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<title>15 March, 2024</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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Exploring associations between the Covid-19 vaccination campaign and fertility trends: A population-level analysis for 22 countries</strong> -
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<div>
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Background At the turn of 2021-2022, monthly birth rates declined in many higher-income countries. We explore how the rollout of COVID-19 vaccination was associated with this decline. Methods Using an interrupted time series design, we evaluate the impact of the onset of the COVID-19 pandemic and the start of COVID-19 vaccination on seasonally-adjusted monthly total fertility rates in 22 high-income countries. We study the associations between COVID-19 vaccination and fertility by additionally controlling for youth unemployment, stringency index, and vaccination coverage. Results The start of the pandemic had an immediate effect on fertility in most countries, although the size and direction of level changes considerably varied across countries. The impact of COVID-19 vaccination was less all-embracing. A negative association between the COVID-19 vaccine rollout and fertility nine months later was found for ten out of 22 countries. For several countries, the decline was preceded by fertility increase that took place after the onset of the pandemic. Only four of 22 countries had post-vaccination fertility declines that resulted in fertility being on a lower level than what the pre-pandemic trend predicted. Additional control variables changed the associations only little. Conclusions The COVID-19 vaccination campaign contributed to the variation in the short-term fertility trends. Several countries experienced declines following the campaign, however, this decline often returned fertility closer to the pre-pandemic trend. Fertility appears to have responded in short run to vaccination, but only in few cases such that the long-term trajectory is below the pre-pandemic trend.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/46qdw/" target="_blank">Exploring associations between the Covid-19 vaccination campaign and fertility trends: A population-level analysis for 22 countries</a>
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<li><strong>Urban birds’ tolerance towards humans was largely unaffected by increased variation in human levels due to COVID-19 shutdowns</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic dramatically altered human activities, and, during shutdowns, potentially changed human pressures on urban-dwelling animals. Here, we evaluated whether urban birds from five countries (Finland, Poland, Czech Republic, Hungary, Australia) changed their tolerance towards humans (measured as flight initiation distance) during the COVID-19 shutdowns. We collected 6369 flight initiation distance estimates for 147 bird species and found that human numbers in parks (at a given hour, day, week or year - before and during the COVID-19 shutdowns) had a little effect on birds tolerance of approaching humans. Apart from the actual human numbers in the area (hourly temporal scale) - which as expected correlated negatively, albeit weakly, with escape distance - the effect of human activity at other temporal scales centered around zero. The results were similar across countries, for most species or when we restricted our analyses only to species sampled both before and during the COVID-19 shutdowns. As expected, the level of daily human presence in parks (measured by Google Mobility Reports) correlated negatively with the stringency of governmental restrictions (a weekly proxy for human presence) and was overall lower during COVID-19 shutdowns than during the post-shutdown year (2022). Our results highlight the resilience of birds to changes in human numbers on multiple temporal scales, the complexities of linking animal fear responses to human behavior, and the challenge of quantifying both simultaneously in situ.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500232v2" target="_blank">Urban birds’ tolerance towards humans was largely unaffected by increased variation in human levels due to COVID-19 shutdowns</a>
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<li><strong>Escherichia coli grown in cost-effective conical tubes produces more plasmid DNA</strong> -
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Before the COVID-19 pandemic, we grew plasmid-transformed Escherichia coli in Falcon round-bottom-polypropylene tubes (F-Round-PP) and isolated plasmid using a Miniprep kit. When obtaining sufficient quantities of F-Round-PP became problematic during the pandemic and the inflation, we grew them using any available tubes. Notably, we observed that plasmid yield from cells grown in a cost-effective Oxford conical-polypropylene tubes (O-Conical-PP) was higher than that from F-Round-PP. We assessed the impact using O-Conical-PP and other conical brand tubes. As a result, the plasmid yield from O-Conical-PP (the list price is nearly 1/3 of F-Round-PP) was 1.5-fold higher than other PP tubes (p<0.001). We propose that researchers may need to re-assess the effectiveness of their laboratory supplies to optimize the budget during this inflationary period.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584835v1" target="_blank">Escherichia coli grown in cost-effective conical tubes produces more plasmid DNA</a>
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<li><strong>Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV</strong> -
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Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584735v1" target="_blank">Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV</a>
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<li><strong>Self-inhibiting percolation and viral spreading in epithelial tissue</strong> -
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SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.12.571279v2" target="_blank">Self-inhibiting percolation and viral spreading in epithelial tissue</a>
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<li><strong>Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform</strong> -
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The burgeoning abilities of pathogens and tumor cells to evade immune responses underscore the urgent need for innovative vaccination platforms based on a variety of biological mechanisms. The current logistical challenges associated with cold-chain (i.e. low-temperature) transportation particularly impacts access to vaccines in the global south. We recently discovered organelles called migrasomes, and herein we investigate the potential of migrasomes as an alternative vaccination platform. Their inherent stability and their enrichment with immune-modulating molecules make migrasomes promising candidates, but their low yield presents a hurdle. We address this problem through our engineered migrasome-like vesicles (eMigrasomes), which emulate the biophysical attributes of natural migrasomes with substantially improved yield. We show that eMigrasomes loaded with a model antigen elicit potent antibody responses and maintain stability at room temperature. We demonstrate that eMigrasomes bearing the SARS-CoV-2 Spike protein induce robust humoral protection against the virus. Our study demonstrates the potential of eMigrasome-based vaccines as a unique, robust, and accessible alternative to traditional methods.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584850v1" target="_blank">Engineered Migrasomes: A Robust, Thermally Stable Vaccination Platform</a>
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<li><strong>CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs</strong> -
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With the increasing discovery of circular RNAs (circRNAs) and their critical roles in gene regulation and disease progression, there is a growing need for more accurate and efficient tools for circRNAs research. In response, we have developed an integrated software suite specifically for circRNAs. This all-in-one tool specializes in detecting differentially expressed circRNAs, including those with the potential to be translated into proteins, and allows for comparing against relevant databases, thereby enabling comprehensive circRNA profiling and annotation. To enhance the accuracy in detecting differentially expressed circRNAs, we incorporated three different software algorithms and cross-validated their results through mutual verification. Additionally, this toolkit improves the effectiveness in identifying translatable circRNAs by optimizing Ribo-seq alignment and verifying against public circRNA databases. The performance of circRNA-pro has been evaluated through its application to public RNA-seq and Ribo-seq datasets on breast cancer and SARS-CoV-2 infected cells, and the results obtained have been validated against previous literature and databases. Overall, our integrated toolkit provides a reliable workflow for circRNA research, facilitating insights into their diverse roles across life sciences.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584785v1" target="_blank">CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs</a>
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<li><strong>Mutability and hypermutation antagonize immunoglobulin codon optimality</strong> -
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The efficacy of polyclonal antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation (SHM). These processes arose in early jawed vertebrates; however, little is known about how immunoglobulin diversity, mutability, and hypermutation have evolved in tandem with another more ubiquitous feature of protein-coding DNA - codon optimality. Here, we explore these relationships through analysis of germline IG genes, natural V(D)J repertoires, serum VH usage, and monoclonal antibody (mAb) expression, each through the lens of multiple optimality metrics. Strikingly, proteomic serum IgG sequencing showed that germline IGHV codon optimality positively correlated with VH representation after influenza vaccination, and in vitro, codon deoptimization of mAbs with synonymous amino acid sequences caused consistent expression loss. Germline V genes exhibit a range of codon optimality that is maintained by functionality, and inversely related to mutability. SHM caused a load-dependent deoptimization of IGH VDJ repertoires within human tonsils, bone marrow, and lymph nodes (including SARS-CoV-2-specific clones from mRNA vaccinees), influenza-infected mice, and zebrafish. Comparison of natural mutation profiles to true random suggests the presence of selective pressures that constrain deoptimization. These findings shed light on immunoglobulin evolution, providing unanticipated insights into the antagonistic relationship between variable region diversification, codon optimality, and antibody secretion; ultimately, the need for diversity takes precedence over that for the most efficient expression of the antibody repertoire.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.13.584690v1" target="_blank">Mutability and hypermutation antagonize immunoglobulin codon optimality</a>
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<li><strong>Understanding Young Caring in the UK Pre- and Post-COVID-19: Prevalence, Correlates, and Insights from Three UK Longitudinal Surveys</strong> -
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Background. Despite increasing awareness of young carers in recent years, there remains a significant gap in our understanding of both the prevalence and the characteristics of young carers. Our study aims to address this gap by examining the impact of the COVID-19 pandemic on the prevalence and characteristics of young carers. Methods. This research utilised data from three UK longitudinal surveys: the UK Household Longitudinal Study (UKHLS), the COVID Social Mobility and Opportunities (COSMO) study, and the Millennium Cohort Study (MCS). We focused on adolescents aged 16-18, and examined two pre-COVID (UKHLS and MCS) and two post-COVID (UKHLS and COSMO) samples. Results. The prevalence of young carers increased from 8.0% pre-COVID to 9.8-11.9% since COVID. Young carers were more commonly found in single-parent and socioeconomically disadvantaged households, with a higher prevalence of young carers in homes where parents were out of paid employment or held lower educational qualifications. Young carers were also more likely to reside in deprived areas. Most young carers engaged in low-intensity caring (< 10 hours/week), but post-COVID there was an increase in high-intensity caring (10+ hours/week), predominantly assumed by young female carers. The primary recipients of care were parents, followed by grandparents and siblings, with no change in the care recipient type since COVID. Conclusion. This study showed an increase in the prevalence of young carers, particularly those providing high-intensity care, since the onset of the COVID pandemic. Further, young carers were more likely to come from socioeconomically disadvantaged households and areas. Given the potential impacts that young caring can have on young peoples’ lives, it is imperative that support for young carers is increased, particularly for those facing multiple disadvantages. In tandem, services that support adult health and social care need to play a key role in identifying young carers.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/65k2m/" target="_blank">Understanding Young Caring in the UK Pre- and Post-COVID-19: Prevalence, Correlates, and Insights from Three UK Longitudinal Surveys</a>
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<li><strong>Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study</strong> -
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Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10μg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3μg BNT162b2, no sex differences were noted, but after a first dose of 5 or 10μg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.08.24303999v1" target="_blank">Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study</a>
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<li><strong>Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variant JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study</strong> -
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A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. During the study period (November 2022-January 2024), 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p=0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p=0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Day-28 mortality of JN.1-infected patients was 14.6%.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304075v1" target="_blank">Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variant JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study</a>
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<li><strong>EpidemicKabu a new method to identify epidemic waves and their peaks and valleys</strong> -
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INTRODUCTION: The dynamical behavior of epidemic curves is an oscillation between a very low and very high number of incident cases throughout the time. These oscillations are commonly called waves of the epidemic curve. The concept of epidemic waves lacks a consensual definition and a simple methodology that can be used for many diseases. OBJECTIVE: We describe in this study the EpidemicKabu method to identify the start and the end of past epidemic waves but also their peaks and valleys. METHOD: The methodology is divided into processing of the curve, waves detection, and peaks and valleys delimitation. For processing the curve, a Gaussian kernel was used to diminish the noise and to smooth the curve. The first and second derivatives of the curve were used for the detection of waves, delimitation of peaks and valleys. The methodology was derived into the open access library. The method was tested using COVID-19 daily cases reported between 2020 and 2022 for different countries. After detection of waves, we made some measures related to the size of the waves for those countries. RESULTS: The results of the method were the dates of start and end of waves, peaks, and valleys. The dates are displayed on graphs and added as a new column in a dataset. We found that Belgium was the country recording the highest ratio of incident cases per 100 people by day in a wave. CONCLUSION: The EpidemicKabu method is simple, easy to use, and very useful in estimating epidemic waves. The methodology requires expert judgment in order to set a parameter that could only have three possible values.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304124v1" target="_blank">EpidemicKabu a new method to identify epidemic waves and their peaks and valleys</a>
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<li><strong>The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment</strong> -
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Background: An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants. Objective: To describe which methodological adjustments were made to the study protocol because of these developments. Methods: We compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan. Discussion: This manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.11.24304097v1" target="_blank">The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment</a>
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<li><strong>The association between prolonged SARS-CoV-2 symptoms and work outcomes</strong> -
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While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms. When asked about missed work due to their SARS-CoV-2 infection at three months, 7.1% of participants reported missing >=10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with >=5 symptoms had a higher adjusted odds ratio (aOR) of missing >=10 workdays (2.96, 95% CI 1.81-4.83) and not returning to work (2.44, 95% CI 1.58-3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with >=5 symptoms at three months. Despite the end of the Federal COVID-19 Public Health Emergency and efforts to “return to normal”, policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people’s employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.10.24304054v1" target="_blank">The association between prolonged SARS-CoV-2 symptoms and work outcomes</a>
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<li><strong>Tight Fit of the SIR Dynamic Epidemic Model to Daily Cases of COVID-19 Reported During the 2021-2022 Omicron Surge in New York City: A Novel Approach</strong> -
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We describe a novel approach to recovering the underlying parameters of the SIR dynamic epidemic model from observed data on case incidence. We formulate a discrete-time approximation to the original continuous-time model and search for the parameter vector that minimizes the standard least squares criterion function. We show that the gradient vector and matrix of second-order derivatives of the criterion function with respect to the parameters adhere to their own systems of difference equations and thus can be exactly calculated iteratively. Applying our new approach, we estimated a four-parameter SIR model from data on daily reported cases of COVID-19 during the SARS-CoV-2 Omicron/BA.1 surge of December 2021 - March 2022 in New York City. The estimated SIR model showed a tight fit to the observed data, but less so when we excluded residual cases attributable to the Delta variant during the initial upswing of the wave in December. Our analyses of both the real-world COVID-19 data and simulated case incidence data revealed an important problem of weak parameter identification. While our methods permitted separate estimation of the infection transmission parameter and the infection persistence parameter, only a linear combination of these two key parameters could be estimated with precision. The SIR model appears to be an adequate reduced-form description of the Omicron surge, but it is not necessarily the correct structural model. Prior information above and beyond case incidence data may be required to sharply identify the parameters and thus distinguish between alternative epidemic models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.13.23287177v3" target="_blank">Tight Fit of the SIR Dynamic Epidemic Model to Daily Cases of COVID-19 Reported During the 2021-2022 Omicron Surge in New York City: A Novel Approach</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>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <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>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman 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>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <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>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <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>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <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>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <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>Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses <br/><b>Sponsors</b>: IRCCS Sacro Cuore Don Calabria di Negrar <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>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC <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>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <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>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <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>Phase 3 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</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>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <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>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
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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>Utilizing sinapic acid as an inhibitory antiviral agent against MERS-CoV PLpro</strong> - Concerns about the social and economic collapse, high mortality rates, and stress on the healthcare system are developing due to the coronavirus onslaught in the form of various species and their variants. In the recent past, infections brought on by coronaviruses severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) as well as middle east respiratory syndrome coronavirus (MERS-CoV) have been reported. There is a severe lack of medications to treat various coronavirus types…</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>Recognition of granulocyte-macrophage colony-stimulating factor by specific S100 proteins</strong> - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic myelopoietic growth factor and proinflammatory cytokine, clinically used for multiple indications and serving as a promising target for treatment of many disorders, including cancer, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, COVID-19. We have previously shown that dimeric Ca^(2+)-bound forms of S100A6 and S100P proteins, members of the multifunctional S100 protein family, are specific to GM-CSF. To…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing inhibitory peptides against SARS-CoV-2 envelope protein</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected approximately 800 million people since the start of the Coronavirus Disease 2019 (COVID-19) pandemic. Because of the high rate of mutagenesis in SARS-CoV-2, it is difficult to develop a sustainable approach for prevention and treatment. The Envelope (E) protein is highly conserved among human coronaviruses. Previous studies reported that SARS-CoV-1 E deficiency reduced viral propagation, suggesting that E inhibition might…</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>Interactions among stress, behavioral inhibition, and delta-beta coupling predict adolescent anxiety during the COVID-19 pandemic</strong> - The COVID-19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near-universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the…</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>Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel</strong> - Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for 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>Neutralization of SARS-CoV-2 and Intranasal Protection of Mice with a nanoCLAMP Antibody Mimetic</strong> - Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring cell-free assays for COVID-19 serosurvey</strong> - Serosurveys to monitor immunity toward COVID-19 in the population are primarily performed using an ELISA to screen samples for SARS-CoV-2 antibodies, followed by confirmation by a virus neutralization test, which is considered the Gold Standard. However, virus neutralization test may not be feasible for some laboratories because of the requirement for specific facilities and trained personnel. In an attempt to address this limitation, we evaluated three cell-free methods as potential…</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 risk of acute infections in new users of antidepressants: An observational cohort study</strong> - CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.</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>Overlaid Lateral Flow Immunoassay for the Simultaneous Detection of Two Variant-Specific SARS-CoV-2 Neutralizing Antibodies</strong> - COVID-19 vaccines have been provided to the general public to build immunity since the 2019 coronavirus pandemic. Once vaccinated, SARS-CoV-2 neutralizing antibodies (NAbs-COVID-19) are needed for excellent protection against COVID-19. However, monitoring NAbs-COVID-19 is complicated and requires hospital visits. Moreover, the resulting NAbs-COVID-19 are effective against different strains of COVID-19 depending on the type of vaccine received. Here, an overlaid lateral flow immunoassay (O-LFIA)…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations</strong> - Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^(pro)) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants are thus urgently needed. We hypothesized that the covalent hepatitis C virus protease…</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>Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19</strong> - COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context,…</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>Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses</strong> - Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Decoding HiPSC-CM’s Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury</strong> - CONCLUSION: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CL(Pro) and PL(Pro)) by Molecular Docking and Dynamic Simulation Studies</strong> - We provide promising computational (in silico) data on phytochemicals (compounds 1-10) from Arabian Peninsula medicinal plants as strong binders, targeting 3-chymotrypsin-like protease (3CL^(Pro)) and papain-like proteases (PL^(Pro)) of SARS-CoV-2. Compounds 1-10 followed the Lipinski rules of five (RO5) and ADMET analysis, exhibiting drug-like characters. Non-covalent (reversible) docking of compounds 1-10 demonstrated their binding with the catalytic dyad (CYS145 and HIS41) of 3CL^(Pro) and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II</strong> - Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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