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183 lines
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<title>24 January, 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>Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay</strong> -
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New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve and adapt to evade vaccine-induced and infection-elicited immunity. Vaccine and therapeutics developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging SARS-CoV-2 variants remains essential as the global community transitions from an emergency response to a long-term management plan. Here, we describe how an authentic virus neutralisation assay using low passage clinical virus isolates has been employed to monitor resistance of emerging virus variants to neutralising antibodies from humans and experimentally infected hamsters. Sera and plasma from people who received three doses of a vaccine as well as those who received a bivalent booster were assessed against SARS-CoV-2 variants, up to and including JN.1. Contemporary or recent virus variants showed substantial resistance to neutralisation by antibodies from those who had received three doses of an ancestral vaccine but were still effectively neutralised by antibodies from individuals who had received a bivalent booster (ancestral/BA.1). In our recent studies, however, the JN.1 VOI was found to be significantly more resistant to neutralisation by antibodies from those who had received the ancestral/BA.1 bivalent boost. Convalescent sera from hamsters that had been experimentally infected with one of seven virus variants (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) were also tested here. The recent contemporary variant, BA.2.86, was effectively neutralised by sera from hamsters infected with XBB.1.5 and XBB.1.16 but it was not neutralised by sera from those infected with BA.5.2.1. These data support the recommendations given by the WHO that a new vaccine was required and should consist of an XBB sub-lineage antigen.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.21.563398v2" target="_blank">Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay</a>
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<li><strong>Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States</strong> -
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There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 188-229) cases per 100,000 persons, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (11-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4" target="_blank">Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States</a>
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</div></li>
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<li><strong>Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs</strong> -
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<div>
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COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.
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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/10.1101/2023.10.23.563669v5" target="_blank">Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs</a>
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</div></li>
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<li><strong>SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis</strong> -
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Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.21.576509v1" target="_blank">SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis</a>
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<li><strong>Policy makers believe money motivates more than it does</strong> -
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To motivate contributions to public goods, should policy makers employ financial incentives like taxes, fines, subsidies, and rewards? While these are widely considered as the classic policy approach, a substantial academic literature suggests the impact of financial incentives is not always positive; they can sometimes fail or even backfire. To test whether policy makers are overly bullish about financial incentives, we asked county heads, mayors, and municipal government representatives of medium-to-large towns in Germany to predict the effects of a financial incentive on COVID-19 vaccination, and tested the exact same incentive in a field experiment involving all 41,548 inhabitants (clustered in 10,032 addresses) of the German town of Ravensburg. Whereas policy makers overwhelmingly predict that the financial incentive will increase vaccination—by 15.3 percentage points on average—the same financial incentive yielded a precisely estimated null effect on vaccination. We discuss when financial incentives are most likely to fail, and conclude that it is critical to educate policy makers on the potential pitfalls of employing financial incentives to promote contributions to public goods.
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🖺 Full Text HTML: <a href="https://osf.io/jq28n/" target="_blank">Policy makers believe money motivates more than it does</a>
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</div></li>
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<li><strong>Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination</strong> -
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<div>
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We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (KD < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC50 ~0.1-1.75 nM) and provided robust protection in vivo. Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization.
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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/10.1101/2024.01.22.576742v1" target="_blank">Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination</a>
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<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
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SARS-CoV-2 employs its spike protein’s receptor binding domain (RBD) to enter host cells. The RBD is constantly subjected to immune responses, while requiring efficient binding to host cell receptors for successful infection. However, our understanding of how RBD’s biophysical properties contribute to SARS-CoV-2’s epidemiological fitness remains largely incomplete. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the discovery of a fitness function based on binding thermodynamics, we unravel the relationship between the biophysical properties of RBD variants and their contribution to viral fitness. We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by binding constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto a epistatic fitness landscape. We validate our findings through experimentally measured and machine learning (ML) estimated binding affinities, coupled with infectivity data derived from population-level sequencing. Our analysis reveals that this model effectively predicts the fitness of novel RBD variants and can account for the epistatic interactions among mutations, including explaining the later reversal of Q493R. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549087v3" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</strong> -
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<div>
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X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory CT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.21.576083v1" target="_blank">Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing</a>
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<li><strong>Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak.</strong> -
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OBJECTIVE At the beginning of 2020, hydroxychloroquine showed promising in vitro activity for Covid-19 and several studies were oriented to assess its safety and efficacy. However, after a few months, hydroxychloroquine has proved ineffective. The randomized controlled trials (RCTs) developed quickly and in different settings represent the scientific community capacity to assess drug repositioning effectiveness during a sanitary crisis. Therefore, a critical evaluation of the evidence generated can guide future efforts in analogous situations. We aimed to analyze the RCTs assessing the efficacy of hydroxychloroquine in treating Covid-19, describe their internal validity and power, and evaluate their contribution to the precision of the combined evidence for assessing the mortality outcome. STUDY DESIGN AND SETTINGS This meta-research included RCTs assessing hydroxychloroquine to treat patients diagnosed with Covid-19. It was part of an umbrella systematic review of methods/meta-research (PROSPERO: CRD42022360331) that included a comprehensive search in MEDLINE, EMBASE, Cochrane Library, and the Latin America Database - Lilacs. We retrieved studies published until January 10th, 2022. The risk of bias was assessed using Cochrane Risk of Bias (RoB) 2.0. We analyzed methodology of the studies, precision and random error change through time from pooled evidence, study comparators, patient important outcome, power in different magnitude of effects proxy. RESULTS A total of 22 RCT were included, from that 17 (77%) assessed hospitalized patients and five (23%) outpatients setting. Mortality was related as primary endpoint in only four studies, however half of the studies included composite endpoints including mortality as a component. The internal validity analysis using RoB2 found that eight studies (36%) had a high risk of bias. Only one study had sufficient power to evaluate a moderate magnitude of effect (RR = 0,7 on mortality). The standard error to evaluate efficacy on mortality did not change appreciably after October 2020. From Oct 2020 to Dec 2021, 18 additional studies were published with 2,429 patients recruited. CONCLUSION This meta-research highlights the impact that collaborative, and network scientific research have on informing clinical decision-making. Duplicate efforts create research waste as precision analysis shows that after October 2020, there was not appreciably changes in the precision of the pooled RCT evidence to estimate the hydroxychloroquine effect on mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.21.24301572v1" target="_blank">Pooled evidence precision of clinical trials on hydroxychloroquine for Covid-19 treatment was stabilized eight months after the outbreak.</a>
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<li><strong>Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions</strong> -
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Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.21.24301574v1" target="_blank">Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions</a>
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<li><strong>Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile</strong> -
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South America suffered large SARS-CoV-2 epidemics between 2020 and 2022 caused by multiple variants of interest and concern, some causing substantial morbidity and mortality. However, their transmission dynamics are poorly characterised. The epidemic situation in Chile enables us to investigate differences in the distribution and spread of variants Alpha, Gamma, Lambda, Mu and Delta. Chile implemented non-pharmaceutical interventions and an integrated genomic and epidemiological surveillance system that included airport and community surveillance to track SARS-CoV-2 variants. Here we combine viral genomic data and anonymised human mobility data from mobile phones to characterise the routes of importation of different variants into Chile, the relative contributions of airport-based importations to viral diversity versus land border crossings and test the impact of the mobility network on the diffusion of viral lineages within the country. We find that Alpha, Lambda and Mu were identified in Chile via airport surveillance six, four and five weeks ahead of their detection via community surveillance, respectively. Further, some variants that originated in South America were imported into Chile via land rather than international air travel, most notably Gamma. Different variants exhibited similar trends of viral dissemination throughout the country following their importation, and we show that the mobility network predicts the time of arrival of imported lineages to different Chilean comunas. Higher stringency of local NPIs was also associated with fewer domestic viral importations. Our results show how genomic surveillance combined with high resolution mobility data can help predict the multi-scale geographic expansion of emerging infectious diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.18.24301504v1" target="_blank">Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile</a>
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<li><strong>Monitoring Report: Respiratory Viruses - December 2023 Data</strong> -
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Background: Few sources regularly monitor hospitalizations associated with respiratory viruses. This study provides current hospitalization trends associated with six common respiratory viruses: COVID-19, influenza, human metapneumovirus (HMPV), parainfluenza virus, respiratory syncytial virus (RSV), and rhinovirus. Objective: This study aims to supplement the surveillance data provided by the CDC by describing trends overall and for each respiratory virus. This study also provides valuable insight into two at-risk populations: infants and children (age 0-4) and older adults (age 65 and over). Methods: Using a subset of real-world electronic health record (EHR) data from Truveta, a growing collective of health systems that provide more than 18% of all daily clinical care in the USA consortium of US healthcare systems, we identified people who were hospitalized between October 01, 2019 and December 31, 2023. We identified people who tested positive for any of the six respiratory virus within 14 days of the hospitalization. We report weekly trends in the rate of hospitalizations associated with each virus per all hospitalizations for the overall population and the two high-risk sub populations, infants and children and older adults. Results: We included 502,484 hospitalizations of 471,401 unique patients who tested positive for a respiratory virus between October 01, 2019 and December 31, 2023. Overall, the rate of hospitalizations associated with respiratory viruses continue to increase through the end of December 2023 (92.8% increase since November 2023). The largest increases over the past month have been seen in influenza- (251.7% increase), HMPV- (115.0% increase), and COVID-associated (88.6% increase) hospitalizations. For infants and children, RSV accounted for the most respiratory virus-associated hospitalizations, despite decreases throughout December 2023. In this population, COVID-associated hospitalizations had the biggest increase in the last month. For the older adult population, respiratory virus-associated hospitalizations increased to 10.3% per all hospitalizations. COVID remained the largest contributor; 5.3% of all hospitalizations were associated with COVID in the older adult population. Discussion: Respiratory virus-associated hospitalizations continued to increase overall, including for the two high risk populations we studied. RSV-associated hospitalizations continue to be the main contributor to illness in infants and children, while COVID-associated hospitalizations are the largest contributor for the older adult population. We will continue to monitor trends in all respiratory viruses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.20.24301528v1" target="_blank">Monitoring Report: Respiratory Viruses - December 2023 Data</a>
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<li><strong>Impact of Vaccination Rates and Gross Domestic Product on COVID-19 Pandemic Mortality Across United States</strong> -
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Objective: To investigate the relationship between vaccination rates and excess mortality during distinct waves of SARS-CoV-2 variant-specific infections, while considering a state9s GDP per capita. Methods: We ranked U.S. states by vaccination rates and GDP and employed the CDC9s excess mortality model for regression and odds ratio analysis. Results: Regression analysis reveals that both vaccination and GDP are significant factors related to mortality when considering the entire U.S. population. Notably, in wealthier states (with GDP above $65,000), excess mortality is primarily driven by slow vaccination rates, while in less affluent states, low GDP plays a major role. Odds ratio analysis demonstrates an almost twofold increase in mortality linked to the Delta and Omicron BA.1 virus variants in states with the slowest vaccination rates compared to those with the fastest (OR 1.8, 95% CI 1.7-1.9, p < 0.01). However, this gap disappeared in the post-Omicron BA.1 period. Conclusion: The interplay between slow vaccination and low GDP per capita drives high mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.21.24301582v1" target="_blank">Impact of Vaccination Rates and Gross Domestic Product on COVID-19 Pandemic Mortality Across United States</a>
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<li><strong>Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C</strong> -
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Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.20.24301525v1" target="_blank">Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C</a>
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<li><strong>Fitness models provide accurate short-term forecasts of SARS-CoV-2 variant frequency</strong> -
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Genomic surveillance of pathogen evolution is essential for public health response, treatment strategies, and vaccine development. In the context of SARS-COV-2, multi- ple models have been developed including Multinomial Logistic Regression (MLR) de- scribing variant frequency growth as well as Fixed Growth Advantage (FGA), Growth Advantage Random Walk (GARW) and Piantham parameterizations describing vari- ant Rt. These models provide estimates of variant fitness and can be used to forecast changes in variant frequency. We introduce a framework for evaluating real-time fore- casts of variant frequencies, and apply this framework to the evolution of SARS-CoV-2 during 2022 in which multiple new viral variants emerged and rapidly spread through the population. We compare models across representative countries with different intensities of genomic surveillance. Retrospective assessment of model accuracy high- lights that most models of variant frequency perform well and are able to produce reasonable forecasts. We find that the simple MLR model provides ∼0.6% median ab- solute error and ∼6% mean absolute error when forecasting 30 days out for countries with robust genomic surveillance. We investigate impacts of sequence quantity and quality across countries on forecast accuracy and conduct systematic downsampling to identify that 1000 sequences per week is fully sufficient for accurate short-term fore- casts. We conclude that fitness models represent a useful prognostic tool for short-term evolutionary forecasting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.30.23299240v3" target="_blank">Fitness models provide accurate short-term forecasts of SARS-CoV-2 variant frequency</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>Beneficial Effects of Natural Products on Management of Xerostomia</strong> - <b>Conditions</b>: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition <br/><b>Interventions</b>: Other: (Manuka honey-green tea- ginger) <br/><b>Sponsors</b>: British University In Egypt <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>Eficacia Ventilatoria y Remolacha</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Muscle Disorder; Fatigue <br/><b>Interventions</b>: Dietary Supplement: Remolacha <br/><b>Sponsors</b>: Hospital de Mataró <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>Diet and Fasting for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Long COVID <br/><b>Interventions</b>: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting <br/><b>Sponsors</b>: Pacific Northwest University of Health Sciences <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>The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia</strong> - <b>Conditions</b>: Post COVID-19 Condition <br/><b>Interventions</b>: Other: Protein powder and Resistance exercise <br/><b>Sponsors</b>: Mahidol University; National Health Security Office, Thailand <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>Treatment of Persistent Post-Covid-19 Smell and Taste Disorders</strong> - <b>Conditions</b>: Post-covid-19 Persistent Smell and Taste Disorders <br/><b>Interventions</b>: Drug: Cerebrolysin; Other: olfactory and gustatory trainings <br/><b>Sponsors</b>: Sherifa Ahmed Hamed <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>Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico</strong> - <b>Conditions</b>: Long Covid19 <br/><b>Interventions</b>: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) <br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH) <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 Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <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>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <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>Identification of amentoflavone as a potent SARS-CoV-2 M<sup>pro</sup> inhibitor: a combination of computational studies and in vitro biological evaluation</strong> - Small-molecule inhibitors of SARS-CoV-2 M^(pro) that block the active site pocket of the viral main protease have been considered potential therapeutics for the development of drugs against SARS-CoV-2. Here, we report the identification of amentoflavone (a biflavonoid) through docking-based virtual screening of a library comprised of 231 compounds consisting of flavonoids and isoflavonoids. The docking results were further substantiated through extensive analysis of the data obtained from…</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>Molecular dynamics simulation study on the binding mechanism between carbon nanotubes and RNA-dependent RNA polymerase</strong> - Carbon nanotubes (CNTs) have potential prospects in disease treatment, so it is of great significance to study CNTs as the possible inhibitors of RNA-dependent RNA polymerase (RdRp). Through the way of using the RdRp of SARS-COV-2 as a model, five armchair single-walled carbon nanotubes (SWCNTs) (namely Dn, which stands for CNTs (n, m = n), n = 3-7) and RdRp have been selected to study the interactions by means of molecular docking and molecular dynamics simulation. After five SWCNT-RdRp complex…</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 novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity</strong> - CONCLUSION: Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.</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 basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models</strong> - Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19</strong> - CONCLUSIONS: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.</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 leisure satisfaction on perceived risk of infectious disease during the COVID-19 pandemic: evidence from new worker classes</strong> - CONCLUSION: This study verified the risk factors that inhibit leisure satisfaction among new worker classes that emerged during the COVID-19 pandemic. Furthermore, the psychological health of people suffering pandemic-related financial constraints was affected, as they experienced a lower quality of life owing to reduced leisure activities and satisfaction.</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-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model</strong> - INTRODUCTION: Because prior immune checkpoint inhibitor (ICI) therapy in cancer patients presenting with COVID-19 may affect outcomes, we investigated the beta-coronavirus, murine hepatitis virus (MHV)-1, in a lethal pneumonia model in the absence (Study 1) or presence of prior programmed cell death ligand-1 (PD-L1) antibody (PD-L1mAb) treatment (Study 2).</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2 spike receptor binding domain mutants and functional screening for immune evaders using a novel lentivirus-based system</strong> - The emergence of rapid and continuous mutations of severe acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein that increased with the Omicron variant points out the necessity to anticipate such mutations for conceiving specific and adaptable therapies to avoid another pandemic. The crucial target for the antibody treatment and vaccine design is the receptor binding domain (RBD) of the SARS-CoV-2 spike. It is also the site where the virus has shown its high ability to mutate 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>The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability</strong> - Paxlovid^(®), a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we…</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>Retinoic Acid-Mediated Inhibition of Mouse Coronavirus Replication Is Dependent on IRF3 and CaMKK</strong> - The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling…</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>Performance Analysis of Serodiagnostic Tests to Characterize the Incline and Decline of the Individual Humoral Immune Response in COVID-19 Patients: Impact on Diagnostic Management</strong> - Serodiagnostic tests for antibody detection to estimate the immunoprotective status regarding SARS-CoV-2 support diagnostic management. This study aimed to investigate the performance of serological assays for COVID-19 and elaborate on test-specific characteristics. Sequential samples (n = 636) of four panels (acute COVID-19, convalescent COVID-19 (partly vaccinated post-infection), pre-pandemic, and cross-reactive) were tested for IgG by indirect immunofluorescence test (IIFT) and EUROIMMUN…</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>AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4</strong> - Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, particularly with the emergence of new SARS-CoV-2 variants. CD147, involved in the regulation of inflammation and required to fight virus infection, can facilitate SARS-CoV-2 entry into megakaryocytes….</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>Transcriptome Analysis of LLC-PK Cells Single or Coinfected with Porcine Epidemic Diarrhea Virus and Porcine Deltacoronavirus</strong> - Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are the two most prevalent swine enteric coronaviruses worldwide. They commonly cause natural coinfections, which worsen as the disease progresses and cause increased mortality in piglets. To better understand the transcriptomic changes after PEDV and PDCoV coinfection, we compared LLC porcine kidney (LLC-PK) cells infected with PEDV and/or PDCoV and evaluated the differential expression of genes by transcriptomic…</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>Structural Basis for the Inhibition of SARS-CoV-2 M<sup>pro</sup> D48N Mutant by Shikonin and PF-07321332</strong> - Preventing the spread of SARS-CoV-2 and its variants is crucial in the fight against COVID-19. Inhibition of the main protease (M^(pro)) of SARS-CoV-2 is the key to disrupting viral replication, making M^(pro) a promising target for therapy. PF-07321332 and shikonin have been identified as effective broad-spectrum inhibitors of SARS-CoV-2 M^(pro). The crystal structures of SARS-CoV-2 M^(pro) bound to PF-07321332 and shikonin have been resolved in previous studies. However, the exact mechanism…</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>Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives</strong> - LCB1 is a computationally designed three-helix miniprotein that precisely targets the spike (S) receptor-binding motif (RBM) of SARS-CoV-2, exhibiting remarkable antiviral efficacy; however, emerging SARS-CoV-2 variants could substantially compromise its neutralization effectiveness. In this study, we constructed two multivalent LCB1 fusion proteins termed LCB1T and LCB1T-Fc, and characterized their potency in inhibiting SARS-CoV-2 pseudovirus and authentic virus in vitro. In the inhibition of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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