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<title>18 September, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Associations of habitual fish oil use with risk of SARS-CoV-2 infection and COVID-19-related outcomes in UK: national population based cohort study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives: To prospectively investigate the associations of habitual fish oil use with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large-scale cohort. Design: Prospective population-based cohort study. Setting: UK Biobank. Participants: A total of 110 440 participants aged 37 -73 years who completed a questionnaire on supplement use, which included fish oil at baseline were enrolled between 2006 and 2010 and followed up until 2022. Main exposure: All participants filled out questionnaires about the habitual use of supplements, including fish oil. Main outcome measures: SARS-CoV-2 infection, COVID-19 hospital admission and COVID-19 mortality. Results: At baseline, 29 424 (26.6%) of the 110 440 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.95 (0.93 to 0.98) for SARS-CoV-2 infection among participants with follow-up time less than 12.1 years but no significant associations were observed for participants with follow-up time more than 12.1 years. For COVID-19-related outcomes, the hazard ratios were 0.79 (95% confidence interval 0.71 to 0.88) for COVID-19 hospital admission and 0.72 (0.60 to 0.87) for COVID-19 mortality. For COVID-19-related outcomes, the association seemed to be stronger among those with longstanding illness. The Cox proportional hazard analysis after propensity-score matching yielded consistent results. Conclusions: Habitual fish oil supplement is associated with a lower risk of hospital admission and mortality with COVID-19, but not associated with SARS-CoV-2 infection in the population with more than 12.1 years of follow-up.
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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/10.1101/2022.09.14.22279933v1" target="_blank">Associations of habitual fish oil use with risk of SARS-CoV-2 infection and COVID-19-related outcomes in UK: national population based cohort study</a>
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</div></li>
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<li><strong>Dynamics-informed deconvolutional neural networks for super-resolution identification of regime changes in epidemiological time series</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Inferring the timing and amplitude of perturbations in epidemiological systems from their stochastically spread low-resolution outcomes is as relevant as challenging. It is a requirement for current approaches to overcome the need to know the details of the perturbations to proceed with the analyses. However, the general problem of connecting epidemiological curves with the underlying incidence lacks the highly effective methodology present in other inverse problems, such as super-resolution and dehazing from computer vision. Here, we develop an unsupervised physics-informed convolutional neural network approach in reverse to connect death records with incidence that allows the identification of regime changes at single-day resolution. Applied to COVID-19 data with proper regularization and model-selection criteria, the approach can identify the implementation and removal of lockdowns and other nonpharmaceutical interventions with 0.93-day accuracy over the time span of a year.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.14.22279935v1" target="_blank">Dynamics-informed deconvolutional neural networks for super-resolution identification of regime changes in epidemiological time series</a>
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</div></li>
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<li><strong>Estimation of mRNA COVID-19 Vaccination Effectiveness in Tokyo for Omicron Variants BA.2 and BA.5 -Effect of Social Behavior-</strong> -
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<div>
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Variability of COVID-19 vaccination effectiveness (VE) should be assessed with a resolution of a few days assuming that VE is influenced by public behavior and social activity. Here the VE for the Omicron variants (BA.2 and BA.5) is numerically derived for Japan9s population for the second and third vaccination doses. We then evaluated the daily VE variation caused by our social behavior from the daily data reports for Tokyo. The vaccination effectiveness for Omicron variants (BA.1, BA.2, and BA.5) are derived from the data of Japan and Tokyo with a computational approach. In addition, the effect of different parameters regarding human behavior on VE is assessed using daily data in Tokyo. The individual VE for the Omicron BA.2 in Japan was 61% (95%CI: 57%-65%) for the vaccination second dose from our computation, whereas that for the third dose was 86% (95% CI: 84%-88%). The individual BA.5 VE for the second and third doses are 37% (95% CI: 33%-40%) and 63% (95% CI: 61%-65%). The reduction of daily VE from estimated value was close correlated to the number of tweets related to social gathering in Twitter. The number of tweets considered here would be one of new candidates for VE evaluation and surveillance affecting the viral transmission.
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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/10.1101/2022.09.15.22280010v1" target="_blank">Estimation of mRNA COVID-19 Vaccination Effectiveness in Tokyo for Omicron Variants BA.2 and BA.5 -Effect of Social Behavior-</a>
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</div></li>
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<li><strong>Prevalence and risk factors for long COVID after mild disease: a longitudinal study with a symptomatic control group.</strong> -
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Background There is limited data on the prevalence and risk factors for long COVID, with a shortage of prospective studies with appropriate control groups and adequate sample size. We therefore performed a prospective study to determine the prevalence and risk factors for long COVID. Methods We recruited patients age ≥ 15 years who were clinically suspected of having acute SARS-CoV-2 infection from September 2020 to April 2021. Nasopharyngeal swabs were collected for RT-PCR 3-5 days post symptom onset. Clinical and sociodemographic characteristics were collected using structured questionnaires from persons positive and negative for SARS-COV-2. Follow-up was performed by telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life. Results We followed 814 participants (412 COVD-19 positive and 402 COVID-19 negative persons) of whom the majority (741 / 814) had mild symptoms. Both the COVID-19 positive and the COVID-19 negative groups had similar sociodemographic and clinical characteristics, except for the rate of hospitalization (15.8% vs 1.5%, respectively). One month after disease onset, 122 (29.6%) individuals reported residual symptoms in the COVID-19 positive group or the long COVID group versus 24 (6%) individuals in the COVID-19 negative group. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms which occurred in the acute phase. Compared to recovered patients, female sex, older age and having > 5 symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID with 57 (55.9%) reporting an impact in at least one dimension of the EuroQol 5D-3L questionnaire. Conclusion In this prospective study consisting predominantly of patients with mild disease, the persistence of symptoms after acute disease was highly associated with long COVID-19 (29.6% vs 6% of COVID negative group). The risk factors for long COVID were older age, female sex, and polysymptomatic acute disease.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.15.22279958v1" target="_blank">Prevalence and risk factors for long COVID after mild disease: a longitudinal study with a symptomatic control group.</a>
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</div></li>
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<li><strong>Neutralizing antibodies following three doses of BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron predominant wave</strong> -
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Background Data on the role of immunogenicity following the third vaccine dose against Omicron infection and coronavirus disease 2019 (COVID–19)–compatible symptoms of infection are limited. Methods First we examined vaccine effectiveness (VE) of the third–dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case–control study of a cohort of third vaccine recipients, we compared the pre–infection levels of live–virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls, who had close contact with COVID–19 patients. Among these cases, we examined the association between pre–infection NAb levels and the number of COVID–19–compatible symptoms experienced during the Omicron wave. Results Among the 1456 participants for VE analysis, 60 (4%) breakthrough infections occurred during the Omicron wave (January to March 2022). The third–dose VE for infection, relative to the second dose was 54.6% (95% CI: 14.0–76.0). Among the recipients of the third vaccine, pre–infection NAb levels against Omicron did not significantly differ between the cases and controls. Among the cases, those who experienced COVID–19–compatible symptoms had lower pre-infection NAb levels against Omicron than those who did not. Conclusions The third vaccine dose was effective in decreasing the risk of severe acute respiratory syndrome coronavirus 2 infection during the Omicron wave compared with the second dose. Among third–dose recipients, higher pre–infection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.15.22280009v1" target="_blank">Neutralizing antibodies following three doses of BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron predominant wave</a>
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</div></li>
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<li><strong>Differential contagiousness of respiratory disease across the United States</strong> -
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The initial contagiousness of a communicable disease within a given population is quantified by the basic reproduction number, denoted R_0. The value of R_0 gives the expected number of new cases generated by an infectious person in a wholly susceptible population and depends on both pathogen and population properties. On the basis of compartmental models that reproduce Coronavirus Disease 2019 (COVID-19) surveillance data, we estimated region-specific R_0 values for 280 of 384 metropolitan statistical areas (MSAs) in the United States (US), which account for 95% of the US population living in urban areas and 82% of the total population. Our estimates range from 1.9 to 7.7 and quantify the relative susceptibilities of regional populations to spread of respiratory diseases.
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</p>
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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/10.1101/2022.09.15.22279948v1" target="_blank">Differential contagiousness of respiratory disease across the United States</a>
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<li><strong>Mathematical modeling identifies optimal dosing schedules for COVID-19 vaccines to minimize breakthrough infections</strong> -
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While the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population, delayed administration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection. Optimizing vaccine dosing schedules could thus make the difference between periodic occurrence of breakthrough infections or effective control of the pandemic. To this end, we have developed a mechanistic mathematical model of adaptive immune response to vaccines and demonstrated its applicability to COVID-19 mRNA vaccines as a proof-of-concept for future outbreaks. The model was thoroughly calibrated against multiple clinical datasets involving immune response to SARS-CoV-2 infection and mRNA vaccines in healthy and immunocompromised subjects (cancer patients undergoing therapy); the model showed robust clinical validation by accurately predicting neutralizing antibody kinetics, a correlate of vaccine-induced protection, in response to multiple doses of mRNA vaccines. Importantly, we estimated population vulnerability to breakthrough infections and predicted tailored vaccination dosing schedules to maximize protection and thus minimize breakthrough infections, based on the immune status of a sub-population. We have identified a critical waiting window for cancer patients (or, immunocompromised subjects) to allow recovery of the immune system (particularly CD4+ T-cells) for effective differentiation of B-cells to produce neutralizing antibodies and thus achieve optimal vaccine efficacy against variants of concern, especially between the first and second doses. Also, we have obtained optimized dosing schedules for subsequent doses in healthy and immunocompromised subjects, which vary from the CDC-recommended schedules, to minimize breakthrough infections. The developed modeling tool is based on generalized adaptive immune response to antigens and can thus be leveraged to guide vaccine dosing schedules during future outbreaks.
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</p>
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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/10.1101/2022.09.14.22279959v1" target="_blank">Mathematical modeling identifies optimal dosing schedules for COVID-19 vaccines to minimize breakthrough infections</a>
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</div></li>
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<li><strong>Epi-Clock: A sensitive platform to help understand pathogenic disease outbreaks and facilitate the response to future outbreaks of concern.</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Determining how viruses originated and diverged and how infectious diseases are transmitted are serious challenges. Surprisingly, some inter-species genetic distances among Coronaviridae were shorter than intra-species distances, possibly representing the intermediate states of different species or subspecies in the evolutionary history of Coronaviridae. The indels of whole genome sequences between different hosts were separately associated with new functions or turning points, clearly indicating their important roles in the host transmission and shifts of Coronaviridae. Furthermore, we believe that non-nucleosomal DNA may play dominant roles in the divergence of different lineages of SARS-CoV-2 in different regions of the world because of the lack of nucleosome protection. We suggest that strong selective variation among different lineages of SARS-CoV-2 is required to produce strong codon usage bias. Interestingly, we found that an increasing number of other types of substitutions, such as those resulting from the hitchhiking effect, have accumulated, especially in the pre-breakout phase. To predict potential epidemic outbreaks, we tested our strategy, Epi-Clock, which applies the ZHU algorithm on different SARS-CoV-2 datasets to search for real significant mutational accumulation patterns correlated with the outbreak events. We could accurately predict the potential pre-phase of outbreaks with a median interval of 5 days before the outbreaks. Using our pipeline, users may review updated information on the website https://bioinfo.liferiver.com.cn with easy registration. Therefore, we propose Epi-Clock, a sensitive platform similar to a clock that can signal the need to assist individuals at focal locations by using diagnostics, isolation control, vaccines or therapy at any time.
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</p>
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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/10.1101/2022.09.14.22279955v1" target="_blank">Epi-Clock: A sensitive platform to help understand pathogenic disease outbreaks and facilitate the response to future outbreaks of concern.</a>
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</div></li>
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<li><strong>Bayesian Prediction of Severe Outcomes in the LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</strong> -
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<b>Objectives:</b> To develop cross-validated prediction models for severe outcomes in COVID-19 using blood biomarker and demographic data; Demonstrate best practices for clinical data curation and statistical modelling decisions, with an emphasis on Bayesian methods. <b>Design:</b> Retrospective observational cohort study. <b>Setting:</b> Multicentre across National Health Service (NHS) trusts in Southwest region, England, UK. <b>Participants:</b> Hospitalised adult patients with a positive SARS-CoV 2 by PCR during the first wave (March - October 2020). 843 COVID-19 patients (mean age 71, 45% female, 32% died or needed ICU stay) split into training (n=590) and validation groups (n=253) along with observations on demographics, coinfections, and 30 laboratory blood biomarkers. <b>Primary outcome measures:</b> ICU admission or death within 28-days of admission to hospital for COVID-19 or a positive PCR result if already admitted. <b>Results:</b> Predictive regression models were fit to predict primary outcomes using demographic data and initial results from biomarker tests collected within 3 days of admission or testing positive if already admitted. Using all variables, a standard logistic regression yielded an internal validation median AUC of 0.7 (95% Interval [0.64,0.81]), and an external validation AUC of 0.67 [0.61, 0.71], a Bayesian logistic regression using a horseshoe prior yielded an internal validation median AUC of 0.78 [0.71, 0.85], and an external validation median AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median AUC of 0.74 [0.67, 0.82], and external validation AUC of 0.70 [0.69, 0.71]. <b>Conclusions:</b> Our study reiterates the predictive value of previously identified biomarkers for COVID-19 severity assessment. Given the small data set, the full and reduced models have decent performance, but would require improved external validation for clinical application. The study highlights a variety of challenges present in complex medical data sets while maintaining best statistical practices with an emphasis on showcasing recent Bayesian methods.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22279985v1" target="_blank">Bayesian Prediction of Severe Outcomes in the LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</a>
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</div></li>
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<li><strong>Post-vaccination neutralization responses to Omicron sub-variants</strong> -
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Background: The emergence of the Omicron variant (B.1.1.529) which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Clinically relevant sub-variants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, and BA.4/5) subsequently emerged rapidly. Methods: We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform. Results: Among 153 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 21.9-fold for BA.4/5; in boosted participants fold-reduction was similar for all sub-variants (5.9-fold to 7.1-fold) except for BA.4/5 which was 12.7-fold. Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.2-fold) except for BA.4/5 which was higher (2.0-fold). Omicron sub-variant specific responder rates were low post-primary vaccination (range median 33.5% to 56.7%) compared to the prototype (median 96.0%), but improved post-booster (range median 85.4% to 92.6%).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22280017v1" target="_blank">Post-vaccination neutralization responses to Omicron sub-variants</a>
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<li><strong>High co-circulation of influenza and SARS-CoV-2</strong> -
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In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially worldwide meaning that health systems were not faced with simultaneous respiratory epidemics. In 2022, however, substantial influenza transmission returned to Nicaragua where it co-circulated with SARS-CoV-2 causing substantial disease burden.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.13.22279740v1" target="_blank">High co-circulation of influenza and SARS-CoV-2</a>
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<li><strong>Using Generalized Structured Additive Regression Models to Determine Factors Associated with and Clusters for COVID-19 Hospital Deaths in South Africa</strong> -
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Background: The first case of COVID-19 in South Africa was reported in March 2020 and the country has since recorded over 3.6 million laboratory-confirmed cases and 100 000 deaths as of March 2022. Transmission and infection of SARS-CoV-2 virus as well as deaths in general due to COVID-19 have been shown to be spatially associated but spatial patterns in hospital deaths have not fully been investigated in South Africa. This study uses national COVID-19 hospitalization data to investigate the spatial effects on hospital deaths after adjusting for known mortality risk factors. Methods: COVID-19 hospitalization data and deaths were obtained from the National Institute for Communicable Diseases (NICD), who together with the South African National Department of Health (SANDoH) collected hospital admissions data through DATCOV, an active electronic hospital surveillance system for COVID-19. We used the generalized structured additive logistic regression model that allows for modelling spatial correlation to realistically estimate risk factors for hospital COVID-19 deaths. The model included patient demographic and clinical factors as well as time in months which accounted for different waves. Continuous covariates were modelled by assuming second-order random walk priors, while spatial autocorrelation was specified with Markov random field prior and fixed effects with vague priors respectively. The inference was fully Bayesian. Results: The risk of COVID-19 in-hospital mortality increased with patient age as well as with admission to intensive care unit (ICU) (aOR=4.16; 95% Credible Interval: 4.05-4.27), being on oxygen (aOR=1.49; 95% Credible Interval: 1.46-1.51) and on invasive mechanical ventilation (aOR=3.74; 95% Credible Interval: 3.61-3.87). Being admitted in a public hospital (aOR= 3.16; 95% Credible Interval: 3.10-3.21) was also a significant risk factor for mortality. Risk of deaths also increased in months following a surge in infections and dropped after months of successive low infections highlighting crest and troughs lagging the epidemic curve. After controlling for these factors, districts such as Vhembe, Capricorn and Mopani in Limpopo province, and Buffalo City, O.R. Tambo, Joe Gqabi and Chris Hani in Eastern Cape province remained with significantly higher odds of COVID-19 hospital deaths suggesting possible health systems challenges in those districts. Conclusion: The results show substantial COVID-19 in-hospital mortality variation across the 52 districts. This highlights the importance of modelling spatial patterns simultaneously with fixed and nonlinear effects of continuous covariates to identify clusters at high risk of health outcome. The flexible approach to modelling data that has spatial patterns helps to account for possible loss of efficiency due to spatial correlation that spatial patterns can induce in data. Our analysis suggests notable COVID-19 hospital deaths clustering in some districts in Limpopo and Eastern Cape provinces and this information can be important for strengthening health policies and the public health system for the benefit of the whole South African population. Understanding differences in in-hospital COVID-19 mortality across space could guide interventions to achieve better health outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22280020v1" target="_blank">Using Generalized Structured Additive Regression Models to Determine Factors Associated with and Clusters for COVID-19 Hospital Deaths in South Africa</a>
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<li><strong>Hospital contact patterns and vulnerability to SARS-CoV-2 outbreaks</strong> -
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The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). Heterogeneity of risk across wards is still poorly described. We measured CPIs in 15 clinical wards across three hospitals using wearable sensors over 36 hours in spring 2020. This data was combined with a transmission model to estimate and compare transmission risks across wards. We found a four-fold range of epidemic risk between wards, with patients frequently presenting high risk to patients and healthcare workers (HCWs). Using a simulation study, we then assessed the potential impact on global risk of targeting individuals for prevention based on their contact patterns. We found that targeting individuals with the highest cumulative contact hours was most impactful. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.13.22279837v1" target="_blank">Hospital contact patterns and vulnerability to SARS-CoV-2 outbreaks</a>
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<li><strong>Low Dimensional Chaotic Attractors in SARS-CoV-2’s Regional Epidemiological Data</strong> -
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Background: Recent studies applying chaos theory methods have found the existence of chaotic markers in SARS-CoV-29s epidemiological data, evidence that has implications on the prediction, modeling and epidemiological analysis of the SARS-CoV-2/COVID-19 pandemic with implications for healthcare management. Aim and Methods: We study the aggregate data for the new cases per million and the new deaths per million from COVID-19 in Africa, Asia, Europe, North and South America and Oceania, applying chaos theory9s empirical methods including embedding dimension estimation, Lyapunov spectra estimation, spectral analysis and state-of-the-art topological data analysis methods combining persistent homology, recurrence analysis and machine learning with the aim of characterizing the nature of the dynamics and its predictability. Results: The results show that for all regions except Oceania there is evidence of low dimensional noisy chaotic attractors that are near the onset of chaos, with a recurrence structure that can be used by adaptive artificial intelligence solutions equipped with nearest neighbors9 machine learning modules to predict with a very high performance the future values of the two target series for each region. The persistent homology analysis uncovers a division into two groups, the first group comprised of Africa and Asia and the second of Europe, North and South America. For Oceania, we found evidence of the occurrence of a bifurcation which we characterize in detail applying a combination of machine learning and topological analysis methods, we find that the bifurcation in the region is related to the emergence of new variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22280044v1" target="_blank">Low Dimensional Chaotic Attractors in SARS-CoV-2’s Regional Epidemiological Data</a>
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<li><strong>Stakeholders’ perspectives on the feasibility of adopting a Healthy Nail Salon Recognition Program in Philadelphia: A qualitative study.</strong> -
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Background: The California Healthy Nail Salon Recognition Program is a statewide initiative to incentivize nail salons to adopt safer practices such as use of safer nail products without certain harmful chemicals, installation of ventilation systems, proper personal protective equipment use, and staff training. This public policy intervention is in response to the call to protect nail care workers, mostly women of color, who bear disproportionate burden of chemical exposure at work. Because there is interest from the community to adopt similar program in the Greater Philadelphia region, we conducted this formative research to document stakeholders9 perspectives on the feasibility of adopting the Healthy Nail Salon Recognition Program in Philadelphia. Methods: We conducted semi-structured interviews with a purposive sample of 31 stakeholders in Philadelphia in 2021. Using the Consolidated Framework for Implementation Science as our theoretical framework, we developed the interview guide and analyzed the data using qualitative research method to identify key facilitators and barriers. Results Key facilitating themes were perceived need and benefits of program to improve workers9 health and working conditions, and willingness of stakeholders to leverage their organizational resources. Barriers included perceived high cost and time commitment from salon owners and employees, lack of funding and implementation leaders at the city government, community members9 willingness to be visible and advocate for the program affected by the stigmas of being immigrant workers, fear of interacting with authorities, as well as the impact of COVID-19 pandemic. Our results suggest successful adoption of the Healthy Nail Salon Recognition Program in Philadelphia will require outreach within the community to raise awareness of the benefits of the program and close partnership with community-based organizations to facilitate mutual understanding between the authority and the ethnically diverse nail salon communities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.15.22280008v1" target="_blank">Stakeholders’ perspectives on the feasibility of adopting a Healthy Nail Salon Recognition Program in Philadelphia: A qualitative 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>Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Olfactory training with essential oils; Other: Olfactory training with fragrance-free oils<br/><b>Sponsor</b>: Ditte Gertz Mogensen<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Fourth Dose Study in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Tozinameran; Biological: Elasomeran; Biological: Bivalent Pfizer-BioNTech; Biological: Bivalent Moderna<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg; Biological: BNT162b4 5 µg; Biological: BNT162b4 10 µg; Biological: BNT162b4 15 µg<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>Trial of 2nd Booster Dose of COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Invitation to get a 2nd booster dose of COVID-19 vaccine<br/><b>Sponsor</b>: Norwegian Institute of Public Health<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PBI-0451; Drug: Placebo<br/><b>Sponsor</b>: Pardes Biosciences, Inc.<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>Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AD17002 + Formulation buffer; Biological: Placebo<br/><b>Sponsors</b>: Advagene Biopharma Co. Ltd.; Gadjah Mada 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>Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Community-based Health Education based on core intervention package; Behavioral: Health Information Sharing Group<br/><b>Sponsors</b>: The Hong Kong Polytechnic University; Food and Health Bureau, Hong Kong<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>Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID)</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Behavioral: Personalized multidisciplinary day-hospital intervention<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia</strong> - <b>Conditions</b>: Olfactory Disorder; COVID-19<br/><b>Intervention</b>: Drug: Simvastatin<br/><b>Sponsors</b>: Washington University School of Medicine; Duke 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>Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin Hospital<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>Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Comirnaty®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Vaxzevria®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Active Intervention Group<br/><b>Sponsor</b>: Pennington Biomedical Research Center<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>More tools for our toolkit: the application of HEL-299 cells and dsRNA-nanoparticles to study human coronaviruses in vitro</strong> - Human coronaviruses (HCoVs) are important human pathogens, as exemplified by the current SARS-CoV-2 pandemic. While the ability of type I interferons (IFNs) to limit coronavirus replication has been established, the ability of double-stranded (ds)RNA, a potent IFN inducer, to inhibit coronavirus replication when conjugated to a nanoparticle is largely unexplored. Additionally, the number of IFN competent cell lines that can be used to study coronaviruses in vitro are limited. In the present…</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 activity of cysteamine against SARS-CoV-2 variants</strong> - Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery</strong> - Uneven worldwide vaccination coverage against SARS-CoV-2 and emergence of variants escaping immunity call for broadly-effective and easily-deployable therapeutics. We previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alfa, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes infectivity and fusogenic activity of Omicron BA.1 and BA.2 variants. Cryo-EM analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope,…</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>GSK3326595 is a promising drug to prevent SARS-CoV-2 Omicron and other variants infection by inhibiting ACE2-R671 di-methylation</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the ACE2 receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by PRMTs is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that…</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>Integrating in silico and in vivo approach for investigating the role of polyherbal oil in prevention and treatment of COVID-19 infection</strong> - Currently, there are no FDA approved antiviral drugs available to treat COVID-19 patients. Also, due to emergence of new SARS-CoV-2 variants, the protective efficacy of vaccines could be reduced, hence it is urgent to have alternative treatments for combating the SARS-CoV-2 infection. Since, there is a long-standing history of herbal medicine in the treatment of respiratory diseases. In the present study, we investigated two polyherbal oil blend viz. Sudarshan AV and Elixir AV (SAV and EAV) 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>Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern</strong> - The coronavirus disease 2019 (COVID-19) pandemic turned the whole world upside down in a short time. One of the main challenges faced has been to understand COVID-19-associated life-threatening hyperinflammation, the so-called cytokine storm syndrome (CSS). We report here the proinflammatory role of Spike (S) proteins from different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern in zebrafish. We found that wild-type/Wuhan variant S1 (S1WT) promoted neutrophil…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular insights on bioactive compounds againstCovid-19: A Network pharmacological and computational study</strong> - CONCLUSION: This work illustrates probable strategy for identification of phytochemical based cocktails and off-targets which are effective against 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>Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern</strong> - Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2^(+)-TMPRSS2 cells, with IC(50) values ranging from 0.32 to 1.22 µM….</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 and the potential of Janus family kinase (JAK) pathway inhibition: A novel treatment strategy</strong> - Recent evidence proposed that the severity of the coronavirus disease 2019 (COVID-19) in patients is a consequence of cytokine storm, characterized by increased IL-1β, IL-6, IL-18, TNF-α, and IFN-γ. Hence, managing the cytokine storm by drugs has been suggested for the treatment of patients with severe COVID-19. Several of the proinflammatory cytokines involved in the pathogenesis of COVID-19 infection recruit a distinct intracellular signaling pathway mediated by JAKs. Consequently, JAK…</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><em>In vitro</em> Screening of Herbal Medicinal Products for Their Supportive Curing Potential in the Context of SARS-CoV-2</strong> - COVID-19 herbal medicinal products may have the potential for symptom relief in nonsevere or moderate disease cases. In this in vitro study we screened the five herbal medicinal products Sinupret extract (SINx), Bronchipret thyme-ivy (BRO-TE), Bronchipret thyme-primula (BRO TP), Imupret (IMU), and Tonsipret (TOP) with regard to their potential to (i) interfere with the binding of the human angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 spike S1 protein, (ii) modulate 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>A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode</strong> - The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to…</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>Complement C5a inhibition: a new form of COVID-19 treatment for mechanically ventilated patients?</strong> - No abstract</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>Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity</strong> - The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. The main protease (M^(pro)) is an promising target for anti-SARS-CoV-2 drug design. Here, we report the discovery of potent non-covalent non-peptide M^(pro) inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified the non-covalent hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged…</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>Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab</strong> - A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293…</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>Therapeutic properties and molecular docking study of some phenolic compounds as anti-human lung cancer potential: A biochemical approach</strong> - Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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