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<title>13 October, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Antecedents and consequences of telework during the COVID-19 pandemic: A natural experiment in Japan</strong> -
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With the outbreak of the COVID-19 pandemic, companies around the world have been introducing telework. However, Japan stands out for its low rate of telework implementation, and it seems there may be cultural factors that have hindered telework use in Japan during the pandemic. In this study, we aim to clarify the antecedents and consequences of telework in Japan, making use of the natural experiment created by the COVID-19 pandemic to examine the following two questions: (1) What socio-psychological factors in workplaces were important for introducing telework in the first place? and (2) How did the implementation of telework subsequently influence socio-psychological factors in these workplaces? Three waves of an online survey were conducted among the same employees working for Japanese companies before and during the pandemic. We found that telework in Japan was more readily introduced in organizations characterized by meritocracy. We also found that the introduction of telework in Japanese companies did not have any negative effects but instead increased levels of independence, organizational commitment and perceived hierarchy mutability. We discuss how telework interacts with culture at both societal and organizational levels.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/rxn4u/" target="_blank">Antecedents and consequences of telework during the COVID-19 pandemic: A natural experiment in Japan</a>
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</div></li>
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<li><strong>An ethnographic analysis virtual peer review panels</strong> -
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In the early months of the COVID-19 pandemic, many research funding organisations were faced with the choice of suspending or else continuing their decision-making processes, including peer review panels, virtually. Although seen part of a longer drive to make peer review more cost and time efficient, it is still not fully understood how peer review panels, more commonly operating in a face-to-face (F2F) setting, function in a virtual environment. Using a series of observation of 4 peer review panels conducted virtually during 2020 at the Research Council of Norway (Forskningsrådet), this research explores the move from face-to-face to virtual panel deliberation and how panellists behaved in this new environment. Despite the virtual panels arguably conducted more efficiently, saving time and money by panellists participating from their home-settings, a number of behaviours around the role of the Panel Chair, and the collective presence during the decision-making process, suggest alternations as to how panels reached and confirmed consensus in the virtual environment. Deliberate mechanisms to confirm consensus was required during panels thus suggesting a more onerous workload mid, and post-panel work for Panel Chairs and managers. In addition, whereas a majority of panel members had experience working together in the past, the introduction of new panel members was restricted in an online environment, leading to instances where new panel members would lead discussions, and present conflicting information during evaluations. These preliminary results indicate that more information is needed about how the virtual environment influences peer review processes before a more permanent change is adopted by funding agencies.
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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://osf.io/preprints/socarxiv/fbkr6/" target="_blank">An ethnographic analysis virtual peer review panels</a>
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</div></li>
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<li><strong>Virtual Simulated Placements in Healthcare Education: A scoping review</strong> -
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Abstract Introduction A virtual simulated placement (VSP) is a computer-generated version of a practice placement. COVID-19 drove increased adoption of virtual technology in clinical education. Accordingly, the number of VSP publications increased from 2020. This review aims to determine the scope of this literature to inform future research questions. Objective Assess the range and types of evidence related to VSPs across the healthcare professions. Inclusion criteria Studies that focussed on healthcare students participating in VSPs. Hybrid, augmented reality (AR) and mixed reality (MR) placements were excluded. Methods Fourteen databases were searched, limited to English, and dated from 1st January 2020. Supplementary searches were employed, and an updated search was conducted on 9th July 2023. Themes were synthesised using the PAGER framework to highlight patterns, advances, gaps, evidence for practice and research recommendations. Results Twenty-eight papers were reviewed. All VSPs were designed in response to pandemic restrictions. Students were primarily from medicine and nursing. Few publications were from developing nations. There was limited stakeholder involvement in the VSP designs and a lack of robust research designs, consistent outcome measures, conceptual underpinnings, and immersive technologies. Despite this, promising trends for student experience, knowledge, communication, and critical thinking skills using VSPs have emerged. Conclusion. This review maps the VSP evidence across medicine, nursing, midwifery and allied health. Before a systematic review is feasible across healthcare, allied health and midwifery research require greater representation. Based on the highlighted gaps, other areas for future research are suggested.
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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/10.1101/2023.10.12.23296932v1" target="_blank">Virtual Simulated Placements in Healthcare Education: A scoping review</a>
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<li><strong>A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes</strong> -
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Background: The Global Burden of Disease study has provided key evidence to inform clinicians, researchers, and policy makers across common diseases, but no similar effort with single study design exists for hundreds of rare diseases. Consequently, many rare conditions lack population-level evidence including prevalence and clinical vulnerability. This has led to the absence of evidence-based care for rare diseases, prominently in the COVID-19 pandemic. Method: This study used electronic health records (EHRs) of more than 58 million people in England, linking nine National Health Service datasets spanning healthcare settings for people alive on Jan 23, 2020. Starting with all rare diseases listed in Orphanet, we quality assured and filtered down to analyse 331 conditions with ICD-10 or SNOMED-CT mappings clinically validated in our dataset. We report 1) population prevalence, clinical and demographic details of rare diseases, and 2) investigate differences in mortality with SARs-CoV-2. Findings: Among 58,162,316 individuals, we identified 894,396 with at least one rare disease. Prevalence data in Orphanet originates from various sources with varying degrees of precision. Here we present reproducible age and gender-adjusted estimates for all 331 rare diseases, including first estimates for 186 (56.2%) without any reported prevalence estimate in Orphanet. We identified 49 rare diseases significantly more frequent in females and 62 in males. Similarly we identified 47 rare diseases more frequent in Asian as compared to White ethnicity and 22 with higher Black to white ratios as compared to similar ratios in population controls. 37 rare diseases were overrepresented in the white population as compared to both Black and Asian ethnicities. In total, 7,965 of 894,396 (0.9%) of rare-disease patients died from COVID-19, as compared to 141,287 of 58,162,316 (0.2%) in the full study population. Eight rare diseases had significantly increased risks for COVID-19-related mortality in fully vaccinated individuals, with bullous pemphigoid (8.07[3.01-21.62]) being worst affected. Interpretation: Our study highlights that National-scale EHRs provide a unique resource to estimate detailed prevalence, clinical and demographic data for rare diseases. Using COVID-19-related mortality analysis, we showed the power of large-scale EHRs in providing insights to inform public health decision-making for these often neglected patient populations.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.12.23296948v1" target="_blank">A nationwide study of 331 rare diseases among 58 million individuals: prevalence, demographics, and COVID-19 outcomes</a>
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<li><strong>Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: Transmission dynamics and epidemiological insights</strong> -
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Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 VOCs, including the Alpha, Delta, and Omicron variants. Materials and Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants across Europe over a period of more than two years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility (∆β) between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants. Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated ∆β between variants, revealing that: (i) ∆β increased progressively from the Alpha to the Omicron variant; (ii) ∆β showed a high degree of variability within Omicron variants; (iii) a higher ∆β was associated with a later emergence of the variant within a country; (iv) a higher degree of immunization of the population against previous variants was associated with a higher ∆β for the Delta variant; (v) larger countries exhibited smaller ∆β, suggesting regionally diverse outbreaks within the same country; and finally (vi) the model reliably captures the dynamics of competing variants, even in complex scenarios. Conclusions: The use of mathematical models allows for the precise and reliable estimation of daily cases of each variant. By quantifying ∆β, we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. On the other hand, we have shown that the country-level increases in transmissibility can always be influenced by the geographical characteristics of the country and the timing of the emergence of the variant.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.12.23296888v1" target="_blank">Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: Transmission dynamics and epidemiological insights</a>
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<li><strong>Evolution of SARS-CoV-2 in the RhineNeckar/Heidelberg Region 01/2021 07/2023</strong> -
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At the beginning of 2021 the monitoring of the circulating variants of SARS-CoV-2 was established in Germany in accordance with the Corona Surveillance Act (discontinued after July 2023) to allow a better containment of the pandemic, because certain amino acid exchanges (especially) in the spike protein lead to higher transmission as well as a reduced vaccination efficacy. Therefore, our group performed whole genome sequencing applying the ARTIC protocol (currently V4) on Illumina9s NextSeq 500 platform (and starting in May 2023 on the MiSeq DX platform) for SARS-CoV-2 positive specimen from patients of the Heidelberg University Hospital (and associated hospitals) as well as the Public health office in Rhine-Neckar/Heidelberg region. Our group sequenced a total of 26,795 SARS-CoV-2-positive samples between January 2021 and July 2023 - valid sequences, according to the requirements for sequence upload to the German electronic sequencing data hub (DESH) operated by the Robert Koch Institute (RKI), could be determined for 24,852 samples, while the lineage/clade could be identified for 25,912 samples. While the year 2021 was very dynamic and changing regarding the circulating variants in the Rhine-Neckar/Heidelberg region with the initial non-variant of concerns, followed by A.27.RN and the rise of B.1.1.7 in winter/spring and its displacement by B.1.617.2 in spring/summer, which remained almost exclusive until the beginning of December and the first B.1.1.529 incidences, which rose to a proportion of 40 percent by the end of 2021 (and superseded B.1.617.2 by January 2022 with a proportion of over 90 percent). The years 2022 and 2023 were then dominated by B.1.1.529 and its numerous sublineages, especially BA.5 and BA.2, and more recently by the rise of recombinant variants, such as XBB.1.5. By the end of July 2023 (and since calendar week 20) the proportion of the recombinant variants amounted to 100 percent of all circulating variants in the Rhine-Neckar/Heidelberg region.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.12.23296928v1" target="_blank">Evolution of SARS-CoV-2 in the RhineNeckar/Heidelberg Region 01/2021 07/2023</a>
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<li><strong>Sarbecovirus disease susceptibility is conserved across viral and host models</strong> -
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Coronaviruses have caused three severe epidemics since the start of the 21st century: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV- and SARS-CoV-2-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one, HrS45, that is present in both groups. Three of these QTL, including HrS45, were also associated with HKU3-CoV MA outcome. HrS45 overlaps with a QTL previously reported by our lab that is associated with SARS-CoV outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across the Sarbecovirus subgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.11.561544v1" target="_blank">Sarbecovirus disease susceptibility is conserved across viral and host models</a>
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<li><strong>Sex-Specific Development of ssRNA Virus Receptor Gene Expression in the Human Brain</strong> -
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Viral infection severity often varies with host factors such as age and sex. The pathogenesis of infections caused by a broad range of viruses, from neurotropic viruses like Rabies and Zika to respiratory viruses such as influenza and SARS-CoV-2, differ between the sexes and across the lifespan. Typically, older males are more susceptible to severe acute outcomes, while females are more vulnerable to the post-acute sequelae of infections. All of these complications can include neuroinflammation, stroke, cognitive dysfunction, and delirium. While these symptoms can be secondary to infection, recent studies suggest that even peripheral infections can lead to neuropathological changes in the brain. However, few studies have characterized the expression of viral receptors in the human brain or examined age- or sex-related differences in such expression. In this study, we used a publicly accessible transcriptomic database to assess the impact of age and sex on the expression of 67 viral host factor genes, associated with ten virus families. Analyzing data from 15 brain areas (n=33, F=14, M=19, age:4 mo-80 yrs), we determined the lifespan trajectory for each gene in each area via LOESS regressions. We used unsupervised hierarchical clustering to determine if a brain-wide pattern or virus family pattern can be detected. Using Dense-tSNE, a dimension-reduction and visualization technique, we discovered four distinct developmental trajectories, clustering the areas into two mixed-sex subcortical clusters and one each of male and female cortical clusters. Applying Differential Expression Sliding Window Analysis (DeSWAN), we identified the genes driving these age- and sex-related differences. Many sex differences were noted in childhood, potentially impacting the brain's susceptibility to viral infections and underscoring a broader dimorphic organization of male and female brains. These insights contribute to our understanding of sex-specific responses to viral infections, offering the potential for more personalized treatment strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.11.561925v1" target="_blank">Sex-Specific Development of ssRNA Virus Receptor Gene Expression in the Human Brain</a>
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<li><strong>Modelling the impact of population mobility, post-infection immunity and vaccination on SARS-CoV-2 transmission in the Dominican Republic</strong> -
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COVID-19 epidemic dynamics are driven by a complex interplay of factors including population behaviour, government interventions, new variants, vaccination campaigns and immunity from prior infections. We aimed to quantify the epidemic drivers of SARS-CoV-2 dynamics in the Dominican Republic, an upper-middle income country of 10.8 million people, and assess the impact of the vaccination campaign implemented in February 2021 in saving lives and averting hospitalisations. We used an age-structured, multi-variant transmission dynamic model to characterise epidemic drivers in the Dominican Republic and explore counterfactual scenarios around vaccination coverage and population mobility. We fit the model to reported deaths, hospital bed occupancy, ICU bed occupancy and seroprevalence data until December 2021 and simulated epidemic trajectories under different counterfactual vaccination scenarios. We estimate that vaccination averted 5040 hospital admissions (95% CrI: 4750 - 5350), 1500 ICU admissions (95% CrI: 1420 - 1590) and 544 deaths (95% CrI: 488 - 606) in the first 6 months of the campaign. We also found that early vaccination with Sinovac-CoronaVac was preferable to delayed vaccination using a product with higher efficacy. We investigated the trade-off between changes in vaccination coverage and population mobility to understand how much relaxation of social distancing measures vaccination was able to 9buy9 in the later stages of a pandemic. We found that if no vaccination had occurred, an additional decrease of 10-20% in population mobility would have been required to maintain the same death and hospitalisation outcomes. We found SARS-CoV-2 transmission dynamics in the Dominican Republic were driven by substantial accumulation of immunity during the first two years of the pandemic but that, despite this, vaccination was essential in enabling a return to pre-pandemic mobility levels without incurring considerable additional morbidity and mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.05.23296586v2" target="_blank">Modelling the impact of population mobility, post-infection immunity and vaccination on SARS-CoV-2 transmission in the Dominican Republic</a>
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<li><strong>The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons</strong> -
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The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes, which was confirmed in a COVID-19 mouse model. These findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295190v3" target="_blank">The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons</a>
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<li><strong>No evidence that analgesic use after COVID-19 vaccination negatively impacts antibody responses</strong> -
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Uptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but studies to measure their impact on immune responses have been limited to relatively small cohorts. We semi-quantitatively measured antibody responses following COVID-19 vaccination in 2354 participants surveyed about analgesic use. Participants who used non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen after vaccination showed elevated antibody levels against the receptor binding domain of Spike protein relative to those who did not use analgesics. This pattern was observed for both mRNA-1273 and BNT162b2 and across age groups. Participants who used analgesics more frequently reported fatigue, muscle aches, and headaches than those who did not use painkillers. Amongst participants who reported these symptoms, we observed no statistically significant differences in antibody levels irrespective of analgesic use. These data suggest that antibody levels are elevated as a function of symptoms and inflammatory processes rather than painkiller use per se. Taken together, we find no evidence that analgesic use reduces antibody responses after COVID-19 vaccination. Recommendation of their use to alleviate symptoms might improve uptake of booster immunizations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.14.22281103v3" target="_blank">No evidence that analgesic use after COVID-19 vaccination negatively impacts antibody responses</a>
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<li><strong>Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations</strong> -
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A multitude of demographic, health, and genetic factors are associated with the risk of developing severe COVID-19 following infection by the SARS-CoV-2. There is a need to perform studies across human societies and to investigate the full spectrum of genetic variation of the virus. Using data from 869 COVID-19 patients in Bahrain between March 2020 and March 2021, we analyzed paired viral sequencing and non-genetic host data to understand host and viral determinants of severe COVID-19. We estimated the effects of demographic variables specific to the Bahrain population and found that the impact of health factors are largely consistent with other populations. To extend beyond the common variants of concern in the Spike protein analyzed by previous studies, we used a viral burden approach and detected a protective effect of low-frequency missense viral mutations in the RNA-dependent RNA polymerase (Pol) gene on disease severity. Our results contribute to the survey of severe COVID-19 in diverse populations and highlight the benefits of studying rare viral mutations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.13.22278740v3" target="_blank">Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations</a>
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<li><strong>Safety of SARS-CoV-2 test-to-stay in daycare: a regression discontinuity in time analysis</strong> -
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Background and Objectives Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess safety of a test-to-stay screening in daycare facilities. Methods 714 daycare facilities and approximately 50,000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-PCR screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children following the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. Results 219,885 Pool-PCRs and 352,305 Single-PCRs were performed. 6,440 (2.93%) Pool-PCRs tested positive, and 17,208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, CI:0.52;1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. Conclusion Our analyses provide evidence that suggest safety of the test-to-stay approach compared to traditional quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.11.23296808v1" target="_blank">Safety of SARS-CoV-2 test-to-stay in daycare: a regression discontinuity in time analysis</a>
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<li><strong>Scenario Design for Infectious Disease Projections: Integrating Concepts from Decision Analysis and Experimental Design</strong> -
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Across many fields, scenario modeling has become an important tool for exploring long-term projections and how they might depend on potential interventions and critical uncertainties, with relevance to both decision makers and scientists. In the past decade, and especially during the COVID-19 pandemic, the field of epidemiology has seen substantial growth in the use of scenario projections. Multiple scenarios are often projected at the same time, allowing important comparisons that can guide the choice of intervention, the prioritization of research topics, or public communication. The design of the scenarios is central to their ability to inform important questions. In this paper, we draw on the fields of decision analysis and statistical design of experiments to propose a framework for scenario design in epidemiology, with relevance also to other fields. We identify six different fundamental purposes for scenario designs (decision making, sensitivity analysis, value of information, situational awareness, horizon scanning, and forecasting) and discuss how those purposes guide the structure of scenarios. We discuss other aspects of the content and process of scenario design, broadly for all settings and specifically for multi-model ensemble projections. As an illustrative case study, we examine the first 17 rounds of scenarios from the U.S. COVID-19 Scenario Modeling Hub, then reflect on future advancements that could improve the design of scenarios in epidemiological settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.11.23296887v1" target="_blank">Scenario Design for Infectious Disease Projections: Integrating Concepts from Decision Analysis and Experimental Design</a>
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<li><strong>An agent-based modeling approach for lung fibrosis in response to COVID-19</strong> -
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The severity of the COVID-19 pandemic has created an emerging need to investigate the long-term effects of infection on patients. Many individuals are at risk of suffering pulmonary fibrosis due to the pathogenesis of lung injury and impairment in the healing mechanism. Fibroblasts are the central mediators of extracellular matrix (ECM) deposition during tissue regeneration, regulated by anti-inflammatory cytokines including transforming growth factor beta (TGF-{beta}). The TGF-{beta}-dependent accumulation of fibroblasts at the damaged site and excess fibrillar collagen deposition lead to fibrosis. We developed an open-source, multiscale tissue simulator to investigate the role of TGF-{beta} sources in the progression of lung fibrosis after SARS-CoV-2 exposure, intracellular viral replication, infection of epithelial cells, and host immune response. Using the model, we predicted the dynamics of fibroblasts, TGF-{beta}, and collagen deposition for 15 days post-infection in virtual lung tissue. Our results showed variation in collagen area fractions between 2% and 40% depending on the spatial behavior of the sources (stationary or mobile), the rate of activation of TGF-{beta}, and the duration of TGF-{beta} sources. We identified M2 macrophages as primary contributors to higher collagen area fraction. Our simulation results also predicted fibrotic outcomes even with lower collagen area fraction when spatially-localized latent TGF-{beta} sources were active for longer times. We validated our model by comparing simulated dynamics for TGF-{beta}, collagen area fraction, and macrophage cell population with independent experimental data from mouse models. Our results showed that partial removal of TGF-{beta} sources changed the fibrotic patterns; in the presence of persistent TGF-{beta} sources, partial removal of TGF-{beta} from the ECM significantly increased collagen area fraction due to maintenance of chemotactic gradients driving fibroblast movement. The computational findings are consistent with independent experimental and clinical observations of collagen area fractions and cell population dynamics not used in developing the model. These critical insights into the activity of TGF-{beta} sources may find applications in the current clinical trials targeting TGF-{beta} for the resolution of lung fibrosis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.03.510677v3" target="_blank">An agent-based modeling approach for lung fibrosis in response to COVID-19</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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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>Pharmacist Management of Paxlovid eVisits</strong> - <b>Conditions</b>: COVID-19; Quality of Care <br/><b>Interventions</b>: Other: Pharmacist Care; Other: AFM Pool Care <br/><b>Sponsors</b>: Kaiser Permanente <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>Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Other: Fact box <br/><b>Sponsors</b>: Harding Center for Risk Literacy <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>tDCS in the Management of Post-COVID Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training <br/><b>Sponsors</b>: Universidade Federal de Pernambuco; São Paulo State 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>Early Awake Alterning Prone Positioning Combined With Non-invasive Oxygen Therapy in Patients With COVID-19.</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Other: Prone position; Other: Standard treatment <br/><b>Sponsors</b>: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran <br/><b>Terminated</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 a Home-Based Exercise Intervention in Subjects With Long COVID</strong> - <b>Conditions</b>: Long COVID-19; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: home-based concurrent exercise <br/><b>Sponsors</b>: University of Vienna <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>ACTIVATE in Public Housing</strong> - <b>Conditions</b>: Pneumonia; Influenza; Varicella Zoster; Meningitis; COVID-19; Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Increasing Willingness and Uptake of Influenza, Pneumonia, Meningitis, HZV, and COVID-19 Vaccination <br/><b>Sponsors</b>: Charles Drew University of Medicine and Science <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>Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile) <br/><b>Sponsors</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation <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>Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC)</strong> - <b>Conditions</b>: Long Covid19; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Dietary Supplement: Flavonoids <br/><b>Sponsors</b>: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado <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>Exercise Interventions in Post-acute Sequelae of Covid-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Exercise <br/><b>Sponsors</b>: University of Virginia <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease <br/><b>Interventions</b>: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing) <br/><b>Sponsors</b>: Sarang K. Yoon, DO, MOH; Westat; Novavax <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects</strong> - <b>Conditions</b>: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection <br/><b>Interventions</b>: Combination Product: RQ-001; Other: Placebo <br/><b>Sponsors</b>: Red Queen Therapeutics, Inc.; PPD <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>Motivational Interviewing for Vaccine Uptake in Latinx Adults</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse <br/><b>Sponsors</b>: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR) <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of in vitro SARS-CoV-2 inactivation by a new quaternary ammonium compound: Bromiphen bromide</strong> - The pneumonia (COVID-19) outbreak caused by the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which unpredictably exploded in late December of 2019 has stressed the importance of being able to control potential pathogens with the aim of limiting their spread. Although vaccines are well known as a powerful tool for ensuring public health and controlling the pandemic, disinfection and hygiene habits remain crucial to prevent infection from spreading 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>An aggregation-induced emission sensor combined with UHPLC-Q-TOF/MS for fast identification of anticoagulant active ingredients from traditional Chinese medicine</strong> - Xuebijing injection (XBJ) has a good therapeutic effect on the patients with severe coronavirus disease, but the material basis of XBJ with the anticoagulant effect to improve the coagulopathy and thromboembolism is still unclear. Herein, we developed a new strategy based on aggregation-induced emission (AIE) for monitoring thrombin activity and screening thrombin inhibitors from XBJ. The molecule AIE(603) and the thrombin substrate peptide S-2238 were formed into AIE nanoparticle (AIENP) which…</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 Cyclophilin A and CD147 to Inhibit Replication of SARS-CoV-2 and SARS-CoV-2-Induced Inflammation</strong> - Identification and development of effective therapeutics for COVID-19 are still urgently needed. The CD147/Spike interaction is involved in the SARS-CoV-2 invasion process, in addition to ACE2. Cyclophilin A (CyPA), the extracellular ligand of CD147, has been found to play a role in the infection and replication of coronaviruses. In this study, our results show that CyPA inhibitors such as Cyclosporine A (CsA) and STG-175 can suppress the intracellular replication of SARS-CoV-2 by inhibiting the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multifunctional natural derived carbon quantum dots from Withania somnifera (L.) - Antiviral activities against SARS-CoV-2 pseudoviron</strong> - Natural carbon dots (NCQDs) are expediently significant in the photo-, nano- and biomedical spheres owing to their facile synthesis, optical and physicochemical attributes. In the present study, three NCQDs are prepared and optimized from Withania somnifera (ASH) by one-step hydrothermal (bottom-up) method: HASHP (without dopant), nitrogen doped HASHNH(3) (surface passivation using ammonia) and HASHEDA (surface passivation with ethylenediamine). The HR-TEM images reveal that HASHP, HASNH(3),…</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>4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1</strong> - In recent years, especially since the outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic, the cell-permeable itaconate derivative 4-octyl itaconate (4-OI) has gained traction as a potential antiviral agent. Here, we demonstrate that 4-OI inhibits replication of multiple influenza A viruses (IAV) by restricting nuclear export of viral ribonucleoproteins, a key step in the IAV replication cycle. This nuclear retention is achieved by deactivation and subsequent degradation of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy</strong> - Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main…</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 Apolipoprotein E neutralizing antibody inhibits SARS-CoV-2 infection by blocking cellular entry of lipoviral particles</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent for coronavirus disease 2019 (COVID-19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS-CoV-2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS-CoV-2 for infection. Preincubation of SARS-CoV-2 with a neutralizing antibody…</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>Unnatural Endotype B PPAPs as Novel Compounds with Activity against <em>Mycobacterium tuberculosis</em></strong> - Pre-SARS-CoV-2, tuberculosis was the leading cause of death by a single pathogen. Repetitive exposure of Mycobacterium tuberculosis(Mtb) supported the development of multidrug- and extensively drug-resistant strains, demanding novel drugs. Hyperforin, a natural type A polyprenylated polycyclic acylphloroglucinol from St. John’s wort, exhibits antidepressant and antibacterial effects also against Mtb. Yet, Hyperforin’s instability limits the utility in clinical practice. Here, we present photo-…</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 reconstitution of SARS-CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g</strong> - SARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted it in vitro on β-globin, EMCV IRES, and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing…</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>Lipid droplets in Zika neuroinfection: Potential targets for intervention?</strong> - Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence…</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>Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release</strong> - The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease</strong> - Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy…</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>W254 in furin functions as a molecular gate promoting anti-viral drug binding: Elucidation of putative drug tunneling and docking by non-equilibrium molecular dynamics</strong> - Furins are serine endoproteases that process precursor proteins into their biologically active forms, and they play essential roles in normal metabolism and disease presentation, including promoting expression of bacterial virulence factors and viral pathogenesis. Thus, furins represent vital targets for development of antimicrobial and antiviral therapeutics. Recent experimental evidence indicated that dichlorophenyl (DCP)-pyridine “BOS” drugs (e.g., BOS-318) competitively inhibit human furin…</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 N-terminal peptide of the main protease of SARS-CoV-2, targeting dimer interface, inhibits its proteolytic activity</strong> - The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of viral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CL<sup>Pro</sup>) activity in silico and in vitro</strong> - Despite the remarkable development of highly effective vaccines, including mRNA-based vaccines, within a limited timeframe, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not been entirely eradicated. Thus, it is crucial to identify new effective anti-3CL^(Pro) compounds, pivotal for the replication of SARS-CoV-2. Here, we identified an antcin-B phytosterol-like compound from Taiwanofungus camphoratus that targets 3CL^(Pro) activity….</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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