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184 lines
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<title>04 June, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Taxpayers’ money for corporate profits: An odd concern?</strong> -
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<div>
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The article on Forbes unveiled the survey on U.S. CEOs regarding their concerns going forward. Besides well-known, and familiar issues such as labor shortages, rising inflation, supply chain disruptions, Covid-19-related disruptions, and cybersecurity, corporate executives are now also worried about future government investments in science?!
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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/x625p/" target="_blank">Taxpayers’ money for corporate profits: An odd concern?</a>
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</div></li>
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<li><strong>Age exacerbates SARS-CoV-2-induced blood-brain barrier leakage and neuropsychiatric dysfunction</strong> -
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<div>
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Persistent cognitive impairment and neuropsychiatric disorders are prevalent sequelae of SARS-CoV-2-induced COVID-19 in middle-aged adults. To model age-related neurological vulnerability to COVID-19, we induced respiratory SARS-CoV-2 MA10 infections by nasal inoculation in young (2 months) and middle-aged (12 months) mice. We hypothesized that aging and SARS-CoV-2 synergistically damage the blood-brain barrier (BBB) to worsen disease. Indeed, the combined action of aging and SARS-CoV-2 infection caused more fibrinogen leakage, T cell infiltration, and neuroinflammation in middle-aged SARS-CoV-2-infected mice than in similarly inoculated young adults. Mechanistically, SARS-CoV-2 exacerbated age-related increases in Caveolin-1 BBB transcellular permeability and loss of Wnt/{beta}-catenin ligands, with no apparent changes in tight junction proteins. Finally, SARS-CoV-2 infection induced age-dependent neuropsychiatric abnormalities including bradykinesia and repetitive behavior. These observations indicate that cerebrovascular aging, including loss of Wnt suppression of Caveolin-1, heightens vulnerability to SARS-CoV-2-induced neuroinflammation and neuropsychiatric sequalae. Our work suggests that modulation of Wnt signaling or its downstream effectors at the BBB could be potential interventional strategies for Long COVID.
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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/10.1101/2022.06.02.494552v1" target="_blank">Age exacerbates SARS-CoV-2-induced blood-brain barrier leakage and neuropsychiatric dysfunction</a>
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</div></li>
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<li><strong>Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias</strong> -
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<div>
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Concerns about the duration of protection conferred by COVID-19 vaccines have arisen in postlicensure evaluations. However, “depletion of susceptibles” bias driven by differential accrual of infection among vaccinated and unvaccinated individuals may contribute to the appearance of waning vaccine effectiveness (VE) in epidemiologic studies, potentially hindering interpretation of estimates. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design case-control study to estimate VE of mRNA-based COVID-19 vaccines between 23 February and 5 December 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from case-based surveillance along with estimated case-to-infection ratios from a population-based serological study to quantify the potential contribution of the “depletion-of-susceptibles” bias to time-varying VE estimates for 2 doses. We also estimated VE for 3 doses relative to 0 doses and 2 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval: 83.8-95.4%) at 14 days after second-dose receipt and declined to 50.8% (31.2-75.6%) at 7 months. Accounting for differential depletion-of-susceptibles among vaccinated and unvaccinated individuals, we estimated VE was 53.2% (23.6-71.2%) at 7 months among individuals who had completed the primary series (2 doses). With receipt of a third dose of BN162b2 or mRNA-1273, VE increased to 95.0% (82.8-98.6%), compared with zero doses. These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.03.22275958v1" target="_blank">Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias</a>
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</div></li>
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<li><strong>Indian Female Migrants Face Greater Barriers to Post-Covid Recovery than Males: Evidence from a Panel Study</strong> -
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<b>Background</b> India9s abrupt nationwide Covid-19 lockdown internally displaced millions of urban migrants, who made arduous journeys to distant rural homes. Documenting their labor market reintegration is a critical aspect of understanding the economic costs of the pandemic for India9s poor. In a country marked by low and declining female labor force participation, identifying gender gaps in labor market reintegration - as a marker of both women9s vulnerability at times of crisis and setbacks in women9s agency - is especially important. Yet most studies of pandemic-displaced Indian migrants are small, rely on highly selected convenience samples, and lack a gender focus. <b>Methods</b> Beginning in April 2020, we enrolled roughly 4,600 displaced migrants who had returned to two of India9s poorest states into a panel survey, which tracked enrollees through July 2021. Survey respondents were randomly selected from the states9 official databases of return migrants, with sampling stratified by state and gender. 85 percent of enrollees (3,950) were working in urban areas prior to the pandemic. Our analysis focuses on a balanced panel of 1,780 workers who were interviewed three times through July 2021, considering labor market re-entry, earnings, and measures of vulnerability by gender. <b>Findings</b> Both men and women struggle to remigrate - by July 2021 (over a year after the nationwide lockdown ended), no more than 63 percent (95% CI [60,66]) of men and 55 percent [51,59] of women had left their home villages since returning. Initially, returning migrants transition from non-agricultural urban employment into agriculture and unemployment in rural areas. Alongside, incomes plummet, with both genders earning roughly 17 percent of their pre-lockdown incomes in July 2020. Remigration is critical to regaining income - male re-migrants report earnings on par with their pre-lockdown incomes by January 2021, while men remaining in rural areas earn only 23 percent [19,27] of their pre-pandemic income. Remigration benefits women to a lesser extent - female remigrants regain no more than 65 percent [57,73] of their pre-pandemic income at any point. This contrast reflects significantly higher rates of unemployment among women, both among those remaining in rural areas (9 percentage points [6,13] higher than men across waves) and among those who remigrate (13 percentage points [9,17] higher than men across waves). As a result, we observe gender gaps in well-being: female migrants were 7 percentage points [4,10] more likely to report reduced consumption of essential goods and fare 6 percentage points [4,7] worse on a food security index. <b>Interpretation</b> Return migrants of both genders experienced persistent hardships for over a year after the initial pandemic lockdown. Female migrants fare worse, driven by both lower rates of remigration and lower rates of labor market re-entry both inside and outside home villages. Some women drop out of the labor force entirely, but most unemployed report seeking or being available to work. In short, pandemic-induced labor market displacement has far-reaching, long-term consequences for migrant workers, especially women.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.03.22275964v1" target="_blank">Indian Female Migrants Face Greater Barriers to Post-Covid Recovery than Males: Evidence from a Panel Study</a>
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</div></li>
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<li><strong>Increase of scabies infestations during the COVID-19 pandemic in Catalonia</strong> -
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During the COVID-19 pandemic, several clinicians in Spain reported an increase in scabies diagnoses. We performed a time-series analysis with data from 2014 to 2022 to quantify this increase. We found an increasing trend during late 2020 and 2021, peaking in March 2022 with an almost 4.5-fold incidence than expected, especially in those aged between 16 and 30 years. Although scabies is more frequent in most socioeconomic deprived areas, the observed rise occurs in all the areas. We recommend increasing surveillance among other countries to detect unexpected increases in scabies outbreaks.
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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/10.1101/2022.06.02.22275934v1" target="_blank">Increase of scabies infestations during the COVID-19 pandemic in Catalonia</a>
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</div></li>
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<li><strong>Genetic Diversity and Evolutionary Convergence of Cryptic SARS-CoV-2 Lineages Detected Via Wastewater Sequencing</strong> -
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Wastewater-based epidemiology (WBE) is an effective way of tracking the appearance and spread of SARS-COV-2 lineages through communities. Beginning in early 2021, we implemented a targeted approach to amplify and sequence the receptor binding domain (RBD) of SARS-COV-2 to characterize viral lineages present in sewersheds. Over the course of 2021, we reproducibly detected multiple SARS-COV-2 RBD lineages that have never been observed in patient samples in 9 sewersheds located in 3 states in the USA. These cryptic lineages contained between 4 to 24 amino acid substitutions in the RBD and were observed intermittently in the sewersheds in which they were found for as long as 14 months. Many of the amino acid substitutions in these lineages occurred at residues also mutated in the Omicron variant of concern (VOC), often with the same substitution. One of the sewersheds contained a lineage that appeared to be derived from the Alpha VOC, but the majority of the lineages appeared to be derived from pre-VOC SARS-COV-2 lineages. Specifically, several of the cryptic lineages from New York City appeared to be derived from a common ancestor that most likely diverged in early 2020. While the source of these cryptic lineages has not been resolved, it seems increasingly likely that they were derived from immunocompromised patients or animal reservoirs. Our findings demonstrate that SARS-COV-2 genetic diversity is greater than what is commonly observed through routine SARS-CoV-2 surveillance. Wastewater sampling may more fully capture SARS-CoV-2 genetic diversity than patient sampling and could reveal new VOCs before they emerge in the wider human population.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.03.22275961v1" target="_blank">Genetic Diversity and Evolutionary Convergence of Cryptic SARS-CoV-2 Lineages Detected Via Wastewater Sequencing</a>
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</div></li>
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<li><strong>Delays in COVID-19 Diagnosis and Hospitalization and Outcomes — New York City, New York, USA, October 2020–November 2021</strong> -
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COVID-19 patients diagnosed ≥3 days after symptom onset had increased odds of hospitalization. The 75th percentile for diagnosis delay was 5 days for residents of low-privilege areas and Black and Hispanic people diagnosed before SARS-CoV-2 Delta predominance, compared with 4 days for other patients, indicating inequities in prompt diagnosis.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.02.22275918v1" target="_blank">Delays in COVID-19 Diagnosis and Hospitalization and Outcomes — New York City, New York, USA, October 2020–November 2021</a>
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</div></li>
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<li><strong>Data Source Concordance for Infectious Disease Epidemiology</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: As highlighted by the COVID-19 pandemic, researchers are eager to make use of a wide variety of data sources, both government-sponsored and alternative, to characterize the epidemiology of infectious diseases. To date, few studies have investigated the strengths and limitations of sources currently being used for such research. These are critical for policy makers to understand when interpreting study findings. Methods: To fill this gap in the literature, we compared infectious disease reporting for three diseases (measles, mumps, and varicella) across four different data sources: Optum (health insurance billing claims data), HealthMap (online news surveillance data), Morbidity and Mortality Weekly Reports (official government reports), and National Notifiable Disease Surveillance System (government case surveillance data). We reported the yearly number of national- and state-level disease-specific case counts and disease clusters according to each of our sources during a five-year study period (2013-2017). Findings: Our study demonstrated drastic differences in reported infectious disease incidence across data sources. When compared against the other three sources of interest, Optum data showed substantially higher, implausible standardized case counts for all three diseases. Although there was some concordance in identified state-level case counts and disease clusters, all four sources identified variations in state-level reporting. Interpretation: Researchers should consider data source limitations when attempting to characterize the epidemiology of infectious diseases. Some data sources, such as billing claims data, may be unsuitable for epidemiological research within the infectious disease context.
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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/10.1101/2022.06.02.22275926v1" target="_blank">Data Source Concordance for Infectious Disease Epidemiology</a>
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<li><strong>Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae</strong> -
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Background: Olfactory dysfunction (OD) often accompanies acute coronavirus disease 2019 (COVID-19) and its sequelae. Herein, we investigated OD during COVID-19 recovery in the context of other symptoms, quality of life, physical and mental health. Methods: Symptom recovery patterns were analyzed in a bi-national, ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and a multi-center observational cross-sectional cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up) with multi-dimensional scaling, association rule mining and partitioning around medoids clustering. Results: Both in the ambulatory collective (72%, n = 655/906) and the cross-sectional ambulatory and hospitalized cohort (41%, n = 44/108) self-reported OD was frequent during acute COVID-19, displayed a slow recovery pace (ambulatory: 28 days, cross-sectional: 90 days median recovery time) and commonly co-occurred with taste disorders. In the ambulatory collective, a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorder (>90 days) was identified. This post-acute smell and taste disorder phenotype was characterized by a low frequency of other leading post-acute symptoms including fatigue, respiratory and neurocognitive complaints. Despite a protracted smell and taste dysfunction, this subset had high ratings of physical performance, mental health, and quality of life. Conclusion: Our results underline the clinical heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype may represent a distinct COVID-19 recovery pathway characterized by a good recovery of other COVID-19 related symptoms. Study registration: ClinicalTrials.gov: NCT04661462 (ambulatory collective), NCT04416100 (cross-sectional cohort).
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.02.22275932v1" target="_blank">Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae</a>
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</div></li>
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<li><strong>Discovery of host-directed modulators of virus infection by probing the SARSCoV-2-host protein-protein interaction network</strong> -
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The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to better understand virus-host interactions. We developed a network-based algorithm that expands the SARS-CoV-2-host protein interaction network and identifies host targets that modulate viral infection. To disrupt the SARS-CoV-2 interactome, we systematically probed for potent compounds that selectively target the identified host proteins with high expression in cells relevant to COVID-19. We experimentally tested seven chemical inhibitors of the identified host proteins for modulation of SARS-CoV-2 infection in human cells that express ACE2 and TMPRSS2. Inhibition of the epigenetic regulators bromodomain-containing protein 4 (BRD4) and histone deacetylase 2 (HDAC2), along with ubiquitin specific peptidase (USP10), enhanced SARS-CoV-2 infection. Such proviral effect was observed upon treatment with compounds JQ1, vorinostat, romidepsin, and spautin-1, when measured by cytopathic effect and validated by viral RNA assays, suggesting that HDAC2, BRD4 and USP10 host proteins have antiviral functions. The network-based approach enables systematic identification of host-targets that selectively modulate the SARS-CoV-2 interactome, as well as reveal novel chemical tools to probe virus-host interactions that regulate virus infection.
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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/10.1101/2022.06.03.494640v1" target="_blank">Discovery of host-directed modulators of virus infection by probing the SARSCoV-2-host protein-protein interaction network</a>
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<li><strong>Atomic-scale Quantum Chemical Calculation of Omicron Mutations Near Cleavage Sites of the Spike Protein</strong> -
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<div>
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The attachment of the Spike-protein in SARS-CoV-2 to host cells and the initiation of viral invasion are two critical processes in the viral infection and transmission processes in which the presence of unique furin (S1/S2) and TMPRSS2 (S2’) cleavage sites play a pivotal role. In this study, we provide detailed analysis of the impact of the BA.1 Omicron variant mutations, vicinal to these two cleavage sites using a novel computational method based on Amino acid-amino acid bond pair unit (AABPU), a specific protein structural unit in 3D as a proxy for quantifying the atomic interaction. We have identified several key features related to the electronic structure as well as bonding of the Omicron mutations near the cleavage sites that significantly increase the size of the relevant AABPUs and the fraction of the positive partial charge. These results of the ultra-large-scale quantum calculations enable us to conjecture on the biological role of Omicron mutations and their specific effects on cleavage sites, as well as identify the principles that can be of some value in analyzing other new variants or subvariants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.03.494698v1" target="_blank">Atomic-scale Quantum Chemical Calculation of Omicron Mutations Near Cleavage Sites of the Spike Protein</a>
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</div></li>
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<li><strong>Single-cell RNA-sequencing data analysis reveals a highly correlated triphasic transcriptional response to SARS-CoV-2 infection</strong> -
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<div>
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Single-cells RNA sequencing (scRNA-seq) is currently one of the most powerful techniques available to study the transcriptional response of cells to external perturbations. However, the use of conventional bulked RNA-seq analysis methods can miss important patterns underlying in the scRNA-seq data. Here, we present a reanalysis of scRNA-seq data from human bronchial epithelial cells and colon and ileum organoids using pseudo-time profiles based on the degree of virus accumulation which reflect the progress of infection. Our analysis revealed a transcriptional response to infection characterized by three distinct up- and down-regulatory phases, that cannot be detected using classical two-group comparisons. Interrogation of results, focused on genes involved in interferon-response, transcription factors and RNA-binding proteins, suggests a highly correlated transcriptional response for most genes. In addition, correlation network analysis revealed a distinct response of genes involved in translation and mitochondrially-encoded genes. Based on our data, we propose a model where modulation of nucleocytoplasmic traffic by the viral protein nsp1 explains the triphasic transcriptional response to SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.03.494642v1" target="_blank">Single-cell RNA-sequencing data analysis reveals a highly correlated triphasic transcriptional response to SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers</strong> -
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<div>
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Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.02.493651v1" target="_blank">Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers</a>
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<li><strong>Taxonium: a web-based tool for exploring large phylogenetic trees</strong> -
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The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. Previous web-based tools for phylogenetic exploration were not able to directly scale to this size of tree. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes. Taxonium allows visualisation of mutation-annotated trees, where the genotypes at each internal node are indicated, and also links each node to associated metadata. An optional server-side backend permits rapid loading for widely used datasets, while a client-only mode allows the exploration of niche or sensitive data. Taxonium is an open-source tool which can be applied to any large tree. We provide an application for exploring a public tree of more than five million SARS-CoV-2 sequences at http://cov2tree.org, the broader Taxonium tool at http://taxonium.org, and source code at https://github.com/theosanderson/taxonium.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.03.494608v1" target="_blank">Taxonium: a web-based tool for exploring large phylogenetic trees</a>
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<li><strong>Urban Exodus? Understanding Human Mobility in Britain During the COVID-19 Pandemic Using Facebook Data</strong> -
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Existing empirical work has focused on assessing the effectiveness of non-pharmaceutical interventions on human mobility to contain the spread of COVID-19. Less is known about the ways in which the COVID-19 pandemic has reshaped the spatial patterns of population movement within countries. Anecdotal evidence of an urban exodus from large cities to rural areas emerged during early phases of the pan- demic across western societies. Yet, these claims have not been empirically assessed. Traditional data sources, such as censuses offer coarse temporal frequency to analyse population movement over short-time intervals. Drawing on a data set of 21 million observations from Facebook users, we aim to analyse the extent and evolution of changes in the spatial patterns of population movement across the rural-urban continuum in Britain over an 18-month period from March, 2020 to August, 2021. Our findings show an overall and sustained decline in population movement during periods of high stringency measures, with the most densely populated areas reporting the largest reductions. During these periods, we also find evidence of higher-than-average mobility from highly dense population areas to low densely populated areas, lending some support to claims of large-scale population movements from large cities. Yet, we show that these trends were temporary. Overall mobility levels trended back to pre-coronavirus levels after the easing of non-pharmaceutical interventions. Following these interventions, we also found a reduction in movement to low density areas and a rise in mobility to high density agglomerations. Overall, these findings reveal that while COVID-19 generated shock waves leading to temporary changes in the patterns of population movement in Britain, the resulting vibrations have not significantly reshaped the prevalent structures in the national pattern of population movement.
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🖺 Full Text HTML: <a href="https://osf.io/6hjv3/" target="_blank">Urban Exodus? Understanding Human Mobility in Britain During the COVID-19 Pandemic Using Facebook Data</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>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Hymecromone tablets; Other: Placebo<br/><b>Sponsor</b>: Shanghai Zhongshan 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>A Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>: University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB<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>Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Eucalyptus Oil; Drug: Standard COVID medication<br/><b>Sponsors</b>: Hasanuddin University; Ministry of Agriculture, Republic of Indonesia<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: Asymptomatic COVID-19<br/><b>Interventions</b>: Drug: Cepharanthine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Jiao Tong University School of Medicine; YUNNAN BAIYAO GROUP 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 Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<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>α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Real-time Quaking-Induced Conversion (RT-QuIC)<br/><b>Sponsor</b>: Medical University Innsbruck<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 of a Third Dose of COVID-19 Vaccine(Vero Cell), Inactivated in the Elderly</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated<br/><b>Sponsor</b>: Sinovac Research and Development Co., Ltd.<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>Efficacy, Safety and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)(Recov)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1a Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure 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 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure 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>Paxlovid in the Treatment of COVID-19 Patients With Uremia</strong> - <b>Conditions</b>: COVID-19; Uremia<br/><b>Interventions</b>: Drug: Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telemedically Assisted Sampling of COVID-19 Patients - Is the Sampling Quality Sufficient</strong> - <b>Conditions</b>: Telemedicine; Pharynx; COVID-19<br/><b>Intervention</b>: Diagnostic Test: telemedically guided oropharyngeal + nasal (OP+N) self-sampling (GSS) and nasopharyngeal (NP) or OP+N sampling performed by health care professionals (HCP)<br/><b>Sponsor</b>: Teststation Praxis Dr. med Bielecki<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>Treatment of COVID-19 Post-acute Cognitive Impairment Sequelae With tDCS</strong> - <b>Conditions</b>: Cognitive Impairment; Post-Acute Sequelae of SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Procedure: Active tDCS and cognitive training; Procedure: Sham tDCS and cognitive training<br/><b>Sponsors</b>: University of Sao Paulo; Fundação de Amparo à Pesquisa do Estado de São Paulo<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>Improving Pediatric COVID-19 Vaccine Uptake Using an mHealth Tool</strong> - <b>Conditions</b>: COVID-19 Vaccines; Telemedicine; Vaccine Hesitancy; Pediatric ALL<br/><b>Interventions</b>: Behavioral: COVID-19 Vaccine Uptake App; Other: General Health App<br/><b>Sponsors</b>: University of Arkansas; National Institutes of Health (NIH); University of Nebraska; University of Montana<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential effects of icariin, the Epimedium-derived bioactive compound in the treatment of COVID-19: a hypothesis</strong> - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world’s health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm-induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major…</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>Ginsenoside Rg1 suppresses paraquat-induced epithelial cell senescence by enhancing autophagy in an ATG12-dependent manner</strong> - Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ-induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ-poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ-induced…</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>Insights into Coronavirus Papain-like Protease Structure, Function and Inhibitors</strong> - Coronavirus are pathogens that seriously affect human and animal health. They mostly cause respiratory or enteric diseases, which can be severe and life threatening, such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East Respiratory Syndrome (MERS) in humans. The conserved coronaviral papain-like protease is an attractive antiviral drug target because it is essential for coronaviral replication and it also inhibits host innate immune responses….</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 comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19)</strong> - Coronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients’ immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are…</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>Cleavage of the selective autophagy receptor SQSTM1/p62 by the SARS-CoV-2 main protease NSP5 prevents the autophagic degradation of viral membrane proteins</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) global pandemic. Omicron, a new variant of SARS-CoV-2, has the characteristics of strong transmission and pathogenicity, short incubation period, and rapid onset progression, and has spread rapidly around the world. The high replication rate and intracellular accumulation of SARS-CoV-2 are remarkable, but the underlying molecular mechanisms remain unclear. Autophagy acts as a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein</strong> - Protein tertiary structure mimetics are valuable tools to target large protein-protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a previously reported three-helix-bundle miniprotein that targets the receptor-binding domain (RBD) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Through truncation of the third helix and optimization of the interhelical loop residues of the miniprotein, we developed a thermostable dimeric…</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>Metformin therapy in COVID-19: inhibition of NETosis</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>What Is an Antibody Test? Characteristics of Antibodies against SARS-CoV-2 and Their Tests</strong> - Antibodies play a major role in immune responses against viruses, which inhibit infection by binding to target viral antigen. Antibodies are induced by viral entry to the body and vaccination that artificially induces immune responses; therefore, antibody tests are used in research for infection history and evaluation of vaccine efficacy. Currently, antibody tests against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by immunochromatography, enzyme-linked immunosorbent assay…</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>Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19</strong> - SARS-CoV-2 is the causative viral pathogen driving the COVID-19 pandemic that prompted an immediate global response to the development of vaccines and antiviral therapeutics. For antiviral therapeutics, drug repurposing allows for rapid movement of the existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. One effective antiviral treatment strategy used early in symptom onset is to prevent viral entry. SARS-CoV-2 enters ACE2-expressing cells…</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>Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction</strong> - Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-Resolution Magic-Angle Spinning NMR Spectroscopy for Evaluation of Cell Shielding by Virucidal Composites Based on Biogenic Silver Nanoparticles, Flexible Cellulose Nanofibers and Graphene Oxide</strong> - Antiviral and non-toxic effects of silver nanoparticles onto in vitro cells infected with coronavirus were evaluated in this study using High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) spectroscopy. Silver nanoparticles were designed and synthesized using an orange flavonoid-hesperetin (HST)-for reduction of silver(I) and stabilization of as obtained nanoparticles. The bio-inspired process is a simple, clean, and sustainable way to synthesize biogenic silver…</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>Unravelling the Therapeutic Potential of Botanicals Against Chronic Obstructive Pulmonary Disease (COPD): Molecular Insights and Future Perspectives</strong> - Background: COPD (chronic obstructive pulmonary disease) is a serious health problem worldwide. Present treatments are insufficient and have severe side effects. There is a critical shortage of possible alternative treatments. Medicinal herbs are the most traditional and widely used therapy for treating a wide range of human illnesses around the world. In several countries, different plants are used to treat COPD. Purpose: In this review, we have discussed several known cellular and molecular…</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>Binding of SARS-CoV-2 protein ORF9b to mitochondrial translocase TOM70 prevents its interaction with chaperone HSP90</strong> - The emergence of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a great threat to global health. ORF9b, an important accessory protein of SARS-CoV-2, plays a critical role in the viral host interaction, targeting TOM70, a member of the mitochondrial translocase of the outer membrane complex. The assembly between ORF9b and TOM70 is implicated in disrupting mitochondrial antiviral signaling, leading to immune evasion. We describe 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>High-throughput drug screening allowed identification of entry inhibitors specifically targeting different routes of SARS-CoV-2 Delta and Omicron/BA.1</strong> - The Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) has continuously evolved, resulting in the emergence of several variants of concern (VOCs). To study mechanisms of viral entry and potentially identify specific inhibitors, we pseudotyped lentiviral vectors with different SARS-CoV-2 VOC spike variants (D614G, Alpha, Beta, Delta, Omicron/BA.1), responsible for receptor binding and membrane fusion. These SARS-CoV-2 lentiviral pseudoviruses were applied to screen 774 FDA-approved…</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>Exploration of potential inhibitors for SARS-CoV-2 Mpro considering its mutants via structure-based drug design, molecular docking, MD simulations, MM/PBSA and DFT calculations</strong> - The main protease (Mpro) of SARS-COV-2 plays a vital role in the viral life cycle and pathogenicity. Due to its specific attributes, this 3-chymotrypsin like protease (3Cl-P) can be a reliable target for the drug design to combat COVID-19. Since the advent of COVID-19, Mpro has undergone many mutations. Here, the impact of 10 mutations based on their frequency and 5 more based on their proximity to the active site was investigated. For comparison purposes, the docking process was also performed…</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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