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192 lines
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<title>14 January, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Structure-based discovery of inhibitors of the SARS-CoV-2 Nsp14 N7-methyltransferase</strong> -
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<div>
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An under-explored target for SARS-CoV-2 is non-structural protein 14 (Nsp14), a crucial enzyme for viral replication that catalyzes the methylation of N7-guanosine of the viral RNA at 5-prime-end; this enables the virus to evade the host immune response by mimicking the eukaryotic post-transcriptional modification mechanism. We sought new inhibitors of the S-adenosyl methionine (SAM)-dependent methyltransferase (MTase) activity of Nsp14 with three large library docking strategies. First, up to 1.1 billion make-on-demand (tangible) lead-like molecules were docked against the enzyme SAM site, seeking reversible inhibitors. On de novo synthesis and testing, three inhibitors emerged with IC50 values ranging from 6 to 43 M, each with novel chemotypes. Structure-guided optimization and in vitro characterization supported their non-covalent mechanism. In a second strategy, docking a library of 16 million tangible fragments revealed nine new inhibitors with IC50 values ranging from 12 to 341 M and ligand efficiencies from 0.29 to 0.42. In a third strategy, a newly created library of 25 million tangible, virtual electrophiles were docked to covalently modify Cys387 in the SAM binding site. Seven inhibitors emerged with IC50 values ranging from 3.2 to 39 M, the most potent being a reversible aldehyde. Initial optimization of a second series yielded a 7 M acrylamide inhibitor. Three inhibitors characteristic of the new series were tested for selectivity against 30 human protein and RNA MTases, with one showing partial selectivity and one showing high selectivity. Overall, 32 inhibitors encompassing eleven chemotypes had IC50 values <50 M and 5 inhibitors in four chemotypes had IC50 values <10 M. These molecules are among the first non-SAM-like inhibitors of Nsp14, providing multiple starting points for optimizing towards antiviral activity.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.12.523677v1" target="_blank">Structure-based discovery of inhibitors of the SARS-CoV-2 Nsp14 N7-methyltransferase</a>
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</div></li>
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<li><strong>Pathogenesis of Breakthrough Infections with SARS-CoV-2 Variants in Syrian Hamsters</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved into multiple variants. Animal models are important to understand variant pathogenesis, particularly for those with mutations that have significant phenotypic or epidemiological effects. Here, cohorts of naive or previously infected Syrian hamsters (Mesocricetus auratus) were infected with variants to investigate viral pathogenesis and disease protection. Naive hamsters infected with SARS-CoV-2 variants had consistent clinical outcomes, tissue viral titers, and pathology, while hamsters that recovered from initial infection and were reinfected demonstrated less severe clinical disease and lung pathology than their naive counterparts. Males had more frequent clinical signs than females in most variant groups, but few sex variations in tissue viral titers and lung pathology were observed. These findings support the use of Syrian hamsters as a SARS-CoV-2 model and highlight the importance of considering sex differences when using this species.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.12.523876v1" target="_blank">Pathogenesis of Breakthrough Infections with SARS-CoV-2 Variants in Syrian Hamsters</a>
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</div></li>
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<li><strong>Burden, Causation, and Particularities of long-COVID in African populations: A rapid systematic review</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: The global estimated prevalence of long COVID-19 is 43%, and the most common symptoms found globally are fatigue, confusion, or lack of confusion, and dyspnea, with prevalence rates of 23%, 14%, and 13%, respectively. However, long COVID still lacks an overall review in African populations. The aim of this review was to determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms. Methods: A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). If the results could not be pooled, a narrative synthesis was performed. Results: We included 14 studies from 7 African countries, totaling 6,030 previously SARS-CoV-2 infected participants and 2,954 long COVID patients. Long COVID had a pooled prevalence of 41% [26%-56%]. Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% [26%-56%], 25% [12%-38%], and 40% [12%-68%], respectively. Long COVID was associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, post-recovery stress, sadness, and sleep disturbances, and loss of appetite at symptoms onset, mild, moderate, and severe, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P ≤0.05). According to our review, high micro clot and platelet poor plasma (PPP) viscosity explain the pathophysiology of long COVID. Conclusion: Long COVID prevalence in Africa was comparable to the global prevalence. However, the prevalence of the most common symptoms was higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.13.23284305v1" target="_blank">Burden, Causation, and Particularities of long-COVID in African populations: A rapid systematic review</a>
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</div></li>
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<li><strong>Effectiveness of Paxlovid - a review</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Paxlovid is an oral treatment for mild to moderate COVID-19 cases with a high risk for severe course of the disease. For this review, we have performed a comprehensive literature review. We present a summary of currently available data on Paxlovid9s ability to reduce the risk of progressing to a severe disease state. Our findings can be concluded as follows: data from the time when the Delta-variant was dominant shows that Paxlovid reduced the risk of hospitalization or death by 87.8% for unvaccinated, non-hospitalized high-risk individuals. Data from the time when the Omicron variant was dominant found decreased risk reductions, varying between 41% and 46%, combining various vaccination statuses. However, one study, which differentiated by age, found that the administration of Paxlovid reduced the risk of hospitalization by 67% for individuals aged 65 and older, but only by 27% for individuals aged 40-64. From the available data, one can conclude that Paxlovid cannot substitute vaccination, but its low manufacturing cost as well as its easy administration make it a valuable tool in fighting COVID-19, especially for countries with a low vaccination rate.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.13.23284506v1" target="_blank">Effectiveness of Paxlovid - a review</a>
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</div></li>
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<li><strong>A Scoping Review of Factors used to Explain Disparities in COVID-19 Vaccination Intentions and Uptake among People of Color: United States, December 1, 2020-April 30, 2021</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Vaccine access, coupled with the belief that vaccines are important, beneficial, and safe, plays a pivotal role in achieving high levels of vaccination to reduce the spread and severity of COVID-19 in the United States (U.S.) and globally. Many factors can influence vaccine intentions and uptake. Methods: We conducted a scoping review of factors (e.g., access-related factors, racism) known to influence vaccine intentions and uptake, using publications from various databases and websites published December 1, 2020-April 30, 2021. Descriptive statistics were used to present results. Results: Overall, 1094 publications were identified through the database search, of which 133 were included in this review. Among the publications included, over 60% included mistrust in vaccines and vaccine-safety concerns, 43% included racism/discrimination, 35% included lack of vaccine access (35%), and 8% had no contextual factors when reporting on vaccine intentions and disparities in vaccine uptake. Conclusions: Findings revealed during a critical period when there was a well-defined goal for adult COVID-19 vaccination in the U.S., some publications included several contextual factors while others provided limited or no contextual factors when reporting on disparities in vaccine intentions and uptake. Failing to contextualize inequities and other factors that influence vaccine intentions and uptake might be perceived as placing responsibility for vaccination status on the individual, consequently, leaving social and structural inequities that impact vaccination rates and vaccine confidence, among people of color, intact.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.12.23284499v1" target="_blank">A Scoping Review of Factors used to Explain Disparities in COVID-19 Vaccination Intentions and Uptake among People of Color: United States, December 1, 2020-April 30, 2021</a>
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</div></li>
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<li><strong>Estimates of COVID-19 deaths in Mainland China after abandoning zero COVID policy</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: China witnessed a surge of Omicron infections after abandoning zero COVID strategies on December 7, 2022. The authorities report very sparse deaths based on very restricted criteria, but massive deaths are speculated. Methods: We aimed to estimate the COVID-19 fatalities in Mainland China until summer 2023 using the experiences of Hong Kong and of South Korea in 2022 as prototypes. Both these locations experienced massive Omicron waves after having had very few SARS-CoV-2 infections during 2020-2021. We estimated age-stratified infection fatality rates (IFRs) in Hong Kong and South Korea during 2022 and extrapolated to the population age structure of Mainland China. We also accounted separately for deaths of residents in long-term care facilities in both Hong Kong and South Korea. Results: IFR estimates in non-elderly strata were modestly higher in Hong Kong than South Korea and projected 987,455 and 619,549 maximal COVID-19 deaths, respectively, if the entire China population was infected. Expected COVID-19 deaths in Mainland China until summer 2023 ranged from 49,962 to 691,219 assuming 25-70% of the non-elderly population being infected and variable protection of elderly (from none to three-quarter reduction in fatalities). The main analysis (45% of non-elderly population infected and fatality impact among elderly reduced by half) estimated 152,886-249,094 COVID-19 deaths until summer 2023. Large uncertainties exist regarding potential changes in dominant variant, health system strain, and impact on non-COVID-19 deaths. Conclusions: The most critical factor that can affect total COVID-19 fatalities in China is the extent to which the elderly can be protected.
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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/10.1101/2022.12.29.22284048v3" target="_blank">Estimates of COVID-19 deaths in Mainland China after abandoning zero COVID policy</a>
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</div></li>
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<li><strong>Diagnostic performance of lateral flow immunoassays for COVID-19 antibodies in Peruvian population</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. Methods We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests. The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. Results A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. Conclusion All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.13.23284518v1" target="_blank">Diagnostic performance of lateral flow immunoassays for COVID-19 antibodies in Peruvian population</a>
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</div></li>
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<li><strong>The COVID-19 antibody responses, isotypes and glycosylation: Why SARS-CoV-2 Spike protein complex binding of IgG3 is potentiated in some and immuno-pathologies manifest.</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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COVID-19 syndrome does not occur in all who are infected with SARS-CoV-2, and symptoms vary. The anti-SARS CoV-2 Spike immune responses is confounded by the Spike proteins ability to bind Igγ3 heavy chains. This appears to be via sialic acid glycans found on the O-Linked glycosylation moieties of this heavy chain extended neck domain. Furthermore glycosylation of light chains, particularly Kappa (κ), is an associated feature of antibodies binding to SARS-CoV-2 antigens nucleocapsid and Spike protein. COVID-19 recovered patients had increased IgG1 and IgM levels and un-glycosylated κ λ light chains; possibly In order to counter this immune system subjugation of IgG3. These molecular finding, together with our previous finding that Spike protein binds glycated human serum albumin (HSA), may explain the micro-vascular inflammatory clots that are a causative feature of COVID-19 acute respiratory syndrome (ARDS). The postulated molecular sequelae are that SARS-CoV-2 virion, entering the blood circulation, being coated with IgG3 and glycated HSA forms a colloid and deposits into micro-focal clots which are also inflammatory. It is not that all IgG3 and albumin is being bound by the virus; this depends on the affinity the SARS-CoV2 virion has for binding an individual IgG3 and albumin due to glycosylation and glycation status. The degree of glycosylation and terminal sialyation of an individuals antibodies is both a genetic and age-maturity dependant feature of the immune system. The degree of HSA glycation is also age related feature particularly related to type 2 diabetes. Thereby establishing the molecular basis of the association of severe COVID-19 disease syndrome and deaths with diabetes, metabolic disorders, and old age. Furthermore, already having cardiovascular disease, with hardened arteries, SARS-CoV2-glycated HSA-IgG3 deposition is going to exacerbate an already compromised circulatory physiology. The binding of IgG3 might also drives a shift in the immune repertoire response to SAR-CoV-2 anti-spike antibodies of increased IgG1 and prolonged IgM levels. This may be associated with Long Covid. In summary, SARS-CoV-2 Spike protein binding of IgG3, via sialic acid glycan residues, along with increased glycosylated κ-light chains and glycated-HSA may form a focal amyloid-like precipitate within blood vessels which in turn leads to the inflammatory micro-thrombosis characteristic of COVID-19 immuno-pathology.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.13.23284524v1" target="_blank">The COVID-19 antibody responses, isotypes and glycosylation: Why SARS-CoV-2 Spike protein complex binding of IgG3 is potentiated in some and immuno-pathologies manifest.</a>
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</div></li>
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<li><strong>Monitoring and responding to emerging infectious diseases in a university setting: A case study using COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Emerging infection diseases (EIDs) are an increasing threat to global public health, especially when the disease is newly emerging. Institutions of higher education (IHEs) are particularly vulnerable to EIDs because student populations frequently share high-density residences and strongly mix with local and distant populations. In fall 2020, IHEs responded to a novel EID, COVID-19. Here, we describe Quinnipiac University’s response to SARS-CoV-2 and evaluate its effectiveness through empirical data and model results. Using an agent-based model to approximate disease dynamics in the student body, the University established a policy of dedensification, universal masking, surveillance testing via a targeted sampling design, and app-based symptom monitoring. After an extended period of low incidence, the infection rate grew through October, likely due to growing incidence rates in the surrounding community. A super-spreader event at the end of October caused a spike in cases in November. Student violations of the University’s policies contributed to this event, but lax adherence to state health laws in the community may have also contributed. The model results further suggest that the infection rate was sensitive to the rate of imported infections and was disproportionately impacted by non-residential students, a result supported by the observed data. Collectively, this suggests that campus-community interactions play a major role in campus disease dynamics. Further model results suggest that app-based symptom monitoring may have been an important regulator of the University’s incidence, likely because it quarantined infectious students without necessitating test results. Targeted sampling had no substantial advantages over simple random sampling when the model incorporated contact tracing and app-based symptom monitoring but reduced the upper boundary on 90% prediction intervals for cumulative infections when either was removed. Thus, targeted sampling designs for surveillance testing may mitigate worst-case outcomes when other interventions are less effective. The results’ implications for future EIDs are discussed.
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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/10.1101/2023.01.13.23284515v1" target="_blank">Monitoring and responding to emerging infectious diseases in a university setting: A case study using COVID-19</a>
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</div></li>
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<li><strong>Bayesian sequential approach to monitor COVID-19 variants through positivity rate from wastewater</strong> -
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Trends in COVID-19 infection have changed throughout the pandemic due to myriad factors, including changes in transmission driven by social behavior, vaccine development and uptake, mutations in the virus genome, and public health policies. Mass testing was an essential control measure for curtailing the burden of COVID-19 and monitoring the magnitude of the pandemic during its multiple phases. However, as the pandemic progressed, new preventive and surveillance mechanisms emerged. Implementing vaccine programs, wastewater (WW) surveillance, and at-home COVID-19 tests reduced the demand for mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. This paper proposes a sequential Bayesian approach to estimate the COVID-19 positivity rate (PR) using SARS-CoV-2 RNA concentrations measured in WW through an adaptive scheme incorporating changes in virus dynamics. PR estimates are used to compute thresholds for WW data using the CDC thresholds for low, substantial, and high transmission. The effective reproductive number estimates are calculated using PR estimates from the WW data. This approach provides insights into the dynamics of the virus evolution and an analytical framework that combines different data sources to continue monitoring the COVID-19 trends. These results can provide public health guidance to reduce the burden of future outbreaks as new variants continue to emerge. The proposed modeling framework was applied to the City of Davis and the campus of the University of California Davis.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.10.23284365v2" target="_blank">Bayesian sequential approach to monitor COVID-19 variants through positivity rate from wastewater</a>
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</div></li>
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<li><strong>Social bonds are related to health behaviours and positive wellbeing globally</strong> -
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<div>
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At times of turmoil – such as during natural disasters, social crises, or pandemics – our social bonds can be key to receiving support and gaining certainty about the right course of action. In an analysis combining two global datasets (N= 13,264) collected during the first wave of the COVID-19 pandemic, this study examined how social bonds with close social circles (i.e., family, friends) and extended groups (i.e., country, government, humanity) relate to engagement in health behaviours and psychological wellbeing. Results revealed that only family bonding was associated with self-reported engagement in health behaviours. Being strongly bonded with both close circles and extended groups predicted less anxiety and depression, and better wellbeing, particularly for those who were bonded with more groups. These findings highlight that close and extended social bonds offer different sources of support and direction during the most challenging of circumstances, and that continuous investment is needed to forge and maintain both.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/r7pd2/" target="_blank">Social bonds are related to health behaviours and positive wellbeing globally</a>
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</div></li>
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<li><strong>Development of an amplicon-based sequencing approach in response to the global emergence of human monkeypox virus</strong> -
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The 2022 multi-country monkeypox (mpox) outbreak concurrent with the ongoing COVID-19 pandemic has further highlighted the need for genomic surveillance and rapid pathogen whole genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early mpox infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there was an urgent need for a more sensitive and broadly applicable sequencing approach. Highly multiplexed amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for SARS-CoV-2. Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented in public health laboratories during the COVID-19 pandemic. We sequenced clinical samples that tested presumptive positive for human monkeypox virus with amplicon-based and metagenomic sequencing approaches. We found notably higher genome coverage across the virus genome, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach, particularly in higher PCR cycle threshold (lower DNA titer) samples. Further testing demonstrated that Ct value correlated with the number of sequencing reads and influenced the percent genome coverage. To maximize genome coverage when resources are limited, we recommend selecting samples with a PCR cycle threshold below 31 Ct and generating 1 million sequencing reads per sample. To support national and international public health genomic surveillance efforts, we sent out primer pool aliquots to 10 laboratories across the United States, United Kingdom, Brazil, and Portugal. These public health laboratories successfully implemented the human monkeypox virus primer scheme in various amplicon sequencing workflows and with different sample types across a range of Ct values. Thus, we show that amplicon based sequencing can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole genome sequencing in response to newly emerging pathogens. Importantly, through the implementation of our primer scheme into existing SARS-CoV-2 workflows and across a range of sample types and sequencing platforms, we further demonstrate the potential of this approach for rapid outbreak response.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.14.22280783v2" target="_blank">Development of an amplicon-based sequencing approach in response to the global emergence of human monkeypox virus</a>
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</div></li>
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<li><strong>Data-driven Targeting of COVID-19 Vaccination Programs: An Analysis of the Evidence on Impact, Implementation, Ethics and Equity</strong> -
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The data-driven targeting of COVID-19 vaccination programs is a major determinant of the ongoing toll of COVID-19. Targeting of access to, outreach about and incentives for vaccination can reduce total deaths by 20-50 percent relative to a first-come-first-served allocation. This piece performs a systematic review of the modeling literature on the relative benefits of targeting different groups for vaccination and evaluates the broader scholarly evidence – including analyses of real-world challenges around implementation, equity, and other ethical considerations – to guide vaccination targeting strategies. Three-quarters of the modeling studies reviewed concluded that the most effective way to save lives, reduce hospitalizations and mitigate the ongoing toll of COVID-19 is to target vaccination program resources to high-risk people directly rather than reducing transmission by targeting low-risk people. There is compelling evidence that defining vulnerability based on a combination of age, occupation, underlying medical conditions and geographic location is more effective than targeting based on age alone. Incorporating measures of economic vulnerability into the prioritization scheme not only reduces mortality but also improves equity. The data-driven targeting of COVID-19 vaccination program resources benefits everyone by efficiently mitigating the worst effects of the pandemic until the threat of COVID-19 has passed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.12.23284481v1" target="_blank">Data-driven Targeting of COVID-19 Vaccination Programs: An Analysis of the Evidence on Impact, Implementation, Ethics and Equity</a>
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</div></li>
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<li><strong>The Role of Individual Characteristics and National Distancing Policies for COVID-19 Protective Behaviour among Older Adults: a Cross-Sectional Study of 27 European Countries.</strong> -
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OBJECTIVES: Evidence on how individual characteristics and distancing policies during the first wave of COVID-19 together influenced health behaviours is scarce. The objective of this study is to fill in this gap by studying how the propensity to engage in protective behaviours in Europe was shaped by the interplay of individual characteristics and national policies. DESIGN: Data on individual behaviour in 27 countries came from the “Corona Survey” module of the Survey of Health, Ageing and Retirement in Europe, collected in summer 2020. As outcomes, we considered avoidant behaviours (never leaving home, reducing frequency of walks, reducing frequency of social meetings) and preventive behaviour (wearing a face mask). Among relevant policies we considered stay-at-home restrictions, mask wearing policies, and gatherings’ restrictions. Individual characteristics comprised gender, health risk of COVID-19 (older age and poor health), and activity (employment and providing help to other households). PARTICIPANTS: Nationally representative samples of older adults (50 years and over); N=51,540 respondents (58% of women). RESULTS: Active people (employed and helping other households) were more likely to wear face masks, but less likely to use avoidant behaviours. People at health risk (older people and those in poor health) were more likely to use all types of protective behaviours. Protective behaviours were also more frequent among women than among men. Longer duration of distancing polices correlated with more frequent protective behaviours. Distancing policies reduced social differences in the rate of protective behaviours only in case of social meetings and mask wearing. CONCLUSIONS: Protective behaviours responded to distancing policies, but our results suggest that people used them voluntarily, especially if they were at health risk.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/md5nq/" target="_blank">The Role of Individual Characteristics and National Distancing Policies for COVID-19 Protective Behaviour among Older Adults: a Cross-Sectional Study of 27 European Countries.</a>
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<li><strong>An Online Trier Social Stress Paradigm to Evoke Affective and Cardiovascular Responses</strong> -
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In response to the COVID-19 pandemic, prior studies have modified the Trier Social Stress Test to be conducted remotely. The current report aimed to extend these studies to test whether a remote Trier Social Stress Test (rTSST) can elicit (a) affective, (b) blood pressure, and (c) heart rate responses relative to a control condition and whether these responses were reliable when assessed one week later. Participants (N = 99, 19.7 ± 3.5 years, 55% female) were randomized to a control or stress condition. Controls completed easier versions of the tasks with a single, friendly researcher. Stress participants performed more difficult versions of the task in front of two judges who participants believed were rating their performance. Blood pressure and heart rate were measured every two minutes throughout, while affect was assessed at baseline, after the final task, and following recovery. The rTSST was feasible to administer with minimal technical issues reported. Results suggest that lower positive affect and higher negative affect were reported during the tasks in the stress condition relative to controls. Similarly, stress participants had higher cardiovascular responses during the tasks relative to controls, except that blood pressure was not elevated during mental arithmetic in stress participants relative to controls. Cardiovascular responses demonstrated good test-retest reliability when assessed one week later, especially when computed using area under the curve methods. Overall, a rTSST can be used to elicit affective and cardiovascular reactivity and provides an opportunity to include participants previously unreachable for in-person laboratory procedures.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/fcyqd/" target="_blank">An Online Trier Social Stress Paradigm to Evoke Affective and Cardiovascular Responses</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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<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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumoia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Jaktinib; Drug: Placebo<br/><b>Sponsor</b>: First Affiliated Hospital of Zhejiang University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Traditional Chinese Medicine Formulation; Other: Placebo Treatment<br/><b>Sponsor</b>: First Affiliated Hospital Xi’an Jiaotong 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>Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 dose 1; Drug: SHEN26 dose 2; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Safety and Efficacy of Meplazumab for Injection in Adults With Mild and Moderate COVID-19 Infections</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies 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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East 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>An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: Prevention of COVID-19 Caused by SARS-CoV-2<br/><b>Intervention</b>: Biological: randomized, double-blinded, placebo-controlled<br/><b>Sponsor</b>: Yu Qin<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>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Ousehold in China</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Huashan Hospital; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Positive Emotions With Long COVID-19</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Microdosing of mindfulness<br/><b>Sponsor</b>: University of California, Davis<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the Outcome of Covid Patients Discharged Home on Oxygen Therapy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Phone satisfaction questionnaire<br/><b>Sponsor</b>: Centre Hospitalier René Dubos<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>Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation</strong> - Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why did air quality experience little improvement during the COVID-19 lockdown in megacities, northeast China?</strong> - To inhibit the COVID-19 (Coronavirus disease 2019) outbreak, unprecedented nationwide lockdowns were implemented in China in early 2020, resulting in a marked reduction of anthropogenic emissions. However, reasons for the insignificant improvement in air quality in megacities of northeast China, including Shenyang, Changchun, Jilin, Harbin, and Daqing, were scarcely reported. We assessed the influences of meteorological conditions and changes in emissions on air quality in the five megacities…</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>Multi-target activity of copper complexes; antibacterial, DNA binding, and molecular docking with SARS-CoV-2 receptor</strong> - A series of pendant-armed mixed-ligand copper(II) complexes of the type [CuL^(1-3)(diimine)] (1-6) have been synthesized by the reaction of pendant-armed ligands N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)benzamide (H(2)L(1)), N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-4-nitrobenzamide (H(2)L(2)) and N,N-bis(2-(((E)-2-hydroxy-5-methylbenzylidene)amino)ethyl)-3,5-dinitrobenzamide (H(2)L(3)) with diimine = 2,2’-bipyridyl (bpy) or 1,10-phenanthroline (phen) in 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>Lidocaine inhibits influenza a virus replication by up-regulating IFNα4 via TBK1-IRF7 and JNK-AP1 signaling pathways</strong> - Influenza A viruses (IAV), significant respiratory pathogenic agents, cause seasonal epidemics and global pandemics in intra- and interannual cycles. Despite effective therapies targeting viral proteins, the continuous generation of drug-resistant IAV strains is challenging. Therefore, exploring novel host-specific antiviral treatment strategies is urgently needed. Here, we found that lidocaine, widely used for local anesthesia and sedation, significantly inhibited H1N1(PR8) replication in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Soluble Signal Inhibitory Receptor on Leukocytes-1 Is Released from Activated Neutrophils by Proteinase 3 Cleavage</strong> - Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an immune inhibitory receptor expressed on human granulocytes and monocytes that dampens antimicrobial functions. We previously showed that sputum neutrophils from infants with severe respiratory syncytial virus (RSV) bronchiolitis have decreased SIRL-1 surface expression compared with blood neutrophils and that SIRL-1 surface expression is rapidly lost from in vitro activated neutrophils. This led us to hypothesize that activated…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection</strong> - CONCLUSIONS: The study identifies 2 TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4. or p47phox as a tool to counteract thrombosis in SARS-CoV-2.</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>How to achieve carbon neutrality while maintaining economic vitality: An exploration from the perspective of technological innovation and trade openness</strong> - The significant drop in global carbon emissions in 2020 was credited to the enormous loss of economic activity from the impact of COVID-19. The challenge is now to reduce carbon emissions without causing massive disruption and damage to economic production. To achieve carbon neutrality while maintaining economic vitality, the impact of technological innovation and trade openness must be considered. This paper sets technological innovation and trade openness as core variables and establishes two…</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>Molecular mechanisms in chloroquine-exposed muscle cells elucidated by combined proteomic and microscopic studies</strong> - CONCLUSION: We demonstrated that CQ exposure (secondarily) impacts biological processes beyond lysosomal function and linked a variety of proteins with known roles in the manifestation of other neuromuscular diseases.</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>Predicting the systemic exposure and lung concentration of nafamostat using physiologically-based pharmacokinetic modeling</strong> - Nafamostat has been actively studied for its neuroprotective activity and effect on various indications, such as coronavirus disease 2019 (COVID-19). Nafamostat has low water solubility at a specific pH and is rapidly metabolized in the blood. Therefore, it is administered only intravenously, and its distribution is not well known. The main purposes of this study are to predict and evaluate the pharmacokinetic (PK) profiles of nafamostat in a virtual healthy population under various dosing…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome</strong> - Dexamethasone (DEX) is a potent synthetic glucocorticoid used for the treatment of variety of inflammatory and immune-mediated disorders. The RECOVERY clinical trial revealed benefits of DEX therapy in COVID-19 patients. Severe SARS-CoV-2 infection leads to an excessive inflammatory reaction commonly known as a cytokine release syndrome that is associated with activation of the toll like receptor 4 (TLR4) signaling pathway. The possible mechanism of action of DEX in the treatment of COVID-19 is…</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>P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions</strong> - BACKGROUND: Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.</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>4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine</strong> - RNA structure plays an important role in regulating cellular function and there is a significant emerging interest in targeting RNA for drug discovery. Here we report the identification of 4-aminoquinolines as modulators of RNA structure and function. Aminoquinolines have a broad range of pharmacological activities, but their specific mechanism of action is often not fully understood. Using electrophoretic mobility shift assays and enzymatic probing we identified 4-aminoquinolines that bind 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>Sleep as a protective factor of children’s executive functions: A study during COVID-19 confinement</strong> - Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children’s sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Novel Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease</strong> - As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M^(Pro)) for pathogenesis and replication. During crystallographic analyses of M^(Pro) crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of M^(Pro), 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>Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium</strong> - Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air…</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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