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<title>21 March, 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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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</strong> -
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<div>
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There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses 48 faecal samples from 16 of the 17 bat species breeding in the UK and collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely-related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown but warrants closer surveillance.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.17.524183v4" target="_blank">Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</a>
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</div></li>
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<li><strong>Introducing the COVID-19 crisis Special Education Needs Coping Survey</strong> -
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<div>
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Individuals with special education needs have been particularly affected by the COVID-19 pandemic as they have been shown to be at high risk of losing medical and institutional support at a time when people are being asked to stay isolated, suffering increased anxiety and depression as a consequence. Their families have often found themselves under tremendous pressure to provide support, engendering financial hardship, and physical and emotional strains. In such times, it is vital that international collaborations assess the impact on the individuals and their families, affording the opportunity to make national and international comparisons of how people have coped and what needs to be done to optimize the measures taken by families, associations and governments. This paper introduces one such collaboration.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rtswa/" target="_blank">Introducing the COVID-19 crisis Special Education Needs Coping Survey</a>
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</div></li>
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<li><strong>An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery</strong> -
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Contingency tables, data represented as counts matrices, are ubiquitous across quantitative research and data-science applications. Existing statistical tests are insufficient however, as none are simultaneously computationally efficient and statistically valid for a finite number of observations. In this work, motivated by a recent application in reference-genome-free inference (Chaung et al., 2022), we develop OASIS (Optimized Adaptive Statistic for Inferring Structure), a family of statistical tests for contingency tables. OASIS constructs a test-statistic which is linear in the normalized data matrix, providing closed form p-value bounds through classical concentration inequalities. In the process, OASIS provides a decomposition of the table, lending interpretability to its rejection of the null. We derive the asymptotic distribution of the OASIS test statistic, showing that these finite-sample bounds correctly characterize the p-value bound derived up to a variance term. Experiments on genomic sequencing data highlight the power and interpretability of OASIS. The same method based on OASIS significance calls detects SARS-CoV-2 and Mycobacterium Tuberculosis strains de novo, which cannot be achieved with current approaches. We demonstrate in simulations that OASIS is robust to overdispersion, a common feature in genomic data like single cell RNA-sequencing, where under accepted noise models OASIS still provides good control of the false discovery rate, while Pearson’s X2 test consistently rejects the null. Additionally, we show on synthetic data that OASIS is more powerful than Pearson’s X2 test in certain regimes, including for some important two group alternatives, which we corroborate with approximate power calculations.
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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/10.1101/2023.03.16.533008v1" target="_blank">An interpretable, finite sample valid alternative to Pearson’s X2 for scientific discovery</a>
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</div></li>
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<li><strong>Defining drivers of under-immunisation and vaccine hesitancy in refugee and migrant populations globally to support strategies to strengthen vaccine uptake for COVID-19: a rapid review</strong> -
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Background Some refugee and migrant populations have been disproportionately impacted by the COVID-19 pandemic, yet evidence suggests lower uptake of COVID-19 vaccines. They are also an under-immunised group for many routine vaccines. We did a rapid review to explore drivers of under-immunisation and vaccine hesitancy among refugee and migrant populations globally to define strategies to strengthen both COVID-19 and routine vaccination uptake. Methods We collected global literature (01/01/2010 - 05/05/2022) pertaining to drivers of under-immunisation and vaccine hesitancy in refugees and migrants, incorporating all vaccines. We searched MEDLINE, Embase, Global Health PsycINFO and the WHO Global Research on COVID-19 database and grey literature. Qualitative data were analysed thematically to identify drivers of under-immunisation and vaccine hesitancy, then categorised using the Increasing Vaccination Model. Results 63 papers were included in this review, reporting data on diverse population groups, including refugees, asylum seekers, labour and undocumented migrants from 22 countries, with six papers reporting on a regional or global scale. Drivers of under-immunisation and vaccine hesitancy pertaining to a wide range of vaccines were covered, including COVID-19 (n=27), HPV (13), measles or MMR (3), influenza (3), tetanus (1), and vaccination in general. We found a range of factors driving under-immunisation and hesitancy in refugee and migrant groups, including unique awareness and access factors that need to be better considered in policy and service delivery. Acceptability of vaccination was often deeply rooted in social and historical context and influenced by personal risk perception. Conclusions These findings hold direct relevance to current efforts to ensure high levels of global immunisation coverage, key to which is to ensure marginalised refugees and migrant populations are included in national vaccination plans of low- middle- and high-income countries. We found a stark lack of research from low- and middle-income and humanitarian contexts on vaccination in mobile groups, a situation that needs to be urgently rectified to ensure high coverage for COVID-19 and routine vaccinations.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.20.23287477v1" target="_blank">Defining drivers of under-immunisation and vaccine hesitancy in refugee and migrant populations globally to support strategies to strengthen vaccine uptake for COVID-19: a rapid review</a>
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</div></li>
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<li><strong>Leveraging global genomic sequencing data to estimate local variant dynamics</strong> -
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Accurate, reliable, and timely estimates of pathogen variant risk are essential for informing public health responses. Unprecedented rates of genomic sequencing have generated new insights into variant dynamics. However, estimating the fitness advantage of a novel variant shortly after emergence, or its dynamics more generally in data-sparse settings, remains difficult. This challenge is exacerbated in countries where surveillance is limited or intermittent. To stabilize inference in these data-sparse settings, we develop a hierarchical modeling approach to estimate variant fitness advantage and prevalence by pooling data across geographic regions. We demonstrate our method by reconstructing SARS-CoV-2 BA.5 variant emergence, and assess performance using retrospective, out-of-sample validation. We show that stable and robust estimates can be obtained even when sequencing data are sparse. Finally, we discuss how this method can inform risk assessment of novel variants and provide situational awareness on circulating variants for a range of pathogens and use-cases.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.02.23284123v4" target="_blank">Leveraging global genomic sequencing data to estimate local variant dynamics</a>
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</div></li>
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<li><strong>Statistical analysis plan for the Identification and Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS with Protection, Paralysis, and Proning: a type-1 hybrid stepped-wedge cluster randomized effectiveness-implementation study</strong> -
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Background: The Identification and Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS with Protection, Paralysis, and Proning (TheraPPP) study is a type-1 hybrid stepped-wedge cluster randomized effectiveness-implementation study involving 17 adult Intensive Care Units (ICUs). This study will evaluate the effectiveness and implementation of an evidence-based, stakeholder-informed, multidisciplinary care pathway called Venting Wisely that standardizes the diagnosis and delivery of life-saving therapies for critically ill patients with Hypoxemic Respiratory Failure (HRF) and acute respiratory distress syndrome (ARDS). Objective: To describe a pre-specified statistical analysis plan (SAP) for the TheraPPP study prior to completion of recruitment, electronic data retrieval, and before any analysis has been conducted. Methods and analysis: The Statistical Analysis Plan (SAP) was designed by the principal investigators and senior biostatistician and reviewed in detail by the Venting Wisely Scientific Steering Group before being approved. This statistical analysis plan is reported in accordance with Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. A study specific CONSORT diagram and baseline characteristics table were developed. We estimate a total of 18816 mechanically ventilated patients will be included in this study with 11424 patients pre-implementation and 7392 patients post implementation. Given that ARDS patients are an important subgroup within this study, we estimate that this will generate a sample size of 2688 sustained ARDS patients within our TheraPPP study cohort. The primary clinical outcome is 28-day ventilator free days (VFDs). For the primary analysis, we will compare the mean 28-day VFDs pre-implementation and post-implementation using a mixed effects linear regression model to account for clustering of patients within site. Secondary clinical outcomes will be similarly compared pre-implementation and post-implementation using mixed effects linear or logistic regression models, as appropriate. All models will be adjusted for age, sex, severity of illness (sequential organ failure assessment score on admission) and severity of hypoxemia on admission based on PF ratio, as well as type and size of ICU. Pre-specified subgroups will include patient sex, age, HRF, ARDS, Covid-19 and cardiac surgical status, body mass index (BMI), height, illness acuity, and ICU volume. Ethics and Trial Registration: The study has received ethics approval from the University of Calgary (20-0646) and the University of Alberta (pro00112232). The trial was registered with ClinicalTrials.gov (NCT04744298) prior to the enrollment of any patients on Feb 8, 2021.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287218v1" target="_blank">Statistical analysis plan for the Identification and Treatment of Hypoxemic Respiratory Failure (HRF) and ARDS with Protection, Paralysis, and Proning: a type-1 hybrid stepped-wedge cluster randomized effectiveness-implementation study</a>
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<li><strong>New Approach to the SIR Inversion Problem: From the 1905-1906 Plague Outbreak in the Isle of Bombay to the 2021-2022 Omicron Surges in New York City and Los Angeles County</strong> -
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We describe a novel approach to recovering the underlying parameters of the SIR dynamic epidemic model from observed data on case incidence or deaths. We formulate a discrete-time approximation to the original continuous-time model and search for the parameter vector that minimizes the standard least squares criterion function. We show that the gradient vector and matrix of second-order derivatives of the criterion function with respect to the parameters adhere to their own systems of difference equations and thus can be exactly calculated iteratively. Applying our new approach, we estimate four-parameter SIR models on two types of datasets: (1) daily reported cases of COVID-19 during the SARS-CoV-2 Omicron/BA.1 surges of December 2021 - March 2022 in New York City and Los Angeles County; and (2) weekly deaths from a plague outbreak on the Isle of Bombay during December 1905 - July 1906, originally studied by Kermack and McKendrick in their now-classic 1927 paper. The estimated parameters from the COVID-19 data suggest a duration of persistent infectivity beyond that reported in small-scale clinical studies of mostly symptomatic subjects. The estimated parameters from the plague data suggest that the Bombay outbreak was in fact driven by pulmonic rather than bubonic plague.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.13.23287177v1" target="_blank">New Approach to the SIR Inversion Problem: From the 1905-1906 Plague Outbreak in the Isle of Bombay to the 2021-2022 Omicron Surges in New York City and Los Angeles County</a>
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</div></li>
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<li><strong>Childhood Adversity and COVID-19 Outcomes: Findings from the UK Biobank</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic has caused global declines in life expectancy; it is therefore critical to understand risk factors related to mortality and morbidity for this infectious disease. Past work indicates that certain pre-existing medical conditions, behavioral patterns, and sociodemographic factors may increase COVID-19-related negative outcomes. Left unexplored, however, is whether COVID-19 outcomes are influenced by exposure to childhood adversity. This is a notable gap given that childhood adversity is associated with lifelong physical health disparities and early mortality. We leverage data from the UK Biobank cohort (N=151,200) to investigate relations between early childhood adversity and COVID-19 mortality and morbidity. As predicted, we show that childhood adversity is associated with a higher risk of COVID-19 hospitalization and mortality, even after adjusting for potential confounding variables. Such results highlight the importance of considering early-life experiences and their impact on COVID-19 outcomes to guide public health intervention and prevention strategies.
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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/10.1101/2023.03.20.23287479v1" target="_blank">Childhood Adversity and COVID-19 Outcomes: Findings from the UK Biobank</a>
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<li><strong>Safety and Effectiveness of SA58 Nasal Spray against SARS-CoV-2 family transmission: an exploratory single-arm trial</strong> -
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Background: This study has assessed the protective effect of a new Anti-COVID-19 SA58 Nasal Spray (SA58 Nasal Spray) against SARS-CoV-2 infection under continuous exposure. Methods: This is an exploratory open-label, single-arm trial. To evaluate the safety and effectiveness of SA58 against SARS-CoV-2 family transmission, SA58 was administered to all enrolled family contacts at 3~6-hour intervals. The frequency of administration and adverse events (AEs) were self-reported by online questionnaire, and RT-PCR tests were used to diagnose SARS-CoV-2 infection. The effectiveness was assessed in comparison to a contemporaneous control group whose information was collected through three follow-up visits. Total effectiveness and single-day effectiveness were calculated. Results: The incidence of SARS-CoV-2 infection was 62.9% (44/70) in the experimental group and 94.8% (343/362) in the control group. Using SA58 nasal spray at least three times per day could possibly reduce the risk of household transmission of SARS-CoV-2 by 46.7%~56.5%. The incidence of AEs was 41.4% and the severity of all AEs was mild. Conclusion: Even under the scenario of continuous exposure to SARS-CoV-2, SA58 nasal spray remained effective in blocking viral transmission and was well tolerated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.19.23287462v1" target="_blank">Safety and Effectiveness of SA58 Nasal Spray against SARS-CoV-2 family transmission: an exploratory single-arm trial</a>
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<li><strong>Data-driven control of airborne infection risk and energy use in buildings</strong> -
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The global devastation of the COVID-19 pandemic has led to calls for a revolution in heating, ventilation, and air conditioning (HVAC) systems to improve indoor air quality (IAQ), due to the dominant role of airborne transmission in disease spread. While simple guidelines have recently been suggested to improve IAQ mainly by increasing ventilation and filtration, this goal must be achieved in an energy-efficient and economical manner and include all air cleaning mechanisms. Here, we develop a simple protocol to directly, quantitatively, and optimally control transmission risk while minimizing energy cost. We collect a large dataset of HVAC and IAQ measurements in buildings and show how models of infectious aerosol dynamics and HVAC operation can be combined with sensor data to predict transmission risk and energy consumption. Using this data, we also verify that a simple safety guideline is able to limit transmission risk in full data-driven simulations and thus may be used to guide public health policy. Our results provide a comprehensive framework for quantitative control of transmission risk using all available air cleaning mechanisms in an indoor space while minimizing energy costs to aid in the design and automated operation of healthy, energy-efficient buildings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.19.23287460v1" target="_blank">Data-driven control of airborne infection risk and energy use in buildings</a>
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<li><strong>COVID-19 primary series and booster vaccination and potential for immune imprinting</strong> -
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Laboratory science evidence suggests possibility of immune imprinting, a negative impact for vaccination on subsequent protective immunity against SARS-CoV-2 infection. We investigated differences in incidence of SARS-CoV-2 reinfection in the cohort of persons who had a primary omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio (AHR) for incidence of reinfection, factoring also adjustment for differences in testing rate, was 0.43 (95% CI: 0.39-0.49) comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23-1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48-0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when incidence was dominated by BA.4/BA.5 and BA.2.75* omicron subvariant. History of primary-series vaccination enhanced immune protection against omicron reinfection, but history of booster vaccination compromised protection against omicron reinfection. These findings do not undermine the short-term public health utility of booster vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.31.22281756v2" target="_blank">COVID-19 primary series and booster vaccination and potential for immune imprinting</a>
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<li><strong>Mouse Adapted SARS-CoV-2 Model Induces “Long-COVID” Neuropathology in BALB/c Mice</strong> -
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The novel coronavirus SARS-CoV-2 has caused significant global morbidity and mortality and continues to burden patients with persisting neurological dysfunction. COVID-19 survivors develop debilitating symptoms to include neuro-psychological dysfunction, termed “Long COVID”, which can cause significant reduction of quality of life. Despite vigorous model development, the possible cause of these symptoms and the underlying pathophysiology of this devastating disease remains elusive. Mouse adapted (MA10) SARS-CoV-2 is a novel mouse-based model of COVID-19 which simulates the clinical symptoms of respiratory distress associated with SARS-CoV-2 infection in mice. In this study, we evaluated the long-term effects of MA10 infection on brain pathology and neuroinflammation. 10-week and 1-year old female BALB/cAnNHsd mice were infected intranasally with 104 plaque-forming units (PFU) and 103 PFU of SARS-CoV-2 MA10, respectively, and the brain was examined 60 days post-infection (dpi). Immunohistochemical analysis showed a decrease in the neuronal nuclear protein NeuN and an increase in Iba-1 positive amoeboid microglia in the hippocampus after MA10 infection, indicating long-term neurological changes in a brain area which is critical for long-term memory consolidation and processing. Importantly, these changes were seen in 40-50% of infected mice, which correlates to prevalence of LC seen clinically. Our data shows for the first time that MA10 infection induces neuropathological outcomes several weeks after infection at similar rates of observed clinical prevalence of “Long COVID”. These observations strengthen the MA10 model as a viable model for study of the long-term effects of SARS-CoV-2 in humans. Establishing the viability of this model is a key step towards the rapid development of novel therapeutic strategies to ameliorate neuroinflammation and restore brain function in those suffering from the persistent cognitive dysfunction of “Long-COVID”.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.18.533204v1" target="_blank">Mouse Adapted SARS-CoV-2 Model Induces “Long-COVID” Neuropathology in BALB/c Mice</a>
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<li><strong>SARS-CoV-2 NSP12 associates with the TRiC complex and the P323L substitution is a host adaption.</strong> -
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SARS-CoV-2 emerged into the human population in late 2019 and human to human transmission has dominated the evolutionary landscape and driven the selection of different lineages. The first major change that resulted in increased transmission was the D614G substitution in the spike protein. This was accompanied by the P323L substitution in the viral RNA dependent RNA polymerase (RdRp) (NSP12). Together, with D614G these changes are the root of the predominant global SARS-CoV-2 landscape. Here, we found that NSP12 formed an interactome with cellular proteins. The functioning of NSP12 was dependent on the T-complex protein Ring Complex, a molecular chaperone. In contrast, there was differential association between NSP12 variants and components of a phosphatase complex (PP2/PP2A and STRN3). Virus expressing NSP12L323 was less sensitive to perturbations in PP2A and supports the paradigm that ongoing genotype to phenotype adaptation of SARS-CoV-2 in humans is not exclusively restricted to the spike protein.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.18.533280v1" target="_blank">SARS-CoV-2 NSP12 associates with the TRiC complex and the P323L substitution is a host adaption.</a>
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<li><strong>Analysis of spike protein variants evolved in a novel mouse model of persistent SARS-CoV-2 infection</strong> -
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SARS-CoV-2 mutation rates have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants; however, there is currently no animal model to recapitulate persistent infection. We established a novel model of persistent infection using xenografts of Calu-3 human lung cancer cells in immunocompromised mice. After infection with wild-type SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three isolated viral clones with defined mutations produced higher virus titers than the wild-type virus in Calu-3 cells without cytotoxic effects. In K18-hACE2 mice, the variants were less lethal than the wild-type virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of wild-type S protein and provided protective immunity against subsequent challenge with wild-type virus. These results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study persistent SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.19.533317v1" target="_blank">Analysis of spike protein variants evolved in a novel mouse model of persistent SARS-CoV-2 infection</a>
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<li><strong>Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</strong> -
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With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly protective antibody and T-cell responses. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, characterized, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Designed immunogens were expressed as soluble proteins with significantly higher purified yield than the Spike ectodomain. Squalene-in-water emulsion (SWE) formulated fusions were highly immunogenic. S2 immunization failed to elicit a neutralizing immune response but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant, while RBD-S2 fusions elicited broad neutralization including against the Clade 1a WIV-1 variant, and were highly efficacious. A lyophilized RBD-S2 fusion retained antigenicity and immunogenicity even after incubation at 37 degrees C for a month. In hamsters, SWE-formulated RBD-S2 showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.19.533338v1" target="_blank">Enhanced protective efficacy of a novel, thermostable, RBD-S2 fusion immunogen against SARS-CoV-2 and its variants</a>
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</div></li>
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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>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, Inc.<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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<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>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<br/><b>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>Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hormone Replacement Therapy<br/><b>Interventions</b>: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch<br/><b>Sponsors</b>: Istanbul University - Cerrahpasa (IUC); Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy<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>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Neoplasms Malignant<br/><b>Interventions</b>: Drug: EGCG; Drug: Placebo<br/><b>Sponsor</b>: Shandong Cancer Hospital and Institute<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<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>Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Balneotherapy and aquatic exercises<br/><b>Sponsors</b>: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund<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 Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: HH-120 nasal spray 1; Drug: HH-120 nasal spray 2; Drug: Placebo Comparator 1; Drug: Placebo Comparator 2<br/><b>Sponsor</b>: Beijing Ditan Hospital<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 FIRST IN HUMAN TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF SARS-CoV-2 UQSC2 VACCINE IN HEALTHY ADULTS.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: UQSC2 Vaccine; Biological: NVX-CoV2373 vaccine<br/><b>Sponsors</b>: The University of Queensland; Coalition for Epidemic Preparedness Innovations<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New bi-phosphonate derivative: Synthesis, characterization, antioxidant activity in vitro and via cyclic voltammetry mode and evaluation of its inhibition of SARS-CoV-2 main protease</strong> - In this study, we have synthesized a new molecule labeled HBPA. Its molecular structure was determined by spectroscopic methods such as: FT-IR, NMR (¹H, ^(13)C and ^(31)P); our compound is subjected to two antioxidant activities assays: DPPH scavenging and ferric reducing antioxidant power (FRAP); in the results, HBPA was expanded remarkable inhibition when compared especially to standard BHT with values of 14.936±0.808 and 7.1486±0.0645 μg/ml, respectively; in addition to the scavenging test 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>Co-pyrolysis of medical protective clothing and oil palm wastes for biofuel: Experimental, techno-economic, and environmental analyses</strong> - The ongoing global pandemic of COVID-19 has devastatingly influenced the environment, society, and economy around the world. Numerous medical resources are used to inhibit the infectious transmission of the virus, resulting in massive medical waste. This study proposes a sustainable and environment-friendly method to convert hazardous medical waste into valuable fuel products through pyrolysis. Medical protective clothing (MPC), a typical medical waste from COVID-19, was utilized 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>An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition</strong> - The main protease from SARS-CoV-2 (M^(pro)) is responsible for cleavage of the viral polyprotein. M^(pro) self-processing is called maturation, and it is crucial for enzyme dimerization and activity. Here we use C145S M^(pro) to study the structure and dynamics of N-terminal cleavage in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed of cleaved and uncleaved particles, indicating that N-terminal processing is not critical for dimerization. A 3.5 Å…</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>Bioactive Compositions of Cinnamon (<em>Cinnamomum verum</em> J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals</strong> - Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals 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>Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor</strong> - The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introduced a relatively large number of mutations, including three mutations in the highly conserved heptad repeat 1 (HR1) region of the spike glycoprotein (S) critical for its membrane fusion activity. We show that one of these mutations, N969K induces a substantial displacement in the structure of the heptad repeat 2 (HR2) backbone in the HR1HR2 postfusion bundle. Due to this mutation, fusion-entry peptide…</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>Omicron-induced interferon signalling prevents influenza A H1N1 and H5N1 virus infection</strong> - Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (α/β) and III (λ) interferons and protected cells from super-infection with influenza A viruses….</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 pharmacokinetic drug-drug interaction study between rosuvastatin and emvododstat, a potent anti-SARS-CoV-2 (COVID-19) DHODH (dihydroorotate dehydrogenase) inhibitor</strong> - A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS-CoV-2 replication. DHODH is the rate-limiting enzyme of the de novo pyrimidine nucleotide…</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>Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19</strong> - Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination 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>Therapeutic developments for SARS-CoV-2 infection-Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice</strong> - This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host…</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>Multiple functions of stress granules in viral infection at a glance</strong> - Stress granules (SGs) are distinct RNA granules induced by various stresses, which are evolutionarily conserved across species. In general, SGs act as a conservative and essential self-protection mechanism during stress responses. Viruses have a long evolutionary history and viral infections can trigger a series of cellular stress responses, which may interact with SG formation. Targeting SGs is believed as one of the critical and conservative measures for viruses to tackle the inhibition of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Erastin inhibits porcine epidemic diarrhea virus replication in Vero cells</strong> - CONCLUSIONS: Since NRF2, ACSL4 and GPX4 are classical Ferroptosis genes, this study speculates that erastin may inhibit the replication of PEDV in Vero cells in part through the regulation of ferroptosis pathway, and erastin may be a potential drug for the treatment of PEDV infection.</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>Treatment of severe covid-19 with interleukin 6 receptor inhibition</strong> - No abstract</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>Wearing N95 masks decreases the odor discrimination ability of healthcare workers: a self-controlled before-after study</strong> - CONCLUSION: Wearing N95 masks decreases the odor discrimination ability of healthcare workers. Therefore, we suggest that healthcare workers seek other clues when diagnosing disease with a characteristic odor.</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 computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 M<sup>pro</sup> inhibitor</strong> - Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library 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>In-silico studies of <em>Momordica charantia</em> extracts as potential candidates against SARS-CoV-2 targeting human main protease enzyme (M<sup>pro</sup>)</strong> - Momordica charintia, a well-known plant called bitter melon, has been shown to have antibacterial, anti-diabetic, and antiviral properties against HIV infection. The goal of this work was to investigate the inhibitory effect of phytocompounds found in Momordica charintia leaf extracts on SARS-CoV-2 3CL protease (also known as the Main protease, M^(pro)) utilizing GC-MS analysis and molecular docking studies. The Crystal Structure of the SARS-CoV-2 3CL protease in complex with an inhibitor N3 was…</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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