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190 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>03 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>“Lessons from the COVID War”: An incomplete analysis of U.S. COVID-19 policies</strong> -
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<div>
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A new book, “Lessons from the COVID War”, attempts to analyze reasons for the failure to contain the SARS-CoV-2 virus in the United States. Based primarily on interviews with government officials and advisors, it neglects the quantitative studies of virus spread and containment associated with testing, tracing, and quarantine. More successful policies of several countries that had a fraction of the U.S. COVID-19 death rate are ignored.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/9x3jy/" target="_blank">“Lessons from the COVID War”: An incomplete analysis of U.S. COVID-19 policies</a>
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</div></li>
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<li><strong>Prothrombotic factors associated with COVID-19 complications: A systematic review preprint.</strong> -
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<div>
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BACKGROUND: The COVID-19 pandemic caused deaths and severe clinical complications associated with thrombosis and hypercoagulability, motivating this literature review. OBJECTIVE: To analyze the scope of scientific publications that demonstrate an association of thromboembolism with complications of COVID-19. METHOD: A systematic literature review was performed to identify clinical complications associated with thrombosis in people exposed to SARS-CoV-2 infection. The articles were selected from MEDLINE database after being screened and filtered to extract the methodologies used and the evidence of clinical complications by compromised organs or systems and pathology description. The evidence was extracted in Cohort Studies for statistical analysis and hypothesis testing (t-test). RESULTS: A total of 208 studies were selected. Observational Studies were predominant, corresponding to 64% of the total, and other methodologies corresponded to 9% in the inclusion. Review articles were excluded and corresponded to the remaining 27% of the selected articles. Subsequently, 150 articles were screened, and 121 were filtered. Among these, 11 Cohort Studies were extracted as the sample, which were eligible for analysis and subsequent Hypothesis Test. This test showed a Mean Difference of 4.74 [Ha (μ=8.08 Exposure) > (μ=3.33 No exposure)], with a p-value of 0.096 for a 95% confidence interval. Despite the numerical value of the difference in the means due to the influence of variance, the test result was not statistically significant due to the small number of the sample of Cohort studies. CONCLUSION: It was observed that prothrombotic conditions were present and translated by hypercoagulability in the evaluated articles. Individuals exposed to SARS-CoV-2 infection have been shown to experience complications caused by thrombosis more often than the unexposed. It is suggested to conduct a Meta-analysis with a larger sample of Cohort Studies to further analyze this association.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/nakmq/" target="_blank">Prothrombotic factors associated with COVID-19 complications: A systematic review preprint.</a>
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</div></li>
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<li><strong>Knowledge graphs and wikidata subsetting</strong> -
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<div>
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Knowledge graphs have successfully been adopted by academia, governement and industry to represent large scale knowledge bases. Open and collaborative knowledge graphs such as Wikidata capture knowledge from different domains and harmonize them under a common format, making it easier for researchers to access the data while also supporting Open Science. Wikidata keeps getting bigger and better, which subsumes integration use cases. Having a large amount of data such as the one presented in a scopeless Wikidata offers some advantages, e.g., unique access point and common format, but also poses some challenges, e.g., performance. Regular wikidata users are not unfamiliar with running into frequent timeouts of submitted queries. Due to its popularity, limits have been imposed to allow for fair access to many. However this suppreses many interesting and complex queries that require more computational power and resources. Replicating Wikidata on one’s own infrastructure can be a solution which also offers a snapshot of the contents of wikidata at some given point in time. There is no need to replicate Wikidata in full, it is possible to work with subsets targeting, for instance, a particular domain. Creating those subsets has emerged as an alternative to reduce the amount and spectrum of data offered by Wikidata. Less data makes more complex queries possible while still keeping the compatibility with the whole Wikidata as the model is kept. In this paper we report the tasks done as part of a Wikidata subsetting project during the Virtual BioHackathon Europe 2020 and SWAT4(HC)LS 2021, which had already started at NBDC/DBCLS BioHackathon 2019 in Japan, SWAT4(HC)LS hackathon 2019, and Virtual COVID-19 BioHackathon 2019. We describe some of approaches we identified to create subsets and some susbsets from the Life Sciences domain as well as other use cases we also discussed.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://biohackrxiv.org/wu9et/" target="_blank">Knowledge graphs and wikidata subsetting</a>
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</div></li>
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<li><strong>Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic</strong> -
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<div>
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The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors’ recruitment and retention during 2020 with respect to the 2017-2019 period, considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented improvement in performances.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/6t72b/" target="_blank">Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>COVID-related anthropause highlights the impact of marine traffic on breeding little penguins</strong> -
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<div>
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The COVID-19 pandemic and its lock-down measures have resulted in periods of reduced human activity, known as anthropause. While this period was expected to be favorable for the marine ecosystem, due to a probable reduction of pollution, shipping traffic, industrial activity and fishing pressure, negative counterparts such as the increased use of disposable plastic and reduced fisheries surveillance and enforcement could counterbalance these positive effects. Simultaneously, on-land pressure due to human disturbance and tourism should have drastically decreased, potentially benefiting land-based marine breeders such as seabirds. Thus, long-term datasets became crucial to differentiate between historical trends and any evident changes resulting from the anthropause. We analyzed 11 years of data on several biological parameters of little penguins (Eudyptula minor) from the Penguin Parade (R), a popular tourist attraction at Phillip Island, Australia. We investigated the impact of anthropogenic activities on penguin behavior during the breeding season measured by (1) distribution at sea, (2) colony attendance, (3) isotopic niche (4) chick meal mass, and (5) offspring investment against shipping traffic and number of tourists. The 2020 lock-downs resulted in a near absence of tourists visiting the Penguin Parade (R), which was otherwise visited by 800,000+ visitors on average per year. However, our long-term analysis showed no effect of the presence of visitors on little penguins' activities. Surprisingly, the anthropause did not triggered any changes in maritime traffic intensity and distribution in the region. While we found significant inter- and intra-annual variations for most parameters, we detected a negative effect of marine traffic on the foraging efficiency. Our results suggest that environmental variations have a greater influence on the breeding behavior of little penguins compared to short-term anthropause events. Our long-term dataset was key to test whether changes in anthropogenic activities affected the wildlife during the COVID-19 pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.30.547199v1" target="_blank">COVID-related anthropause highlights the impact of marine traffic on breeding little penguins</a>
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</div></li>
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<li><strong>Preclinical and Human Phase 1 Studies of Aerosolized Hydroxychloroquine: Implications for Antiviral COVID-19 Therapy</strong> -
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Based on early reports of the efficacy of hydroxychloroquine sulfate (HCQS) to inhibit SARS-CoV-2 viral replication in vitro, and since severe pulmonary involvement is the major cause of COVID-19 mortality, we assessed the safety and efficacy of aerosolized HCQS (aHCQS) therapy in animals and humans. In a Phase 1 study of aHCQS in healthy volunteers, doses up to 50 mg were well tolerated and estimated epithelial lining fluid concentrations immediately after inhalation (>2,000 uM) exceeded the in vitro concentrations needed for suppression of viral replication (>=119 uM). A study in rats comparing HCQS solution administered orally (13.3 mg/kg) and by intratracheal installation (IT 0.18 mg/kg, <5% of oral dose) demonstrated that at 2 minutes, IT administration was associated with 5X higher mean hydroxychloroquine (HCQ) concentrations in the lung (IT: 49.5 +/- 6.5 ug HCQ/g tissue, oral: 9.9 +/- 3.4; p<0.01). A subsequent study of IT and intranasal HCQS in the Syrian hamster model of SARS-CoV-2 infection, however, failed to show clinical benefit. We conclude that aHCQS alone is unlikely to be effective for COVID-19, but based on our aHCQS pharmacokinetics and current viral entry data, adding oral HCQS to aHCQS, along with a transmembrane protease inhibitor, may improve efficacy.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.22.23291702v1" target="_blank">Preclinical and Human Phase 1 Studies of Aerosolized Hydroxychloroquine: Implications for Antiviral COVID-19 Therapy</a>
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</div></li>
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<li><strong>Community Antibiotic Prescribing in Patients with COVID-19 Across Three Pandemic Waves: A Population-Based Cohort Study</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Reported changes in antibiotic prescribing during the COVID-19 pandemic have focused on hospital prescribing or community population trends. Community antibiotic prescribing for individuals with COVID-19 are less well described. Methods: Data covering a complete geographic population (~800,000) were utilized. SARS-CoV-2 virus test results from February 1, 2020- March 31, 2022 were included. Anonymized data were linked to prescription data +/-28 days of the test, GP data for high-risk comorbidities, and demographic data. Multivariate binary logistic regression examined associations between patient factors and the odds of antibiotic prescription. Results: Data included 768,206 tests for 184,954 individuals, identifying 16,240 COVID-19 episodes involving 16,025 individuals. There were 3,263 antibiotic prescriptions +/-28 days for 2,385 patients. 35.6% of patients had a prescription only before the test date, 52.5% patients after, and 11.9% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave one, 17.7% in wave two, and 12.0% in wave three. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19,1.45), older (OR 3.02, 95% CI 2.50, 3.68 75+ vs <25 years), having a high-risk comorbidity (OR 1.45, 95% CI 1.31, 1.61), a hospital admission +/-28 days of an episode (OR 1.58, 95% CI 1.42, 1.77), and health board region (OR 1.14, 95% CI 1.03, 1.25, board B versus A) increased the odds of receiving an antibiotic. Conclusion: Community antibiotic prescriptions in COVID-19 episodes were uncommon in this population and likelihood was associated with patient factors. The reduction over pandemic waves may represent increased knowledge regarding COVID-19 treatment and/or evolving symptomatology.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23291797v1" target="_blank">Community Antibiotic Prescribing in Patients with COVID-19 Across Three Pandemic Waves: A Population-Based Cohort Study</a>
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</div></li>
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<li><strong>Polymerized type I collagen down-regulates STAT-1 phosphorylation through engagement to LAIR-1 in M1-macrophages avoiding long COVID</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: The polymerized type I collagen (PTIC) is a g-irradiated mixture of pepsinized porcine type I collagen and polyvinylpyrrolidone (PVP). It has immunomodulatory properties. However, the receptor and signaling pathway through which it exerts its therapeutic effects has not yet been identified. Aim: To evaluate LAIR-1 as a potential receptor for PTIC and the signaling pathway evoked by ligand-receptor binding. Methods: LAIR-1 binding assay was performed by incubating various concentrations of recombinant human LAIR-1 with native type I collagen or PTIC. Macrophages M1-derived from THP-1 cells were cultured with 2-10% PTIC for 24 h. Cell lysates from THP-1, monocytes-like cells (MLCs), M1, M1+IFN-γ, M1+LPS, and 2 or 10% PTIC treated M1 were analyzed by western blot for the transcription factors NF-κB (p65), p38, STAT-1, and pSTAT-1. Cytokines, Th1 cells, and M1/M2 macrophages were analyzed by luminometry and flow cytometry from blood samples of symptomatic COVID-19 outpatients on treatment with intramuscular administration of PTIC. Results: PTIC binds LAIR-1 with a similar affinity to native collagen. This binding decreases STAT-1 signaling IFN-γ-induced and IL-1β expression in M1 macrophages by down-regulating STAT-1 phosphorylation. Moreover, intramuscular PTIC treatment of symptomatic COVID-19 outpatients decreased at statistically significant levels the percentage of M1 macrophages and cytokines (IP-10, MIF, eotaxin, IL-8, IL-1RA, and M-CSF) associated with STAT-1 transcription factor and increased M2 macrophages and Th1 cells. The downregulation of inflammatory mediators was related to better oxygen saturation and decreased dyspnea, chest pain, cough, and chronic fatigue syndrome in the acute phase of infection and the long term. Conclusion: PTIC is an agonist of LAIR-1 and down-regulates STAT-1 phosphorylation. PTIC could be relevant for treating STAT-1-mediated inflammatory diseases, including COVID-19 and long COVID.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.01.23292108v1" target="_blank">Polymerized type I collagen down-regulates STAT-1 phosphorylation through engagement to LAIR-1 in M1-macrophages avoiding long COVID</a>
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</div></li>
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<li><strong>Genome-wide Association Study of Long COVID</strong> -
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Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction(3-5). The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative(6,7) to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity(6), lung function(8), and cancers(9), suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23292056v1" target="_blank">Genome-wide Association Study of Long COVID</a>
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<li><strong>Intention to be vaccinated against COVID-19 in Benin and Senegal: a structural equation modelling (SEM)</strong> -
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Vaccination is considered one of the solutions to the COVID-19 pandemic. However, a small proportion of the population was fully vaccinated in Benin (20.9%) and Senegal (7.6%) by December 2022. This study explores the determinants of intent to vaccinate. This was a cross-sectional, descriptive, and analytical study of 865 Beninese and 607 Senegalese aged 18 years and older. Marginal quota sampling by age, gender and region was adopted. Data collection, using a survey instrument based on the Random Digit Dialing (RDD) method, was conducted from December 24, 2020, to January 16, 2021, in Senegal and from March 29 to May 14, 2021, in Benin. The questionnaire used the Theory of Planned Behavior (TPB) and the Health Belief Model (HBM). The influence of factors was tested using a structural equation model. All analyses were conducted in R. Results show that a good perception of the benefits of vaccination ( =0.33<strong><em>; =0.12</em></strong>), a positive attitude (=0.22<strong><em>; =0.20</em></strong>), and sensitivity to subjective norms ( =0.19<strong><em>; =0.32</em></strong>) positively influence the intention to vaccinate. Low trust in health care providers (=-0.40<strong><em>; =-0.36</em></strong>) amplifies the perceived risk of vaccination (=-0.14<strong><em>; =-0.25</em></strong>), which negatively impacts intention to vaccinate. Perceived vaccine efficacy was affected by perceived risk (=-0.12<strong><em>; =-0.05</em></strong>) of the disease and improved by good apprehension of the benefits of vaccination (=0.60<strong><em>; =0.13</em></strong>). Aspects related to behavioral control, vaccine information seeking, efficacy, or fairness did not appear as correlates of vaccine intention (P>0.05). Beninese and Senegalese public health authorities could develop additional intervention strategies to improve immunization coverage by considering these influencing factors, the basis of which could be better understood through subsequent qualitative studies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23292061v1" target="_blank">Intention to be vaccinated against COVID-19 in Benin and Senegal: a structural equation modelling (SEM)</a>
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</div></li>
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<li><strong>Pre-pandemic activity on a myalgic encephalomyelitis/chronic fatigue syndrome support forum is highly associated with later activity on a long COVID support forum for a variety of reasons: a mixed methods study.</strong> -
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Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID share some clinical and social characteristics. We predicted that this would lead to an increased interaction between pre-pandemic members of a ME/CFS online support community and a long COVID community. We performed a mixed-methods retrospective observational study of the Reddit activity of 7,544 users active on Reddit9s long COVID forum. From among 1600 forums, pre-pandemic activity specifically on a ME/CFS forum is the top predictor of later participation on the long COVID forum versus an acute COVID support forum. In the qualitative portion, motives for this co-participation included seeking mutual support and dual identification with both conditions. Some of this effect may be explained by pre-existing ME/CFS possibly being a risk factor for long COVID and/or SARS-CoV-2 infection being a cause of ME/CFS relapse. The high rate of ME/CFS patients seeking mutual support on a long COVID forum speaks to the long-suffering experience of these patients not feeling heard or respected, and the hope of some ME/CFS patients to gain legitimacy through the public9s growing recognition of long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.30.23292087v1" target="_blank">Pre-pandemic activity on a myalgic encephalomyelitis/chronic fatigue syndrome support forum is highly associated with later activity on a long COVID support forum for a variety of reasons: a mixed methods study.</a>
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<li><strong>Patterns in Repeat Reinfections: Pre and Post Omicron Emergence</strong> -
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Our understanding of SARS-CoV-2 reinfection patterns remains limited. We conducted a longitudinal study using Qatar national SARS-CoV-2 data from February 28, 2020 to June 11, 2023 to investigate incidence of reinfections both prior to and after omicron emergence. The latter analysis excluded individuals with pre-omicron infections. Before omicron introduction, the proportion of incident infections classified as reinfections gradually increased but remained minimal, reaching 1.8% just before omicron emerged. During the first omicron wave, this proportion reached 9.0%, a 5-fold increase. After the conclusion of the first omicron wave, the proportion of incident infections identified as reinfections rapidly increased, reaching 43.3% towards the end of the study. In the pre-omicron era, a total of 3,131 reinfections were documented, of which 99.6% were first reinfections and 0.4% were second reinfections. Meanwhile, a total of 20,962 reinfections were documented after an omicron primary infection of which 99.0% were first reinfections, 1.0% were second reinfections, and 0.01% were third reinfections. Reinfections were rare before omicron9s emergence but became widespread during the omicron era, including among individuals previously infected with omicron. Our findings may indicate accelerated viral evolution in the omicron era aimed at evading population immunity, but with minimal impact on COVID-19 severity, or potentially suggest immune imprinting effects that require further investigation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23292041v1" target="_blank">Patterns in Repeat Reinfections: Pre and Post Omicron Emergence</a>
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<li><strong>Distinct and overlapping immunological responses to SARS-CoV-2 and Mycobacterium tuberculosis identified by single-cell RNA-seq of co-infected whole blood</strong> -
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Introduction: COVID-19 and tuberculosis (TB) exhibit similar symptomatic presentation and clinical parameters. Common underlying immunological mechanisms also highlight potential routes of immunopathogenic interaction between these diseases during co-infection. To explore immunological similarities, differences and interactions, single-cell RNA-seq (scRNA-seq) was performed on whole blood infected with Mycobacterium tuberculosis (Mtb), SARS-CoV-2, or both pathogens. Methods: Whole blood from four healthy adults, were subjected to ex vivo infection with Mtb and/or SARS-CoV-2 ancestral strain, or were maintained in an uninfected state, for 24 or 96 hours. At each timepoint, for each condition, the four biological replicates were captured, fixed and cryopreserved to be processed for scRNA-seq as a single batch. Following quality control filtering, genotype-based demultiplexing was performed to obtain data from each biological replicate for pseudobulk differential expression analysis. Results: Thirteen distinct clusters of cells were identified based on marker gene expression. Profound differences in the proportions of monocytes, T cells and neutrophils were observed between infection conditions and timepoints. The greatest divergence between pathogen responses occurred within myeloid cells at early timepoints of infection. Co-infection had the greatest synergistic effect 24 hours post-infection with 238 immunological pathways uniquely enriched, including IFN-γ and TNF production, whilst by 96 hours post-infection there was a large overlap of 182 shared pathways between Mtb, SARS-CoV-2 and co-infection. SARS-CoV-2-only infection resulted in widespread cell death by 96 hours post-infection, while Mtb-only and co-infected samples remained enriched for monocyte, T cell and NK cell signatures, sharing negative regulation of extrinsic apoptotic signalling. Distinct from Mtb, SARS-Co-V-2 had unique regulating of αβ T cell activation and differentiation at both time points. Conclusion: These data provide a high-resolution characterisation of distinct and overlapping immunological responses generated by SARS-CoV-2 and Mtb when a single infection or co-infection occurs. This sheds light on the potential effects of novel or existing host-directed therapies that target these pathways, which is particularly crucial for settings where dual presentation is common.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.24.23290499v2" target="_blank">Distinct and overlapping immunological responses to SARS-CoV-2 and Mycobacterium tuberculosis identified by single-cell RNA-seq of co-infected whole blood</a>
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<li><strong>Reverse engineering of a pathogenic antibody reveals the molecular mechanism of vaccine-induced immune thrombotic thrombocytopenia</strong> -
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The massive COVID-19 vaccine roll-out campaign illuminated a range of rare side effects, the most dangerous of which - vaccine-induced immune thrombotic thrombocytopenia (VITT) - is caused by adenoviral (Ad)-vectored vaccines. VITT occurrence had been linked to production of pathogenic antibodies that recognize an endogenous chemokine, platelet factor 4 (PF4). Mass spectrometry (MS)-based evaluation of the ensemble of anti-PF4 antibodies obtained from a VITT patient's blood indicates that its major component is a monoclonal antibody. Structural characterization of this antibody reveals several unusual characteristics, such as the presence of an N-glycan in the Fab segment and high density of acidic amino acid residues in the CDR regions. A recombinant version of this antibody (RVT1) was generated by transient expression in mammalian cells based on the newly determined sequence. It captures the key properties of VITT antibodies, such as their ability to activate platelets in a PF4-dependent fashion. Homology modeling of the Fab segment reveals a well-defined polyanionic paratope, and the docking studies indicate that the polycationic segment of PF4 readily accommodates two Fab segments, cross-linking the antibodies to yield polymerized immune complexes. Their existence was verified with native MS by detecting assemblies as large as (RVT1)3(PF4)2, pointing out at FcGammaRIIa-mediated platelet activation as the molecular mechanism underlying VITT clinical manifestations. In addition to high PF4 affinity, RVT1 readily binds other polycationic targets, indicating a polyreactive nature of this antibody. This surprising polyspecificity not only sheds light on VITT etiology, but also opens up a range of opportunities to manage this pathology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.30.547300v1" target="_blank">Reverse engineering of a pathogenic antibody reveals the molecular mechanism of vaccine-induced immune thrombotic thrombocytopenia</a>
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<li><strong>Use of antimicrobials during the COVID-19 pandemic: a qualitative study among stakeholders in Nepal</strong> -
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Introduction The COVID-19 pandemic was a major public health threat and posed tremendous pressure to develop a cure for it. Apart from ongoing efforts in developing vaccines, a lot of empirical treatments were recommended, that may have expedited the use of antimicrobials. The main objective of this study was to explore if and how the pandemic posed pressure on antimicrobials in Nepal using semi-structured interviews (SSIs) among patients, clinicians and drug dispensers. Methods A total of 30 stakeholders (10 each among clinicians, dispensers and COVID-19 patients) were identified purposively and were approached for SSIs. Clinicians and dispensers working in three tertiary hospitals in Kathmandu were first approached and were asked for their support to reach out to COVID-19 patients who were on follow-up at their out-patient department. SSIs were audio recorded, translated and transcribed into English, and were analyzed for thematic synthesis. Results Over-the-counter (OTC) uses of antibiotics was widespread during the pandemic, and were mostly rooted to patients attempts to halt the potential severity due to respiratory like illnesses, and the fear of being identified as a COVID-19 patients. Being identified as a COVID-19 patient was feared because of the stigmatization and social isolation. Patients who visited the drug shops and physicians were reported to make demands on specific medicines including antibiotics that may have added pressure among physicians and dispensers. Clinicians reported a degree of uncertainty related to treatment and that may have added pressure to prescribe antimicrobials. All stakeholders, although mostly patients and dispensers with limited understanding of what constitutes antimicrobials and the mechanisms underpinning it reported that the pressure during the pandemic may have added to the adversities such as antimicrobials resistance. Conclusions COVID-19 added a pressure to prescribe, dispense and overuse antimicrobials and may have accentuated the pre-existing OTC use of antimicrobials. Future pandemics including infectious disease outbreaks are major public health incidents that warrant a special caution on inappropriate pressure on antimicrobials. Strict policies related to the use of antimicrobials are urgent to redress their use during normal and pandemic situations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.23.23291835v2" target="_blank">Use of antimicrobials during the COVID-19 pandemic: a qualitative study among stakeholders in Nepal</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>Probiotic and Colchicine in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hospitalized COVID-19 Patients<br/><b>Interventions</b>: Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)<br/><b>Sponsors</b>: Lebanese University; Hospital Saydet Zgharta 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>Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: sensory re-education training; Other: traditional treatment<br/><b>Sponsor</b>: Cairo 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>Comprehensive Imaging Exam of Convalesced COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; COVID Long-Haul<br/><b>Interventions</b>: Other: Magnetic Resonance Imaging; Other: Ultra-High Resolution Computed Tomography (CT) Scan<br/><b>Sponsors</b>: Johns Hopkins University; Canon Medical Systems, USA<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>UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<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>Evaluate the Safety and Immunogenicity of Different Booster Dose Levels of Monovalent and Bivalent SARS-CoV-2 rS Vaccines in Adults ≥ 50 Years</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2540 (5, 10, 25 μg); Biological: NVX-CoV2373 (5 μg); Biological: Bivalent BA.4/5 Omicron subvariant<br/><b>Sponsor</b>: Novavax<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>Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Drug: Remdesivir<br/><b>Sponsors</b>: University of Derby; University of Exeter; Peninsula Clinical Trials Unit; University Hospitals of Derby and Burton NHS Foundation Trust<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19</strong> - <b>Conditions</b>: Coronavirus Disease; COVID-19; Long Covid-19; Telerehabilitation<br/><b>Interventions</b>: Device: KNEESUP smart knee assistive device + KNEESUP care APP; Device: KNEESUP care APP; Behavioral: Healthy consulation<br/><b>Sponsor</b>: Shang-Lin Chiang<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>Open Label Extension of Efgartigimod in Adults With Post-COVID-19 POTS</strong> - <b>Condition</b>: Post-COVID Postural Orthostatic Tachycardia Syndrome Postural Orthostatic Tachycardia Syndrome<br/><b>Intervention</b>: Drug: Efgartigimod<br/><b>Sponsors</b>: argenx; Iqvia Pty Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Digital Interventions to Understand and Mitigate Stress Response</strong> - <b>Conditions</b>: Distress, Emotional; Stress Response Among Nursing Professionals During the COVID-19; Stress Reaction; Acute<br/><b>Intervention</b>: Behavioral: Digital Intervention Group<br/><b>Sponsors</b>: Unity Health Toronto; Toronto Metropolitan University; University of Toronto; University of Ontario Institute of Technology; Boston University; University of Ottawa; Western University, Canada; Centre for Addiction and Mental Health<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>PREPARE-iVAC Trial</strong> - <b>Conditions</b>: COVID-19 Vaccines; Varicella Zoster Vaccine; Vaccine Response; Immunosuppression<br/><b>Intervention</b>: Biological: COVID-19 vaccination<br/><b>Sponsors</b>: University Medical Center Groningen; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Radboud University Medical Center; Erasmus Medical Center; UMC Utrecht; Leiden University Medical Center; Maastricht University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development<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>NC Testing in LC & POTS</strong> - <b>Conditions</b>: Postural Orthostatic Tachycardia Syndrome; Post Acute Sequelae of SARS CoV 2 Infection<br/><b>Intervention</b>: Other: IV normal saline (1 Litre)<br/><b>Sponsor</b>: University of Calgary<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 Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID</strong> - <b>Condition</b>: Long Covid<br/><b>Intervention</b>: Drug: BC 007 or matching placebo<br/><b>Sponsor</b>: Berlin Cures GmbH<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, Synthesis and Structure-Activity Relationship Studies of Protein Kinase CK2 Inhibitors Containing a Purine Scaffold</strong> - Protein kinase CK2 (CK2) is involved in the suppression of gene expression, protein synthesis, cell proliferation, and apoptosis, thus making it a target protein for the development of therapeutics toward cancer, nephritis, and coronavirus disease 2019. Using the solvent dipole ordering-based method for virtual screening, we identified and designed new candidate CK2α inhibitors containing purine scaffolds. Virtual docking experiments supported by experimental structure-activity relationship…</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 fish perspective on SARS-CoV-2: toxicity of benzalkonium chloride on Danio rerio</strong> - SARS-CoV-2 outbreak lead to an increased marketing of disinfectants, creating a potential environmental problem. For instance, pre-pandemic environmental levels of the disinfectant benzalkonium chloride (BAC) ranging from 0.5 to 5 mgL^(-1) in effluents were expected to further increase threatening aquatic life. Our aim was to characterize potential adverse effects after an acute exposure of zebrafish to different concentrations of BAC. An increase in the overall swimming activity, thigmotaxis…</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>Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein</strong> - Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan interactions. We hypothesize that polyvalent nano-lectins with flexibly linked…</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>Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-β</strong> - Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and 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>Anti-Inflammatory Effects of Dexamethasone in COVID-19 Patients: Translational Population PK/PD Modeling and Simulation</strong> - Dexamethasone (DEX) given at a dose of 6 mg once-daily for 10 days is a recommended dosing regimen in patients with COVID-19 requiring oxygen therapy. We developed a population pharmacokinetic and pharmacodynamic (popPK/PD) model of DEX anti-inflammatory effects in COVID-19 and provide simulations comparing the expected efficacy of four dosing regimens of DEX. Nonlinear mixed-effects modeling and simulations were performed using Monolix Suite version 2021R1 (Lixoft, France). Published data for…</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 ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2</strong> - The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (Momordica charantia), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC50 ~ 0.2 μM) with…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease</strong> - The SARS-CoV-2 main protease (M^(pro)) plays an essential role in the coronavirus lifecycle by catalyzing hydrolysis of the viral polyproteins at specific sites. M^(pro) is the target of drugs, such as nirmatrelvir, though resistant mutants have emerged that threaten drug efficacy. Despite its importance, questions remain on the mechanism of how M^(pro) binds its substrates. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to evaluate structural and dynamical…</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>Restriction of SARS-CoV-2 replication by receptor transporter protein 4 (RTP4)</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is subject to restriction by several interferon-inducible host proteins. To identify novel factors that limit replication of the virus, we tested a panel of genes that we found were induced by interferon treatment of primary human monocytes by RNA sequencing. Further analysis showed that one of the several candidates genes tested, receptor transporter protein 4 (RTP4), that had previously been shown to restrict flavivirus replication,…</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>Characterization of SARS-CoV-2 humoral immune response in a subject with unique sampling: A case report</strong> - CONCLUSION: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.</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 Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial</strong> - CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8.</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>Endotyping of IgE-mediated polyethylene glycol and/or polysorbate 80 allergy</strong> - CONCLUSION: PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whilst PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels and enhanced BAT reactivity. Spherical PEG-exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines.</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>Hindered visibility improvement despite marked reduction in anthropogenic emissions in a megacity of southwestern China: An interplay between enhanced secondary inorganics formation and hygroscopic growth at prevailing high RH conditions</strong> - The PM(2.5)-bound visibility improvement remains challenging in China despite vigorous control on anthropogenic emissions in recent years. One critical issue could exist in the distinct physicochemical properties especially of secondary aerosol components. Taken the COVID-19 lockdown as an extreme case, we focus on the relationship between visibility, emission cuts, and secondary formation of inorganics with changing optical and hygroscopic behaviors in Chongqing, a representative city…</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>Anthracyclines inhibit SARS-CoV-2 infection</strong> - Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks….</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>Statins: Beneficial Effects in Treatment of COVID-19</strong> - The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important…</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>mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway</strong> - Coronaviruses (CoVs), which pose a serious threat to human and animal health worldwide, need to hijack host factors to complete their replicative cycles. However, the current study of host factors involved in CoV replication remains unknown. Here, we identified a novel host factor, mammalian lethal with sec-13 protein 8 (mLST8), which is a common subunit of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is critical for CoV replication. Inhibitor and knockout (KO) experiments revealed…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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