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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>21 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Development of a fast feature extraction method for SARS-CoV-2 spike sequences using amino acid physicochemical properties</strong> -
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<div>
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COVID-19 continues to spread today, leading to an accumulation of SARS-CoV-2 virus mutations in databases, and large amounts of genomic datasets are currently available. However, due to these large datasets, utilizing this amount of sequence data without random sampling is challenging. Major difficulties for downstream analyses include the increase in the dimension size along with the conversion of sequences into numerical values when using conventional amino acid representation methods, such as one-hot encoding and k-mer-based approaches that directly reflect sequences. Moreover, these sequences are deficient in physicochemical characteristics, such as structural information and hydrophilicity; hence, they fail to accurately represent the inherent function of the given sequences. In this study, we utilized the physicochemical properties of amino acids to develop a rapid and efficient approach for extracting feature parameters that are suitable for downstream processes of machine learning, such as clustering. A fixed-length feature vector representation of a spike sequence with reduced dimensionality was obtained by converting amino acid residues into physicochemical parameters. Next, t-distributed stochastic neighbor embedding (t-SNE), a method for dimensionality reduction and visualization of high-dimensional data, was performed, followed by density-based spatial clustering of applications with noise (DBSCAN). The results show that by using the physicochemical properties of amino acids rather than conventional methods that directly represent sequences into numerical values, SARS-CoV-2 spike sequences can be clustered with sufficient accuracy and a shorter runtime. Interestingly, the clusters obtained by using amino acid properties include subclusters that are distinct from those produced utilizing the method for the direct representation of amino acid sequences. A more detailed analysis indicated that the contributing parameters of this novel cluster identified exclusively when utilizing the physicochemical properties of amino acids significantly differ from one another. This suggests that representing amino acid sequences by physicochemical properties might enable the identification of clusters with enhanced sensitivity compared to conventional methods.
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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/10.1101/2023.11.18.567675v1" target="_blank">Development of a fast feature extraction method for SARS-CoV-2 spike sequences using amino acid physicochemical properties</a>
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</div></li>
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<li><strong>Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15</strong> -
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<div>
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SARS-CoV-2 non-structural protein 15 (Nsp15) is critical for productive viral replication and evasion of host immunity. The uridine-specific endoribonuclease activity of Nsp15 mediates the cleavage of the polyuridine [poly(U)] tract of the negative-strand coronavirus genome to minimize the formation of dsRNA that activates the host antiviral interferon signaling. However, the molecular basis for the recognition and cleavage of the poly(U) tract by Nsp15 is incompletely understood. Here, we present cryogenic electron microscopy (cryoEM) structures of SARS-CoV-2 Nsp15 bound to viral replication intermediate dsRNA containing poly(U) tract at 2.7-3.3 [A] resolution. The structures reveal one copy of dsRNA binds to the sidewall of an Nsp15 homohexamer, spanning three subunits in two distinct binding states. The target uracil is dislodged from the base-pairing of the dsRNA by amino acid residues W332 and M330 of Nsp15, and the dislodged base is entrapped at the endonuclease active site center. Up to 20 A/U base pairs are anchored on the Nsp15 hexamer, which explains the basis for a substantially shortened poly(U) sequence in the negative strand coronavirus genome compared to the long poly(A) tail in its positive strand. Our results provide mechanistic insights into the unique immune evasion strategy employed by coronavirus Nsp15.
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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/10.1101/2023.11.17.567629v1" target="_blank">Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15</a>
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</div></li>
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<li><strong>Tropism of AAV.CPP.16 in the respiratory tract and its application for a CRISPR-based gene therapy against SARS-CoV-2</strong> -
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<div>
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Efficient gene delivery vectors are essential for developing gene therapies for respiratory diseases. Here, we report that AAV.CPP.16, a novel AAV9-derived adeno-associated virus vector, can efficiently transduce airway epithelium systems and lung parenchyma cells in both mice and non-human primates after intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism to respiratory tract tissues, and can target major cell types in the respiratory tract and the lung. We also report an all-in-one, CRISPR-Cas13d-based AAV gene therapy vector that targets the highly conserved RNA-dependent RNA polymerase (Rdrp) gene in SARS-CoV-2, and show the potential of such gene therapy against a broad range of circulating and emergent SARS-CoV-2 variants. Thus, AAV.CPP.16 could be a useful gene delivery vector for treating genetic respiratory diseases and airborne infections including for developing a potential prophilaxis to SARS-CoV-2.
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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/10.1101/2023.11.17.567583v1" target="_blank">Tropism of AAV.CPP.16 in the respiratory tract and its application for a CRISPR-based gene therapy against SARS-CoV-2</a>
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</div></li>
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<li><strong>Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine</strong> -
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<div>
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As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN[γ]+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains.
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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/10.1101/2023.11.17.567633v1" target="_blank">Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine</a>
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<li><strong>Lung inflammation is associated with lipid deposition</strong> -
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<div>
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Lung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.30.522299v2" target="_blank">Lung inflammation is associated with lipid deposition</a>
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</div></li>
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<li><strong>Wastewater surveillance pilot at US military installations: a cost model analysis</strong> -
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Background: The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for pathogen surveillance systems to augment both early warning and outbreak monitoring/control efforts. Wastewater samples provide a rapid and accurate source of environmental surveillance data to complement direct patient sampling. Due to its global presence and critical missions, the US military is a leader in global pandemic preparedness efforts. Clinical testing for COVID-19 on US Air Force (USAF) bases (AFBs) was effective, but costly with respect to direct costs and indirect costs of lost time. To remain operating at peak capacity such bases sought a more passive surveillance option and piloted wastewater surveillance (WWS) at 17 AFBs to demonstrate feasibility, safety, and utility from May 2021 to January 2022. Objective: Here we model the costs of a wastewater program for pathogens of pandemic potential within the specific context of US military installations using assumptions based on the results of the USAF and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) pilot program. The objective was to determine the cost of deploying WWS to all AFBs, relative to clinical swab testing surveillance regimes. Methods: A simple WWS cost projection model was built based on subject matter expert input and actual costs incurred during a WWS pilot program at USAF AFBs. Several SARS-CoV-2 circulation scenarios were considered and costs of both WWS and clinical swab testing were projected. Break even analysis was conducted to determine how reduction in swab testing could open up space to enable WWS to occur in complement. Results: Our model confirms that wastewater surveillance is complimentary and highly cost-effective when compared to existing alternative forms of biosurveillance. We find that the cost of WWS was between $10.5 - $18.5 million less expensive annually in direct costs as compared to clinical swab testing surveillance. When indirect cost of lost work is incorporated, including assumed lost work required to go obtain a clinical swab test, we estimate that over two thirds of clinical swab testing could be maintained with no additional costs upon implementation of WWS. Conclusions: Our results support adoption of wastewater surveillance across US military installations as part of a more comprehensive and early warning system that will enable adaptive monitoring during disease outbreaks.
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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/10.1101/2023.11.14.23298310v2" target="_blank">Wastewater surveillance pilot at US military installations: a cost model analysis</a>
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</div></li>
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<li><strong>Protocol for VIVALDI Social Care: Pilot Study to reduce Infections, Outbreaks and Antimicrobial Resistance in Care Homes for Older Adults</strong> -
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Care home residents are vulnerable to severe outcomes from infections such as COVID-19 and influenza. However, measures to control outbreaks, such as care home closures to visitors and new admissions, have a detrimental impact on their quality of life. Many infections and outbreaks could be prevented but the first step is to measure them reliably. This is challenging in care homes due to the lack of data and research infrastructure. During the pandemic, the VIVALDI study measured COVID-19 infections in residents and staff by partnering with care providers and using routinely collected data. This study aims to establish sentinel surveillance and a research database to enable observational and future interventional studies in care homes. The project has been co-produced with care providers, staff, residents, relatives, and researchers. The study (October 2023 to March 2025) will explore the feasibility of establishing a network of 500-1500 care homes for older adults in England that is underpinned by a linked data platform. No data will be collected from staff. The cohort will be created by regularly extracting resident identifiers from Digital Social Care Records (DSCR), followed by pseudonymisation and linkage to routinely collected datasets. Following extensive consultation, we decided not to seek informed consent from residents for data collection, but they can opt out of the study. Our goal is to be inclusive, and it is challenging to give every resident the opportunity to opt in due to cognitive impairment and the requirement for consultees. The project, and all requests to use the data will be overseen by relatives, residents, staff, and care providers. The study has been provisionally approved by the Health Research Authority Confidentiality Advisory Group and the South-West Frenchay Research Ethics Committee. It is funded by the UK Health Security Agency.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.20.23298504v1" target="_blank">Protocol for VIVALDI Social Care: Pilot Study to reduce Infections, Outbreaks and Antimicrobial Resistance in Care Homes for Older Adults</a>
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</div></li>
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<li><strong>Uniting to Advance Diversity, Equity, and Inclusion in a Pandemic and Post-Pandemic World</strong> -
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This contribution examines the context for the newly-founded Diversity, Equity, and Inclusion (DEI) Committee of the European Association of Geochemistry. The report summarises the work to advance DEI undertaken during 2020 under conditions of the COVID-19 global pandemic, acknowledges the various impacts for community members, and takes a forward view to opportunities of a post-pandemic world.
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🖺 Full Text HTML: <a href="https://osf.io/d6z72/" target="_blank">Uniting to Advance Diversity, Equity, and Inclusion in a Pandemic and Post-Pandemic World</a>
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<li><strong>Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</strong> -
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Background: Previous studies have documented a decline in fertility desires following the COVID-19 outbreak, but reasons for this decline are not well understood. This study examined whether greater childcare burden on mothers during the lockdowns and quarantines, COVID-related stress and COVID-19 exposure were associated with a change in desired number of children. Methods: The survey was conducted in Poland in April–July 2021 and completed by 622 non-pregnant mothers without diagnosed infertility. Women were asked whether the COVID-19 pandemic has changed their reproductive plans. Childcare burden was reported during lockdown and quarantines. Results: Almost 30% of mothers reported decrease in their fertility desires because of the pandemic. Associations were observed between childcare responsibilities during the quarantine (but not lockdown) and fertility desires: mothers who solely or mainly took care of their children during the quarantine(s) were more likely to decrease their desired number of children ([adjusted] aOR = 1.91, 95% CI = 1.16–3.15). Mothers with higher levels of COVID-related stress (aOR = 1.81, 95% CI = 1.48–2.22) and greater COVID exposure index (aOR = 1.39, 95% CI = 1.12–1.72) were more likely to decrease their fertility desires. Conclusions: Mothers who bare more childcare responsibilities during quarantine had lower desire to have more children. At the same time, both greater COVID-related stress and exposure were associated with a decreased wish to have children, regardless of the childcare responsibilities during the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3m9zs/" target="_blank">Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</a>
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<li><strong>Feasibility of a Digital Parent Support Group Chat Intervention to Prevent Child and Adolescent Maltreatment in the Philippines: A Pilot Mixed Methods Study</strong> -
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This study examined the preliminary outcomes, feasibility, and acceptability of MaPaChat, a parent support group intervention delivered using Viber group chat delivered to Filipino caregivers during the COVID-19 pandemic. Forty caregivers of children aged 4-17 from predominantly low-income households participated in a culturally adapted version of the Parenting for Lifelong Health ParentChat program. A single-group pre-post design was used to assess changes in the primary outcomes of child maltreatment, positive parenting, and parenting stress; and secondary outcomes of parent depression, child behavior problems, parenting self-efficacy to reduce sexual abuse risk, intimate partner violence, and attitudes toward punishment. Feasibility was assessed by enrollment, attendance, and dropout rates. Semi-structured interviews with caregivers and program facilitators explored program acceptability. Pre-post comparisons showed reductions in physical and emotional abuse, parenting stress, parent depressive symptoms, child behavior problems, child behavior problem intensity, women’s intimate partner violence victimization; and an increase in parental efficacy in preventing sexual abuse risk. The mean attendance rate was 82% and the dropout rate was 10%. Caregivers and facilitators found the program helpful in enhancing parenting knowledge and skills and were satisfied with the program delivery using Viber group chat but also reported experiencing technological challenges.
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🖺 Full Text HTML: <a href="https://osf.io/tz67u/" target="_blank">Feasibility of a Digital Parent Support Group Chat Intervention to Prevent Child and Adolescent Maltreatment in the Philippines: A Pilot Mixed Methods Study</a>
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<li><strong>Making Sense of Uncertainty in the Science Classroom: A Bayesian Approach</strong> -
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Uncertainty is ubiquitous in science, but scientific knowledge is often represented to the public and in educational contexts as certain and immutable. This contrast can foster distrust when scientific knowledge develops in ways that can be perceived as reversals, as we have observed during the ongoing COVID-19 pandemic. Drawing on research in statistics, child development, and several studies in science education, we argue that a Bayesian approach can support science learners to make sense of uncertainty. In this paper, we review prior research on uncertainty and Bayesian approaches to scientific reasoning and provide a brief primer on Bayes’ Theorem. We then describe three ways to make Bayesian reasoning practical in K-12 science education contexts: using principles informed by Bayes’ Theorem that relate to the nature of knowing and knowledge, interacting with a web-based application (or widget—Confidence Updater) that makes the calculations needed to apply Bayes’ Theorem more practical, and adopting strategies for supporting even young learners to engage in Bayesian reasoning. We conclude with directions for future research and sum up how viewing science and scientific knowledge from a Bayesian perspective can build trust in science.
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🖺 Full Text HTML: <a href="https://osf.io/aznyq/" target="_blank">Making Sense of Uncertainty in the Science Classroom: A Bayesian Approach</a>
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<li><strong>Impact of State Telehealth Parity Laws for Private Payers on Hypertension Management before and during the COVID-19 Pandemic</strong> -
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BACKGROUND: Telehealth has emerged as an effective tool for managing common chronic conditions such as hypertension, especially during the COVID-19 pandemic. However, the impact of state telehealth payment and coverage parity laws on hypertension management remains uncertain. METHODS: Data from the MerativeTM MarketScan® Commercial Claims and Encounters Database from January 1, 2016 to December 31, 2021 were used to construct the study cohort. The sample included non-pregnant individuals aged 25?64 years with hypertension. We reviewed and coded telehealth parity laws related to hypertension management in all 50 states and the District of Columbia, distinguishing between payment parity laws and coverage parity laws. The primary outcomes were antihypertension medication use, measured by the average medication possession ratio (MPR), medication adherence (MPR ?80%), and average number of days of drug supply. We used a generalized difference-in-difference (DID) design to examine the impact of these laws. Results were presented as marginal effects and 95% confidence intervals (CI). RESULTS: Among 353,220 individuals, states with payment parity laws were significantly linked to increased average MPR by 0.43 percentage point (95% CI: 0.07 - 0.79), and an increase of 0.46 percentage point (95% CI: 0.06 - 0.92) in the probability of medication adherence. Payment parity laws also led to an average increase of 2.14 days (95% CI: 0.11 - 4.17) in antihypertensive drug supply, after controlling for state-fixed effects, year-fixed effects, individual sociodemographic characteristics and state time-varying covariates including unemployment rates, GDP per capita, and poverty rates. In contrast, coverage parity laws were associated with a 2.13-day increase (95% CI: 0.19 - 4.07) in days of drug supply, but did not significantly increase the average MPR or probability of medication adherence. In addition, telehealth payment or coverage parity laws were positively associated with the number of hypertension-related telehealth visits, but this effect did not reach statistical significance. These findings were consistent in sensitivity analyses. CONCLUSIONS: State telehealth payment parity laws were significantly associated with greater medication adherence, whereas coverage parity laws were not. With the increasing adoption of telehealth parity laws across states, these findings may support policymakers in understanding potential implications on management of hypertension.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.16.23298658v1" target="_blank">Impact of State Telehealth Parity Laws for Private Payers on Hypertension Management before and during the COVID-19 Pandemic</a>
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<li><strong>Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients - March 2022 - April 2023.</strong> -
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<b>Objective</b>: Develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for clinical and research applications. <b>Material and Methods</b>: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors , including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to model risks. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. <b>Results</b>: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. <b>Discussion</b>: These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. <b>Conclusions</b>: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.17.23298653v1" target="_blank">Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients - March 2022 - April 2023.</a>
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<li><strong>Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021 to June 2022</strong> -
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To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.17.23298700v1" target="_blank">Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021 to June 2022</a>
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<li><strong>Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub</strong> -
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Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023–April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023–April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023–April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November–January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000–4,270,000) hospitalizations and 209,000 (90% PI: 139,000–461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000–355,000) fewer hospitalizations and 33,000 (95% CI: 12,000–54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI: 29,000–69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297581v2" target="_blank">Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub</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>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <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>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <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>Safety and Immunogenicity of BNT162b2 Coadministered With SIIV in Adults 18 Through 64 Years of Age</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2; Other: Placebo; Biological: Seasonal Inactivated Influenza Vaccine <br/><b>Sponsors</b>: Pfizer <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ <br/><b>Sponsors</b>: Abbott Rapid Dx <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 Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial</strong> - <b>Conditions</b>: Long COVID-19 Syndrome; Chronic Fatigue Syndrome <br/><b>Interventions</b>: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet <br/><b>Sponsors</b>: Cardresearch <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>Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes</strong> - <b>Conditions</b>: Normobaric Hypoxia; Hypoventilation; Normoxia <br/><b>Interventions</b>: Other: Repeated sprint <br/><b>Sponsors</b>: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. <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>Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities</strong> - <b>Conditions</b>: COVID-19; Vaccine <br/><b>Interventions</b>: Behavioral: REDES; Behavioral: Control <br/><b>Sponsors</b>: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray</strong> - <b>Conditions</b>: SARS-CoV-2; Prevention <br/><b>Interventions</b>: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient <br/><b>Sponsors</b>: The Second Affiliated Hospital of Chongqing Medical University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening</strong> - <b>Conditions</b>: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance <br/><b>Interventions</b>: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot <br/><b>Sponsors</b>: Tulane University; National Heart, Lung, and Blood Institute (NHLBI) <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>Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation without maintenance program <br/><b>Sponsors</b>: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design) <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel <br/><b>Sponsors</b>: Abbott Rapid Dx <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>Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention</strong> - <b>Conditions</b>: Child Mental Health <br/><b>Interventions</b>: Behavioral: Child Mental Health Literacy Program <br/><b>Sponsors</b>: Universidad de Valparaiso <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>Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression</strong> - <b>Conditions</b>: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19 <br/><b>Interventions</b>: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging <br/><b>Sponsors</b>: City University of New York, School of Public Health; University of North Carolina, Chapel Hill <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>SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia</strong> - CONCLUSION: The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.</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 exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects</strong> - CONCLUSIONS: The comparison between the salivary CPC concentration and EC50/CC50 values from in vitro antiviral experiments suggests that CPC buccal tablets may inhibit SARS-CoV-2 activity, and the inhibition may last for approximately 30 min without cytotoxicity.</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>Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions</strong> - Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds. Upon screening, we identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus…</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>Licochalcone A regulates viral IRES activity to inhibit enterovirus replication</strong> - Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses…</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>AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity</strong> - An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5…</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>SARS-CoV-2 ORF6 protein targets TRIM25 for proteasomal degradation to diminish K63-linked RIG-I ubiquitination and type-I interferon induction</strong> - Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host’s innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction 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>Highly potent dual-targeting angiotensin-converting enzyme 2 (ACE2) and Neuropilin-1 (NRP1) peptides: A promising broad-spectrum therapeutic strategy against SARS-CoV-2 infection</strong> - The efficacy of approved vaccines has been diminishing due to the increasing advent of SARS-CoV-2 variants with diverse mutations that favor sneak entry. Nonetheless, these variants recognize the conservative host receptors angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) for entry, rendering the dual blockade of ACE2 and NRP1 an advantageous pan-inhibition strategy. Here, we identified a highly potent dual-targeting peptide AP-1 using structure-based virtual screening protocol….</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>Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors</strong> - The COVID-19 pandemic, caused by SARS-CoV-2, has had a huge impact on global health. To respond to rapidly mutating viruses and to prepare for the next pandemic, there is an urgent need to develop small molecule therapies that target critical stages of the SARS-CoV-2 life cycle. Inhibiting the entry process of the virus can effectively control viral infection and play a role in prevention and treatment. Host factors involved in this process, such as ACE2, TMPRSS2, ADAM17, furin, PIKfyve, TPC2,…</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>Lianhua Qingwen protects LPS-induced acute lung injury by promoting M2 macrophage infiltration</strong> - CONCLUSIONS: Taken together, our data demonstrate that LHQW reduces the inflammatory response and ameliorates acute lung injury by promoting anti-inflammatory polarization of macrophages.</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>Chrysin 7-O-β-D-glucuronide, a dual inhibitor of SARS-CoV-2 3CL<sup>pro</sup> and PL<sup>pro</sup>, for the prevention and treatment of COVID-19</strong> - The evolution of SARS-CoV-2 virus has resulted in the global pandemic COVID-19. Given the advent of subvariants, it is urgent to develop novel drugs. This work aims to discover SARS-CoV-2 inhibitors from Scutellaria baicalensis Georgi targeting the proteases 3CL^(pro) and PL^(pro). After screening 25 flavonoids, we revealed that chrysin 7-O-β-D-glucuronide could potently inhibit SARS-CoV-2 on Vero E6 cells, with EC(50) of 8.72 μM. Surface plasmon resonance, site-directed mutagenesis 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>SARS-CoV-2 Variant-Specific Differences in Inhibiting the Effects of the PKR-Activated Integrated Stress Response</strong> - The integrated stress response (ISR) is a eukaryotic cell pathway that triggers translational arrest and the formation of stress granules (SGs) in response to various stress signals, including those caused by viral infections. The SARS-CoV-2 nucleocapsid protein has been shown to disrupt SGs, but SARS-CoV-2 interactions with other components of the pathway remains poorly characterized. Here, we show that SARS-CoV-2 infection triggers the ISR through activation of the eIF2α-kinase PKR while…</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>Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract</strong> - Inflammatory airway diseases like cystic fibrosis, asthma and COVID-19 are characterized by high levels of pulmonary cytokines. Two well-established antiparasitic drugs, niclosamide and ivermectin, are intensively discussed for the treatment of viral inflammatory airway infections. Here, we examined these repurposed drugs with respect to their anti-inflammatory effects in airways in vivo and in vitro. Niclosamide reduced mucus content, eosinophilic infiltration and cell death in asthmatic mouse…</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 synthetically tractable MERS-CoV main protease inhibitors using structure-based virtual screening and molecular dynamics potential of mean force (PMF) calculations</strong> - The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially lethal infection that presents a substantial threat to health, especially in Middle East nations. Given that no FDA-approved specific therapy for MERS infection exists, designing and discovering a potent antiviral therapy for MERS-CoV is crucial. One pivotal strategy for inhibiting MERS replication is to focus on the viral main protease (M^(pro)). In this study, we identify potential novel M^(pro) inhibitors employing…</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>CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation</strong> - The G protein-coupled receptor ADGRE5 (CD97) binds to various metabolites that play crucial regulatory roles in metabolism. However, its function in the antiviral innate immune response remains to be determined. In this study, we report that CD97 inhibits virus-induced type-I interferon (IFN-I) release and enhances RNA virus replication in cells and mice. CD97 was identified as a new negative regulator of the innate immune receptor RIG-I, and RIG-1 degradation led to the suppression of the IFN-I…</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>Inhibition of SARS-CoV-2 3CL protease by the anti-viral chimeric protein RetroMAD1</strong> - COVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CL^(pro) and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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