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186 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>01 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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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication</strong> -
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G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.29.546885v1" target="_blank">Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication</a>
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</div></li>
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<li><strong>In vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies.</strong> -
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The non-invasive monitoring of the hemodynamics and metabolism of the sternocleidomastoid muscle (SCM) during respiration became a topic of increased interest partially due to the increased use of mechanical ventilation during the COVID-19 pandemic. Near-infrared diffuse optical spectroscopies were proposed as potential practical monitors of increased recruitment of SCM during respiratory distress. They can provide clinically relevant information on the degree of the patient's respiratory effort that is needed to maintain an optimal minute ventilation, with potential clinical application ranging from evaluating chronic pulmonary diseases to more acute settings, such as acute respiratory failure, or to determine the readiness to wean from invasive mechanical ventilation. In this paper, we present a detailed characterization of the optical properties (wavelength dependent absorption and reduced scattering coefficients) and hemodynamic properties (oxy-, deoxy- and total hemoglobin concentrations, blood flow, blood oxygen saturation and metabolic rate of oxygen extraction) of the human SCM, obtained by measuring sixty-five subjects through ultrasound-guided near-infrared time-resolved and diffuse correlation spectroscopies. We provide detailed tables of the results related to SCM baseline (i.e. muscle at rest) properties, and reveal significant differences on the measured parameters due to variables such as side of the neck, sex, age, body mass index and thickness of the overlaying tissues, allowing future clinical studies to take into account such dependencies.
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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/10.1101/2023.06.30.544760v1" target="_blank">In vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies.</a>
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<li><strong>Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform</strong> -
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Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc_dataapp/main/Co asc_DataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.29.547094v1" target="_blank">Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform</a>
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</div></li>
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<li><strong>SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity</strong> -
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The glycosylation of viral envelope proteins can play important roles in virus biology and immune evasion. The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 22 N-linked glycosylation sequons and 17 O-linked glycosites. Here, we investigated the effect of individual glycosylation sites on SARS-CoV-2 S function in pseudotyped virus infection assays and on sensitivity to monoclonal and polyclonal neutralizing antibodies. In most cases, removal of individual glycosylation sites decreased the infectiousness of the pseudotyped virus. For glycosylation mutants in the N-terminal domain (NTD) and the receptor binding domain (RBD), reduction in pseudotype infectivity was predicted by a commensurate reduction in the level of virion-incorporated spike protein. Notably, the presence of a glycan at position N343 within the RBD had diverse effects on neutralization by RBD-specific monoclonal antibodies (mAbs) cloned from convalescent individuals. The N343 glycan reduced overall sensitivity to polyclonal antibodies in plasma from COVID-19 convalescent individuals, suggesting a role for SARS-CoV-2 spike glycosylation in immune evasion. However, vaccination of convalescent individuals produced neutralizing activity that was resilient to the inhibitory effect of the N343 glycan.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.30.547241v1" target="_blank">SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity</a>
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<li><strong>Vaccines at Velocity: Evaluating Potential Lives Saved by Earlier Vaccination in the COVID-19 Pandemic</strong> -
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Fast development of COVID-19 vaccines likely averted millions of deaths. We estimate how many more lives could have been saved if safe and effective vaccines were available earlier in the pandemic, in particular, before the epidemic waves in winter of 2020. We fit an epidemiological model informed by retrospective data and simulate counterfactual vaccination scenarios for the United Kingdom and the United States in which vaccines are available between 30 and 90 days earlier. We find that up to 1 July 2021 reductions in mortality range from 10,000 to 48,000 in the UK and 53,000 to 130,000 in the US, depending on when vaccinations start. This corresponds to a maximum of 7.1 and 4 deaths averted per 10,000 people in the UK and US respectively. We find that our model is sensitive to uncertain vaccine parameters and benefits depend on the time horizon of the analysis. However, the large average reductions we estimate suggests that it is highly cost-effective to make large investments in strategies to expedite vaccine availability.
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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/10.1101/2023.06.16.23291442v2" target="_blank">Vaccines at Velocity: Evaluating Potential Lives Saved by Earlier Vaccination in the COVID-19 Pandemic</a>
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<li><strong>The Colloido Osmotic Pressure as a useful biomarker of fatal outcome in pregnant COVID-19 patients</strong> -
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Background: Pregnancy was considering a health condition that could support high severity in COVID-19, among others the cardiologic and respiratory systems express some physiologic change in the pregnant women and could specially affected in COVID-19. Pregnant women characteristically have an increase volume of blood, with a higher cardiac output and lower peripheral vascular resistance, these could be negative affected by hypoalbuminemia frequently observed in COVID-19. Then, an early recognition of hypoalbuminemia in pregnant women with COVID-19 would help us to predict fatal outcome. Objective: We conduct a study to analyzed the demographic, clinical, blood gas test results, laboratory and ultrasonographic doppler data in pregnant women with COVID-19 that demand medical attention for labor. Study design: Ninety-two pregnant women with COVID-19 were included in our study from may 30th 2020 to august 12th 2022, and data was analyzed in survival and fatal outcome patients. Normality test were applied to data and parametric or non-parametric test were used to determine statistical difference between or among data. Results: Demographic and clinical data were quite similar between survival and fatal outcome pregnant patients with COVID-19. Also, blood gas test shown similar results among groups (asymptomatic, mild, or severe patients who survive COVID-19 or fatal outcome patients). We observed that serum albumin was consistently low in pregnant patients with fatal outcome by COVID-19, then based on Total Protein concentration in serum we calculated the colloido-osmotic pressure and we evaluate its utility as predictor of fatal outcome. ROC analysis and Kaplan-Meier of survival curves suggest that the colloido-osmotic pressure could be a potential predictor. Also, we observed an association of low colloido-osmotic pressure and low amniotic fluid index. Conclusion: Our study suggests that early evaluation of pregnant with COVID-19 must include the calculation of colloido-osmotic pressure and the doppler analysis to early recognition of fatal outcome in pregnant women with COVID-19.
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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/10.1101/2023.06.29.23292050v1" target="_blank">The Colloido Osmotic Pressure as a useful biomarker of fatal outcome in pregnant COVID-19 patients</a>
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<li><strong>Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population</strong> -
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SARS-CoV-2 reinfections increased substantially after Omicron variants emerged. Large-scale community-based comparisons across multiple Omicron waves of reinfection characteristics, risk factors, and protection afforded by previous infection and vaccination, are limited, especially after widespread national testing stopped. We studied 245,895 adults >=18y in the UK9s national COVID-19 Infection Survey with at least one infection (identified from positive swab tests done within the study, linked from national testing programmes, or self-reported by participants, up to their last study assessment). We quantified the risk of reinfection in multiple infection waves, including those driven by BA.1, BA.2, BA.4/5, and most recently BQ.1/CH.1.1/XBB.1.5 variants, in which most reinfections occurred. Reinfections had higher cycle threshold (Ct) values (lower viral load) and lower percentages self-reporting symptoms compared with first infections. Across multiple Omicron waves, protection against reinfection was significantly higher in those previously infected with more recent than earlier variants, even at the same time from previous infection. Protection against Omicron reinfections decreased over time from the most recent infection if this was the previous or penultimate variant (generally within the preceding year), but did not change or even slightly increased over time if this was with an even earlier variant (generally >1 year previously). Those 14-180 days after receiving their most recent vaccination had a lower risk of reinfection with all Omicron variants except BA.2 than those >180 days from their most recent vaccination. Reinfection risk was independently higher in those aged 30-45 years, and with either low or high Ct values in their most recent previous infection. Overall, the risk of Omicron reinfection is high, but with lower severity than first infections; reinfection risk is likely driven as much by viral evolution as waning immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23292043v1" target="_blank">Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population</a>
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<li><strong>Synthesis and new evidence from the PROTECT UK National Core Study: Determining occupational risks of SARS-CoV-2 infection and COVID-19 mortality</strong> -
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Introduction: The PROTECT National Core Study was funded by the UK Health and Safety Executive (HSE) to investigate routes of transmission for SARS-CoV-2 and variation between settings. Methods: A workshop was organised in Oct 2022.We brought together evidence from five published epidemiological studies that compared risks of SARS-CoV-2 infection or COVID-19 mortality by occupation or sector funded by PROTECT relating to three non-overlapping data sets, plus additional unpublished analyses relating to the Omicron period. We extracted descriptive study level data and model results. We investigated risk across four pandemic waves using forest plots for key occupational groups by time-period. Results: Results were largely consistent across different studies with different expected biases. Healthcare and social care sectors saw elevated risks of SARS-CoV-2 infection and COVID-19 mortality early in the pandemic, but thereafter this declined and varied by specific occupational subgroup. The education sector saw sustained elevated risks of infection after the initial lockdown period with little evidence of elevated mortality. Conclusions: Increased in risk of infection and mortality were consistently observed for occupations in high risk sectors particularly during the early stage of the pandemic. The education sector showed a different pattern compared to the other high risk sectors, as relative risk of infections remained high in the later phased of the pandemic, although no increased in COVID-19 mortality (compared to low-risk occupations) was observed in this sector in any point during the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.30.23292079v1" target="_blank">Synthesis and new evidence from the PROTECT UK National Core Study: Determining occupational risks of SARS-CoV-2 infection and COVID-19 mortality</a>
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<li><strong>Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease</strong> -
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Background COVID-19 is associated with a higher risk of cardiovascular outcomes in the general population, but it is unknown whether people with pre-existing chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related risk factors may modify this risk in these people. Methods Primary and secondary care data from the National Health Service and COVID-19-specific linked data were used to define a population of adults in England with COVID-19 (index date) between 01/01/2020-30/11/2021. Adjusted Cox Proportional Hazard regression was used to quantify the association between CRD, asthma-related factors, COPD-related factors, and risk of cardiovascular events. CRD included asthma, COPD, bronchiectasis, cystic fibrosis, or pulmonary fibrosis prior to COVID-19 diagnosis. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS prescriptions and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. Results Of 3,670,455 people, those with CRD had a modest higher risk of cardiovascular events (HRadj 1.11, 95%CI 1.07-1.14), heart failure (HRadj 1.15, 1.09-1.21), and pulmonary emboli (HRadj 1.20, 1.11-1.30) compared with people without CRD. In people with asthma, baseline exacerbations and high-dose ICS were associated with a higher risk of cardiovascular outcomes (HRadj 1.24, 1.15-1.34 and 1.12, 1.01-1.24, respectively). In people with COPD, exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj 1.40, 1.28-1.52). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. Conclusions Higher risk of cardiovascular events following COVID-19 might be explained at least in part by the underlying CRD and severity of that condition. In addition, COVID-19 vaccines were beneficial to both people with and without CRD with regards to CV events.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.01.23286624v2" target="_blank">Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease</a>
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<li><strong>Idiographic Personality Coherence: A Quasi Experimental Longitudinal ESM Study</strong> -
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Personality is a study of persons. However, persons exist within contexts, and personality coherence emerges from persons in contexts. But persons and environments bidirectionally influence each other, with persons selecting into and modifying their contexts, which also have lasting influences on personality. Thus, environmental change should produce changes in personality. Alternatively, environmental changes may produce few changes. This paradoxical viewpoint is based on the idea that novel environments have no predefined appropriate way to behave, which allows preexisting personality systems to stay coherent (Caspi & Moffitt, 1993). We test these two perspectives by examining longitudinal consistency idiographic personality coherence using a quasi-experimental design (N = 50; total assessments = 5,093). Personality coherence was assessed up to one year before the COVID-19 pandemic and again during lockdown. We also test antecedents and consequences of consistency, examining both what prospectively predicts consistency as well as what consistency prospectively predicts. Overall, consistency was modest but there were strong individual differences, indicating some people were quite consistent despite environmental upheaval. Moreover, there were relatively few antecedents and consequences of consistency, with the exception of some goals and domains of satisfaction predicting consistency, leaving open the question of why changes in coherence occurs.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/pvfg2/" target="_blank">Idiographic Personality Coherence: A Quasi Experimental Longitudinal ESM Study</a>
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<li><strong>Knowledge of COVID-19 Symptoms, Transmission, and Prevention: Evidence from Health and Demographic Surveillance in Southern Mozambique</strong> -
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Over 230,000 COVID-19 cases and over 2,200 deaths have been reported in Mozambique though May 2023. Understanding community members9 knowledge of SARS-CoV-2 transmission and prevention is essential for directing public health interventions to reduce disease spread and improve vaccination coverage. Here, we describe knowledge of COVID-19 transmission, prevention, and symptoms among community residents in Mozambique. We conducted a cross-sectional survey among 33,087 households in a Health and Demographic Surveillance System in Manhica, Mozambique. Participants were recruited at the tail end of the Delta variant wave in September 2021 to the peak of Omicron cases in January 2022. Principal components analysis was used to create scores representing knowledge of COVID-19 symptoms, transmission, and prevention. Multiple imputation and quasi-Poisson regression were used to examine associations between demographic characteristics and sources of COVID-19 information, and knowledge of COVID-19 symptoms, transmission, and prevention. We examined whether sources of COVID-19 information mediated the relationship between educational attainment and knowledge of symptoms, transmission, and prevention. Across this rural community, 98.2%, 97.0%, and 85.1% of respondents reported knowing how COVID-19 could be prevented, that SARS-CoV-2 can cause disease, and how SARS-CoV-2 is transmitted, respectively. Most cited symptoms were cough (51.2%), headaches (44.9%), and fever (44.5%); transmission mechanisms were droplets (50.5%) or aerosol (46.9%) from an infected person; and prevention measures were handwashing (91.9%) and mask-wearing (91.8%). Characteristics associated with greater knowledge of symptoms, transmission, and prevention included having at least primary education, older age, employment, higher wealth, and Christian religion. Respondents who had had COVID-19 symptoms were also more likely to have knowledge of symptoms, transmission, and prevention. Gathering information from TV, WhatsApp, radio, and hospital mediated the relationship between educational attainment and knowledge scores. These findings support the need for outreach and for community-engaged messaging to promote prevention measures, particularly among people with low education.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.31.23288026v2" target="_blank">Knowledge of COVID-19 Symptoms, Transmission, and Prevention: Evidence from Health and Demographic Surveillance in Southern Mozambique</a>
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<li><strong>Mycobiome analyses of critically ill COVID-19 patients</strong> -
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Rationale: Covid-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID -19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and Candida colonisation. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality. However, specific mycobiome signatures associated with severe COVID-19 in the context of survival and antifungal drug prophylaxis have not yet been determined and such knowledge could have an important impact on treatment. Objectives: To understand the composition of the respiratory mycobiome in critically ill COVID -19 patients with and without CAPA, the impact of antifungal use and its role in patient outcome. Methods: We performed a multi-national study of 39 COVID-19 patients in intensive care units (ICU) with and without CAPA. Respiratory mycobiome was profiled using ITS1 sequencing and Aspergillus fumigatus burden was further validated using qPCR. Fungal communities were investigated using alpha diversity, beta diversity, taxa prevalence and taxa abundances. Measurements and Main Results: Respiratory mycobiomes were dominated by Candida and Aspergillus. There was no significant association with corticosteroid use or CAPA diagnosis and respiratory fungal communities. Increased A. fumigatus burden was associated with mortality. The use of antifungals at ICU admission was associated with an absence of A. fumigatus. Conclusions: Our findings suggest that systemic antifungal treatment at ICU admission may be protective against A. fumigatus-associated mortality in CAPA.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.13.543274v2" target="_blank">Mycobiome analyses of critically ill COVID-19 patients</a>
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<li><strong>Identification of cross-reacting IgG hotspots to prevent immune evasion of SARS-CoV-2 variants</strong> -
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The major factor that shapes the global perspective for increase or diminution of successive pandemic waves of COVID-19 is the immunological protection. The SARS-CoV-2 virus constantly develops new variants, and capability of immune evasion is among the major factors that promote variant spreading in the human population. After two years of the pandemic and virus evolution, it is almost impossible to explain effects of all possible combinations different viral strains, a few types of vaccinations or new variants infecting an individual patient. Instead of variant-to-variant comparisons, identification of key protein regions linked to immune evasion could be efficient. Here we report an approach for experimental identification of SARS-CoV-2 protein regions that (i) have characteristics of cross-reacting IgG hot-spots, and (ii) are highly immunogenic. Cross-reacting IgG hot spots are regions of protein frequently recognized in many variants by cross-reacting antibodies. Immunogenic regions efficiently induce specific IgG production in SARS-CoV-2 infected patients. We determined four regions that demonstrate both significant immunogenicity and the activity of a cross-reacting IgG hot-spot in protein S, and two such regions in protein N. Their distribution within the proteins suggests that they may be useful in vaccine design and in serological diagnostics of COVID?19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.27.546805v1" target="_blank">Identification of cross-reacting IgG hotspots to prevent immune evasion of SARS-CoV-2 variants</a>
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<li><strong>A Rationally Designed Antimicrobial Peptide from Structural and Functional Insight of Clostridium difficile Translation Initiation Factor 1</strong> -
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A significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem. Clostridioides difficile is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of C. difficile infection and antibiotic resistance in C. difficile has led to an unmet need for discovery of new compounds distinctly different from present antimicrobials, while antimicrobial peptides as promising alternatives to conventional antibiotics have attracted growing interest recently. Protein synthesis is an essential metabolic process in all bacteria and a validated antibiotic target. Initiation factor 1 from C. difficile (Cd-IF1) is the smallest of the three initiation factors that acts to establish the 30S initiation complex to initiate translation during protein biosynthesis. Here we report the solution NMR structure of Cd-IF1 which adopts a typical {beta}-barrel fold and consists of a five-stranded {beta}-sheet and one short -helix arranged in the sequential order {beta}1-{beta}2-{beta}3-1-{beta}4-{beta}5. The interaction of Cd-IF1 with the 30S ribosomal subunit was studied by NMR titration for the construction of a structural model of Cd-IF1 binding with the 30S subunit. The short -helix in IF1 was found to be critical for IF1 ribosomal binding. A peptide derived from this -helix was tested and displayed a high ability to inhibit the growth of C. difficile and other bacterial strains. These results provide a clue for rational design of new antimicrobials.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.30.547268v1" target="_blank">A Rationally Designed Antimicrobial Peptide from Structural and Functional Insight of Clostridium difficile Translation Initiation Factor 1</a>
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<li><strong>Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes</strong> -
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Background: During the winter of 2022-2023, high rates of all-cause mortality, not seen since April 2020, were recorded in France, with excess all-cause mortality being related to the Omicron and influenza epidemics during that period. Moreover, that period saw a significant increase in the proportion of residents in long-term care facilities among cases of death in the population. Studies have found that increased influenza vaccination coverage in healthcare workers can result in a substantial reduction (up to 20%-30% during the course of select influenza seasons in the pre-pandemic period) in all-cause mortality in residents in nursing homes. Methods: We applied the previously developed methodology to estimate the contribution of influenza infections to all-cause mortality in France for the 2014-2015 through the 2018-2019 influenza seasons, and the contribution of both SARS-CoV-2 and influenza infections to all-cause mortality between week 33, 2022 through week 12, 2023. Results: For the 2014-2015 through the 2018-2019 seasons, influenza was associated with an average of 15654 (95% CI (13013,18340)) deaths, while between week 33, 2022 through week 12, 2023, we estimated 7851 (5213,10463) influenza-associated deaths and 32607 (20794,44496) SARS-CoV-2 associated deaths. The number of SARS-CoV-2-associated deaths during the Omicron epidemic was significantly higher than the number of deaths with COVID-19 listed on the death certificate or the hospitalization record; for example, between weeks 33-52 in 2022, we estimated 23983 (15307,32620) SARS-CoV-2-associated deaths in France, compared with 12811 deaths with COVID-19 listed on the death certificate, and 8639 in-hospital deaths with COVID-19 during the same period. Examination of US mortality data suggests a significant contribution of Omicron infections to mortality for cardiac disease and mental/behavioral disorders with COVID-19 not listed on the death certificate. Conclusions: Our results suggest the need for boosting influenza vaccination coverage in different population groups (including healthcare workers, particularly nurse assistants for whom influenza vaccination coverage rates in France are low), as well as for wider use of influenza antiviral medications in influenza-related respiratory hospitalizations with different diagnoses (including pneumonia). Wider detection and treatment of Omicron infections, particularly in older individuals/persons with underlying health conditions such as cardiac disease and mental/behavioral disorders, and wider use of bivalent COVID-19 boosters would be needed in the event of the recrudescence of Omicron circulation in France.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.05.23290994v2" target="_blank">Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes</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>Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 capsule; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>A Study to Investigate the Safety, Immunogenicity of Bivalent mRNA Vaccine RQ3027 and RQ3025 as a Booster Dose in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: RQ3025; Biological: RQ3027<br/><b>Sponsors</b>: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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</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>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Validity of Rapid Antibody Testing for COVID-19 Vaccine in Homeless People</strong> - (1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were…</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>Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates</strong> - COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as…</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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