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<title>29 December, 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>Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</strong> -
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<div>
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Understanding and targeting functional RNA structures towards treatment of coronavirus infection can help us to prepare for novel variants of SARS-CoV-2 (the virus causing COVID-19), and any other coronaviruses that could emerge via human-to-human transmission or potential zoonotic (inter-species) events. Leveraging the fact that all coronaviruses use a mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to replicate, we apply algorithms to predict the most energetically favourable secondary structures (each nucleotide involved in at most one pairing) that may be involved in regulating the -1 PRF event in coronaviruses, especially SARS-CoV-2. We compute previously unknown most stable structure predictions for the frameshift site of coronaviruses via hierarchical folding, a biologically motivated framework where initial non-crossing structure folds first, followed by subsequent, possibly crossing (pseudoknotted), structures. Using mutual information from 181 coronavirus sequences, in conjunction with the algorithm KnotAli, we compute secondary structure predictions for the frameshift site of different coronaviruses. We then utilize the Shapify algorithm to obtain most stable SARS-CoV-2 secondary structure predictions guided by frameshift sequence-specific and genome-wide experimental data. We build on our previous secondary structure investigation of the singular SARS-CoV-2 68 nt frameshift element sequence, by using Shapify to obtain predictions for 132 extended sequences and including covariation information. Previous investigations have not applied hierarchical folding to extended length SARS-CoV-2 frameshift sequences. By doing so, we simulate the effects of ribosome interaction with the frameshift site, providing insight to biological function. We contribute in-depth discussion to contextualize secondary structure dual-graph motifs for SARS-CoV-2, highlighting the energetic stability of the previously identified 3_8 motif alongside the known dominant 3_3 and 3_6 (native-type) -1 PRF structures. Integrating experimental data within minimum free energy (MFE) hierarchical folding algorithms provides novel structure predictions to distill the relationship between RNA structure and function. In particular, fully categorizing most stable secondary structure predictions via hierarchical folding supports our identification of motif transitions and critical site targets for future therapeutic research.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.28.573501v1" target="_blank">Tying the Knot: Unraveling the Intricacies of the Coronavirus Frameshift Pseudoknot</a>
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</div></li>
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<li><strong>CParty: Conditional partition function for density-2 RNA pseudoknots</strong> -
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<div>
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RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we provide the theoretical framework and implementation for our algorithm, CParty, that follows the hierarchical folding hypothesis, i.e., the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted structures, i.e., density-2 structures G U G’ for non-crossing disjoint structure G’. Notably, this can enable sampling from the hierarchical distribution P(G’|G). With CParty we develop for the first time an unambiguous scheme based on HFold, i.e., the minimum free energy hierarchical folding algorithm based on a realistic pseudoknot energy model. Thus, we develop the first partition function variant for density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots (and follows a different strategy, mapped from a pure minimum free energy structure prediction), our method covers a much larger structure class; at the same time, it is significantly more efficient—reducing the time as well as the space complexity by a quadratic factor. Summarizing, we provide an efficient, cubic time, algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. We discuss one such application, i.e., how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 can provide insight into RNA structure formation.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541023v2" target="_blank">CParty: Conditional partition function for density-2 RNA pseudoknots</a>
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</div></li>
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<li><strong>The 8C model of vaccination readiness: A common framework to facilitate cross-study comparisons.</strong> -
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Several factors can potentially influence an individual’s vaccination readiness. To facilitate cross-study comparisons, it is essential that researchers use a shared framework to measure these factors. This would not only help determine their relative importance cross different contexts but also would aid in tailoring interventions to enhance vaccine uptake. Historically, five psychological antecedents of vaccination were identified: confidence, complacency, constraints, calculation, and collective responsibility. This 5C scale was later expanded to a 7C model by incorporating two additional components: compliance and conspiracy. Building upon this framework, we propose an eighth component, certification, defined as the person’s self-report that, in the past, they have had to provide evidence of vaccination. This component addresses a significant gap in the 7C model, as some individuals reported taking the COVID-19 vaccine primarily to obtain proof of vaccination, a motivation not captured by the 7C model. Our confirmatory factor analysis (N = 406) of a bifactor model of US citizens9 self-reported COVID-19 vaccination status showed that this eighth component had good psychometric properties and the 8C model had slightly higher criterion validity than the 7C model. We present the 8C model as a framework that provides a richer and more complete descriptions of the factors that determine vaccination readiness and encourage future studies of vaccination readiness to utilise it.
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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/10.1101/2023.12.22.23300464v1" target="_blank">The 8C model of vaccination readiness: A common framework to facilitate cross-study comparisons.</a>
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</div></li>
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<li><strong>BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults</strong> -
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Importance Data describing the early additional protection afforded by recently recommended XBB1.5-adapted COVID-19 vaccines are limited. Objective We estimated the association between receipt of BNT162b2 XBB1.5-adapted vaccine (Pfizer-BioNTech 2023-2024 formulation) and medically attended COVID-19 outcomes among adults >=18 years of age. Design, Setting, and Participants We performed a test-negative case-control study to compare the odds of BNT162b2 XBB1.5-adapted vaccine receipt between COVID-19 cases and test-negative controls among adults in the Kaiser Permanente Southern California health system between October 11 and December 10, 2023. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. Exposure The primary exposure was receipt of BNT162b2 XBB1.5-adapted vaccine compared to not receiving an XBB1.5-adapted vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. We also compared receipt of prior (non-XBB1.5-adapted) versions of COVID-19 vaccines to the unvaccinated to estimate remaining protection from older vaccines. Main Outcomes and Measures Cases were those with a positive SARS-CoV-2 polymerase chain reaction test, and controls tested negative. Analyses were done separately for COVID-19 hospital admissions, emergency department (ED) and urgent care (UC) encounters, and outpatient visits. Results Among 4232 cases and 19,775 controls with median age of 54 years, adjusted ORs for testing positive for SARS-CoV-2 among those who received BNT162b2 XBB1.5-adapted vaccine a median of 30 days ago (vs not having received an XBB1.5-adapted vaccine of any kind) were 0.37 (95% CI: 0.20-0.67) for COVID-19 hospitalization, 0.42 (0.34-0.53) for ED/UC visits, and 0.42 (0.27-0.66) for outpatient visits. Compared to the unvaccinated, those who had received only older versions of COVID-19 vaccines did not show significantly reduced risk of COVID-19 outcomes, including hospital admission. Conclusions and Relevance Our findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) XBB1.5-adapted vaccines provided significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, additional protection, including against hospital admission, regardless of the number or type of prior doses received.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.24.23300512v1" target="_blank">BNT162b2 XBB1.5-adapted Vaccine and COVID-19 Hospital Admissions and Ambulatory Visits in US Adults</a>
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<li><strong>Dengue Virus Serotype 2 Cosmopolitan C Genotype Reemerges with a New Subclade in Southwest Region of Bangladesh</strong> -
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In 2023, the Dengue virus (DENV) outbreak infected over 0.3 million cases and 1500 deaths in Bangladesh. Although the the serotype and genotype data were unavailable. Our study conducted serotyping and genomic surveillance in four districts of Southwest Bangladesh between September and October 2023. The surveillance data from 2019 to 2023 extracted from the Directorate General of Health Services in Bangladesh indicated a significant increase of Dengue infections in 2023, particularly during September-November. The two-layered hypothesis examination confirmed that, despite endemic months, 2023 dengue outbreak had a higher morbidity rate compared to previous years (2019-2022) in Southwest of Bangladesh. Serotyping and E gene sequence analysis of 25 randomly selected positive samples reveals that DENV-2 was the sole serotype circulating in this region during the study period. Genomic analysis exposed a new subclade of DENV-2, classified under Cosmopolitan genotype within C clade, distinct from previous years Bangladeshi variants until 2022. This subclade, possibly migrating from India, might be emerged during COVID-19 pandemic years and exhibited higher morbidity rates, thus challenging our existing mitigation strategies. This investigation provides valuable insights for public health interventions and underscores the importance of continuous genomic surveillance in managing Dengue outbreaks. Key words: Dengue serotype 2, Bangladesh, New Subclade, Cosmopolitan C, Phylogenetic tree
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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/10.1101/2023.12.24.23300504v1" target="_blank">Dengue Virus Serotype 2 Cosmopolitan C Genotype Reemerges with a New Subclade in Southwest Region of Bangladesh</a>
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<li><strong>Learning the fitness dynamics of pathogens from phylogenies</strong> -
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The dynamics of pathogen genetic diversity, including the emergence of lineages with increased fitness, is a foundational concept of disease ecology with key public health implications. However, the identification of distinct lineages and estimation of associated fitness remain challenging, and are rarely done outside densely sampled systems. Here, we present a scalable framework that summarizes changes in population composition in phylogenies, allowing for the automatic detection of lineages based on shared fitness and evolutionary relationships. We apply our approach to a broad set of viruses and bacteria (SARS-CoV-2, H3N2 influenza, Bordetella pertussis and Mycobacterium tuberculosis) and identify previously undiscovered lineages, as well as specific amino acid changes linked to fitness changes, the findings of which are robust to uneven and limited observation. This widely-applicable framework provides an avenue to monitor evolution in real-time to support public health action and explore fundamental drivers of pathogen fitness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.23.23300456v1" target="_blank">Learning the fitness dynamics of pathogens from phylogenies</a>
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<li><strong>Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.</strong> -
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COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N=416 including n=224 COVID-19 cases; Mage=58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF).We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing. COVID-19 case status was not significantly associated with DBSI-RF (all |B|<0.28, pFDR >0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (all B>0.3, all pFDR=0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology. Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.20.549891v3" target="_blank">Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.</a>
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<li><strong>The double bind of communicating about zoonotic origins: Describing exotic animal sources of COVID-19 increases both healthy and discriminatory avoidance behaviors</strong> -
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<div>
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Many novel diseases are of zoonotic origin, likely including COVID-19. Describing diseases as originating from diverse exotic animals can increase risk perceptions and protective avoidance behaviors, but may also activate stereotypes, increasing discriminatory behaviors and disease stigma. Data from the first several weeks of the US COVID-19 pandemic tested how communications about zoonotic disease origins affect people’s risk perceptions, health behaviors, and stigma. Participants (N = 677) who read news articles describing exotic animals (e.g., snakes) as sources of COVID-19 viewed the virus as riskier and reported stronger intentions to engage in preventative behaviors (e.g., handwashing), relative to those who read about a familiar source (pigs). Reading exotic origin descriptions was associated with stronger intentions to avoid Asian individuals and animal products, both of which contributed to greater stigma for COVID-19. Results have implications for public health communicators who aim to increase risk perceptions without activating stigma or prejudice.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/948qn/" target="_blank">The double bind of communicating about zoonotic origins: Describing exotic animal sources of COVID-19 increases both healthy and discriminatory avoidance behaviors</a>
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<li><strong>Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target</strong> -
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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay and the best hit compound had an IC50 of 14 M. Three validated HTS hits have the same 2-amide-3-methylester thiophene scaffold and the scaffold was selected for structure-activity relationship (SAR) studies through commercial and synthesized analogs. We studied the compound binding mode in detail using X-ray crystallography and this allowed us to focus on specific features of the compound and design analogs. Compound 27 (MDOLL-0229) had an IC50 of 2.1 M and was generally selective for CoV Mac1 proteins after profiling for activity against a panel of viral and human ADP-ribose binding proteins. The improved potency allowed testing of its effect on virus replication and indeed, 27 inhibited replication of both MHVa prototype CoV, and SARS-CoV-2. Furthermore, sequencing of a drug-resistant MHV identified mutations in Mac1, further demonstrating the specificity of 27. Compound 27 is the first Mac1 targeted small molecule demonstrated to inhibit coronavirus replication in a cell model. This, together with its well-defined binding mode, makes 27 a good candidate for further hit/lead-optimization efforts.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.28.555062v2" target="_blank">Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target</a>
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<li><strong>Effect of Heparin and Tocilizumab in Patients with Severe COVID-19: The HEPMAB Randomized Clinical Trial</strong> -
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Background Clinical presentation of severe Coronavirus disease 2019 (COVID-19) is associated to an intense inflammatory response and thrombogenesis. The benefits of the association of interleukin-6 receptor blockade (tocilizumab) and therapeutic-dose anticoagulation remains unclear. We aimed to assess whether heparin and tocilizumab could effectively reduce inflammation and thrombogenesis in severe COVID-19 patients. Methods This is an open-label, multicenter, randomized, clinical trial, involving patients with severe COVID-19 infection. Eligible patients were randomly assigned in a 1:1:1:1 ratio to receive either therapeutic or prophylactic anticoagulation with heparin, with or without an intravenous single dose of tocilizumab. The participants in the study were assigned to one of the four distinct arms: 1) therapeutic anticoagulation; 2) prophylactic anticoagulation; 3) therapeutic anticoagulation plus a single intravenous dose of tocilizumab; and 4) prophylactic anticoagulation plus a single intravenous dose of tocilizumab. The primary outcome was clinical improvement at day 30, defined as a composite of hospital discharge and/or a reduction of at least 2 points of the modified ordinal scale of 7 points recommended by the World Health Organization. Results We enrolled 308 patients. Patients randomized to receive therapeutic anticoagulation more frequently had clinical improvement at day 30 when compared to the prophylactic anticoagulation patients [64/75 (85%) versus 51/80 (64%), odds ratio, 3.31; 95% confidence interval, 1.51; 7.26 P=0.003]. Major bleeding was more frequent in the therapeutic anticoagulation group (6.7%) and in the therapeutic anticoagulation plus tocilizumab group (5.0%), compared to the prophylactic anticoagulation group (P=0.02). All-cause mortality at day 30 was significantly lower in therapeutic anticoagulation group (9.3%), when compared to prophylactic anticoagulation group (28.7%), therapeutic anticoagulation plus tocilizumab group (21.5%) and prophylactic anticoagulation plus tocilizumab group (25.7%), P=0.02. Conclusions In this randomized clinical trial involving severe COVID-19 patients, therapeutic anticoagulation resulted in clinical improvement at 30 days. Even if therapeutic anticoagulation increased bleeding, it was associated with a reduced overall mortality. Tocilizumab did not provide additional benefits to heparin in COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300466v1" target="_blank">Effect of Heparin and Tocilizumab in Patients with Severe COVID-19: The HEPMAB Randomized Clinical Trial</a>
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<li><strong>Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells</strong> -
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The fight against COVID-19 pandemic has gained a strong consensus about the importance of developing mRNA vaccines to rapidly respond to an outbreak. Several studies have shown that mRNA vaccines formulated as mRNA-lipid nanoparticles (LNPs) for vaccination can elicit a robust and efficient immune response. In this study, we report the preparation of mRNA-bifunctional lipid nanoparticles (mRNA-BLNPs) as vaccines for targeted delivery to dendritic cells (DCs) to improve safety and enhance immune response. Using this DC-targeted delivery system, mice immunized with SARS-CoV-2 spike mRNA-BLNP vaccine elicited a stronger immune response with higher titer of neutralizing IgG antibody response than the LNP-formulated vaccine against SARS-CoV-2. In addition, the spike mRNA-BLNP vaccine with deletion of glycosites in the stem elicited a broadly protective immune response against SARS-CoV-2 and variants. These findings suggest the importance and potential of developing DC-targeted mRNA vaccines to elicit broadly protective immune responses against human viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.26.572282v1" target="_blank">Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells</a>
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<li><strong>Inferring the sensitivity of wastewater metagenomic sequencing for pathogen early detection</strong> -
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Detecting novel pathogens at an early stage requires robust early warning that is both sensitive and pathogen-agnostic. Wastewater metagenomic sequencing (W-MGS) could meet these goals, but its sensitivity and financial feasibility depend on the relative abundance of novel pathogen sequences in W-MGS data. Here we collate W-MGS data from a diverse range of studies to characterize the relative abundance of known viruses in wastewater. We then develop a Bayesian statistical model to integrate these data with epidemiological estimates for 13 human-infecting viruses, and use it to estimate the expected relative abundance of different viral pathogens for a given prevalence or incidence in the community. Our results reveal pronounced variation between studies, with estimates differing by one to three orders of magnitude for the same pathogen: for example, the expected relative abundance of SARS-CoV-2 at 1% weekly incidence varied between 10^-7 and 10^-10. Integrating these estimates with a simple cost model highlights similarly wide inter-study and inter-pathogen variation in the cost of W-MGS-based early detection, with a mean yearly cost estimate of roughly $19,000 for a Norovirus-like pathogen and $2.9 million for a SARS-CoV-2-like pathogen at 1% incidence. The model and parameter estimates presented here represent an important resource for future investigation into the performance of wastewater MGS, and can be extended to incorporate new wastewater datasets as they become available.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300450v1" target="_blank">Inferring the sensitivity of wastewater metagenomic sequencing for pathogen early detection</a>
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<li><strong>Predicting poor mental health amongst older Syrian refugees in Lebanon during the COVID-19 pandemic: a multi-wave longitudinal study</strong> -
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Background: The COVID-19 pandemic has worsened pre-existing vulnerabilities among older Syrian refugees in Lebanon, potentially impacting their mental health. This study aimed to identify predictors of poor mental health amongst older Syrian refugees living in Lebanon during the pandemic. Methods: This study used repeated cross-sectional data from a multi-wave telephone survey (September 2020-March 2022). It was conducted among Syrian refugees aged 50 years or older from households that received assistance from a humanitarian organization. Poor mental health was defined as a Mental Health Inventory-5 score of 60 or less. Its trend over time was assessed using growth curve model; and, its predictors were identified using wave one data, through backwards stepwise logistic regression. The model9s internal validation was conducted using bootstrapping. Findings: There were 3,229 participants (median age=56 [IQR=53-62]) and 47.5% were female. At wave one, 76.7% had poor mental health, and this increased to 89.2% and to 92.7% at waves three and five, respectively (β = 0.52; 95% CI: 0.44-0.63; p-value<0.001). Predictors for poor mental health were younger age, food insecurity, water insecurity, lack of legal status documentation, irregular employment, higher intensity of bodily pain, having debt, and having chronic illnesses. The final model demonstrated good discriminative ability and calibration. Interpretation: Mental health predictors were related to basic needs, rights and financial barriers. These allow humanitarian organizations to identify high risk individuals, organizing interventions, and addressing root causes to boost resilience and well-being among older Syrian refugees in Lebanon. Funding: ELRHA9s Research for Health in Humanitarian Crisis Programme.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300447v1" target="_blank">Predicting poor mental health amongst older Syrian refugees in Lebanon during the COVID-19 pandemic: a multi-wave longitudinal study</a>
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<li><strong>CitySEIRCast: An Agent-Based City Digital Twin for Pandemic Analysis and Simulation</strong> -
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The COVID-19 pandemic has dramatically highlighted the importance of developing simulation systems for quickly characterizing and providing spatio-temporal forecasts of infection spread dynamics that take specific accounts of the population and spatial heterogeneities that govern pathogen transmission in real-world communities. Developing such computational systems must also overcome the cold start problem related to the inevitable scarce early data and extant knowledge regarding a novel pathogen9s transmissibility and virulence, while addressing changing population behavior and policy options as a pandemic evolves. Here, we describe how we have coupled advances in the construction of digital or virtual models of real-world cities with an agile, modular, agent-based model of viral transmission and data from navigation and social media interactions, to overcome these challenges in order to provide a new simulation tool, CitySEIRCast, that can model viral spread at the sub-national level. Our data pipelines and workflows are designed purposefully to be flexible and scalable so that we can implement the system on hybrid cloud/cluster systems and be agile enough to address different population settings and indeed, diseases. Our simulation results demonstrate that CitySEIRCast can provide the timely high resolution spatio-temporal epidemic predictions required for supporting situational awareness of the state of a pandemic as well as for facilitating assessments of vulnerable sub-populations and locations and evaluations of the impacts of implemented interventions, inclusive of the effects of population behavioral response to fluctuations in case incidence. This work arose in response to requests from county agencies to support their work on COVID-19 monitoring, risk assessment, and planning, and using the described workflows, we were able to provide uninterrupted bi-weekly simulations to guide their efforts for over a year from late 2021 to 2023. We discuss future work that can significantly improve the scalability and real-time application of this digital city-based epidemic modelling system, such that validated predictions and forecasts of the paths that may followed by a contagion both over time and space can be used to anticipate the spread dynamics, risky groups and regions, and options for responding effectively to a complex epidemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300481v1" target="_blank">CitySEIRCast: An Agent-Based City Digital Twin for Pandemic Analysis and Simulation</a>
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<li><strong>Mild and moderate COVID-19 during Alpha, Delta and Omikron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: a population-based surveillance study</strong> -
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In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations9 younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, households of a population cohort in Polana Canico, Maputo, Mozambique, were contacted biweekly. Residents reporting any respiratory sign, anosmia, or ageusia, were asked to self-administer a nasal swab, for SARS-CoV-2 PCR testing. Of a subset of 1400 participants, dried blood spots were repeatedly collected three-monthly from finger pricks at home. Antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein were detected using an in-house developed multiplex antibody assay. We estimated the incidence of respiratory illness and COVID-19, and SARS-CoV-2 seroprevalence. We used Cox regression models, adjusting for age and sex, to identify factors associated with first symptomatic COVID-19 and with SARS-CoV-2 sero-conversion in the first six months. During 11925 household visits in 1561 households, covering 6049 participants (median 21 years, 54.8% female, 7.3% disclosed HIV positive), 1895.9 person-years were followed up. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes of which 72.2 (95%CI 60.6-83.9) COVID-19 confirmed, were reported. Of 1412 participants, 2185 blood samples were tested (median 30.6 years, 55.2% female). Sero-prevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age (strong gradient in hazard ratio, HR, up to 15.70 in >=70 year olds, 95%CI 3.74-65.97), leukaemia, chronic lung disease, hypertension, and overweight increased risk of COVID-19. We found no increased risk of COVID-19 in people with HIV or tuberculosis. Risk of COVID-19 was lower among residents in the lowest socio-economic quintile (HR 0.16, 95%CI 0.04-0.64), with no or limited handwashing facilities, and who shared bedrooms (HR 0.42, 95%CI 0.25-0.72). Older age also increased the risk of SARS-CoV-2 seroconversion (HR 1.57 in 60-69 year olds, 95%CI 1.03-2.39). We found no associations between SARS-CoV-2 infection risk and socio-economic, behavioural factors and comorbidities. Active surveillance in an urban population cohort confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to industrialised countries, deprivation did not increase the risk of infection nor disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.22.23300474v1" target="_blank">Mild and moderate COVID-19 during Alpha, Delta and Omikron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: a population-based surveillance 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>TDCS Stimulation After Covid-19 Infection</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: Transcranial Direct Stimulation <br/><b>Sponsors</b>: Istanbul Medipol University Hospital; Alanya Alaaddin Keykubat 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>Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5 <br/><b>Sponsors</b>: Hipra Scientific, S.L.U <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>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza.</strong> - <b>Conditions</b>: Influenza; COVID-19 <br/><b>Interventions</b>: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo <br/><b>Sponsors</b>: BioNTech SE; Pfizer <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>Transcranial Pulse Stimulation (TPS) in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Fatigue <br/><b>Interventions</b>: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham <br/><b>Sponsors</b>: Medical University of Vienna; Campus Bio-Medico 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>Evaluate the Efficacy and Safety of “Formosa 1-Breath Free (NRICM101)” in Subjects With the Symptoms of COVID-19 or Influenza-like Disease</strong> - <b>Conditions</b>: Influenza Viral Infections; COVID-19 <br/><b>Interventions</b>: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug <br/><b>Sponsors</b>: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. <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 Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo <br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. <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>Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Exercise Intolerance, Riboflavin-Responsive <br/><b>Interventions</b>: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises <br/><b>Sponsors</b>: Columbia University; New York University <br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> study of inhibition activity of boceprevir drug against 2019-nCoV main protease</strong> - Boceprevir drug is a ketoamide serine protease inhibitor with a linear peptidomimetic structure that exhibits inhibition activity against 2019-nCoV main protease. This paper reports electronic properties of boceprevir and its molecular docking as well as molecular dynamics simulation analysis with protein receptor. For this, the equilibrium structure of boceprevir has been obtained by DFT at B3LYP and ωB97XD levels with 6-311+G(d,p) basis set in gas and water mediums. HOMO-LUMO and absorption…</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>Novel sofosbuvir derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective</strong> - The human coronavirus, SARS-CoV-2, had a negative impact on both the economy and human health, and the emerging resistant variants are an ongoing threat. One essential protein to target to prevent virus replication is the viral RNA-dependent RNA polymerase (RdRp). Sofosbuvir, a uridine nucleotide analog that potently inhibits viral polymerase, has been found to help treat SARS-CoV-2 patients. This work combines molecular docking and dynamics simulation (MDS) to test 14 sofosbuvir-based…</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>Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases</strong> - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can lead to a cytokine storm, unleashed in part by pyroptosis of virus-infected macrophages and monocytes. Interleukin-6 (IL-6) has emerged as a key participant in this ominous complication of COVID-19. IL-6 antagonists have improved outcomes in patients with COVID-19 in some, but not all, studies. IL-6 signaling involves at least 3 distinct pathways, including classic-signaling, trans-signaling, and trans-presentation…</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>Excessive daytime sleepiness is associated with impaired antibody response to influenza vaccination in older male adults</strong> - CONCLUSION: Our results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults.</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>Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)</strong> - CONCLUSIONS: Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.</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>Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease</strong> - Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of host proteins interacting with non-structural protein nsp9 of porcine epidemic diarrhea virus on viral replication</strong> - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that can cause acute intestinal infectious diseases in both piglets and fattening pigs. The virus encodes at least 16 non-structural proteins, including nsp9, which has been shown to bind to single-stranded RNA. However, its function and mechanism remain unclear. In this study, we aimed to identify potential host proteins that interact with PEDV nsp9 using immunoprecipitation combined with mass spectrometry. The interactions…</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 in Dental Practice Is Prevented by Eugenol Responsible for the Ambient Odor Specific to Dental Offices: Possibility and Speculation</strong> - Dental professionals routinely work in proximity to patients even when either or both of them have suspected or confirmed COVID-19. The oral cavity also serves as a reservoir for SARS-CoV-2 because the virus is present in and replicates in oral secretions (saliva and gingival crevicular fluid), oral tissues (salivary gland and periodontal tissue), and oral microenvironments (gingival sulcus and periodontal pocket). Despite a high risk of SARS-CoV-2 infection, the prevalence of COVID-19 in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of Porcine Deltacoronavirus Entry and Replication by Cepharanthine</strong> - Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. 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>Does denosumab exert a protective effect against COVID-19? Results of a large cohort study</strong> - CONCLUSION: Our study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.</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>Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques</strong> - Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P 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>Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there’s no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers…</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>Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication</strong> - INTRODUCTION: Since its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses.</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>Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity</strong> - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize…</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 the tissue factor coagulation initiation complex prevents antiphospholipid antibody development</strong> - Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. While autoimmune aPL cross-react with various coagulation regulatory proteins, lipid-reactive and COVID-19 patient-derived aPL recognize the endo-lysosomal phospholipid lysobisphosphatidic acid (LBPA) presented by the cell surface expressed endothelial protein C receptor…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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