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<title>15 June, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Prosocial behaviours under collective quarantine conditions. A latent class analysis study during the 2020 COVID-19 lockdown in Italy</strong> -
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<div>
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Aim. To identify patterns of prosocial behaviours under collective quarantine conditions. Method. Survey data was collected from a sample of Italian adults during the March ̶ May 2020 COVID-19 lockdown in Italy. Participants reported on offline and online prosocial behaviours, Sense of Community Responsibility (SoC-R) and perceptions of community resilience. Latent class analysis (LCA) was used for data analysis. Results. A total of 4,045 participants completed the survey and 2,562 were eligible (72% female; mean age 38.7 years). LCA revealed four classes of prosocial behaviours: Money donors (7%), Online & offline helpers (59%), Online health information sharers (21%), and Neighbour helpers (13%). The classes were partially invariant across age groups (18 ̶ 35 and > 35 years). Being a man and higher SoC-R scores were associated with belonging to the Online & offline helper class. Members of this class also reported the greatest perceptions of community resilience. Conclusions. Results offer insight on the multidimensionality of prosociality under collective quarantine conditions. Online & offline helpers could be targeted for promoting sustained altruism and involvement in community organisations. For the other groups, programmes should aim to eliminate barriers to help others in multiple ways.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/jb5hw/" target="_blank">Prosocial behaviours under collective quarantine conditions. A latent class analysis study during the 2020 COVID-19 lockdown in Italy</a>
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</div></li>
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<li><strong>The “Quiet Quitting” Scale: Development and initial validation</strong> -
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<div>
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Introduction: COVID-19 pandemic causes drastic changes in workplaces that are likely to increase quite quitting among employees. Although quite quitting is not a new phenomenon, there is no instrument to measure it. Aim: To develop and validate an instrument assessing quiet quitting among employees. Methods: We identified and generated items through an extensive literature review and interviews with employees. We carried out the content validity by content experts and we calculated the content validity ratio. We checked face validity by conducting cognitive interviews with employees and calculating the item-level face validity index. We performed exploratory and confirmatory factor analysis to assess the “Quiet Quitting” Scale (QQS) factorial structure. We checked the concurrent validity of the QQS using four other scales, i.e., “Job Satisfaction Survey” (JSS), “Copenhagen Burnout Inventory” (CBI), “Single Item Burnout” (SIB) measure, and a single item to measure turnover intention. We estimated the reliability of the QQS measuring Cronbach’s alpha, McDonald’s Omega, Cohen’s kappa, and intraclass correlation coefficient. Results: After expert panel review and item analysis, nine items with acceptable corrected item-total correlations, inter-item correlations, floor and ceiling effects, skewness, and kurtosis were retained. Exploratory factor analysis extracted three factors, namely detachment, lack of initiative, and lack of motivation, with a total of nine items. Confirmatory factor analysis confirmed this factorial structure for QQS. We found statistically significant correlations between QQS and JSS, CBI, SIB, and turnover intention confirming that the concurrent validity of the QQS was very good. Cronbach’s alpha and McDonald’s Omega of the QQS were 0.803 and 0.806 respectively. Intraclass correlation coefficient for the total QQS score was 0.993 (p < 0.001). Cohen’s kappa for the nine items ranged from 0.836 to 0.945 (p < 0.001 in all cases). Conclusions: QQS, a three-factor nine-item scale, has robust psychometric properties. QQS is a brief, easy-to-administer, valid, and reliable tool to measure employees’ quiet quitting. We recommend the use of the QQS in different societies and cultures to assess the validity of the instrument.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/5tgpm/" target="_blank">The “Quiet Quitting” Scale: Development and initial validation</a>
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<li><strong>Efficacy of Pranayama in Preventing COVID-19 in Exposed Healthcare Professionals: A Randomized Controlled Trial</strong> -
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Background: The global outbreak of COVID-19 has created a challenging situation, especially among the frontline Health Care Professionals (HCPs), who are routinely exposed and thus at a relatively higher risk of infection. A few studies have shown the practice of Pranayama, a component of Yoga, to be effective in improving immune function and reducing infection. However, no clinical trial on the efficacy of Pranayama in preventing COVID-19 has been conducted. Aim & Objective: This randomized clinical trial assessed the effect of Pranayama in preventing COVID-19 infection in Health Care Professionals (HCPs) routinely exposed to COVID-19 cases. Methodology: The study was conducted at 5 different COVID-19 hospitals in New Delhi, India during September-November, 2020. 280 HCPs assigned duties with COVID-19 patients who were found negative in COVID-19 antibody test in pre-intervention assessment were recruited and randomly assigned to intervention and control groups. The intervention group practiced especially designed Pranayama modules twice a day (morning and evening) for 28 days under the supervision of Yoga instructors through online mode, while those in the control group were advised general fitness practices (like walking, jogging, running). Participants who became symptomatic underwent RTPCR / Point of Care Rapid Antigen test for confirmation of COVID 19 diagnosis. All the patients also underwent antibody testing for COVID-19 on 28th day of the intervention to detect asymptomatic infection. Results: 250 participants, comprising 123 in the intervention group and 127 in the control group, completed the study . The intervention and control groups had comparable demographics and baseline characteristics. Three participants (all controls) developed COVID 19 symptoms during the study. On the completion of the study, only one participant in the Intervention group tested positive, while 9 participants in the control group (Including three symptomatic participants) tested positive for COVID-19 antibodies. This difference was statistically significant (P-value: 0.01). Conclusion: Practice of our especially designed Pranayama module, every day for 28 days was highly effective in preventing COVID-19 infection in exposed healthcare professionals (HCPs).
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/c3qub/" target="_blank">Efficacy of Pranayama in Preventing COVID-19 in Exposed Healthcare Professionals: A Randomized Controlled Trial</a>
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</div></li>
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<li><strong>Listen to the Scientists: Effects of exposure to scientists and general media consumption on cognitive, affective and behavioral mechanisms during the COVID-19 pandemic</strong> -
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<div>
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Throughout the COVID-19 crisis, in an unprecedented amount, scientists around the globe engaged in science communication to provide first-hand epidemiological knowledge and information on preventive measures. Based on the extended parallel process model, the present work aimed to empirically investigate (N = 698) the impact of direct exposure to scientists in comparison to a general COVID-19 related media consumption. The results revealed that direct exposure to scientists positively affected recipients´ knowledge and self-efficacy. General media consumption on the other hand, positively affected perceived threat as well as fear and uncertainty. Both sources positively affected the adherence to protective measures.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/6j8qd/" target="_blank">Listen to the Scientists: Effects of exposure to scientists and general media consumption on cognitive, affective and behavioral mechanisms during the COVID-19 pandemic</a>
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<li><strong>FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system</strong> -
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<div>
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Large Phase 3 clinical trials of the two FDA-authorized COVID-19 vaccines, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech), have demonstrated efficacies of 94.1% (n = 30,420, 95% CI: 89.3-96.8) and 95% (n = 43,448, 95% CI: 90.3-97.6) in preventing symptomatic COVID-19, respectively. Given the ongoing vaccine rollout to healthcare personnel and residents of long-term care facilities, here we provide a preliminary assessment of real-world vaccination efficacy in 62,138 individuals from the Mayo Clinic and associated health system (Arizona, Florida, Minnesota, Wisconsin) between December 1st 2020 and February 8th 2021. Our retrospective analysis contrasts 31,069 individuals receiving at least one dose of either vaccine with 31,069 unvaccinated individuals who are propensity-matched based on demographics, location (zip code), and number of prior SARS-CoV-2 PCR tests. 8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose. Administration of two COVID-19 vaccine doses was 88.7% effective in preventing SARS-CoV-2 infection (95% CI: 68.4-97.1%) with onset at least 36 days after the first dose. Furthermore, vaccinated patients who were subsequently diagnosed with COVID-19 had significantly lower 14-day hospital admission rates than propensity-matched unvaccinated COVID-19 patients (3.7% vs. 9.2%; Relative Risk: 0.4; p-value: 0.007). Building upon the previous randomized trials of these vaccines, this study demonstrates their real-world effectiveness in reducing the rates of SARS-CoV-2 infection and COVID-19 severity among individuals at highest risk for infection.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/y6pdw/" target="_blank">FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system</a>
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</div></li>
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<li><strong>Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin</strong> -
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<div>
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The emergence of a heavily mutated SARS-CoV-2 variant (B.1.1.529, Omicron) and it’s spread to 6 continents within a week of initial discovery has set off a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its shared or distinctive clinical phenotypes with other SARS-CoV-2 variants. We compared the mutations of Omicron with prior variants of concern (Alpha, Beta, Gamma, Delta), variants of interest (Lambda, Mu, Eta, Iota and Kappa), and all 1523 SARS-CoV-2 lineages constituting 5.4 million SARS-CoV-2 genomes. Omicron’s Spike protein has 26 amino acid mutations (23 substitutions, two deletions and one insertion) that are distinct compared to other variants of concern. Whereas the substitution and deletion mutations have appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) has not been previously observed in any SARS-CoV-2 lineage other than Omicron. The nucleotide sequence encoding for ins214EPE could have been acquired by template switching involving the genomes of other viruses that infect the same host cells as SARS-CoV-2 or the human transcriptome of host cells infected with SARS-CoV-2. For instance, given recent clinical reports of co-infections in COVID-19 patients with seasonal coronaviruses (e.g. HCoV-229E), single cell RNA-sequencing data showing co-expression of the SARS-CoV-2 and HCoV-229E entry receptors (ACE2 and ANPEP) in respiratory and gastrointestinal cells, and HCoV genomes harboring sequences homologous to the nucleotide sequence that encodes ins214EPE, it is plausible that the Omicron insertion could have evolved in a co-infected individual. There is a need to understand the function of the Omicron insertion and whether human host cells are being exploited by SARS-CoV-2 as an ‘evolutionary sandbox’ for host-virus and inter-viral genomic interplay.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/f7txy/" target="_blank">Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin</a>
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<li><strong>Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system</strong> -
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<div>
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Cerebral venous sinus thrombosis (CVST) has been reported in a small number of individuals who have received the mRNA vaccines1 or the adenoviral vector vaccines for COVID-19 in the US2 and Europe3. Continued pharmacovigilance is integral to mitigating the risk of rare adverse events that clinical trials are underpowered to detect, however, these anecdotal reports have led to the pause or withdrawal of some vaccines in many jurisdictions and exacerbated vaccine hesitancy at a critical moment in the fight against the COVID-19 pandemic. We investigated the frequencies of CVST seen among individuals who received FDA-authorized COVID-19 vaccines from Pfizer-BioNTech (n = 94,818 doses), Moderna (n = 36,350 doses) and Johnson & Johnson - J&J (n = 1,745 doses), and among individuals receiving one of 10 FDA-approved non-COVID-19 vaccines (n = 771,805 doses). Comparing the incidence rates of CVST in 30-day time windows before and after vaccination, we found no statistically significant differences for the COVID-19 vaccines or any other vaccines studied in this population. In total, we observed 3 cases of CVST within the 30 days following Pfizer-BioNTech vaccination (2 females, 1 male; Ages (years): [79, 80, 84]), including one individual with a prior history of thrombosis and another individual with recent trauma in the past 30 days. We did not observe any cases of CVST among the patients receiving Moderna or J&J vaccines in this study population. We further found the baseline CVST incidence in the study population between 2017 and 2021 to be 45 to 98 per million patient years. Overall, this real-world evidence-based study highlights that CVST is rare and is not significantly associated with COVID-19 vaccination. In addition, there is a need for a concerted international effort to monitor EHR data across diverse patient populations and to investigate the underlying biological mechanisms leading to these rare clotting events.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/czn7j/" target="_blank">Cerebral venous sinus thrombosis (CVST) is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state US health system</a>
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<li><strong>COVID-19 hospitalization and ICU admission trends in younger patients and the pediatric population</strong> -
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Media reports this week are suggesting a potential spike up in COVID-19 genetic variants-associated intensive care unit (ICU) admissions for younger patients from the continents of North America, South America, and Europe. Here, we conducted an observational study on the health records of 60,539 patients (March 1-28, 2021) and 60,256 patients (February 1-28, 2021) from the multi-state Mayo Clinic health system for whom the SARS-CoV-2 PCR test results were also available. Interestingly, we note a significant drop in the ICU admission rates during March (1.45%; 87 of 6017 COVID-positive patients) compared to February (1.99%; 121 of 6078 COVID-positive patients) with a Rate Ratio of 0.78 (p-value = 0.0002; Figure 1). In this study population, there is a slight shift in the peak of ICU admissions towards the younger population in March relative to February (Figure 2). While this trend is not statistically significant at this time, this requires close monitoring over the coming weeks. Restricting the study population to younger COVID-positive patients (age < 55), we observe a drop in the number of ICU admissions in March compared to February (not statistically significant; Figure 3). Consistent with the drop in the ICU admission rate, we also see a statistically significant drop in the hospitalization rate in March 2021 (10.97%; 660 of 6017 COVID-positive patients) compared to February 2021 (13.64%; 829 of 6078 COVID-positive patients) with a rate ratio of 0.8 (p-value: 2.34e-12; Figure 4). Focusing the study population to the younger COVID-positive patients (age < 55), we observe a drop in the number of hospitalizations in March compared to February (not statistically significant; Figure 5). Independently, the national data from the US government (https://healthdata.gov/) also shows a steady drop over recent months in hospitalized pediatric patients with confirmed or suspected COVID-19 (Figure 6a). We observe similar trends in the top-10 states by population as well (Figure 6b). This preliminary analysis shows that there is a decreasing trend in ICU admissions and hospitalization of COVID-19 patients across a large multi-state health system as of March 2021. Furthermore, there is no apparent nation-wide spike in pediatric hospitalizations in March compared to February 2021. Decreased hospitalizations and ICU admission rates may be reflective of advances in early diagnosis and intervention. As the proportion of circulating viruses shift towards more variants, these results may change. Overall, amidst recent concerns about emergent SARS-CoV-2 strains, there is an imminent need to develop a real-time system that integrates various national surveillance efforts in order to guide public health policies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/cj4sf/" target="_blank">COVID-19 hospitalization and ICU admission trends in younger patients and the pediatric population</a>
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<li><strong>Evaluation and Treatment of Severe SARS-CoV-2 Pneumonia: A Scoping Review</strong> -
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Purpose: Severe SARS-CoV-2 pneumonia remains incompletely understood. We aimed to summarize current evidence regarding clinical features, laboratory findings, and treatment of severe SARS-CoV-2 pneumonia. Methods: Online databases were searched from December 1, 2019, to April 15, 2020. Studies performed in adults, with the definition of severe SARS-CoV-2 pneumonia, enough case number (>10), and data on clinical features or laboratory findings were included. Data were extracted independently by two reviewers. Results: Eighteen articles of 2,435 severe cases were eligible for analysis, with the average ages ranging from 49 to 70 years old, hypertension as the most common comorbidity, fever as the most common manifestation, and acute respiratory distress syndrome (ARDS) as the most common complication. As compared to non-severe cases, severe pneumonia was featured with the lower counts of lymphocytes, CD8+ and CD4+ T cells, and higher levels of D-dimer, lactate dehydrogenase (LDH), IL-6 and IL-10. Antiviral therapy was the mainstay of treatment for severe SARS-CoV-2 pneumonia, and oseltamivir was the most commonly used antiviral reagent. Ventilation therapy, especially mechanical ventilation, was the primary and effective treatment. Conclusions: This study represents the first systematic summarization of the aspects of severe SARS-CoV-2 pneumonia, and its comparison with non-severe cases in symptoms and laboratory findings. Research including elder cases and from regions outside China, especially western countries, would generate benefits in a full understanding of severe SARS-CoV-2 pneumonia. High-quality studies are urgently required to confirm or exclude the possibility of a treatment benefit.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.13.23291341v1" target="_blank">Evaluation and Treatment of Severe SARS-CoV-2 Pneumonia: A Scoping Review</a>
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<li><strong>Structured Ethical Review for Wastewater-Based Testing</strong> -
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Wastewater-based testing (WBT) for SARS-CoV-2 has rapidly expanded over the past three years due to its ability to provide a comprehensive measurement of disease prevalence independent of clinical testing. The development and simultaneous application of the field blurred the boundary between measuring biomarkers for research activities and for pursuit of public health goals, both areas with well-established ethical frameworks. Currently, WBT practitioners do not employ a standardized ethical review process (or associated data management safeguards), introducing the potential for adverse outcomes for WBT professionals and community members. To address this deficiency, an interdisciplinary group developed a framework for a structured ethical review of WBT. The workshop employed a consensus approach to create this framework as a set of 11-questions derived from primarily public health guidance because of the common exemption of wastewater samples to human subject research considerations. This study retrospectively applied the set of questions to peer-reviewed published reports on SARS-CoV-2 monitoring campaigns covering the emergent phase of the pandemic from March 2020 to February 2022 (n=53). Overall, 43% of the responses to the questions were unable to be assessed because of lack of reported information. It is therefore hypothesized that a systematic framework would at a minimum improve the communication of key ethical considerations for the application of WBT. Consistent application of a standardized ethical review will also assist in developing an engaged practice of critically applying and updating approaches and techniques to reflect the concerns held by both those practicing and being monitored by WBT supported campaigns.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.12.23291231v1" target="_blank">Structured Ethical Review for Wastewater-Based Testing</a>
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<li><strong>Partially hydrolyzed guar gum attenuates the symptoms of SARS-CoV-2 infection through gut microbiota modulation in an animal model.</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic has caused worldwide health issues. Although several vaccines have been developed, it is still difficult to prevent and reduce the inflammation caused by the infection. Studies have shown that there are correlations between the gut environment and severity of symptoms caused by SARS-CoV-2 infection. Several gut metabolites produced by the gut microbiota such as SCFAs and the secondary bile acid UDCA are reported to improve the survival rate of the host after viral infection in an animal model through modulation of the host immune system. Therefore, in this study, we attempted to use the prebiotic dietary fiber PHGG to modulate the gut microbiome and intestinal metabolites for improvement of host survival rate after SARS-CoV-2 infection in a Syrian hamster model. We were able to show that PHGG significantly improved the host survival rate and body weight reduction. Analysis of the gut microbiome, serum, and intestinal metabolites revealed that PHGG significantly increased the concentrations of several intestinal SCFAs, fecal secondary bile acids, and serum secondary bile acids. Furthermore, several microbial species and metabolites identified in this study are consistent with reports in humans. Taken together, our data suggest that PHGG is a candidate prebiotic food for reducing the morbidity of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.13.544519v1" target="_blank">Partially hydrolyzed guar gum attenuates the symptoms of SARS-CoV-2 infection through gut microbiota modulation in an animal model.</a>
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<li><strong>Biophysical evolution of the receptor binding domains of SARS-CoVs</strong> -
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With hundreds of coronaviruses (CoVs) identified in bats that are capable of infecting humans, it is important to understand how CoVs that affected the human population have evolved. Seven known coronaviruses have infected humans, of which three CoVs caused severe disease with high mortality rates: SARS-CoV emerged in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. Both SARS-CoV and SARS-CoV-2 belong to the same family, follow the same receptor pathway, and use their receptor binding domain (RBD) of spike protein to bind to the ACE2 receptor on the human epithelial cell surface. The sequence of the two RBDs is divergent, especially in the receptor binding motif (RBM) that directly interacts with ACE2. We probed the biophysical differences between the two RBDs in terms of their structure, stability, aggregation, and function. Since RBD is being explored as an antigen in protein subunit vaccines against CoVs, determining these biophysical properties will also aid in developing stable protein subunit vaccines. Our results show that despite RBDs having a similar three-dimensional structure, they differ in their thermodynamic stability. RBD of SARS-CoV-2 is significantly less stable than that of SARS-CoV. Correspondingly, SARS-CoV-2 RBD shows a higher aggregation propensity. Regarding binding to ACE2, less stable SARS-CoV-2 RBD binds with a higher affinity than more stable SARS-CoV RBD. In addition, SARS-CoV-2 RBD is more homogenous in terms of its binding stoichiometry towards ACE2, compared to SARS-CoV RBD. These results indicate that SARS-CoV-2 RBD differs from SARS-CoV RBD in terms of its stability, aggregation, and function, possibly originating from the diverse RBMs. Higher aggregation propensity and decreased stability of SARS-CoV-2 RBD warrants further optimization of protein subunit vaccines that use RBD as an antigen either by inserting stabilizing mutations or formulation screening.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.13.544630v1" target="_blank">Biophysical evolution of the receptor binding domains of SARS-CoVs</a>
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<li><strong>AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor</strong> -
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Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays and AlphaFold-Multimer predictions. Using the quantitative assay LuTHy together with our machine learning algorithm, we identified high-confidence interactions among SARS-CoV-2 proteins for which we predicted three-dimensional structures using AlphaFold Multimer. We employed VirtualFlow to target the contact interface of the NSP10-NSP16 SARS-CoV-2 methyltransferase complex by ultra-large virtual drug screening. Thereby, we identified a compound that binds to NSP10 and inhibits its interaction with NSP16, while also disrupting the methyltransferase activity of the complex, and SARS-CoV-2 replication. Overall, this pipeline will help to prioritize PPI targets to accelerate the discovery of early-stage drug candidates targeting protein complexes and pathways.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.14.544560v1" target="_blank">AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor</a>
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</div></li>
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<li><strong>Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes</strong> -
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In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents during the pandemic, the prevalence of obesity increased by ~37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced diabetes, and explored neural changes that may underlie such an interaction. We find that isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes. We observed fasted hyperglycemia, diminished glucose clearance in response to an insulin tolerance test, decreased insulin signaling in skeletal muscle, decreased insulin staining of pancreatic islets, increased nociception, and diminished plasma cortisol levels compared to group-housed control mice. Using Promethion metabolic phenotyping chambers, we observed dysregulation of sleep and eating behaviors, as well as a time-dependent shift in respiratory exchange ratio of the adolescent-isolation mice. We profiled changes in neural gene transcription from several brain areas and found that a neural circuit between serotonin-producing and GLP-1-producing neurons is affected by this isolation paradigm. Overall, spatial transcription data suggest decreased serotonin neuron activity (via decreased GLP-1-mediated excitation) and increased GLP-1 neuron activity (via decreased serotonin-mediated inhibition). This circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes, as well as a pharmacologically-relevant circuit to explore the effects of serotonin and GLP-1 receptor agonists.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.12.544498v1" target="_blank">Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes</a>
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</div></li>
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<li><strong>Keeping Kids Busy: Family Factors Associated with Hands-on Play and Screen Time During the COVID-19 Pandemic</strong> -
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Parent-child interactions are crucial for child development. The COVID-19 pandemic has negatively affected mental health and increased parenting challenges impacting parent-child functioning. The aim of the current study was to examine the relationship between parent factors and child activities to identify parental needs. A convenience sample of parents (N = 708), primarily mothers (n = 610; 87.4%) aged 35.59 years old (SD = 5.59; range = 21-72), with children ages 2-8 years completed an online questionnaire between April 14-June 1, 2020. Participants mostly resided in Canada and had an income of >$100,000. Parent-child activities were measured as total weekly time and combined time across activities within two categories: hands-on play and screen time. Bivariate correlations informed block-wise linear regression models. For families with childcare needs, parental anxiety was associated with higher total hands-on play (F(3,142) = 14.01, p < .001), combined hands-on play (F(2,85) = 6.82, p = .011), and combined screen time (F(2,82) = 6.25, p = .014). Families without childcare needs indicated parenting stress was associated with lower total hands-on play (F(3,212) = 7.95, p < .005) and combined hands-on play (F(2,110) = 5.67, p = .019), and higher supervised screen time (F(3,138) = 6.14, p = .014). Family structure and indices of socioeconomic status were also predictive of activities across childcare needs and child ages. To promote high-quality parent-child interactions and positive developmental outcomes in the pandemic, policy makers should support childcare needs, parent mental health and stress, and provide evidence-based guidelines for child screen time.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/prtyf/" target="_blank">Keeping Kids Busy: Family Factors Associated with Hands-on Play and Screen Time During the COVID-19 Pandemic</a>
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</div></li>
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</ul>
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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 Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation<br/><b>Sponsors</b>: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety Study of COVID19 Vaccine on the Market</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant new coronavirus vaccine (CHO cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention<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>Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<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 Home Use COVID-19 Frequent Antigen Testing and Data Reporting</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Diagnostic Test: SARS CoV-2 antigen tests<br/><b>Sponsors</b>: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)<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>Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19</strong> - <b>Conditions</b>: SARS-CoV Infection; COVID-19<br/><b>Interventions</b>: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo<br/><b>Sponsor</b>: University of Texas Southwestern Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Placebo; Drug: Montelukast<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Evaluating Emetine for Viral Outbreaks (EVOLVE)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Emetine Hydrochloride; Drug: Placebo<br/><b>Sponsors</b>: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pycnogenol® in Post-COVID-19 Condition</strong> - <b>Conditions</b>: Post COVID-19 Condition; Long COVID<br/><b>Interventions</b>: Drug: Pycnogenol®; Drug: Placebo<br/><b>Sponsor</b>: University of Zurich<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Bailing capsule<br/><b>Sponsor</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.<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 Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07817883<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>Cupping Therapy on Immune System in Post Covid -19</strong> - <b>Condition</b>: Covid-19 Patients<br/><b>Interventions</b>: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</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>Recent advances in RNA sample preparation techniques for the detection of SARS-CoV-2 in saliva and gargle</strong> - Molecular detection of SARS-CoV-2 in gargle and saliva complements the standard analysis of nasopharyngeal swabs (NPS) specimens. Although gargle and saliva specimens can be readily obtained non-invasively, appropriate collection and processing of gargle and saliva specimens are critical to the accuracy and sensitivity of the overall analytical method. This review highlights challenges and recent advances in the treatment of gargle and saliva samples for subsequent analysis using reverse…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An efflux pump in genomic island GI-M202a mediates the transfer of polymyxin B resistance in Pandoraea pnomenusa M202</strong> - CONCLUSIONS: These findings demonstrated that GI-M202a along with the MFS transporter FKQ53_RS21695 in P. pnomenusa M202 could mediate the transmission of polymyxin B resistance.</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>Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon</strong> - Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity 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>Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor</strong> - Acute lung injury is significantly associated with the aberrant activation and pyroptosis of alveolar macrophages. Targeting the GPR18 receptor presents a potential therapeutic approach to mitigate inflammation. Verbenalin, a prominent component of Verbena in Xuanfeibaidu (XFBD) granules, is recommended for treating COVID-19. In this study, we demonstrate the therapeutic effect of verbenalin on lung injury through direct binding to the GPR18 receptor. Verbenalin inhibits the activation of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, Characterization, and Antibacterial Activity of New Isatin Derivatives</strong> - 1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by…</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>Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication</strong> - The papain-like protease (PLpro) plays a critical role in SARS-CoV-2 (SCoV-2) pathogenesis and is essential for viral replication and for allowing the virus to evade the host immune response. Inhibitors of PLpro have great therapeutic potential, however, developing them has been challenging due to PLpro’s restricted substrate binding pocket. In this report, we screened a 115 000-compound library for PLpro inhibitors and identified a new pharmacophore, based on a mercapto-pyrimidine fragment that…</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>Sulfated Glycomimetic α-Helical Polypeptides for Antiviral Activity</strong> - In this work, we developed a library of sulfated glycomimetic polypeptides with a high sulfated degree (up to 99%) via a click reaction and sulfation modification, enabling control over the helicity, molecular weight, rigidity, and side-chain structure. Their potentials as the inhibitors of SARS-CoV-2 and common enterovirus were investigated, and the structure-activity relationship was explored in detail. The in vitro results revealed the crucial role of α-helical conformation and sulfated sugar…</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>Stakeholder perspectives and experiences of the implementation of remote mental health consultations during the COVID-19 pandemic: a qualitative study</strong> - CONCLUSIONS: Remote mental health consultations were welcomed as a means to continue care during the COVID-19 pandemic. Their swift and necessary adoption placed pressure on providers and organisations to adapt quickly, navigating challenges and adjusting to a new way of working. This implementation created changes to workflows and dynamics that disrupted the traditional method of mental health care delivery. Further consideration of the importance of the therapeutic relationship and fostering…</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>AEROSOLIZED SULFATED HYALURONAN DERIVATIVES PROLONG THE SURVIVAL OF K18 ACE2 MICE INFECTED WITH A LETHAL DOSE OF SARS-COV-2</strong> - Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 binding and entry in human cells involves interactions of its spike (S) protein with several host cell surface factors, including heparan sulfate proteoglycans (HSPGs), transmembrane protease serine 2 (TMPRSS2), and angiotensin-converting enzyme 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>β-Cyclodextrins as affordable antivirals to treat coronavirus infection</strong> - The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and β coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin…</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>Novel SARS-CoV-2 entry inhibitors, 2-anilinoquinazolin-4(3H)-one derivatives, show potency as SARS-CoV-2 antivirals in a human ACE2 transgenic mouse model</strong> - The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2-anilinoquinazolin-4(3H)-one…</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>Antibody responses to mRNA versus non-mRNA COVID vaccines among the Mongolian population</strong> - CONCLUSIONS: The BNT162b2 vaccine showed the highest level of antibody against SARS-CoV-2, followed by the BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 n-CoV-19 vaccines. The level of antibodies was increased in people infected with SARS-CoV-2 after vaccination, as compared to uninfected but vaccinated individuals.</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>Inhibiting C5 in patients with severe COVID-19-the incorrect target? - Authors’ reply</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>Inhibiting C5 in patients with severe COVID-19-the incorrect target?</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>Pharmacological properties and derivatives of saikosaponins-a review of recent studies</strong> - CONCLUSIONS: An increasing amount of data have indicated diverse SS pharmacological properties, indicating crucial clues for future studies and the production of novel saikosaponin-based anti-inflammatory, efficacious anticancer, and anti-novel-coronavirus agents with improved efficacy and reduced toxicity.</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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