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<title>08 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C)</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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Objective To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.
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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/10.1101/2022.08.04.22278439v1" target="_blank">Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C)</a>
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</div></li>
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<li><strong>Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial</strong> -
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Background: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac<sup>®</sup> is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac<sup>®</sup> separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-g and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-g secretion. Conclusions: Immunization with CoronaVac<sup>®</sup> in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial number: NCT04651790.
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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/10.1101/2022.08.05.22278464v1" target="_blank">Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial</a>
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</div></li>
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<li><strong>Two years of COVID-19 Pandemic: Framework of Health Interventions in a Brazilian City</strong> -
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<div>
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The COVID-19 pandemic and its effects on public health have urgently demanded effective health policies to avoid the spread of COVID-19. Thus, public administrators have implemented non-pharmacological and pharmacological interventions to mitigate the pandemic9s impacts and strengthen health services. The aim of this ecological study is to describe the scenario of COVID-19 pandemic in a Brazilian city, during two years. This ecological study was carried out in Nova Friburgo, a Brazilian city, for 105 weeks (two years), from March 29, 2020 (week 1) to April 02, 2022 (week 105). Data on COVID-19 cases and COVID-19 deaths, occupation of COVID-19 exclusive beds in hospitals, community mobility, vaccination, government regulation on the opening of city establishments and city risk assessment were collected from public datasets. Four waves of COVID-19 cases and deaths were observed during this period. The first case occurred in week 1 and first death in week 3 of this study. The highest peaks of cases and deaths were observed during the third wave with 1,131 cases (week 54) and 47 deaths (week 55) and where the highest occupation of COVID-19 exclusive beds in local hospitals occurred. Interventions from more restrictive to more flexible, were implemented throughout this study, including lockdown and gradual return in economic and social strata levels. Vaccination began on week 43 and at the end of this study 89.91% of the total population was vaccinated with at least one dose, being 83.22% fully vaccinated. A deep description of several interventions used to avoid COVID-19 spread in a Brazilian city during two years of this pandemic can help promote better decision-making in the future while it exposes the challenges of conducting public health policies in a pandemic scenario.
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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/10.1101/2022.08.05.22278481v1" target="_blank">Two years of COVID-19 Pandemic: Framework of Health Interventions in a Brazilian City</a>
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</div></li>
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<li><strong>Heterologous vaccination as a strategy to minimize inequity in COVID-19 vaccine access: A modeling study in Thailand</strong> -
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Background: Vaccinations are the best hope to control the COVID-19 pandemic and save lives. Due to the high demand and failure to share vaccines equitably, there were not enough vaccine supplies to cover the majority of people in low- and middle-income countries during the early stage of vaccination. To cope with this problem, Thailand, an upper-middle-income country, decided to employ a heterologous vaccination strategy as the primary COVID-19 vaccination regimen in the country. The CoronaVac (CV) vaccine was administered as the first dose, followed by the ChAdOx1 nCoV-19 (AZ) vaccine as the second dose. However, there is no study to assess the effectiveness of the heterologous vaccination employed in Thailand compared to the standard homologous vaccination. Methods: We delineated the course and timeline of COVID-19 vaccination in Thailand. An age-structured compartmental model for COVID-19 transmission and vaccination was constructed and employed to assess the effectiveness of the heterologous vaccination strategy. The impact of the vaccine prioritization strategies on COVID-19 mortality and infections was also investigated. Results: We found that the CV+AZ heterologous vaccination strategy outperforms the CV and AZ homologous vaccinations in reducing cumulative cases and deaths when combined with other non-pharmaceutical interventions. Furthermore, the results suggested that prioritizing vaccines for the elderly could be optimal in reducing COVID-19 mortality for a wide range of vaccination rates and transmission dynamics. Conclusions: Our modeling results suggested that to minimize inequity in COVID-19 vaccine access in low- and middle-income countries, those countries may use early accessible but maybe lower-efficacy vaccines as the first dose of heterologous vaccination in combination with higher-efficacy vaccines as the second dose.
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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/10.1101/2022.08.05.22278489v1" target="_blank">Heterologous vaccination as a strategy to minimize inequity in COVID-19 vaccine access: A modeling study in Thailand</a>
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</div></li>
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<li><strong>Evaluation of a process to implement advance care planning conversations in primary care: uptake and patient experience</strong> -
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Objective: Advance care planning (ACP) can support patients in achieving current and future medical care that aligns with their values and goals. In primary care, a lack of standardized processes hinders implementation of ACP conversations. This study reports a quality improvement process to identify and engage patients and clinicians in ACP. Methods: Primary care clinicians received training in conversations based on the Serious Illness Conversation Guide and tools to support ACP. In December 2019, patients 65 years of age and older with chronic obstructive pulmonary disease were systematically identified, mailed ACP resources and telephoned by the clinic to invite them to an ACP appointment. We tracked the attendance of the patients and evaluated patient experience using a survey. Results: Of the 91 patients telephoned, 50 were reached, and 27 attended the appointment. Further efforts were suspended in March 2020 due to the COVID-19 pandemic. Thirteen patients completed the survey. There were statistically significant increases in the patient9s perception of being heard and understood by their physician, feeling hopeful about quality of life and feeling peaceful. Conclusion: This study provides evidence that with training, tools and processes, patients and primary care clinicians can be effectively engaged in ACP conversations.
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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/10.1101/2022.08.04.22278435v1" target="_blank">Evaluation of a process to implement advance care planning conversations in primary care: uptake and patient experience</a>
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</div></li>
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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>
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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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<li><strong>An Effective mRNA-LNP Vaccine Against the Lethal Plague Bacterium</strong> -
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<div>
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Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of mankind and is caused by the gram-negative bacterium Yersinia pestis. Currently, the disease is treated effectively with antibiotics. However, in the case of an outbreak caused by a multiple-antibiotic-resistant strain, alternative countermeasures are required. Despite the many efforts to develop a safe vaccine against the disease, there is still no vaccine approved for use in western countries. mRNA Lipid Nanoparticle (mRNA-LNP) vaccines have been demonstrated during the Covid-19 pandemic to be a versatile, clinically relevant, and rapidly manufactured vaccine platform. However, harnessing this platform for bacterial pathogens remains a formidable challenge. Here, we describe the design of several mRNA-LNP vaccine versions against Y. pestis, based on the F1 capsular antigen. We demonstrate that mRNA-LNP vaccines encoding the F1 antigen with either no signal sequences or conjugated to human Fc, provide substantial cellular and humoral responses. Most importantly, these vaccine candidates fully protect animals against Y. pestis infection. The results of this study suggest that mRNA-LNPs can be effective as anti-bacterial vaccines, and further developed to combat other bacterial pathogens, which are urgently needed, given the looming threat of antibiotic resistance.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.07.503096v1" target="_blank">An Effective mRNA-LNP Vaccine Against the Lethal Plague Bacterium</a>
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</div></li>
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<li><strong>Interpretable RNA Foundation Model from Unannotated Data for Highly Accurate RNA Structure and Function Predictions</strong> -
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Non-coding RNA structure and function are essential to understanding various biological processes, such as cell signaling, gene expression, and post-transcriptional regulations. These are all among the core problems in the RNA field. With the rapid growth of sequencing technology, we have accumulated a massive amount of unannotated RNA sequences. On the other hand, expensive experimental observatory results in only limited numbers of annotated data and 3D structures. Hence, it is still challenging to design computational methods for predicting their structures and functions. The lack of annotated data and systematic study causes inferior performance. To resolve the issue, we propose a novel RNA foundation model (RNA-FM) to take advantage of all the 23 million non-coding RNA sequences through self-supervised learning. Within this approach, we discover that the pre-trained RNA-FM could infer sequential and evolutionary information of non-coding RNAs without using any labels. Furthermore, we demonstrate RNA-FM’s effectiveness by applying it to the downstream secondary/3D structure prediction, SARS-CoV-2 genome structure and evolution prediction, protein-RNA binding preference modeling, and gene expression regulation modeling. The comprehensive experiments show that the proposed method improves the RNA structural and functional modelling results significantly and consistently. Despite only being trained with unlabelled data, RNA-FM can serve as the foundational model for the field.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.06.503062v1" target="_blank">Interpretable RNA Foundation Model from Unannotated Data for Highly Accurate RNA Structure and Function Predictions</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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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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🖺 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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<li><strong>Early Side Effects after Administration of the 1st Dose of Oxford-AstraZeneca Vaccine</strong> -
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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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<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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<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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🖺 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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<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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🖺 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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<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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<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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<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>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>Cardiovascular Function and Physical Activity in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Active-at-home-HF<br/><b>Sponsor</b>: Coventry University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University 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>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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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</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>Interleukin 6: A biomarker for COVID-19 progression</strong> - COVID-19 was discovered in China for the first time in December 2019 and was declared a pandemic by the World Health Organization on March 11, 2020. Due to its rapid geographic expansion over the last three years, it has now become a global health issue. The infection is caused by SARS-CoV-2, which is obtained from a zoonotic source and transmitted directly or through contact. Following exposure, the immune system becomes hyperactive resulting in the production of pro-inflammatory cytokines,…</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>Exploring the Potential of Chemical Inhibitors for Targeting Post-translational Glycosylation of Coronavirus (SARS-CoV-2)</strong> - The Spike (S) protein of SARS-CoV-2 expressed on the viral cell surface is of particular importance as it facilitates viral entry into the host cells. The S protein is heavily glycosylated with 22 N-glycosylation sites and a few N-glycosylation sites. During the viral surface protein synthesis via the host ribosomal machinery, glycosylation is an essential step in post-translational modifications (PTMs) and consequently vital for its life cycle, structure, immune evasion, and cell 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>The impact of social support and stress on academic burnout among medical students in online learning: The mediating role of resilience</strong> - CONCLUSION: The results of this study can provide a reference for the future development of appropriate educational strategies and coping measures to ameliorate the academic burnout of medical students.</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 information-driven resource allocation on the propagation of epidemic with incubation period</strong> - In the pandemic of COVID-19, there are exposed individuals who are infected but lack distinct clinical symptoms. In addition, the diffusion of related information drives aware individuals to spontaneously seek resources for protection. The special spreading characteristic and coevolution of different processes may induce unexpected spreading phenomena. Thus we construct a three-layered network framework to explore how information-driven resource allocation affects SEIS…</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>Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer</strong> - IgGFc-binding protein (FCGBP) is a mucin first detected in the intestinal epithelium. It plays an important role in innate mucosal epithelial defense, tumor metastasis, and tumor immunity. FCGBP forms disulfide-linked heterodimers with mucin-2 and members of the trefoil factor family. These formed complexes inhibit bacterial attachment to mucosal surfaces, affect the motility of pathogens, and support their clearance. Altered FCGBP expression levels may be important in the pathologic processes…</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>Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2 Omicron variant BA.1 infection of human airway epithelial organoids</strong> - Sublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron variant BA.1 (B.1.1.529.1) to four repurposable drugs, Methylene blue (MB), Mycophenolic acid (MPA), Posaconazole (POS), and Niclosamide (Niclo) in post-exposure treatments of primary human airway 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>SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection</strong> - Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein 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>Synthesis and Evaluation of Diterpenic Mannich Bases as Antiviral Agents against Influenza A and SARS-CoV-2</strong> - A chemical library was constructed based on the resin acids (abietic, dehydroabietic, and 12-formylabietic) and its diene adducts (maleopimaric and quinopimaric acid derivatives). The one-pot three-component CuCl-catalyzed aminomethylation of the abietane diterpenoid propargyl derivatives was carried out by formaldehyde and secondary amines (diethylamine, pyrrolidine, morpholine, and homopiperazine). All compounds were tested for cytotoxicity and antiviral activity against influenza virus…</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>Targeting Emerging RNA Viruses by Engineered Human Superantibody to Hepatitis C Virus RNA-Dependent RNA Polymerase</strong> - RNA-dependent RNA polymerase (RdRp) is a unique and highly conserved enzyme across all members of the RNA virus superfamilies. Besides, humans do not have a homolog of this protein. Therefore, the RdRp is an attractive target for a broadly effective therapeutic agent against RNA viruses. In this study, a formerly generated cell-penetrating human single-chain antibody variable fragment (superantibody) to a conformational epitope of hepatitis C virus (HCV) RdRp, which inhibited the polymerase…</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>Medical students’ perspectives on how COVID-19 has impacted their otolaryngology educational experience: A nationwide survey study</strong> - CONCLUSIONS: According to students, COVID-19 negatively impacted a broad array of otolaryngology educational experiences including research, faculty interaction, and interest group involvement. Students also indicated several well-received adaptations, such as virtual mentorship programs, curated video materials, remote research opportunities, and online question banks. This feedback helps contextualize selection committee decisions and, importantly, assists clerkship directors and undergraduate…</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>Phytoncides could potentially inhibit the spike protein of SARS-CoV-2 variants</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking</strong> - CONCLUSION: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.</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>Complement activation in COVID-19 and targeted therapeutic options: A scoping review</strong> - Increasing evidence suggests that activation of the complement system plays a key role in the pathogenesis and disease severity of Coronavirus disease 2019 (COVID-19). We used a systematic approach to create an overview of complement activation in COVID-19 based on histopathological, preclinical, multiomics, observational and clinical interventional studies. A total of 1801 articles from PubMed, EMBASE and Cochrane was screened of which 157 articles were included in this scoping review….</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>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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