less is known about the thrombosis risk in PASC. Approach and Results: PASC patients and age-matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under venous shear stress conditions. While only a mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed platelet activation through the glycoprotein VI (GPVI) receptor was markedly decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under venous shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed using age- and sex-matched platelets from healthy individuals. Conclusions: PASC patients demonstrate dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating plasma-derived molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.18.545507v1" target="_blank">Dysregulated Platelet Function and Thrombosis in Patients with Post-Acute Sequelae of COVID-19</a>
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</div></li>
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<li><strong>SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model.</strong> -
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The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken its toll on worldwide public health infrastructure. SARS-CoV-2 is reported to exhibit wide tissue tropism, contributing to its severe pathogenicity that often culminates in multiple-organ failure. The onslaught of this disease has intensified due to the emergence of variants of concern (VOC), such as Delta and Omicron. These variants have been linked to gastrointestinal (GI) symptoms, suggesting a potential fecal-oral route of viral transmission. Here we compared the broad tissue tropism of ancestral Hong-Kong SARS-CoV-2 (SARS-CoV-2 HK) against Delta and Omicron VOCs in aa hamster model by analyzing tissue samples collected from the upper and lower respiratory system and the GI tract. We observed an overall increase in vRNA load and pro-inflammatory cytokines, especially in GI tracts of animals infected with Delta virus, indicating selective virus tropism and pathology in these tissues. However, no apparent spike in Delta viral load was observed in the large intestine and fecal matter. Overall, our research investigates the wide range of tissues that various SARS-CoV-2 strains can infect in hamsters and presents evidence supporting the increased preference of Delta VOCs for infecting the GI tract.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.19.545534v1" target="_blank">SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model.</a>
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<li><strong>Tracking national opinion about wastewater monitoring as a standard complement of public health tools in the United States</strong> -
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National opinion on a wide variety of public health topics can change over time or have highly contextual nuisances. As the COVID-19 pandemic has progressed, we aimed to see how public perceptions have changed regarding the acceptance of using wastewater for community health monitoring in the metropolitan United States. This study is an annual update of prior inquiry into knowledge of wastewater-based epidemiology, privacy concerns surrounding the collection of wastewater samples and the use of data acquired along with privacy awareness from an online survey administered in the winter of 2023. We found public support for monitoring of toxins (90.8%), disease (90.6%), terror (86.8%), gun residue (59.8%), alcohol (49%), illicit drugs (70.5%), and prescription medications (68.6%) remained high. Most respondents supported monitoring of the entire city (77.6%). This longitudinal research has shown year-upon-year only slight increases in public support of wastewater monitoring for public health protection and continues to show an absence of significant nationwide privacy concerns as long as catchment population sizes ensure fully anonymous households. This support is conditional and is probably best understood through the lens of the COVID-19 pandemic where the value proposition of public protection was popularized. The survey also consistently showed the public would support expansion of wastewater monitoring as a standard complement of public health tools into other areas of public health protection.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.16.23291485v1" target="_blank">Tracking national opinion about wastewater monitoring as a standard complement of public health tools in the United States</a>
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</div></li>
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<li><strong>Anti SARS-CoV-2 Antibody Kinetics up to 6 months of follow-up: Result from a Nation-wide Population-based, Age Stratified Sero-Epidemiological Prospective Cohort Study in India</strong> -
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Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.15.23291475v1" target="_blank">Anti SARS-CoV-2 Antibody Kinetics up to 6 months of follow-up: Result from a Nation-wide Population-based, Age Stratified Sero-Epidemiological Prospective Cohort Study in India</a>
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<li><strong>Effective vaccination strategies to control COVID-19 outbreak: A modeling study</strong> -
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OBJECTIVES Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge. METHODS A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals. RESULTS As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023. CONCLUSIONS Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.18.23291573v1" target="_blank">Effective vaccination strategies to control COVID-19 outbreak: A modeling study</a>
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<li><strong>HPV Vaccination in immunosuppressed patients with established skin warts and non-melanoma skin cancer: A single-institutional cohort study</strong> -
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Background: cSCC (cutaneous squameous cell carcinom) and its precursors are a major cause of morbidity especially in immunosuppressed patients and are frequently associated with human papilloma virus (HPV) infections. Objective: The purpose of this study is to investigate the therapeutically potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. Methods: In this retrospective study, all patients who received Gardasil-9, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. Results: The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p <0.001) between pre- and post Gardasil-9 intervention. Gardasil-9 vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 case loads during the observational period. Limitation: The retrospective study design and the rather low number of patients may influence study results. Furthermore, analysis of HPV types and data collection on vaccine-specific HPV antibody measurements was not possible. Conclusion: Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions in immunosuppressed patients with high skin tumor burden.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.16.23291486v1" target="_blank">HPV Vaccination in immunosuppressed patients with established skin warts and non-melanoma skin cancer: A single-institutional cohort study</a>
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<li><strong>Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: A systematic review and meta-analysis</strong> -
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Background Surrogates of antiviral efficacy are needed for COVID-19. We investigated the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in unvaccinated outpatients treated for mild to moderate COVID-19. Methods We searched PubMed, Scopus and medRxiv from inception to 27th September 2022, for randomised controlled trials (RCTs) which tested potential treatments for COVID-19 in non-hospitalized patients. We included studies that reported both clinical and virological outcomes. Clinical outcomes were the rate of disease progression (generally hospitalization or death within 28 days of commencing treatment) and virological outcomes were viral load (viral RNA copies in upper respiratory tract swabs) within the first 7 days of treatment. Studies were excluded if they did not report on the outcome of a primary randomised controlled trial, or if results were reported in a more complete form in another publication. Risk of Bias assessment was performed using the RoB 2.0 tool. We used generalised linear models with random effects to assess the association between outcomes and account for study heterogeneity. Findings We identified 1372 unique studies of which 14 (with a total of 9257 participants) met inclusion criteria. Larger virological treatment effects at both day 3 and day 5 were associated with decreased odds of progression to hospitalisation or death in unvaccinated ambulatory subjects. The odds ratio (OR) for each extra two-fold reduction in viral load in treated compared to control subjects was 0.54 on both days 3 and 5 post treatment (day 3 95% CI 0.38 to 0.74, day 5 95%CI 0.41 to 0.72). There was no relationship between the odds of hospitalisation or death and virological treatment effect at day 7 (OR 0.91, 95%CI 0.74 to 1.13). Interpretation Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. Funding The authors were supported by the Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council and the University of New South Wales.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.18.23291566v1" target="_blank">Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: A systematic review and meta-analysis</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: manual therapy; Other: breathing exercise and prone position alone<br/><b>Sponsor</b>: Cairo 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>Safety Study of COVID19 Vaccine on the Market</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant new coronavirus vaccine (CHO cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention<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>Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 capsule; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Placebo; Drug: Montelukast<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: RQ3025<br/><b>Sponsors</b>: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical 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>Pycnogenol® in Post-COVID-19 Condition</strong> - <b>Conditions</b>: Post COVID-19 Condition; Long COVID<br/><b>Interventions</b>: Drug: Pycnogenol®; Drug: Placebo<br/><b>Sponsor</b>: University of Zurich<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 Bailing Capsule on Pulmonary Fibrosis After COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Bailing capsule<br/><b>Sponsor</b>: Second Affiliated Hospital, School of Medicine, Zhejiang 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>To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy 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>A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation</strong> - <b>Conditions</b>: COVID-19; Hematopoietic Stem Cell Transplantation<br/><b>Intervention</b>: Biological: COVID Convalescent Plasma<br/><b>Sponsor</b>: Institute of Hematology & Blood Diseases Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)<br/><b>Sponsors</b>: Immuno Cure 3 Limited; The University of Hong Kong<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>Cupping Therapy on Immune System in Post Covid -19</strong> - <b>Condition</b>: Covid-19 Patients<br/><b>Interventions</b>: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19)</strong> - Context and objective: The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.Results: During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis</strong> - CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.</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>2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly by blocking infection-induced mitochondria depolarization</strong> - The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world’s healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified 2’,3’ cyclic-nucleotide 3’-phosphodiesterase (CNP) as a late-stage inhibitor of SARS-CoV-2 replication….</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 evolutionarily conserved strategy for ribosome binding and inhibition by β-coronavirus non-structural protein 1</strong> - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Nsp1, which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs through an unknown mechanism. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-CoV inhibits translation through ribosome binding. The C-terminal domain of all β-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>Green and rapid and instrumental one-pot method for the synthesis of imidazolines having potential anti-SARS-CoV-2 main protease activity</strong> - The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is responsible for ongoing epidemics in humans and some other mammals and has been declared a public health emergency of international concern. In this project, several small non-peptide molecules were synthesized to inhibit the major proteinase (M^(pro)) of SARS-CoV-2 using rational strategies of drug design and medicinal chemistry. M^(pro) is a key enzyme of coronaviruses and plays an essential role in mediating viral replication…</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>Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients</strong> - CONCLUSIONS: This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trial registration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420.</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>Covalent-reversible peptide-based protease inhibitors. Design, synthesis, and clinical success stories</strong> - Dysregulated human peptidases are implicated in a large variety of diseases such as cancer, hypertension, and neurodegeneration. Viral proteases for their part are crucial for the pathogens’ maturation and assembly. Several decades of research were devoted to exploring these precious therapeutic targets, often addressing them with synthetic substrate-based inhibitors to elucidate their biological roles and develop medications. The rational design of peptide-based inhibitors offered a rapid…</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>Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation</strong> - CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.</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>Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2</strong> - COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles’ inherent…</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>Tocilizumab for the treatment of COVID-19</strong> - INTRODUCTION: Since the beginning of the COVID-19 pandemic, the repurposing of medicines has been pursued to find interventions effective in preventing fatal outcome of the disease. One of these drugs was tocilizumab, an interleukin-6 inhibiting monoclonal antibody, previously used to treat several immune-related disorders.</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>Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review</strong> - The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people’s general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties 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>COVID-19 PCR: frequency of internal control inhibition in clinical practice</strong> - CONCLUSIONS: This study showed a low percentage of inhibition using RNase P as an internal control in COVID-19 PCRs using the CDC protocol, thus proving the effectiveness of this protocol for identification of SARS-CoV-2 in clinical samples. Re-extraction was efficacious for samples that showed little or no fluorescence for the RNase P gene.</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 suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study</strong> - In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for…</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>Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV</strong> - The main protease (M^(pro)) of SARS-CoV-2 is essential for viral replication, which suggests that the M^(pro) is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 M^(pro) in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 M^(pro) in cis- and trans-cleavage proteolytic assays….</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-Based Drug Design of RdRp Inhibitors against SARS-CoV-2</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing…</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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