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188 lines
52 KiB
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<title>15 May, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Ability to detect fake news predicts sub-national variation in COVID-19 vaccine uptake across the UK</strong> -
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Susceptibility to believing false or misleading information is associated with a range of adverse outcomes. However, it is notoriously difficult to study the link between susceptibility to misinformation and consequential real-world behaviors such as vaccine uptake. In this preregistered study, we devise a large-scale socio-spatial model that combines the rigor of a psychometrically validated test of misinformation susceptibility administered to a nationally representative sample of 16,477 individuals with COVID-19 vaccine uptake data of 129 sub-national regions published by the United Kingdom (UK) government, to show that the general ability to detect misinformation strongly and positively predicts regional vaccine uptake in the UK. We put this practically significant correlational effect size into perspective by noting how psychological interventions that reduce individuals9 misinformation susceptibility could be associated with additional vaccine uptake.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289764v1" target="_blank">Ability to detect fake news predicts sub-national variation in COVID-19 vaccine uptake across the UK</a>
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</div></li>
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<li><strong>Effectiveness of drugs for COVID-19 inpatients in Japanese medical claim data as average treatment effects with inverse probability weighted regression adjustment</strong> -
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Background: Earlier studies and clinical trials have indicated that drugs such as antiviral drugs, antibody cocktails, and steroids and anti-inflammatory drugs are expected to prevent severe coronavirus disease 2019 (COVID-19) outcomes and death. Object: We used observational data for Japan to assess the effectiveness of these drugs for treating COVID-19. Method: We applied an average treatment effect model with inverse probability weighted regression adjustment, which can treat the choice of administered drug as a random assignment to inpatients, to the Medical Information Analysis Databank operated by National Hospital Organization in Japan. The outcome was defined as mortality. Subjects were all inpatients, inpatients with oxygen administration, and inpatients using respiratory ventilators, classified by three age classes: all ages, 65 years old or older, and younger than 65 years old. Information about physical characteristics, underlying disease, administered drug, the proportion of mutated strains, and vaccine coverage were used as explanatory variables for logistic regression. Result: Estimated results indicated that only an antibody cocktail (sotrovimab, casirivimab and imdevimab) raised the probability of saving life consistently, even though these drugs were administered in few cases. By contrast, other drugs might reduce the probability of saving life. Discussion: Results indicate that an antiviral drug (remdesivir), a steroid (dexamethasone), and an anti-inflammatory drug (baricitinib and tocilizumab) might not contribute to the saving of life, even in the pseudo-situation of random assignment.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289913v1" target="_blank">Effectiveness of drugs for COVID-19 inpatients in Japanese medical claim data as average treatment effects with inverse probability weighted regression adjustment</a>
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</div></li>
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<li><strong>Insight into risk associated phenotypes behind COVID-19 from phenotype genome-wide association studies</strong> -
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Long COVID presents a complex and multi-systemic disease that poses a significant global public health challenge. Symptoms can vary widely, ranging from asymptomatic to severe, making the condition challenging to diagnose and manage effectively. Furthermore, identifying appropriate phenotypes in genome-wide association studies of COVID-19 remains unresolved. This study aimed to address these challenges by analyzing 220 deep-phenotype genome-wide association data sets (159 diseases, 38 biomarkers and 23 medication usage) from BioBank Japan (BBJ) (n=179,000), UK Biobank and FinnGen (n=628,000) to investigate pleiotropic effects of known COVID-19 risk associated single nucleotide variants. Our findings reveal 32 different phenotypes that share the common genetic risk factors with COVID-19 (p < 7.6×10−11), including two diseases (myocardial infarction and type 2 diabetes), 26 biomarkers with seven categories (blood cell, metabolic, liver-related, kidney-related, protein, inflammatory and anthropometric), and four medications (antithrombotic agents, HMG CoA reductase inhibitors, thyroid preparations and anilides). As long COVID continues to coexist with humans, our results highlight the need for targeted screening to support specific vulnerable populations to improve disease prevention and healthcare delivery.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.09.23289706v1" target="_blank">Insight into risk associated phenotypes behind COVID-19 from phenotype genome-wide association studies</a>
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<li><strong>Projecting the potential impact of an Omicron XBB.1.5 wave in Shanghai, China</strong> -
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China experienced a major nationwide wave of SARS-CoV-2 infections in December 2022, immediately after lifting strict interventions, despite the majority of the population having already received inactivated COVID-19 vaccines. Due to the rapid waning of protection and the emergence of Omicron XBB.1.5, the risk of another COVID-19 wave remains high. It is still unclear whether the health care system will be able to manage the demand during this potential XBB.1.5 wave and if the number of associated deaths can be reduced to a level comparable to that of seasonal influenza. Thus, we developed a mathematical model of XBB.1.5 transmission using Shanghai as a case study. We found that a potential XBB.1.5 wave is less likely to overwhelm the health care system and would result in a death toll comparable to that of seasonal influenza, albeit still larger, especially among elderly individuals. Our analyses show that a combination of vaccines and antiviral drugs can effectively mitigate an XBB.1.5 epidemic, with a projected number of deaths of 2.08 per 10,000 individuals. This figure corresponds to a 70-80% decrease compared to the previous Omicron wave and is comparable to the level of seasonal influenza. The peak prevalence of hospital admissions and ICU admissions are projected at 28.89 and 2.28 per 10,000 individuals, respectively, suggesting the need for a moderate increase in the capacity of the health care system. Our findings emphasize the importance of improving vaccination coverage, particularly among the older population, and the use of antiviral treatments.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289761v1" target="_blank">Projecting the potential impact of an Omicron XBB.1.5 wave in Shanghai, China</a>
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<li><strong>“Now you see me”: detecting asymptomatic infectious individuals in the population</strong> -
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Quarantine is an effective countermeasure to stop or slow the spread of an emerging infectious disease when no other preventive measures are available to protect the population. However, when the disease results in a proportion of asymptomatic infections, the spread dynamics are affected, and quarantine efficiency is impaired. Here, we introduce an extended susceptible-infected-recovered (SIR) model to study the effects of asymptomatic individuals at the onset of an emerging infectious disease when no vaccination is yet available and/or when a vaccine is available but only a subset of the population can be vaccinated due to limited supply or the unwillingness of susceptible individuals to receive an injection. These aspects have been indirectly incorporated into the model using a time-dependent vaccination rate. With this model, we confirm that, in the case of a missing vaccine, quarantine is effective in stopping the spread of an infectious disease, but its efficiency can be substantially reduced in the presence of individuals developing asymptomatic infection. Moreover, we show that vaccination is effective only if available early during the epidemic and if the vaccination rate is sufficiently high. By applying this model to Zurich and all of Switzerland in case of the COVID-19 pandemic, we found that the following two strategies have similar outcomes: either placing infectious individuals into quarantine when no vaccine is available or dropping quarantine measures but administering a vaccine at a daily rate of 1%, starting no later than 105 days after the onset of the epidemic. Beyond this time period, a vaccination campaign will have no effect in stopping the spread of the disease if 25% of the susceptible population is asymptomatic. We also found that the option of deploying a vaccination campaign was more effective for all of Switzerland than for only the city of Zurich.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.08.23289685v1" target="_blank">“Now you see me”: detecting asymptomatic infectious individuals in the population</a>
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<li><strong>Immune response to SARS CoV2 infection by TLR3, TLR4 and TLR7 expression</strong> -
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Toll like receptors (TLRs) may be involved both in the initial failure of viral clearance and in the subsequent development of fatal clinical manifestations of severe COVID19, essentially ARDS (acute respiratory distress syndrome) with fatal respiratory failure. While TLR3 recognizes viral double stranded RNA (dsRNA), TLR7 recognizes viral single stranded RNA and is therefore likely to be involved in SARS CoV2 clearance. On the other hand, TLR4, at the surface of cells, toll like receptor 4 (TLR4) in the induction of damaging inflammatory responses during acute viral infections as it functions as a sensor for damage associated molecular patterns (DAMPs). These include a wide variety of molecules released from injured or dying tissues as well as molecules actively released in response to cellular stress from intact cells. We present the gene expression of TLR 3, 4, and 7 in nasopharyngeal total RNA samples from 150 individuals positive for SARS Cov2 (DET) by molecular techniques of isothermal amplification (Neokit SA) and 152 SARS CoV2 non detectable (ND) ambulatory and hospitalizedpatients with a non-defined respiratory disease, and we compared with the symptomatology developed by all those patients. We analyzed 4 cohorts: 1 SARS Cov2 genome detected patients with severe to high symptomatology (n=107);2 SARS Cov2 genome detected patients low to mild symptomatology (n=43); 3 SARS Cov2 genome non detected patients with severe to high symptomatology (n=109); and 4 SARS Cov2 genome non detected patients low to mild symptomatology (n=41). Our results showed no significant differences of expression for TLR3, TLR4 and TLR7 between SARS Cov2 detected and non-detected total cohort of patients (Non Paired T test p Value>0.1). When compared severity of symptoms (presence of symptoms from the COVID19 12 diagnosis symptoms) and gene expression by a Spearman9s Correlation Coefficient there was significant positive correlation between severe symptomatology, and the number of symptoms and death for TLR4 and TLR7 for both infected and non COVID19 infected patients. When the cohort was construct with low/middle and severe symptoms, the Correlation Coefficient showed that expression of TLR4 and TLR7 was significantly amplified in those ND patients with severe symptomatology (p Value= 0.00311) as well as for TLR3 in ND low to mild symptoms cohort of patients. We also showed and discussed the results obtained of these genes expression and the sex and age of patients. In summary, our data suggest that although our innate immune system with TLRs contributes to the elimination of viruses, it can also be associated with harm to the host due to persistent inflammation and tissue destruction. We confirmed that principally TLR4 and TLR7 could be involved not only in the pathogenesis of COVID19 but also in other respiratory diseases with same symptomatology. We suggest that treatments focus on TLR4 and TLR7 expression in inflammatory respiratory diseases could be a start point against severe symptoms development.
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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/10.1101/2023.05.12.23288889v1" target="_blank">Immune response to SARS CoV2 infection by TLR3, TLR4 and TLR7 expression</a>
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<li><strong>From Collection to Analysis: A Comparison of GISAID and the Covid-19 Data Portal</strong> -
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We analyse ongoing efforts to share genomic data about SARS-COV-2 through a comparison of the characteristics of the Global Initiative on Sharing All Influenza Data and the Covid-19 Data Portal with respect to the representativeness and governance of the research data therein. We focus on data and metadata on genetic sequences posted on the two infrastructures in the period between January 2020 and January 2023, thus capturing a period of acute response to the COVID-19 pandemic. Through a variety of data science methods, we compare the extent to which the two portals succeeded in attracting data submissions from different countries around the globe and look at the ways in which submission rates varied over time. We go on to analyse the structure and underlying architecture of the infrastructures, reviewing how they organise data access and use, the types of metadata and version tracking they provide. Finally, we explore usage patterns of each infrastructure based on publications that mention the data to understand how data reuse can facilitate forms of diversity between institutions, cities, countries, and funding groups. Our findings reveal disparities in representation between the two infrastructures and differing practices in data governance and architecture. We conclude that both infrastructures offer useful lessons, with GISAID demonstrating the importance of expanding data submissions and representation, while the COVID-19 data portal offers insights into how to enhance data usability.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.13.540634v1" target="_blank">From Collection to Analysis: A Comparison of GISAID and the Covid-19 Data Portal</a>
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<li><strong>Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.</strong> -
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T-cell receptor (TCR) recognition of foreign peptides presented by the major histocompatibility complex (MHC) initiates the adaptive immune response against pathogens. A large number of TCR sequences specific to different antigens are known to date, however, the structural data describing the conformation and contacting residues for TCR:antigen:MHC complexes is relatively limited. In the present study we aim to extend and analyze the set of available structures by performing highly accurate template-based modeling of TCR:antigen:MHC complexes using TCR sequences with known specificity. Using the set of 29 complex templates (including a template with SARS-CoV-2 antigen) and 732 specificity records, we built a database of 1585 model structures carrying substitutions in either TCR or TCR{beta} chains with some models representing the result of different mutation pathways for the same final structure. This database allowed us to analyze features of amino acid contacts in TCR:antigen interfaces that govern antigen recognition preferences and interpret these interactions in terms of physicochemical properties of interacting residues. Our results provide a methodology for creating high-quality TCR:antigen:MHC models for antigens of interest that can be utilized to predict TCR specificity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.29.533758v3" target="_blank">Large-scale template-based structural modeling of T-cell receptors with known antigen specificity reveals complementarity features.</a>
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<li><strong>Moving online: Experiences and potential benefits of digital dance for older adults and individuals with Parkinson’s disease</strong> -
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Background. Dance is found to provide a range of beneficial effects for older adults including individuals with age-related neurological conditions such as Parkinson’s disease (PD). The COVID-19 pandemic accelerated the development of at-home dance programs delivered digitally through live and pre-recorded media, but little is known about how participants may engage with and benefit from these resources. Objective. This study explored experiences and potential benefits of digital dance resources among healthy older adults and individuals with neurological conditions. Methods. An online survey consisting of fixed-choice and open questions was designed in collaboration with dance program providers and distributed between June and November 2020. Results. High levels of engagement in at-home dance programs were found among healthy older adults (N = 149) and individuals with PD (N = 178). Sensorimotor outcomes (e.g., balance, posture) were more widely reported among individuals with PD, while older adults reported similar numbers of sensorimotor and non-motor (e.g., mood, confidence) outcomes. The use of strategies (imagery and vocalising) during participation were differentially associated with outcomes in older adults and PD groups. At-home dance was found to offer convenience and flexibility, but participants missed the interaction, support and routine of in-person classes. The majority expressed a preference to continue with both digital and in-person participation in the future. Qualitative analysis of participants’ comments reinforced the quantitative findings, while also revealing that online dance could help to maintain connection and well-being, and identifying further considerations for improving accessibility and facilitating digital engagement. Conclusions. At-home dance programs appear to be accessible and engaging for older adults, including individuals with PD, although potential barriers to participation need to be addressed. Digital resources for home-based activities will be increasingly important to enable cost-effective, large-scale provision of therapeutic activities for older adults.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/954f2/" target="_blank">Moving online: Experiences and potential benefits of digital dance for older adults and individuals with Parkinson’s disease</a>
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<li><strong>Dance at home for people with Parkinson’s during COVID-19 and beyond: Participation, perceptions and prospects</strong> -
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Emerging evidence shows that dance can provide both physical and non-physical benefits for people living with Parkinson’s disease (PD). The suspension of in-person dance classes during the COVID-19 pandemic necessitated a transition to remote provision via live and recorded digital media. An online survey explored accessibility of and engagement with these home-based dance programs, as well as perceived benefits. The survey was co-developed by researchers and dance program providers, with input from people with PD and physiotherapists. Responses were collected from 276 individuals, including 178 current users of home-based programs, the majority of whom were participating at least once per week. Among respondents not currently using digital resources, lack of knowledge and motivation were the primary barriers. Most participants (94.9%) reported that home based practice provided some benefits, including physical (e.g., balance, posture) and non-physical (e.g., mood, confidence) improvements. Participants valued the convenience and flexibility of digital participation, but noted limitations including reductions in social interaction, support from instructors and peers, and routine. There was a strong preference (70.8%) for continuing with home-based practice alongside in-person classes in the future. The results indicate that at-home dance is accessible and usable for people with PD, and that some of the previously-reported benefits of dance may be replicated in this context. While COVID-19 expedited the development of digital programs, these will likely remain a key element of future provision for people with PD. The findings will inform the further development of resources and research into outcomes of home-based dance participation.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/4wep9/" target="_blank">Dance at home for people with Parkinson’s during COVID-19 and beyond: Participation, perceptions and prospects</a>
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<li><strong>Regulation of coronavirus nsp15 cleavage specificity by RNA structure</strong> -
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SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, has had an enduring impact on global public health. However, SARS-CoV-2 is only one of multiple pathogenic human coronaviruses (CoVs) to have emerged since the turn of the century. CoVs encode for several nonstructural proteins (NSPS) that are essential for viral replication and pathogenesis. Among them is nsp15, a uridine-specific viral endonuclease that is important in evading the host immune response and promoting viral replication. Despite the established function of nsp15 as a uridine-specific endonuclease, little is known about other determinants of its cleavage specificity. In this study we investigate the role of RNA secondary structure in SARS-CoV-2 nsp15 endonuclease activity. Using a series of in vitro endonuclease assays, we observed that thermodynamically stable RNA structures were protected from nsp15 cleavage relative to RNAs lacking stable structure. We leveraged the s2m RNA from the SARS 3'UTR as a model for our structural studies as it adopts a well-defined structure with several uridines, two of which are unpaired and thus high probably targets for nsp15 cleavage. We found that SARS-CoV-2 nsp15 specifically cleaves s2m at the unpaired uridine within the GNRNA pentaloop of the RNA. Further investigation revealed that the position of uridine within the pentaloop also impacted nsp15 cleavage efficiency, suggesting that positioning within the pentaloop is necessary for optimal presentation of the scissile uridine and alignment within the nsp15 catalytic pocket. Our findings indicate that RNA secondary structure is an important determinant of nsp15 cleavage and provides insight into the molecular mechanisms of recognition of RNA by nsp15.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.12.540483v1" target="_blank">Regulation of coronavirus nsp15 cleavage specificity by RNA structure</a>
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<li><strong>Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</strong> -
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Reverse genetic systems enable engineering of RNA virus genomes and are instrumental to study RNA virus biology. With the recent outbreak of the COVID-19 pandemic, already established methods were challenged by the large genome of SARS-CoV-2. Herein we present an elaborated strategy for the rapid and straightforward rescue of recombinant plus-stranded RNA-viruses with high sequence fidelity, using the example of SARS-CoV-2. The strategy called CLEVER (CLoning-free and Exchangeable system for Virus Engineering and Rescue) is based on the intracellular recombination of transfected overlapping DNA fragments allowing the direct mutagenesis within the initial PCR-amplification step. Furthermore, by introducing a linker fragment (harboring all heterologous sequences) viral RNA can directly serve as template for manipulation and rescue of recombinant mutant virus, without any cloning-step needed. Overall, this strategy will facilitate recombinant SARS-CoV-2 rescue and accelerate its manipulation. Using our protocol, newly emerging variants can quickly be engineered to further elucidate its biology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.11.540343v1" target="_blank">Rapid cloning-free mutagenesis of new SARS-CoV-2 variants using a novel reverse genetics platform</a>
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<li><strong>Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design</strong> -
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Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH’s REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.27.23289228v2" target="_blank">Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design</a>
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<li><strong>Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</strong> -
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This paper presents the findings from a detailed study investigating UK undergraduate students’ experience of practical science in their post-16 studies during the COVID-19 pandemic. It also examines the perceived confidence and preparedness of the students in relation to areas of practical science skills at the start of their degree courses. The study employed an exploratory sequential mixed methods design, with the findings from focus groups with students at the end of their post-16 studies used to support the development of a comprehensive quantitative survey for incoming undergraduate students. Survey data were collected in September and October 2021 from 275 students commencing Biological Science/Life Science, Chemistry, Physics and Natural Science degrees at two universities in England. The research is significant for its finding that although almost all students had the opportunity to undertake practical work as part of their post-16 studies during the COVID-19 pandemic, there was significant variation in students’ experiences. The data indicate that students’ self-efficacy in relation to practical science was impacted by the closures of post-16 education establishments, ongoing social distancing and the removal of the assessment criteria for students to have ‘routinely and consistently’ undertaken each of the practical assessment requirements. The research presents important considerations which are relevant for educators supporting students’ transition from post-16 to Higher Education.
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🖺 Full Text HTML: <a href="https://edarxiv.org/gx2jh/" target="_blank">Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</a>
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<li><strong>Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study</strong> -
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Objectives To quantify healthcare resource utilisation (HCRU) and costs to the National Health Service (NHS) associated with acute COVID-19 in adults in England. Design Population-based retrospective cohort study, using Clinical Practice Research Datalink (CPRD) Aurum primary care electronic medical records linked when available to Hospital Episode Statistics (HES) secondary care administrative data. Setting Patients registered to primary care practices in England. Population 1,706,368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13,105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1,693,263 within the primary care cohort indexed between August 2020 and January 2022. Main outcome measures Primary and secondary care HCRU and associated costs during the acute phase of COVID-19 (≤4 weeks following positive test), stratified by age group, risk of severe COVID-19 and immunocompromised status. Results Among the hospitalised cohort, average total length of stay, as well as in critical care wards, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75 - 84 (£8,942) and ≥85 years (£8,835) than in those aged <50 years (£7,703). Whilst few (6.0%) patients in critical care required mechanical ventilation, its use was higher in older adults (50 - 74 years: 8.3%; <50 years: 4.3%). HCRU and associated costs were often greater in those at higher risk of severe COVID-19 when compared to the overall cohort, although minimal differences in HCRU were found across the three different high-risk definitions implemented. Among the primary care cohort, GP or nurse consultations were more frequent among older adults and the immunocompromised. Conclusions COVID-19 related hospitalisations in older adults, particularly critical care admissions, were the primary drivers of high resource use of COVID-19 in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289557v2" target="_blank">Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study</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>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Glucocorticoid<br/><b>Sponsor</b>: Huashan Hospital<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>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Arginine Hydrochloride<br/><b>Sponsor</b>: Emory University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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>Long COVID-19 Syndrome Lifestyle Intervention Study</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: Low carbohydrate diet intervention<br/><b>Sponsor</b>: University of Southern California<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>: Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>: Vielight 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>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>: Post COVID-19 Condition, Unspecified; SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir/ritonavir; Drug: Placebo<br/><b>Sponsors</b>: Haukeland University Hospital; University of Bergen<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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<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>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Vitamin-D<br/><b>Sponsor</b>: Sulaimany Polytechnic university<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>: Sars-CoV-2 Infection<br/><b>Interventions</b>: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>: Alvea Holdings, LLC<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>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Dysautonomia<br/><b>Interventions</b>: Procedure: Rehabilitation; Procedure: Standard of Care<br/><b>Sponsors</b>: Evangelismos Hospital; National and Kapodistrian University of Athens; LONG COVID GREECE; 414 Military Hospital of Special Diseases<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>COVID-19 Vaccination Detoxification in LDL-C</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<br/><b>Active, not 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>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>: Long COVID<br/><b>Intervention</b>: Other: Rehabilitation program<br/><b>Sponsors</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome.</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition<br/><b>Sponsors</b>: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión<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 in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation<br/><b>Sponsor</b>: Aligos Therapeutics<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>Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition<br/><b>Interventions</b>: Device: Immunoadsorption; Device: Sham-apheresis<br/><b>Sponsor</b>: University Medical Center Mainz<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aqueous cannabidiol β-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex-vivo SARS-CoV-2-induced cytokine storms</strong> - Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB(1) and CB(2). CBD may be involved in anti-inflammatory processes via CB(1) and CB(2) receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD’s poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with β-cyclodextrin (β-CD) at a…</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>Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial</strong> - CONCLUSIONS: High PASI100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar response by Week 96.</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>Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products</strong> - CONCLUSION: Overall, more recent Ig products (expiration dates: 2023 - 2025) contained significantly higher binding and inhibition activities against SARS-CoV-2 proteins, as compared to earlier, or pre-pandemic products. Normal donor SARS-CoV-2 antibodies are capable of inhibiting ACE2-binding activities and may provide a therapeutic benefit for patients who do not make a robust vaccine response.</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>Small molecule inhibitor CRT0066101 inhibits cytokine storm syndrome in a mouse model of lung injury</strong> - Pneumonia is an acute inflammation of the lungs induced by pathogenic microorganisms, immune damage, physical and chemical factors, and other factors, and the latest outbreak of novel coronavirus pneumonia is also an acute lung injury (ALI) induced by viral infection. However, there are currently no effective treatments for inflammatory cytokine storms in patients with ALI/acute respiratory distress syndrome (ARDS). Protein kinase D (PKD) is a highly active kinase that has been shown to be…</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 the Recognition Part of Dipeptidyl Nitroalkene Compounds on the Inhibition Mechanism of Cysteine Proteases Cruzain and Cathepsin L</strong> - Cysteine proteases (CPs) are an important class of enzymes, many of which are responsible for several human diseases. For instance, cruzain of protozoan parasite Trypanosoma cruzi is responsible for the Chagas disease, while the role of human cathepsin L is associated with some cancers or is a potential target for the treatment of COVID-19. However, despite paramount work carried out during the past years, the compounds that have been proposed so far show limited inhibitory action against these…</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>Comparing online and face-to-face administration of a neuropsychological computerized attention test: Assessment modality does not influence performance</strong> - CONCLUSION: The CVAT can be administered online or face-to-face without learning upon retesting. The data on agreement (online vs. face-to-face, test vs. retest, Americans vs. Brazilians) indicate that VRT is the most reliable variable.</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>Exercise With a Novel Digital Device Increased Serum Anti-influenza Antibody Titers After Influenza Vaccination</strong> - It has been reported that some exercise could enhance the anti-viral antibody titers after vaccination including influenza and coronavirus disease 2019 vaccines. We developed SAT-008, a novel digital device, consists of physical activities and activities related to the autonomic nervous system. We assessed the feasibility of SAT-008 to boost host immunity after an influenza vaccination by a randomized, open-label, and controlled study on adults administered influenza vaccines in the previous…</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>Glycolytic stress deteriorates 229E virulence to improve host defense response</strong> - Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose…</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 Omicron subvariant spike N405 unlikely to rapidly deamidate</strong> - The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVβ3 and α5β1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVβ3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins. Two…</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 anesthetic management on catheter ablation for premature ventricular complexes: insights during the COVID-19 outbreak</strong> - CONCLUSION: Ablation of PVC under LA presented significantly higher AAS rate compared to GA. The procedure under GA might be complicated by PVC inhibition (after catheter insertion/during mapping) and PVC disinhibition post-extubation.</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>Viricidal Activity of Thermoplastic Polyurethane Materials with Silver Nanoparticles</strong> - The use of diverse Ag-based nanoparticulated forms has shown promising results in controlling viral propagation. In this study, a commercial nanomaterial consisting of ceramic-coated silver nanoparticles (AgNPs) was incorporated into thermoplastic polyurethane (TPU) plates using an industrial protocol, and the surface composition, ion-release dynamics and viricidal properties were studied. The surface characterization by FESEM-EDX revealed that the molar composition of the ceramic material was…</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>Computational and Enzymatic Studies of Sartans in SARS-CoV-2 Spike RBD-ACE2 Binding: The Role of Tetrazole and Perspectives as Antihypertensive and COVID-19 Therapeutics</strong> - This study is an extension of current research into a novel class of synthetic antihypertensive drugs referred to as “bisartans”, which are bis-alkylated imidazole derivatives bearing two symmetric anionic biphenyltetrazoles. Research to date indicates that bisartans are superior to commercially available hypertension drugs, since the former undergo stronger docking to angiotensin-converting enzyme 2 (ACE2). ACE2 is the key receptor involved in SARS-CoV-2 entry, thus initiating COVID-19…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Vitro and In Vivo Therapeutic Potential of 6,6’-Dihydroxythiobinupharidine (DTBN) from <em>Nuphar lutea</em> on Cells and K18-<em>hACE2</em> Mice Infected with SARS-CoV-2</strong> - We have previously published research on the anti-viral properties of an alkaloid mixture extracted from Nuphar lutea, the major components of the partially purified mixture found by NMR analysis. These are mostly dimeric sesquiterpene thioalkaloids called thiobinupharidines and thiobinuphlutidines against the negative strand RNA measles virus (MV). We have previously reported that this extract inhibits the MV as well as its ability to downregulate several MV proteins in persistently MV-infected…</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 Binding and Neutralization Properties of Peptides Derived from N-Terminus of Human ACE2</strong> - The binding properties of synthetic and recombinant peptides derived from N-terminal part of ACE2, the main receptor for SARS-CoV-2, were evaluated. Additionally, the ability of these peptides to prevent virus entry in vitro was addressed using both pseudovirus particles decorated with the S protein, as well as through infection of Vero cells with live SARS-CoV-2 virus. Surprisingly, in spite of effective binding to S protein, all linear peptides of various lengths failed to neutralize the viral…</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>AI-Driven De Novo Design and Molecular Modeling for Discovery of Small-Molecule Compounds as Potential Drug Candidates Targeting SARS-CoV-2 Main Protease</strong> - Over the past three years, significant progress has been made in the development of novel promising drug candidates against COVID-19. However, SARS-CoV-2 mutations resulting in the emergence of new viral strains that can be resistant to the drugs used currently in the clinic necessitate the development of novel potent and broad therapeutic agents targeting different vulnerable spots of the viral proteins. In this study, two deep learning generative models were developed and used in combination…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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