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<title>07 August, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Different interventions for different vaccinations? Effects of psychological factors and health policies on COVID-19 primary and booster vaccine uptake</strong> -
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<div>
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Mitigation of the COVID-19 pandemic requires continued uptake of SARS-CoV-2 vaccines. Using experimental data collected in Germany in February 2022 (N = 2,701), this study investigated (a) predictors of primary and booster vaccination and (b) potential effects of policies combining vaccination mandates and monetary incentives. Compared to unvaccinated participants, those with primary vaccination were less complacent, more often understood the collective protection afforded by vaccination, and less often endorsed conspiracy-based misinformation. Compared to participants with primary vaccination, boosted individuals were even less complacent, exhibited fewer conspiracy-based beliefs, perceived fewer constraints, and more often favored compliance with official vaccination recommendations. Support for and reactance about vaccination mandates depended on vaccination status rather than policy characteristics, regardless of mandate type or incentives (up to 500 euro). While unvaccinated individuals rejected policy provisions and declined vaccination, boosted individuals indicated mid-level support for mandates and showed high vaccination intention. Among vaccinated individuals, higher incentives of up to 2,000 EUR had a considerable effect on the willingness to get boosted, especially in the absence of a mandate. The results indicate that mandates may be needed to increase primary vaccination numbers while incentives could be an alternative to promote booster uptake. However, combining both measures for the same target group seems inadvisable.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/xsh48/" target="_blank">Different interventions for different vaccinations? Effects of psychological factors and health policies on COVID-19 primary and booster vaccine uptake</a>
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</div></li>
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<li><strong>Social Pathways to Side-Effects: Personal Contacts and Social Media Predict COVID-19 Vaccine Side-Effect Expectations and Experience</strong> -
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<div>
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COVID-19 vaccine side-effects remain a substantial barrier to vaccination. Previous studies suggest that the experience of vaccination side-effects is exacerbated by expectations, but the extent to which social communication influences these expectations is currently unclear. A prospective longitudinal study (N=551) assessed whether three different information sources, face-to-face reports from personal acquaintances, social media posts, and news reports predict the development of COVID-19 vaccination side-effects and whether side-effect expectations mediate the relationship between the information sources and side-effect experiences. The number of pre-vaccination social media post views and impressions of severity conveyed from personal acquaintances significantly predicted pre-vaccination side-effect expectations and post-vaccination side-effects. Moreover, pre-vaccination side-effect expectations fully mediated the relationship between both sources of social communication and experienced side-effects. These data illuminate the pathways between social communication and COVID-19 vaccination side-effects and suggest that modifying side-effect expectations can change the COVID-19 vaccination experience.
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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/e2bfv/" target="_blank">Social Pathways to Side-Effects: Personal Contacts and Social Media Predict COVID-19 Vaccine Side-Effect Expectations and Experience</a>
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</div></li>
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<li><strong>‘All together now’: Facilitators and barriers to mutual aid during the first UK COVID-19 lockdown, and implications for community resilience</strong> -
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<div>
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Despite undeniable hardship, the onset of the COVID-19 pandemic also saw an outpour of community solidarity and mutual aid towards those in need. This study explored why people participated in mutual aid, as well as the factors that contributed to continued involvement and/or its decline. We conducted remote interviews with 18 people in South-east England who had been involved in volunteering and local community support groups during the first UK lockdown from March to May 2020. Using thematic approaches to data analysis, we identified two broad themes: 1) Shared social identities and mutual support, and 2) Enduring connections and barriers to continued participation. Participants often reported an emergent shared identity, preferring the localised nature of these groups and the associated mutual nature of support. They also reported intentions to continue providing such support, should the need arise again, and any barriers to continued involvement in mutual aid were better explained by structural and systemic issues, rather than individual, motivational factors. Implications for pandemic response are discussed and future research suggested.
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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/8gsr2/" target="_blank">‘All together now’: Facilitators and barriers to mutual aid during the first UK COVID-19 lockdown, and implications for community resilience</a>
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</div></li>
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<li><strong>Slovak parents’ mental health and socioeconomic changes during the COVID-19 pandemic</strong> -
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<div>
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Studying changes in people’s mental health has become one of the hot topics during the current COVID-19 pandemic. Parents were said to be among the most vulnerable groups, considering the nature of the imposed anti-pandemic measures. The present paper analyzes trends in mental health indicators in a sample of Slovak parents (N = 363) who participated in four waves of data collection across a year and a half of the COVID-19 pandemic. Mental health indicators were represented by general levels of depression and anxiety and the COVID-related stress and anxiety. Only minor changes in depression and anxiety were observed, however, the dynamic in COVID-related stress and especially anxiety was more noteworthy. Besides some exceptions, the results hold even after controlling for the socioeconomic situation. Gender differences in the mental health trends were mostly negligible. These results indicate that, in general, parents have successfully adapted to the pandemic situation.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/86m3y/" target="_blank">Slovak parents’ mental health and socioeconomic changes during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Early Side Effects after Administration of the 1st Dose of Oxford-AstraZeneca Vaccine</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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Vaccines have played a central role in minimizing new infections, the rate of hospitalizations, and the overall burden on the health sector. Fear of side effects is the biggest and commonest reason for avoiding getting vaccinated. It is, therefore, essential to maintain the clarity and consistency of message, to support and encourage people to get vaccinated. This study aims to contribute in that regard, by registering and quantifying the early side-effects of the Oxford-AstraZeneca COVID-19 vaccine in Pakistan. This study employs a non-random cross-sectional design. Data collected from 477 participants using a structured questionnaire was used to investigate the relationship between socio-demographic characteristics and side effect profiles of the participants. Binomial Logistic Regression was used to analyze the data. Odds Ratio (OR) gives the likelihood of having a side effect versus the reference group. Significance level (α) for the probability value (p-value) is set at 0.05. Fever (30.19%) was the most commonly experienced side effect, followed closely by fatigue (22.01%). 71.11% of those with fever experienced low grade fever (99-100F) while 62.69% of body aches experienced were moderate in intensity (Grades 4-6). In general, younger people are significantly more likely (p=0.023) to experience side effects (OR -1 = 1.023: interpreted as 1.023 times increase per unit decrease in age). Similarly, they are more likely (p= 0.029) to have a headache (OR -1 =1.039). Also, they are more likely (p= 0.007) to have a body ache (OR -1 =1.038). The Oxford-AstraZeneca COVID-19 vaccine side-effects seem to be more prevalent among younger age groups, which points to increased vaccine safety among older individuals that are usually more susceptible to severe COVID-19 infection. In addition, we found a substantially reduced number of side-effects, as compared to the clinical trials, which is an encouraging indicator for vaccine safety.
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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/10.1101/2022.08.04.22278415v1" target="_blank">Early Side Effects after Administration of the 1st Dose of Oxford-AstraZeneca Vaccine</a>
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</div></li>
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<li><strong>Optimization of Ventilation Therapy Prioritization Strategies among Patients with COVID-19: Lessons Learned from Real-World Data of nearly 600,000 Hospitalized Patients</strong> -
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Objective To investigate the benefit of ventilation therapy among various patient groups with COVID-19 admitted to hospitals, based on the real-world data of hospitalized adult patients. Methods Data used in the longitudinal study included 599,340 records of hospitalized patients. All participants were categorized based on demographics and their date of hospitalization. Two models were used in this study: firstly, participants were assessed by their probability of receiving ventilation therapy during hospitalization using mixed-effects logistic regression. Secondly, the clinical benefit of receiving ventilation therapy among various patient groups was quantified while considering the probability of receiving ventilation therapy during hospital admission, as estimated in the first model. Findings Among participants, 60,113 (10.0%) received ventilation therapy, 85,158 (14.2%) passed away due to COVID-19, and 514,182 (85.8%) recovered. Among all groups with sufficient data for analysis, patients aged 40-64 years who had chronic respiratory diseases (CRD) and malignancy benefitted the most from ventilation therapy; followed by patients aged 65+ years who had malignancy, cardiovascular diseases, and diabetes; and patients aged 18-39 years who had malignancy. Patients aged 65+ who had CRD and cardiovascular disease gained the least benefit from ventilation therapy. Conclusion This study promotes a new aspect of treating patients for ventilators: it could be suggested that rather than focusing on the scarcity of ventilators, guidelines focus on decision-making algorithms to also take the usefulness of the intervention into account, whose beneficial effect is dependent on the selection of the right time in the right patient.
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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/10.1101/2022.08.04.22278438v1" target="_blank">Optimization of Ventilation Therapy Prioritization Strategies among Patients with COVID-19: Lessons Learned from Real-World Data of nearly 600,000 Hospitalized Patients</a>
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</div></li>
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<li><strong>Determining population-level allocation strategies for COVID-19 treatments in the United States using a quantitative framework, a case study using nirmatrelvir/ritonavir</strong> -
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Background: New COVID-19 medications force decision makers to weigh limited evidence of efficacy and cost in determining which patient populations to target for treatment. A case in point is nirmatrelvir/ritonavir, a drug that has been recommended for elderly, high-risk individuals, regardless of vaccination status, even though clinical trials have only evaluated it in unvaccinated patients. A simple optimization framework might inform a more reasoned approach to the tradeoffs implicit in the treatment allocation decision. Methods: We used a mathematical model to analyze the cost-effectiveness of four nirmatrelvir/ritonavir allocation strategies, stratified by vaccination status and risk for severe disease. We considered treatment effectiveness at preventing hospitalization ranging from 21% to 89%. Sensitivity analyses were performed on major parameters of interest. A web-based tool was developed to permit decision-makers to tailor the analysis to their settings and priorities. Results: Providing nirmatrelvir/ritonavir to unvaccinated patients at high-risk for severe disease was cost-saving when effectiveness against hospitalization exceeded 33% and cost-effective under all other data scenarios we considered. The cost-effectiveness of other allocation strategies, including those for vaccinated adults and those at lower-risk for severe disease, depended on willingness-to-pay thresholds, treatment cost and effectiveness, and the likelihood of severe disease. Conclusions: Priority for nirmatrelvir/ritonavir treatment should be given to unvaccinated persons at high-risk of severe disease from COVID-19. Further priority may be assigned by weighing treatment effectiveness, disease severity, drug cost, and willingness to pay for deaths averted.
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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/10.1101/2022.08.04.22278431v1" target="_blank">Determining population-level allocation strategies for COVID-19 treatments in the United States using a quantitative framework, a case study using nirmatrelvir/ritonavir</a>
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</div></li>
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<li><strong>Intra-pulmonary and intra-cardiac shunts in adult COVID-19 versus non-COVID ARDS ICU patients using echocardiography and contrast bubble studies (COVID-Shunt Study): a prospective, observational cohort study</strong> -
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Importance: Studies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes. Objective: To evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality. Design, Setting, Participants: We conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021). Intervention: Contrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) ± transesophageal echocardiography (TEE) assessed for the presence of R-L shunts. Main Outcomes and Measures: Primary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt presence/absence with covariables. Results: The study enrolled 226 patients (182 COVID-19 vs. 42 non-COVID). Median age was 58 years (interquartile range [IQR]: 47-67) and APACHE II scores of 30 (IQR: 21-36). In COVID-19 patients, the incidence of R-L shunt was 31/182 patients (17.0%; intra-pulmonary: 61.3%; intra-cardiac: 38.7%) versus 10/44 (22.7%) non-COVID patients. No evidence of difference was detected between the COVID-19 and non-COVID-19 shunt rates (risk difference [RD]: -5.7%, 95% CI: -18.4-7.0, p=0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared to those without (54.8% vs 35.8%, RD: 19.0%, 95% CI 0.1-37.9, p=0.05). But this did not persist at 90-day mortality, nor after regression adjustments for age and illness severity. Conclusions: There was no evidence of increased R-L shunt rates in COVID-19 compared to non-COVID controls. Right-to-left shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.
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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/10.1101/2022.08.04.22278445v1" target="_blank">Intra-pulmonary and intra-cardiac shunts in adult COVID-19 versus non-COVID ARDS ICU patients using echocardiography and contrast bubble studies (COVID-Shunt Study): a prospective, observational cohort study</a>
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</div></li>
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<li><strong>Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland: A population-based study</strong> -
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The direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. We modelled excess mortality and the direct and indirect effects of the pandemic on mortality in Switzerland. We analyzed yearly population data and weekly all-cause deaths by age, sex, and canton 2010-2019 and all-cause and laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). Bayesian models predicted the expected number of deaths. A total of 13,130 laboratory-confirmed COVID-19 deaths were reported. The model estimated that COVID-19-related mortality was underestimated by a factor of 0.72 [95% Credible Interval: 0.46-0.78] resulting in 18,140 [15,962-20,174] excess deaths. After accounting for COVID-19 deaths, the observed mortality was 3% [-1-7] lower than expected, corresponding to a deficit of 4,406 deaths, with a wide credibility interval [-1,776-10,700]. Underestimation of COVID-19 deaths was greatest for ages 70 years and older; the mortality deficit was most pronounced in age groups 40 to 69 years. We conclude that shortcomings in testing caused underestimation of COVID-19-related deaths in Switzerland, particularly in older people. Although COVID-19 control measures may have negative effects (e.g., delays in seeking care or mental health impairments), after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures on mortality were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures.
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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/10.1101/2022.08.05.22278458v1" target="_blank">Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland: A population-based study</a>
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</div></li>
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<li><strong>Differential Impacts of Perceived Social Support on Alcohol and Cannabis Use in Young Adults: Lessons from the COVID-19 Pandemic</strong> -
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Coronavirus (COVID-19) lockdowns provided a unique opportunity to examine how changes in the social environment impact mental health and wellbeing. We addressed this issue by assessing how perceived social support across COVID-19 restrictions alters alcohol and cannabis use in emerging adults, a population vulnerable to adverse outcomes of substance use. Four hundred sixty-three young adults in Canada and the United States completed online questionnaires for three retrospective time points: Pre-Covid, Lockdown and Eased Restrictions. Sociodemographic factors, perceived social support, and substance use were assessed. Overall, alcohol use decreased while cannabis use increased during Lockdown. Interestingly, social support negatively predicted alcohol use and positively predicted cannabis use during Lockdown. These findings suggest a difference in motives underlying alcohol and cannabis use in emerging adults. Importantly, these changes were not sustained when restrictions eased, suggesting that emerging adults exhibit resiliency to the impacts of COVID-19 restrictions on substance use.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278446v1" target="_blank">Differential Impacts of Perceived Social Support on Alcohol and Cannabis Use in Young Adults: Lessons from the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study</strong> -
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Background: Performance of Rapid Antigen Tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance is not well established among asymptomatic individuals. Objective: Evaluate performance of Ag-RDT for detection of SARS-CoV-2 in relation to onset of infection for symptomatic and asymptomatic participants. Design, Setting, and Participants: Prospective cohort study conducted from October 2021 to February 2022 among participants > 2 years-old from across the US who enrolled using a smartphone app. During each testing encounter, participants self-collected one nasal swab and performed Ag-RDT at home; at-least fifteen minutes later, a second nasal swab was self-collected and shipped for SARS-CoV-2 RT-PCR at a central lab. Both nasal swabs were collected 7 times at 48-hour intervals (over approximately 14 days) followed by an extra nasal swab collection with home Ag-RDT test 48-hours after their last PCR sample. Each participant was assigned to one of the three emergency use authorized (EUA) Ag-RDT tests used in this study. This analysis was limited to participants who were asymptomatic and tested negative by antigen and molecular test on their first day of study participation. Exposure: SARS-CoV-2 positivity was determined by testing a single home-collected anterior nasal sample with three FDA EUA molecular tests, where 2 out 3 positive test results were needed to determine a SARS-CoV-2 positive result. Onset of infection was defined as day on which the molecular PCR comparator result was positive for the first time. Main Outcomes and Measures: Sensitivity of Ag-RDT was measured based on testing once (same-day), twice (at 48-hours) and thrice (at 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status on a given DPIPP. Results: A total of 7,361 participants enrolled in the study and 5,609 were eligible for this analysis. Among 154 eligible participants who tested positive for SARS-CoV-2 infection based on RT-PCR, 97 were asymptomatic and 57 had symptoms at onset of infection (DPIPP 0). Serial testing with Ag-RDT twice over 48-hours resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Among the 97 people who were asymptomatic at the onset of infection, 19 were singleton RT-PCR positive, i.e., their positive test was preceded and followed by a negative RT-PCR test within 48-hours. Excluding these singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with serial testing three times at 48-hour interval. Discussion: Performance of Ag-RDT within first week of infection was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v1" target="_blank">Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study</a>
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</div></li>
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<li><strong>Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020</strong> -
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As of January 2021, Australia had effectively controlled local transmission of COVID-19 despite a steady influx of imported cases and several local, but contained, outbreaks in 2020. Throughout 2020, state and territory public health responses were informed by weekly situational reports that included an ensemble forecast for each jurisdiction. We present here an analysis of one forecasting model included in this ensemble across the variety of scenarios experienced by each jurisdiction from May to October 2020. We examine how successfully the forecasts characterised future case incidence, subject to variations in data timeliness and completeness, showcase how we adapted these forecasts to support decisions of public health priority in rapidly-evolving situations, evaluate the impact of key model features on forecast skill, and demonstrate how to assess forecast skill in real-time before the ground truth is known. Conditioning the model on the most recent, but incomplete, data improved the forecast skill, emphasising the importance of developing strong quantitative models of surveillance system characteristics, such as ascertainment delay distributions. Forecast skill was highest when there were at least 10 reported cases per day, the circumstances in which authorities were most in need of forecasts to aid in planning and response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278391v1" target="_blank">Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020</a>
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</div></li>
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<li><strong>A Reagent and Virus Benchmarking Panel for a Uniform Analytical Performance Assessment of N Antigen-Based Diagnostic Tests for COVID-19</strong> -
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Rapid diagnostic tests (RDTs) that detect antigen indicative of SARS-CoV-2 infection can help in making quick health care decisions and regularly monitoring groups at risk of infection. With many RDT products entering the market, it is important to rapidly evaluate their relative performance. Comparison of clinical evaluation study results is challenged by protocol design variations and study populations. Laboratory assays were developed to quantify nucleocapsid (N) and spike (S) SARS-CoV-2 antigens. Quantification of the two antigens in nasal eluates confirmed higher abundance of N than S antigen. The median concentration of N antigen was 10 times greater than S per genome equivalent. The N antigen assay was used in combination with quantitative RT-PCR to qualify a panel composed of recombinant antigens, inactivated virus, and clinical specimen pools. This benchmarking panel was applied to evaluate the analytical performance of the SD Biosensor STANDARD Q COVID-19 Ag test, Abbott Panbio COVID-19 Ag Rapid Test, Abbott BinaxNOW COVID-19 Ag test, and the LumiraDx SARS-CoV-2 Ag Test. The four tests displayed different sensitivities toward the different panel members, but all performed best with the clinical specimen pool. The concentration for a 90% probability of detection across the four tests ranged from 21 pg/mL to 102 pg/mL of N antigen in the extracted sample. Benchmarking panels provide a quick way to verify the baseline performance of a diagnostic and enable direct comparison between diagnostic tests.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.03.22278351v1" target="_blank">A Reagent and Virus Benchmarking Panel for a Uniform Analytical Performance Assessment of N Antigen-Based Diagnostic Tests for COVID-19</a>
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<li><strong>Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19</strong> -
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Background: The generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. Methods: We analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. Results: We analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics. Conclusions: The proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.05.22278461v1" target="_blank">Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19</a>
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<li><strong>COVID-19 rebound after Paxlovid treatment during Omicron BA.5 vs BA.2.12.1 subvariant predominance period</strong> -
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Paxlovid was authorized by FDA to treat mild-to-moderate COVID-19. In May 2022, the Centers for Disease Control and Prevention (CDC) issued a Health Alert Network Health Advisory on potential COVID-19 rebound after Paxlovid treatment. Since June 2022, Omicron BA.5 has become the dominant subvariant in the US, which is more resistant to neutralizing antibodies than the previous subvariant BA.2.12.1. Questions remain as to how COVID-19 rebound after Paxlovid treatment differs between the BA.5 and BA.2.12.1 subvariants. This is a retrospective cohort study of 15,913 patients who contracted COVID-19 between 5/8/2022-7/18/2022 and were prescribed Paxlovid within 5 days of their COVID-19 infection. The study population was divided into 2 cohorts: (1) BA.5 cohort (n=5,161) that comprised patients who contracted COVID-19 during 6/19/22-7/18/22 when BA.5 was the predominant subvariant2. (2) BA.2.12.1 cohort (n=10,752) that comprised patients who contracted COVID-19 during 5/8/22-6/18/22 when the BA.2.12.1 was the predominant subvariant. The risks of both COVID-19 rebound infections and symptoms 2-8 days after Paxlovid treatment were higher in the BA.5 cohort than in the propensity-score matched BA.2.12.1 cohort: rebound infections (Hazard Ratio or HR: 1.32, 95% CI: 1.06-1.66), rebound symptoms (HR: 1.32, 95% CI: 1.04-1.68). As SARS-CoV-2 evolves with successive subvariants more evasive to antibodies, continuous vigilant monitoring is necessary for COVID-19 rebounds after Paxlovid treatment and longer time duration of Paxlovid treatment warrants evaluation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278450v1" target="_blank">COVID-19 rebound after Paxlovid treatment during Omicron BA.5 vs BA.2.12.1 subvariant predominance period</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 Study to Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br/><b>Sponsors</b>: BioNTech SE; 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>Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Dietary Supplement: SmartProbio C; Dietary Supplement: Placebo<br/><b>Sponsors</b>: Medi Pharma Vision; Veterinary Research Institute; Brno University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07321332 (nirmatrelvir)/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>Effect of Pulmonary Rehabilitation Program on Post Hospitalization Severe COVID- 19 Patients</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Combination Product: respiratory exercises - incentive spirometer - walking<br/><b>Sponsor</b>: Fayoum University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physiotherapy in Post COVID-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Cognitive behavioral principles-based treatment program; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Rehabilitation for People With Post COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Multidimensional intervention; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>: COVID-19; Vaccine Uptake<br/><b>Intervention</b>: Behavioral: Tough Talks COVID<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)<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>rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray<br/><b>Sponsor</b>: Sichuan Huiyang Life Science and Technology Corporation<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 CHW Intervention to Identify and Decrease Barriers to COVID 19 Testing & Vaccination</strong> - <b>Conditions</b>: Vaccine Hesitancy; COVID-19 Testing; Community Health Workers<br/><b>Intervention</b>: Behavioral: Community Health Worker led curriculum<br/><b>Sponsors</b>: Charles Drew University of Medicine and Science; Los Angeles County Department of Public Health; National Library of Medicine (NLM)<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>Lollipop COVID-19 Testing Study</strong> - <b>Conditions</b>: COVID-19; SARS CoV 2 Infection; COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: Lollipop Swab<br/><b>Sponsor</b>: University of Wisconsin, Madison<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 Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: ZR202-CoV; Biological: ZR202a-CoV; Biological: Comirnaty®<br/><b>Sponsor</b>: Shanghai Zerun Biotechnology 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>Immunogenicity and Safety of BBIBP-Corv Coadministered With PPV23 and IIV4 in Hemodialysis Population</strong> - <b>Conditions</b>: Hemolysis; COVID-19<br/><b>Interventions</b>: Biological: coadministration; Biological: COVID-19 vaccine; Biological: IIV4+PPV23<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Hunan Provincial Center for Disease Control and Prevention; Sichuan Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Xiangya Hospital of Central South University; Beijing Institute of Biological Products Co Ltd.; Chengdu Institute of Biological Products Co.,Ltd.; Shanghai Institute Of Biological Products<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: CV0501 (3 μg); Biological: CV0501 (6 μg); Biological: CV0501 (12 μg); Biological: CV0501 (25 μg); Biological: CV0501 (50 μg); Biological: CV0501 (75 μg); Biological: CV0501 (100 μg); Biological: CV0501 (150 μg); Biological: CV0501 (200 μg)<br/><b>Sponsor</b>: GlaxoSmithKline<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test</strong> - <b>Conditions</b>: Anxiety; Fear<br/><b>Interventions</b>: Behavioral: The Kaleidescope; Behavioral: The visual illusion cards<br/><b>Sponsor</b>: Ondokuz Mayıs University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2 Study to Evaluate the Efficacy and Safety of TNX-102 SL in Patients With Multi-Site Pain Associated With Post-Acute Sequelae of SARS-CoV-2 Infection</strong> - <b>Conditions</b>: Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection; COVID-19; Long COVID; Long Haul COVID<br/><b>Interventions</b>: Drug: TNX-102 SL; Drug: Placebo SL Tablet<br/><b>Sponsor</b>: Tonix Pharmaceuticals, Inc.<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC)</strong> - CONCLUSIONS: Fibrin amyloid microclots that block capillaries and inhibit the transport of O(2) to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Potential Utility of Lead Compound, E18, in Inhibiting Docking of SARS-CoV-2 by inhibiting ACE2-B<sup>0</sup>AT1 Complex</strong> - Null.</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 Nutritional Blend Suppresses the Inflammatory Response from Bronchial Epithelial Cells Induced by SARS-CoV-2</strong> - Even after virus elimination, numerous sequelae of coronavirus disease 2019 (COVID-19) persist. Based on accumulating evidence, large amounts of proinflammatory cytokines are released to drive COVID-19 progression, severity, and mortality, and their levels remain elevated after the acute phase of COVID-19, playing a central role in the disease’ sequelae. In this manner, bronchial epithelial cells are the first cells hyperactivated by severe acute respiratory syndrome coronavirus-2 (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>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</strong> - CONCLUSIONS: S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches</strong> - The COVID-19 pandemic has become a global health challenge because of the emergence of distinct variants. Omicron, a new variant, is recognized as a variant of concern (VOC) by the World Health Organization (WHO) because of its higher mutations and accelerated human infection. The infection rate is strongly dependent on the binding rate of the receptor binding domain (RBD) against human angiotensin converting enzyme-2 (ACE2^(human)) receptor. Inhibition of protein-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>Affinity selection-mass spectrometry in the discovery of anti-SARS-CoV-2 compounds</strong> - Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the cause of the COVID-19 pandemic. To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection-mass spectrometry (AS-MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS-MS assays have been used…</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>Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling</strong> - CONCLUSION: In clinical practice, IL-6 inhibition should be individualised based on pathophysiology to achieve full blockade of CRP production.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites</strong> - Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human milk inhibits some enveloped virus infections, including SARS-CoV-2, in an intestinal model</strong> - Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome…</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>Discovery and Mechanistic Study of <em>Mycobacterium tuberculosis</em> PafA Inhibitors</strong> - Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (Mtb) and is ranked as the second killer infectious disease after COVID-19. Proteasome accessory factor A (PafA) is considered an attractive target because of its low sequence conservation in humans and its role in virulence. In this study, we designed a mutant of Mtb PafA that enabled large-scale purification of active PafA. Using a devised high-throughput screening assay, two PafA inhibitors were discovered. ST1926 inhibited…</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>Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19</strong> - CONCLUSIONS: Our data suggest that patients with severe COVID-19 harbor IgA against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).</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>Proteolytic Processing of the Coronavirus Replicase Nonstructural Protein 14 Exonuclease Is Not Required for Virus Replication but Alters RNA Synthesis and Viral Fitness</strong> - Coronaviruses (CoVs) initiate replication by translation of the positive-sense RNA genome into the replicase polyproteins connecting 16 nonstructural protein domains (nsp1-16), which are subsequently processed by viral proteases to yield mature nsp. For the betacoronavirus murine hepatitis virus (MHV), total inhibition of translation or proteolytic processing of replicase polyproteins results in rapid cessation of RNA synthesis. The nsp5-3CLpro (Mpro) processes nsps7-16, which assemble into…</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>Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I-Mediated Antiviral Responses in Primary Human Dendritic Cells</strong> - Dendritic cells (DCs) are important mediators of the induction and regulation of adaptive immune responses following microbial infection and inflammation. Sensing environmental danger signals including viruses, microbial products, or inflammatory stimuli by DCs leads to the rapid transition from a resting state to an activated mature state. DC maturation involves enhanced capturing and processing of antigens for presentation by major histocompatibility complex (MHC) class I and class II,…</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>Breathability performance of antiviral cloth masks treated with silver nanoparticles for protection against COVID-19</strong> - The global widespread of coronavirus disease 2019 (COVID-19) has caused shortage of medical face masks and led to developing of various types of cloth masks with different levels of protection and comfort to meet the market demands. Breathing comfort is a significant aspect that should be considered during the design of cloth masks along with the filtration efficiency; otherwise, the wearer will feel suffocated. In this work, different types of cotton and polyester knitted fabrics blended with…</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>Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies</strong> - Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA…</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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