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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>09 May, 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>Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis</strong> -
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<div>
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One of the fundamental mechanisms developed by the host to contain the highly infectious and rapidly proliferating SARS coronavirus is elevation of body temperature, a natural fallout of which is Heat Shock Protein (HSP) over-expression. Here, for the first time, we demonstrate that the SARS-CoV-2 virus exploits the host Hsp70 chaperone for its entry and propagation and blocking it can combat the infection. SARS-CoV-2 infection as well as febrile temperature enhanced Hsp70 overexpression in host Vero E6 cells. In turn, Hsp70 overexpression elevated the host cell autophagic response that is a prerequisite for viral propagation. Suppressive and prophylactic treatment of Vero E6 cells with HSP70 inhibitor PES-Cl, a small molecule derivative of Pifithrin-, abrogated viral infection more potently than the currently used drug Remdesivir by suppressing host HSP70 and autophagic response. In conclusion, our study not only provides a fundamental insight into the role of host Hsp70 in SARS-CoV-2 pathogenesis, it paves the way for the development of potent and irresistible anti-viral therapeutics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.05.539661v1" target="_blank">Host inducible-HSP70A1A is an irresistible drug target to combat SARS-CoV-2 infection and pathogenesis</a>
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</div></li>
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<li><strong>Emergency department visits and boarding for pediatric patients with suicidality before and during the COVID-19 pandemic</strong> -
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Objective: To quantify the increase in pediatric patients presenting to the emergency department with suicidality before and during the COVID-19 pandemic, and the subsequent impact on emergency department length of stay and boarding. Methods: This retrospective cohort study from June 1, 2016, to October 31, 2022, identified patients presenting to the emergency department with suicidality using ICD-10 codes. Number of emergency department encounters for suicidality, demographic characteristics of patients with suicidality, and emergency department length of stay were compared before and during the COVID-19 pandemic. Unobserved components models were used to describe monthly counts of emergency department encounters for suicidality. Results: There were 179,736 patient encounters to the emergency department during the study period, 6,168 (3.4%) for suicidality. There were, on average, more encounters for suicidality each month during the COVID-19 pandemic than before the COVID-19 pandemic. A time series unobserved components model demonstrated an initial drop in encounters for suicidality in April and May of 2020, followed by an increase starting in July 2020. The average length of stay for patients that boarded in the emergency department with a diagnosis of suicidality was 37.4 hours longer during the COVID-19 pandemic compared to before the COVID-19 pandemic. Conclusions: The number of encounters for suicidality among pediatric patients and the emergency department length of stay for psychiatry boarders has increased during the COVID-19 pandemic. There is a need for acute care mental health services and solutions to emergency department capacity issues.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.08.23289659v1" target="_blank">Emergency department visits and boarding for pediatric patients with suicidality before and during the COVID-19 pandemic</a>
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<li><strong>Vaccine effectiveness of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years in German Primary Care</strong> -
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Background Despite the approval of BNT162b2 mRNA vaccine for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, no data on vaccine effectiveness (VE) of BNT162b2 are available in this age group. We here report on the VE of BNT162b2 during an Omicron BA.1-2 dominant period. Methods An authentication-based retrospective survey was performed between April 14th 2022 and May 9th 2022 in individuals that had registered children for off-label SARS-CoV-2 vaccination in Germany. We used Cox regression to estimate relative VE of two BNT162b2 doses, with the period between first and second vaccine dose as reference period (24.8+-0.6 days) and >=7 days after Dose 2 to before Dose 3 as post-vaccination period (59.5+-23.6 days). Results The present analysis included 4615 children aged 2.8+-1.2 years (mean+-standard deviation) who had received their first dose of BNT162b2 on January 1st 2022 or thereafter. VE was substantial for protection from any SARS-CoV-2 infection (VE: 53.1% [95% confidence interval (CI): 36.3-69.6%], p<0.001), symptomatic SARS-CoV-2 infections (VE: 57.5% [95% CI: 40.8-74.2%], p<0.001), and SARS-CoV-2 infections leading to medication use (VE: 66.2% [95% CI: 43.7-88.7%], p<0.001). Differences in dosage of BNT162b2 yielded no change in VE. Conclusion This study offers a first industry-independent insight in the potential VE of two doses of the BNT162b2 vaccine in children aged below 5 years, as currently only immunogenicity data by the manufacturer Pfizer/BioNTech are available. Limitations include the retrospective study design, and that the reported VE does not necessarily correspond to currently circulating SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289209v1" target="_blank">Vaccine effectiveness of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years in German Primary Care</a>
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<li><strong>SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway</strong> -
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We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the human in vivo biosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the presence of an extended panel of urinary and serum metabolites during the acute viral phase. The structure of eight of nucleoside analogues was elucidated (six of which have not previously been reported in human urine), and subsequently confirmed by total-synthesis and matrix spiking. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defense mechanism against viral infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.08.23289637v1" target="_blank">SARS-CoV-2 Infection Biomarkers Reveal an Extended RSAD2 Dependant Metabolic Pathway</a>
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<li><strong>Mobilizing faith-based COVID-19 health ambassadors to address COVID-19 health disparities among African American older adults in under-resourced communities: A hybrid, community-based participatory intervention</strong> -
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The COVID-19 pandemic disproportionately affected older adults, particularly those with pre-existing chronic health conditions. To address the health disparity gap and challenges faced by under-resourced African American older adults in South Los Angeles during this period, we implemented a hybrid (virtual/in-person), pre-post, community-based participatory intervention research project utilizing a faith-based lay health advisor model (COVID-19 Health Ambassador Program (CHAP)). We recruited COVID-19 Health Ambassadors (CHAs) and African American older adults (participants) from faith-based organizations who partook in CHA-led meetings and follow-ups that educated and supported the participants. This paper seeks to evaluate this intervention9s implementation using the Consolidated Framework for Implementation Research (CFIR) as a reporting tool with an emphasis on fidelity, challenges, and adaptations based on data collected via stakeholder interviews and surveys. Results: CHAP was delivered to 152 participants by 19 CHAs from 17 faith-based organizations. CHAs assisted with chronic disease management, resolved medication-related challenges, encouraged COVID-19 vaccination, reduced psychological stress and addressed healthcare avoidance behaviors such as COVID-19 vaccine hesitancy among the participants. Challenges encountered include ensuring participant engagement and retention in the virtual format and addressing technological barriers for CHAs and participants. Adaptations made to better suit the needs of participants included providing communication tools and additional training to CHAs to improve their proficiency in using virtual platforms in addition to adapting scientific/educational materials to suit our participants’ diverse cultural and linguistic needs. Conclusion: The community-centered hybrid approach in addition to our partnership with faith-based organizations and their respective COVID-19 health ambassadors proved to be essential in assisting underserved African American older adults manage chronic health conditions and address community-wide health disparities during the COVID-19 pandemic. Adaptability, cultural sensitivity, and teamwork are key to implementing health interventions especially in underserved populations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.07.23289636v1" target="_blank">Mobilizing faith-based COVID-19 health ambassadors to address COVID-19 health disparities among African American older adults in under-resourced communities: A hybrid, community-based participatory intervention</a>
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<li><strong>Assessing Contributing and Mediating Factors of Telemedicine on Provider Burnout</strong> -
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Scientific Abstract: Objective: The prevalence of burnout among healthcare providers has been steadily increasing, with a call to action issued in 2019. Immediately following this call to action, the COVID-19 pandemic drastically changed demand. Use of telemedicine expanded in response to COVID-19 and changed the experience of care delivery for healthcare providers. The impact of telemedicine use during COVID-19 on the provider well-being is less well known. This study aims to assess the prevalence of burnout in providers who used telemedicine and to better understand how specific factors of telemedicine can impact workplace stress. Methods: Providers in urgent care clinics were invited to participate in a burnout assessment survey using the Maslach Burnout Inventory questionnaire. The prevalence of burnout, burnout profiles, and correlations were analyzed in the resulting data. Follow-up interviews provided further insight on contributing and mediating factors of telemedicine on provider burnout. Results: The findings from this study provide technology- and organizational-level recommendations to prevent increased risk of burnout among telemedicine providers. The classification of contributing and mediating factors also provides a framework for understanding the risks that this technology can pose to workplace stress. Future research recommendations to better quantify the relationship between burnout and telemedicine use and to effectively design intervention and implementation strategies are discussed. Public Interest Summary: Considering the high rates of burnout in the healthcare industry prior to the pandemic, the severe demands the COVID-19 pandemic had on healthcare workers, and the drastic changes in workflow due to the widespread adoption of telemedicine, it is important to assess current levels of provider burnout and to collect information from frontline clinicians on how telemedicine impacts workplace stress. A survey was administered to assess burnout in healthcare workers who provided care via telemedicine. The interviews provided additional insight on how telemedicine affected workplace stress. Survey results showed that 25% of the respondents reported one or more manifestations of burnout; and there was a correlation between personal accomplishment scores and reported months of telemedicine use. Findings from the interviews and review of literature identified what design and use characteristics of telemedicine contributed to and/or alleviated burnout. Results address how organizations can best support their employees who administer care via telemedicine and guide researchers with direction for future studies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.08.23289673v1" target="_blank">Assessing Contributing and Mediating Factors of Telemedicine on Provider Burnout</a>
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</div></li>
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<li><strong>The impact of remote consultations on the quality of primary care: A systematic review</strong> -
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Background: The adoption of remote consultations, catalysed by the COVID-19 pandemic, has transformed the delivery of primary care services. We evaluated the impact of remote consultations on the quality of primary care. Methods: Six databases were searched. Studies evaluating the impact of remote consultations, for any disease, were included. Title and abstract screening, and full-text screening were performed by two pairs of investigators. Risk of bias was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis of the results was performed. Findings: Thirty studies (5,469,333 participants) were included in the review. Remote consultations generally had a positive or equivalent impact compared to face-to-face (F2F) consultations, particularly in reducing patient costs and improving time efficiency. The effectiveness of remote consultations was non-inferior to F2F care in six out of seven studies evaluating this aspect. Two studies found that remote consultations reduced wait times for appointments. Younger, female patients were more likely to use remote consultations and those of lower socioeconomic status were less likely to use video consultations than telephone appointments. The impacts on safety and patient-centeredness were largely inconclusive. Interpretation: Remote consultations may be equally as effective as F2F care and have a potentially positive impact on the efficiency and timeliness of care. Those of lower socioeconomic status were more likely to use consultations delivered via telephone than videoconference. Developing a strong evidence-base capitalising on real-world data as well as clinical trials is crucial for the future development of remote consultations and tailoring them to patient needs and preferences.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289593v1" target="_blank">The impact of remote consultations on the quality of primary care: A systematic review</a>
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<li><strong>Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis</strong> -
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Objective: Seizure following immunization, especially in persons with epilepsy (PwE), has long been a concern, and seizure aggravation followed by Coronavirus Disease 2019 (COVID-19) vaccines is a serious issue for PwE. The immunization rate in PwE has been lower compared to same-age controls due to vaccine hesitancy and concerns about seizure control. Herein, we systematically reviewed the seizure activity-related events in PwE following COVID-19 vaccination. Methods: Four search engines were searched from inception until January 31, 2023, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. Random- and fixed-effect models using the logit transformation method were used for meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale. Outcomes of interest included (a) pooled proportion of increased seizure frequency and (b) pooled incidence proportion of status epilepticus (SE) in PwE receiving COVID-19 vaccines. Results: Of the 2207 studies identified, 18 met eligibility criteria, of which 16 entered the meta-analysis. The pooled proportion of increased seizure frequency (16 studies-4197 PwE) was 5% (95CI: 3%-6%, I2 =57%), further subcategorized into viral vector (3%, 95CI: 2%-7%, I2 =0%), mRNA (5%, 95CI: 4%-7%, I2 =48%), and inactivated (4%, 95CI: 2%-8%, I2 =77%) vaccines. The pooled incidence proportion of SE (15 studies-2480 PwE) was 0.08% (95CI: 0.02%-0.32%, I2 =0%), further subcategorized into the viral vector (0.00%, 95CI: 0.00%-1.00%, I2 =0%), mRNA (0.09%, 95CI: 0.01%-0.62%, I2 =0%), and inactivated (0.00%, 95CI: 0.00%-1.00%, I2 =0%) vaccines. No significant difference was observed between mRNA and viral vector vaccines (5 studies, 1122 vs. 198 PwE, respectively) regarding increased seizure frequency (OR: 1.10, 95CI: 0.49-2.50, p-value=0.81, I2 =0%). Significance: The meta-analysis proposed a 5% increased seizure frequency following COVID-19 vaccination in PwE, with no difference between mRNA and viral vector vaccines. Furthermore, we found a 0.08% incidence proportion for SE. While this safety evidence is noteworthy, this cost should be weighed against vaccination benefits.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.06.23289604v1" target="_blank">Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis</a>
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<li><strong>Bivalent booster effectiveness against severe COVID-19 outcomes in Finland, September 2022 - March 2023</strong> -
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Bivalent COVID-19 vaccines were introduced in 2022 but knowledge of their effectiveness against severe COVID-19 outcomes is currently limited. In Finnish register-based cohort analyses, we compared the risk of severe COVID-19 outcomes among those who received bivalent vaccination (exposed) between September 2022 and March 2023 to those who did not (unexposed). Among elderly aged 65-110 years, bivalent vaccination reduced the risk of hospitalisation and death due to COVID-19 in September-December 2022; the hazard ratios comparing exposed and unexposed ranged from 0.37 to 0.45 during the first 31-60 days since bivalent vaccination. However, in January-March 2023 the effect disappeared possibly indicating immune evasion of new SARS-CoV-2 variants, waning of vaccine effectiveness and increased presence of hybrid immunity. Among the chronically ill aged 18-64 years bivalent vaccination did not reduce the risk of severe COVID-19 outcomes. These results are important for developing COVID-19 vaccines and programmes worldwide.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286561v3" target="_blank">Bivalent booster effectiveness against severe COVID-19 outcomes in Finland, September 2022 - March 2023</a>
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<li><strong>A diagnostic and economic evaluation of the complex artificial intelligence algorithm aimed to detect 10 pathologies on the chest CT images</strong> -
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Background: Artificial intelligence (AI) technologies can help solve the significant problem of missed findings in radiology studies. An important issue is assessing the economic benefits of implementing AI. Aim: to evaluate the frequency of missed pathologies detection and the economic potential of AI technology for chest CT, validated by expert radiologists, compared with radiologists without access to AI in a private medical center. Methods: An observational, single-center retrospective study was conducted. The study included chest CTs without IV contrast performed from 01.06.2022 to 31.07.2022 in “Yauza Hospital” LLC, Moscow. The CTs were processed using a complex AI algorithm for ten pathologies: pulmonary infiltrates, typical for viral pneumonia (COVID-19 in pandemic conditions); lung nodules; pleural effusion; pulmonary emphysema; thoracic aortic dilatation; pulmonary trunk dilatation; coronary artery calcification; adrenal hyperplasia; osteoporosis (vertebral body height and density changes). Two experts analyzed CTs and compared results with AI. Further routing was determined according to clinical guidelines for all findings initially detected and missed by radiologists. The lost potential revenue (LPR) was calculated for each patient according to the hospital price list. Results: From the final 160 CTs, the AI identified 90 studies (56%) with pathologies, of which 81 studies (51%) were missing at least one pathology in the report. The “second-stage” LPR for all pathologies from 81 patients was RUB 2,847,760 (＄37,251 or CNY 256,218). LPR only for those pathologies missed by radiologists but detected by AI was RUB 2,065,360 (＄27,017 or CNY 185,824). Conclusion: Using AI for chest CTs as an “assistant” to the radiologist can significantly reduce the number of missed abnormalities. AI usage can bring 3.6 times more benefits compared to the standard model without AI. The use of complex AI for chest CT can be cost-effective.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.19.23288584v2" target="_blank">A diagnostic and economic evaluation of the complex artificial intelligence algorithm aimed to detect 10 pathologies on the chest CT images</a>
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<li><strong>Alpha-1-antitrypsin and its variant-dependent role in COVID-19 pathogenesis</strong> -
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Rationale: SARS-CoV-2 entry into host cells is facilitated by endogenous and exogenous proteases that proteolytically activate the spike glycoprotein and antiproteases inhibiting this process. Understanding the key actors in viral entry is crucial for advancing knowledge of virus tropism, pathogenesis, and potential therapeutic targets. Objectives: We aimed to investigate the role of naive serum and alpha-1-antitrypsin (AAT) in inhibiting protease-mediated SARS-CoV-2 entry and explore the implications of AAT deficiency on susceptibility to different SARS-CoV-2 variants. Findings: Our study demonstrates that naive serum exhibits significant inhibition of SARS-CoV-2 entry, with AAT identified as the major serum protease inhibitor potently restricting entry. Using pseudoparticles, replication-competent pseudoviruses, and authentic SARS-CoV-2, we show that AAT inhibition occurs at low concentrations compared with those in serum and bronchoalveolar tissues, suggesting physiological relevance. Furthermore, sera from subjects with an AAT-deficient genotype show reduced ability to inhibit entry of both Wuhan-Hu-1 (WT) and B.1.617.2 (Delta) but exhibit no difference in inhibiting B.1.1.529 (Omicron) entry. Conclusions: AAT may have a variant-dependent therapeutic potential against SARS-CoV-2. Our findings highlight the importance of further investigating the complex interplay between proteases, antiproteases, and spike glycoprotein activation in SARS-CoV-2 and other respiratory viruses to identify potential therapeutic targets and improve understanding of disease pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.08.14.248880v2" target="_blank">Alpha-1-antitrypsin and its variant-dependent role in COVID-19 pathogenesis</a>
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<li><strong>Syariah Governance and Disclosure Islamic Corporate Social Responsibility: A Comparative Study of Indonesian and Malaysian Islamic Banking</strong> -
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The existence of the Sharia Supervisory Board in the Sharia banking GCG structure is a unique feature that distinguishes it from the GCG structure of conventional banks. The inconsistency of the results of previous research related to the relationship between GCG and CSR disclosure is the motivation of this study, in addition to the differences in the progress of Indonesian and Malaysian Islamic banks. The research population of Islamic banking is listed on the Indonesia Stock Exchange and the Malaysia Stock Exchange. Research period on 2016 – 2019 before covid 19 pandemic. The research sample was determined based on purposive sampling, 12 Islamic banks in Indonesia and 14 Islamic banks in Malaysia was selected. The method of analysis is multi group using Partial Least Squares. The results of this study provide empirical evidence that the Sharia Supervisory Board, Board of Commissioners and Board of Directors have not succeeded in playing a role in increasing I-CSR disclosure except for the Independent Board of Commissioners and Independent Board of Directors. The results of the study also have not shown any differences in the influence of GCG on I-CSR in Indonesian and Malaysian Islamic banking.
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🖺 Full Text HTML: <a href="https://osf.io/3xqrb/" target="_blank">Syariah Governance and Disclosure Islamic Corporate Social Responsibility: A Comparative Study of Indonesian and Malaysian Islamic Banking</a>
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<li><strong>Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue</strong> -
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Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, enhanced infectivity maps to the step of cellular entry and evolved recently through mutations unique to Omicron Spike. Unlike earlier variants of SARS-CoV-2, Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon matrix metalloproteinases to catalyze membrane fusion. This entry pathway unlocked by Omicron Spike enables evasion of interferon-induced factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.06.539698v1" target="_blank">Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue</a>
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</div></li>
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<li><strong>A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice</strong> -
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Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL-NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.05.539395v1" target="_blank">A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice</a>
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</div></li>
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<li><strong>Robust identification of perturbed cell types in single-cell RNA-seq data</strong> -
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Single-cell transcriptomics has emerged as a powerful tool for understanding how different cells contribute to disease progression by identifying cell types that change across diseases or conditions. However, detecting changing cell types is challenging due to individual-to-individual and cohort-to-cohort variability and naive approaches based on current computational tools lead to false positive findings. To address this, we propose a computational tool, scDist, based on a mixed-effects model that provides a statistically rigorous and computationally efficient approach for detecting transcriptomic differences. By accurately recapitulating known immune cell relationships and mitigating false positives induced by individual and cohort variation, we demonstrate that scDist outperforms current methods in both simulated and real datasets, even with limited sample sizes. Through the analysis of COVID-19 and immunotherapy datasets, scDist uncovers transcriptomic perturbations in dendritic cells, plasmacytoid dendritic cells, and FCER1G+NK cells, that provide new insights into disease mechanisms and treatment responses. As single-cell datasets continue to expand, our faster and statistically rigorous method offers a robust and versatile tool for a wide range of research and clinical applications, enabling the investigation of cellular perturbations with implications for human health and disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.06.539326v1" target="_blank">Robust identification of perturbed cell types in single-cell RNA-seq data</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID-19 Syndrome Lifestyle Intervention Study</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: Low carbohydrate diet intervention<br/><b>Sponsor</b>: University of Southern California<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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<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>A Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19</strong> - <b>Conditions</b>: GERD; Post COVID-19 Condition; Diaphragm Issues<br/><b>Interventions</b>: Other: modified diaphragmatic training; Other: standard diaphragmatic training<br/><b>Sponsor</b>: Indonesia University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>: Sars-CoV-2 Infection<br/><b>Interventions</b>: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>: Alvea Holdings, LLC<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>Role of Anthropometric Indices and Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response Against SARS-CoV-2 in Individuals Infected With COVID-19; A Randomized Control Trial</strong> - <b>Condition</b>: Role of Anthropometric Indices and Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and IgG Response Against SARS-CoV-2<br/><b>Intervention</b>: Combination Product: Vitamin-D<br/><b>Sponsor</b>: Sulaimany Polytechnic university<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccination Detoxification in LDL-C</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech 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>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>: Long COVID<br/><b>Intervention</b>: Other: Rehabilitation program<br/><b>Sponsors</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus 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>Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome.</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition<br/><b>Sponsors</b>: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión<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 in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation<br/><b>Sponsor</b>: Aligos Therapeutics<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>Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition<br/><b>Interventions</b>: Device: Immunoadsorption; Device: Sham-apheresis<br/><b>Sponsor</b>: University Medical Center Mainz<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>REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue Syndrome, Chronic<br/><b>Interventions</b>: Other: Anhydrous Enol-Oxaloacetate, a “Medical Food”; Other: White Rice Flour<br/><b>Sponsors</b>: Terra Biological LLC; Bateman Horne 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>A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2; Influenza<br/><b>Interventions</b>: Biological: Fluarix; Biological: mRNA-1083.1; Biological: mRNA-1083.2; Biological: mRNA-1083.3; Biological: mRNA-1010.4; Biological: mRNA-1283.222; Biological: mRNA-1273.222; Biological: mRNA-1010; Biological: Fluzone HD<br/><b>Sponsor</b>: ModernaTX, Inc.<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<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>Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against <em>Neisseria gonorrhoeae</em> in preclinical studies</strong> - CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Potential TMPRSS2 Inhibitors for COVID-19 Treatment in Chinese Medicine by Computational Approaches and Surface Plasmon Resonance Technology</strong> - CONCLUSIONS: Specific active compounds including narirutin, saikosaponin B1, and rutin in CM recipes potentially target and inhibit TMPS2, probably exerting a therapeutic effect on COVID-19.</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>Comparison of antibody responses following natural infection with Severe Acute Respiratory Syndrome Coronavirus 2 or receipt of CoronaVac or ChAdOx1 (AZD1222) vaccination in Chiang Mai, Thailand</strong> - CONCLUSIONS: ChAdOx1 vaccine may provide superior immunogenicity than CoronaVac and natural 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>In-Silico Approaches for the Screening and Discovery of Broad-Spectrum Marine Natural Product Antiviral Agents Against Coronaviruses</strong> - The urgent need for SARS-CoV-2 controls has led to a reassessment of approaches to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. There are yet no clinically approved broad-spectrum antivirals available for beta-coronaviruses. Discovery pipelines for pan-virus medications against a broad range of betacoronaviruses are therefore a priority. A variety of marine natural product (MNP) small molecules have shown inhibitory activity against…</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>Heat-Denatured Lysozyme is a Novel Potential Non-alcoholic Disinfectant Against Respiratory Virus</strong> - Respiratory diseases are significant recurrent threats to global public health. Since the 1918 Spanish flu pandemic, seasonal influenza viruses continue to cause epidemics around the world each year. More recently, the COVID-19 global pandemic conducted a public health crisis with more than 6 million deaths and it also severely affected the global economy. Due to the phenomenon that people get infection from objects carrying viruses, it has aroused people’s attention to home disinfection. As…</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 Nucleocapsid Proteins of SARS-CoV-2 and Its Close Relative Bat Coronavirus RaTG13 Are Capable of Inhibiting PKR- and RNase L-Mediated Antiviral Pathways</strong> - Coronaviruses (CoVs), including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2, produce double-stranded RNA (dsRNA) that activates antiviral pathways such as PKR and OAS/RNase L. To successfully replicate in hosts, viruses must evade such antiviral pathways. Currently, the mechanism of how SARS-CoV-2 antagonizes dsRNA-activated antiviral pathways is unknown. In this study, we demonstrate that the SARS-CoV-2 nucleocapsid (N)…</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>Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler’s virus</strong> - Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Increased inflammatory cytokines and oxidative stress enhanced antibody production in breast and prostate cancer patients with COVID-19 related depression</strong> - Cancer management is highly dependent on the immune status of the patient. During the COVID-19 pandemic, a large number of people suffered from anxiety and depression, especially cancer patients. The effect of depression on breast cancer (BC) and prostate cancer (PC) patients, during the pandemic has been analyzed in this study. Levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers malondialdehyde (MDA) and carbonyl content (CC) were estimated in patients’…</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>“Super” SERPINs-A stabilizing force against fibrinolysis in thromboinflammatory conditions</strong> - The superfamily of serine protease inhibitors (SERPINs) are a class of inhibitors that utilise a dynamic conformational change to trap and inhibit their target enzymes. Their powerful nature lends itself well to regulation of complex physiological enzymatic cascades, such as the haemostatic, inflammatory and complement pathways. The SERPINs α2-antiplasmin, plasminogen-activator inhibitor-1, plasminogen-activator inhibitor-2, protease nexin-1, and C1-inhibitor play crucial inhibitory roles 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>Deficient Radiation Transcription Response in COVID-19 Patients</strong> - CONCLUSIONS: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19.</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>Application of single-cell RNA sequencing on human testicular samples: a comprehensive review</strong> - So far there has been no comprehensive review using systematic literature search strategies to show the application of single-cell RNA sequencing (scRNA-seq) in the human testis of the whole life cycle (from embryos to aging males). Here, we summarized the application of scRNA-seq analyses on various human testicular biological samples. A systematic search was conducted in PubMed and Gene Expression Omnibus (GEO), focusing on English researches published after 2009. Articles related to GEO…</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><em>In silico</em> study of potential SARS-CoV-2 antagonist from <em>Clitoria ternatea</em></strong> - CONCLUSION: From these results, it was concluded that C. ternatea possess potential therapeutic properties against COVID-19.</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>Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses</strong> - Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11’,13’-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4…</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>Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway</strong> - Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-β promoter activities, but how this mechanism used by PEDV ORF3 inhibits…</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>Development and validation of an LC-MS/MS method for quantification of favipiravir in human plasma</strong> - Favipiravir (FVP) is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, first trialled for the treatment of influenza infection. It has been shown to be effective against a number of RNA virus families including arenaviruses, flaviviruses and enteroviruses. Most recently, FVP has been investigated as a potential therapeutic for severe acute respiratory syndrome coronavirus 2 infection. A liquid chromatography tandem mass spectrometry method for the…</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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