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188 lines
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<title>24 January, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Prediction of SARS-CoV-2 spike protein mutations using Sequence-to-Sequence and Transformer models</strong> -
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In the study of viral epidemics, having information about the structural evolution of the virus can be very helpful in controlling the disease and making vaccines. Various deep learning and natural language processing techniques (NLP) can be used to analyze genetic structure of viruses, namely to predict their mutations. In this paper, by using Sequence-to-Sequence (Seq2Seq) model with Long Short-Term Memory (LSTM) cell and Transformer model with the attention mechanism, we investigate the spike protein mutations of SARS-CoV-2 virus. We make time-series datasets of the spike protein sequences of this virus and generate upcoming spike protein sequences. We also determine the mutations of the generated spike protein sequences, by comparing these sequences with the Wuhan spike protein sequence. We train the models to make predictions in December 2021, February 2022, and October 2022. Furthermore, we find that some of our generated spike protein sequences have been reported in December 2021 and February 2022, which belong to Delta and Omicron variants. The results obtained in the present study could be useful for prediction of future mutations of SARS-CoV-2 and other viruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.23.525130v1" target="_blank">Prediction of SARS-CoV-2 spike protein mutations using Sequence-to-Sequence and Transformer models</a>
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</div></li>
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<li><strong>Wastewater-based surveillance can be used to model COVID-19-associated workforce absenteeism</strong> -
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Wastewater-based surveillance (WBS) is a powerful tool for understanding community COVID-19 disease burden and informing public health policy. The potential of WBS for understanding COVID-19 impact in non-healthcare settings has not been explored to the same degree. Here we examined how SARS-CoV-2 measured from municipal wastewater treatment plants (WWTPs) correlates with local workforce absenteeism. SARS-CoV-2 RNA N1 and N2 were quantified three times per week by RT-qPCR in samples collected at three WWTPs servicing Calgary and surrounding areas, Canada (1.3 million residents) between June 2020 and March 2022. Wastewater trends were compared to workforce absenteeism using data from the largest employer in the city (>15,000 staff). Absences were classified as being COVID-19-related, COVID-19-confirmed, and unrelated to COVID-19. Poisson regression was performed to generate a prediction model for COVID-19 absenteeism based on wastewater data. SARS-CoV-2 RNA was detected in 95.5% (85/89) of weeks assessed. During this period 6592 COVID-19-related absences (1896 confirmed) and 4,524 unrelated absences COVID-19 cases were recorded. Employee absences significantly increased as wastewater signal increased through pandemic waves. Strong correlations between COVID-19-confirmed absences and wastewater SARS-CoV-2 signals (N1 gene: r=0.824, p<0.0001 and N2 gene: r=0.826, p<0.0001) were observed. Linear regression with adjusted R2-value demonstrated a robust association (adjusted R2=0.783), when adjusted by 7 days, indicating wastewater provides a one-week leading signal. A generalized linear regression using a Poisson distribution was performed to predict COVID-19-confirmed absences out of the total number of absent employees using wastewater data as a leading indicator (P<0.0001). We also assessed the variation of predictions when the regression model was applied to new data, with the predicted values and corresponding confidence intervals closely tracking actual absenteeism data. Wastewater-based surveillance has the potential to be used by employers to anticipate workforce requirements and optimize human resource allocation in response to trackable respiratory illnesses like COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284878v1" target="_blank">Wastewater-based surveillance can be used to model COVID-19-associated workforce absenteeism</a>
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<li><strong>Real-world effectiveness of Azvudine in hospitalized patients with COVID-19: a retrospective cohort study</strong> -
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Current guidelines prioritize the use of the Azvudine in coronavirus disease 2019 (COVID-19) patients. However, the clinical effectiveness of Azvudine in real-world studies was lacking, despite the clinical trials showed shorter time of nucleic acid negative conversion. To evaluate the clinical effectiveness following Azvudine treatment in hospitalized COVID-19 patients, we identified 1505 hospitalized COVID-19 patients during the study period, with a follow-up of up to 29 days. After exclusions and propensity score matching, we included 226 Azvudine recipients and 226 matched controls. The lower crude incidence rate of composite disease progression outcome (4.21 vs. 10.39 per 1000 person-days, P=0.041) and all-cause mortality (1.57 vs. 6.00 per 1000 person-days, P=0.027) were observed among Azvudine recipients compared with matched controls. The incidence rates of initiation of invasive mechanical ventilation were also statistically different between the groups according to the log-rank tests (P=0.020). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome (hazard ratio [HR]: 0.43; 95% confidence interval [CI]: 0.18 to 0.99) and all-cause death (HR: 0.26; 95% CI: 0.07 to 0.94) compared with matched controls. Subgroup analyses indicated robustness of the point estimates of HRs (ranged from 0.14 to 0.84). Notably, male Azvudine recipients had a stronger effectiveness than female recipients with respect to both composite outcome and all-cause death. These findings suggest that Azvudine treatment showed substantial clinical benefits in hospitalized COVID-19 patients, and should be considered for use in this population of patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.23.23284899v1" target="_blank">Real-world effectiveness of Azvudine in hospitalized patients with COVID-19: a retrospective cohort study</a>
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</div></li>
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<li><strong>In-silico Analysis of SARS-Cov2 Spike Proteins of Different Field Variants</strong> -
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Background: Coronaviruses belong to the group of RNA family of viruses which trigger diseases in birds, humans, and mammals, which can cause respiratory tract infections. The COVID-19 pandemic has badly affected every part of the world, and the situation in the world is getting worse with the emergence of novel variants. Our study aims to explore the genome of SARS-CoV2 followed by in silico analysis of its proteins. Methods: Different nucleotide and protein variants of SARS-Cov2 were retrieved from NCBI. Contigs & consensus sequences were developed to identify variations in these variants by using SnapGene. Data of variants that significantly differ from each other was run through Predict Protein software to understand changes produced in protein structure The SOPMA web server was used to predict the secondary structure of proteins. Tertiary structure details of selected proteins were analyzed using the online web server SWISS-MODEL. Findings: Sequencing results shows numerous single nucleotide polymorphisms in surface glycoprotein, nucleocapsid, ORF1a, and ORF1ab polyprotein. While envelope, membrane, ORF3a, ORF6, ORF7a, ORF8, and ORF10 genes have no or few SNPs. Contigs were mto identifyn of variations in Alpha & Delta Variant of SARs-CoV-2 with reference strain (Wuhan). The secondary structures of SARs-CoV-2 proteins were predicted by using sopma software & were further compared with reference strain of SARS-CoV-2 (Wuhan) proteins. The tertiary structure details of only spike proteins were analyzed through the SWISS-MODEL and Ramachandran plot. By Swiss-model, a comparison of the tertiary structure model of SARS-COV-2 spike protein of Alpha & Delta Variant was made with reference strain (Wuhan). Alpha & Delta Variant of SARs-CoV-2 isolates submitted in GISAID from Pakistan with changes in structural and nonstructural proteins were compared with reference strain & 3D structure mapping of spike glycoprotein and mutations in amino acid were seen. Conclusion: The surprising increased rate of SARS-CoV-2 transmission has forced numerous countries to impose a total lockdown due to an unusual occurrence. In this research, we employed in silico computational tools to analyze SARS-CoV-2 genomes worldwide to detect vital variations in structural proteins and dynamic changes in all SARS-CoV-2 proteins, mainly spike proteins, produced due to many mutations. Our analysis revealed substantial differences in functional, immunological, physicochemical, & structural variations in SARS-CoV-2 isolates. However real impact of these SNPs can only be determined further by experiments. Our results can aid in vivo and in vitro experiments in the future.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.22.525048v1" target="_blank">In-silico Analysis of SARS-Cov2 Spike Proteins of Different Field Variants</a>
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<li><strong>COVision: Convolutional Neural Network for the Differentiation of COVID-19 from Common Pulmonary Conditions using CT Scans</strong> -
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With the growing amount of COVID-19 cases, especially in developing countries with limited medical resources, it is essential to accurately diagnose COVID-19 with high specificity. Due to characteristic ground-glass opacities (GGOs), present in both COVID-19 and other acute lung diseases, misdiagnosis occurs often: 26.6% of the time in manual interpretations of CT scans. Current deep-learning models can identify COVID-19 but cannot distinguish it from other common lung diseases like bacterial pneumonia. COVision is a multi-classification convolutional neural network (CNN) that can differentiate COVID-19 from other common lung diseases, with a low false-positivity rate. This CNN achieved an accuracy of 95.8%, AUROC of 0.970, and specificity of 98%. We found a statistical significance that our CNN performs better than three independent radiologists with at least 10 years of experience. especially in differentiating COVID-19 from pneumonia. After training our CNN with 105,000 CT slices, we analyzed the activation maps of our CNN and found that lesions in COVID-19 presented peripherally, closer to the pleura, whereas pneumonia lesions presented centrally. Finally, using federated averaging, we ensemble our CNN with a pretrained clinical factors neural network (CFNN) to create a comprehensive diagnostic tool.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284880v1" target="_blank">COVision: Convolutional Neural Network for the Differentiation of COVID-19 from Common Pulmonary Conditions using CT Scans</a>
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<li><strong>Delirium in a Young Predominantly Hispanic Population with COVID-19</strong> -
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Abstract Purpose: To study a primarily Hispanic population of adults younger than 65 to determine if COVID-19 patients with a concurrent delirium diagnosis had worse clinical outcomes in terms of hospital stay, ventilation and mortality, than those without a delirium diagnosis. Methods: After approval by the appropriate Institutional Review Board, a retrospective cohort study was performed looking at demographics, vital statistics, and clinical outcomes of patients aged 18-65 admitted to a hospital in the United States - Mexico border region with COVID-19 between March 1 and June 30, 2020. Data were analyzed using Fisher9s exact test, or an unpaired t-test where appropriate, and a univariate analysis was performed to establish relative risk. Confidence intervals were set at 95% and p values ≤0.05 were considered significant. Results: 133 patients with confirmed COVID-19 diagnoses (58% men, 92% Hispanic) were included. Mean age was 50.5 with a standard deviation of 11.7 years (range 20-65 years). The prevalence of delirium was 6%. Fifty percent of delirium patients died during hospitalization compared to 15% of patients without delirium. Patients with delirium were found to spend more days hospitalized, in the intensive care unit, and intubated than their counterparts without delirium. Delirium was associated with increased risk of being placed on mechanical ventilation (RR 3.91, 95% CI 1.46-10.41, p value 0.006). Conclusions: Delirium was associated with worse COVID-19 outcomes independent of age. COVID-19 patients need to be actively assessed for signs of delirium and appropriate precautionary measures should be implemented. Proper documentation of delirium is key to continue learning about the incidence of delirium in COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284879v1" target="_blank">Delirium in a Young Predominantly Hispanic Population with COVID-19</a>
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<li><strong>A New Approach for Active Coronavirus Infection Identification by Targeting the Negative RNA Strand- A Replacement for the Current Positive RNA-based qPCR Detection Method</strong> -
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This manuscript describes the development of an alternative method to detect active coronavirus infection, in light of the current COVID-19 pandemic caused by the SARS-CoV-2 virus. The pandemic, which was first identified in Wuhan, China in December 2019, has had a significant impact on global health as well as on the economy and daily life in the world. The current positive RNA-based detection systems are unable to discriminate between replicating and non-replicating viruses, complicating decisions related to quarantine and therapeutic interventions. The proposed method targets the negative strand of the virus and has the potential to effectively distinguish between active and inactive infections, which could provide a more accurate means of determining the spread of the virus and guide more effective public health measures during the current pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.22.525117v1" target="_blank">A New Approach for Active Coronavirus Infection Identification by Targeting the Negative RNA Strand- A Replacement for the Current Positive RNA-based qPCR Detection Method</a>
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<li><strong>Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters</strong> -
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The SARS-CoV-2 Omicron variant has continued to evolve. XBB is a recombinant between two BA.2 sublineages, XBB.1 includes the G252V mutation, and XBB.1.5 includes the G252V and F486P mutations. XBB.1.5 has rapidly increased in frequency and has become the dominant virus in New England. The bivalent mRNA vaccine boosters have been shown to increase neutralizing antibody (NAb) titers to multiple variants, but the durability of these responses remains to be determined. We assessed humoral and cellular immune responses in 30 participants who received the bivalent mRNA boosters and performed assays at baseline prior to boosting, at week 3 after boosting, and at month 3 after boosting. Our data demonstrate that XBB.1.5 substantially escapes NAb responses but not T cell responses after bivalent mRNA boosting. NAb titers to XBB.1 and XBB.1.5 were similar, suggesting that the F486P mutation confers greater transmissibility but not increased immune escape. By month 3, NAb titers to XBB.1 and XBB.1.5 declined essentially to baseline levels prior to boosting, while NAb titers to other variants declined less strikingly.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.22.525079v1" target="_blank">Waning Immunity Against XBB.1.5 Following Bivalent mRNA Boosters</a>
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<li><strong>A modeling study on the impact of COVID-19 pandemic responses on the community transmission of antibiotic-resistant bacteria</strong> -
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Non-pharmaceutical COVID-19 interventions have dramatically modified the transmission dynamics of pathogens other than SARS-CoV-2. In many countries, reports have shown that implementation of population-wide lockdowns led to substantial reductions in invasive bacterial disease caused by respiratory bacteria such as Streptococcus pneumoniae. By contrast, most European countries reported increased antibiotic resistance among S. pneumoniae isolates from 2019 to 2020. To disentangle impacts of the COVID-19 pandemic responses on bacterial epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. The impacts of population-wide lockdowns, isolation of COVID-19 cases, changes in antibiotic consumption due to altered healthcare-seeking behavior and prophylactic use in the early pandemic were explored across six pandemic scenarios. Our model was able to reproduce the observed trends, showing how lockdowns substantially reduce invasive pneumococcal disease incidence, while surges in prophylactic antibiotic prescribing favor disease caused by resistant strains. Surges in COVID-19 cases were associated with increased antibiotic resistance rates across all pandemic scenarios. Introducing synergistic within-host SARS-CoV-2-pneumococcus interactions further exacerbates increasing incidence of resistant disease. When data availability is limited, mathematical modeling can help improve our understanding of the complex interactions between COVID-19 and antibiotic resistance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.08.503267v2" target="_blank">A modeling study on the impact of COVID-19 pandemic responses on the community transmission of antibiotic-resistant bacteria</a>
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<li><strong>A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant</strong> -
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In the present study we report the functional and structural characterization of 17T2, a new highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody (mAb) isolated from a convalescent COVID-19 individual infected during the first wave of the COVID-19 pandemic. 17T2 is a class 1 VH1-58/{kappa}3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell and developed as a human recombinant IgG1. Functional characterization revealed that 17T2 mAb has a high and exceptionally broad neutralizing activity against all SARS-CoV-2 spike variants tested, including BQ.1.1. Moreover, 17T2 mAb has in vivo prophylactic activity against Omicron BA.1.1 infection in K18-hACE2 transgenic mice. 3D reconstruction from cryogenic-electron microscopy (cryo-EM) showed that 17T2 binds the Omicron BA.1 spike protein with the RBD domains in up position and recognizes an epitope overlapping with the receptor binding motif, as it is the case for other structurally similar neutralizing mAbs, including S2E12. Yet, unlike S2E12, 17T2 retains its high neutralizing activity against all Omicron sublineages tested, probably due to a larger contact area with the RBD, which could confer a higher resilience to spike mutations. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 mAb as a potential candidate for future therapeutic and prophylactic interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.20.524748v1" target="_blank">A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant</a>
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<li><strong>Finding a Needle in the Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection</strong> -
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Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test9s performance in asymptomatic individuals when used serially. Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting: Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants: Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements: Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations: New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the 9Test Us At Home9 study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.04.22278274v2" target="_blank">Finding a Needle in the Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection</a>
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<li><strong>Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study</strong> -
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Background: Performance of Rapid Antigen Tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance is not well established among asymptomatic individuals. Objective: Evaluate performance of Ag-RDT for detection of SARS-CoV-2 in relation to onset of infection for symptomatic and asymptomatic participants. Design, Setting, and Participants: Prospective cohort study conducted from October 2021 to February 2022 among participants > 2 years-old from across the US who enrolled using a smartphone app. During each testing encounter, participants self-collected one nasal swab and performed Ag-RDT at home; at-least fifteen minutes later, a second nasal swab was self-collected and shipped for SARS-CoV-2 RT-PCR at a central lab. Both nasal swabs were collected 7 times at 48-hour intervals (over approximately 14 days) followed by an extra nasal swab collection with home Ag-RDT test 48-hours after their last PCR sample. Each participant was assigned to one of the three emergency use authorized (EUA) Ag-RDT tests used in this study. This analysis was limited to participants who were asymptomatic and tested negative by antigen and molecular test on their first day of study participation. Exposure: SARS-CoV-2 positivity was determined by testing a single home-collected anterior nasal sample with three FDA EUA molecular tests, where 2 out 3 positive test results were needed to determine a SARS-CoV-2 positive result. Onset of infection was defined as day on which the molecular PCR comparator result was positive for the first time. Main Outcomes and Measures: Sensitivity of Ag-RDT was measured based on testing once (same-day), twice (at 48-hours) and thrice (at 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status on a given DPIPP. Results: A total of 7,361 participants enrolled in the study and 5,609 were eligible for this analysis. Among 154 eligible participants who tested positive for SARS-CoV-2 infection based on RT-PCR, 97 were asymptomatic and 57 had symptoms at onset of infection (DPIPP 0). Serial testing with Ag-RDT twice over 48-hours resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Among the 97 people who were asymptomatic at the onset of infection, 19 were singleton RT-PCR positive, i.e., their positive test was preceded and followed by a negative RT-PCR test within 48-hours. Excluding these singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with serial testing three times at 48-hour interval. Discussion: Performance of Ag-RDT within first week of infection was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v2" target="_blank">Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study</a>
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<li><strong>Monitoring and responding to emerging infectious diseases in a university setting: A case study using COVID-19</strong> -
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Emerging infection diseases (EIDs) are an increasing threat to global public health, especially when the disease is newly emerging. Institutions of higher education (IHEs) are particularly vulnerable to EIDs because student populations frequently share high-density residences and strongly mix with local and distant populations. In fall 2020, IHEs responded to a novel EID, COVID-19. Here, we describe Quinnipiac University’s response to SARS-CoV-2 and evaluate its effectiveness through empirical data and model results. Using an agent-based model to approximate disease dynamics in the student body, the University established a policy of dedensification, universal masking, surveillance testing via a targeted sampling design, and app-based symptom monitoring. After an extended period of low incidence, the infection rate grew through October, likely due to growing incidence rates in the surrounding community. A super-spreader event at the end of October caused a spike in cases in November. Student violations of the University’s policies contributed to this event, but lax adherence to state health laws in the community may have also contributed. The model results further suggest that the infection rate was sensitive to the rate of imported infections and was disproportionately impacted by non-residential students, a result supported by the observed data. Collectively, this suggests that campus-community interactions play a major role in campus disease dynamics. Further model results suggest that app-based symptom monitoring may have been an important regulator of the University’s incidence, likely because it quarantined infectious students without necessitating test results. Targeted sampling had no substantial advantages over simple random sampling when the model incorporated contact tracing and app-based symptom monitoring but reduced the upper boundary on 90% prediction intervals for cumulative infections when either was removed. Thus, targeted sampling designs for surveillance testing may mitigate worst-case outcomes when other interventions are less effective. The results’ implications for future EIDs are discussed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.13.23284515v2" target="_blank">Monitoring and responding to emerging infectious diseases in a university setting: A case study using COVID-19</a>
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<li><strong>Scaling rules for pandemics: Estimating infected fraction from identified cases for the SARS-Cov-2 Pandemic</strong> -
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Using a modified form of the SIR model, we show that, under general conditions, all pandemics exhibit certain scaling rules. Using only daily data for symptomatic, confirmed cases, these scaling rules can be used to estimate: (i) reff, the effective pandemic R-parameter; (ii) ftot, the fraction of exposed individuals that were infected (symptomatic and asymptomatic); (iii) Leff, the effective latency, the average number of days an infected individual is able to infect others in the pool of susceptible individuals; and (iv) alpha, the probability of infection per contact between infected and susceptible individuals. We validate the scaling rules using an example and then apply our method to estimate reff, ftot, Leff and alpha for the first phase of the SARS-Cov-2, Covid-19 pandemic for several countries where there was a well separated first peak in identified infected daily cases after the outbreak of the pandemic in early 2020. Our results are general and can be applied to any pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.05.22279599v2" target="_blank">Scaling rules for pandemics: Estimating infected fraction from identified cases for the SARS-Cov-2 Pandemic</a>
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<li><strong>Remote working: Thriving or Surviving?</strong> -
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Covid-19 and the subsequent lockdowns certainly expediated the idea of working and learning in a remote environment. Nevertheless, remote working as a concept has long been an option for employers and employees. Some organisations previously enabled their workers to opt-in a homeworking on Fridays, or build up flexitime, as an example. Despite being around for decades, only a relatively small proportion of people worked in this way. A seismic shift caused by the pandemic now meant that millions of people migrated to a remote format.
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🖺 Full Text HTML: <a href="https://edarxiv.org/rb8hu/" target="_blank">Remote working: Thriving or Surviving?</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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Phone satisfaction questionnaire<br/><b>Sponsor</b>: Centre Hospitalier René Dubos<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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Chatbot to Enhance COVID-19 Knowledge</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: chatbot; Other: Printed educational booklet<br/><b>Sponsor</b>: Sun Yat-sen 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>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Safety and Efficacy of Meplazumab for Injection Patients COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical 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>Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical 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 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical Co., Ltd.<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>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<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>Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).<br/><b>Sponsor</b>: Hospital General Nuestra Señora del Prado<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Ousehold in China</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Huashan Hospital; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<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>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>: Vitamin C; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Vitamin C; Drug: Placebo<br/><b>Sponsor</b>: Zhujiang 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>A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: DNA vaccine OC-007; Other: Placebo<br/><b>Sponsor</b>: Matti Sällberg<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>Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsor</b>: Peking Union Medical College Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: Prevention of COVID-19 Caused by SARS-CoV-2<br/><b>Intervention</b>: Biological: randomized, double-blinded, placebo-controlled<br/><b>Sponsor</b>: Yu Qin<br/><b>Active, not recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Epitope-directed anti-SARS-CoV-2 scFv engineered against the key spike protein region could block membrane fusion</strong> - The newly emerged SARS-CoV-2 causing coronavirus disease (COVID-19) resulted in >500 million infections. A great deal about the molecular processes of virus infection in the host is getting uncovered. Two sequential proteolytic cleavages of viral spike protein by host proteases are prerequisites for the entry of the virus into the host cell. The first cleavage occurs at S1/S2 site by the furin protease, and the second cleavage at a fusion activation site, the S2’ site, by the TMPRSS2 protease….</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>Potent Dual Polymerase/Exonuclease Inhibitory Activities of Antioxidant Aminothiadiazoles Against the COVID-19 Omicron Virus: A Promising In Silico/In Vitro Repositioning Research Study</strong> - Recently, natural and synthetic nitrogenous heterocyclic antivirals topped the scene as first choices for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying disease, the coronavirus disease 2019 (COVID-19). Meanwhile, the mysterious evolution of a new strain of SARS-CoV-2, the Omicron variant and its sublineages, caused a new defiance in the continual COVID-19 battle. Hitting the two principal coronaviral-2 multiplication enzymes…</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>Neutralization activity of IgG antibody in COVID‑19‑convalescent plasma against SARS-CoV-2 variants</strong> - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the anti-SARS-CoV-2 antibody levels, anti-spike (S)-immunoglobulin G (IgG) and anti-nucleocapsid (N)-IgG, and the neutralization activity of IgG antibody in COVID‑19‑convalescent plasma against variants of SARS-CoV-2, alpha, beta, gamma, delta, kappa, omicron and R.1 strains. The study included 30 patients with clinically diagnosed COVID-19. The anti-S-IgG and anti-N-IgG…</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>Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective</strong> - Throughout the SARS-CoV-2 pandemic, the use of botanical dietary supplements in the United States has increased, yet their safety and efficacy against COVID-19 remains underexplored. The Quave Natural Product Library is a phylogenetically diverse collection of botanical and fungal natural product extracts including popular supplement ingredients. Evaluation of 1867 extracts and 18 compounds for virus spike protein binding to host cell ACE2 receptors in a SARS-CoV-2 pseudotyped virus system…</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>Potential Self-Peptide Inhibitors of the SARS-CoV-2 Main Protease</strong> - The SARS-CoV-2 main protease (M^(pro)) plays an essential role in viral replication, cleaving viral polyproteins into functional proteins. This makes M^(pro) an important drug target. M^(pro) consists of an N-terminal catalytic domain and a C-terminal α-helical domain (M^(pro)C). Previous studies have shown that peptides derived from a given protein sequence (self-peptides) can affect the folding and, in turn, the function of that protein. Since the SARS-CoV-1 M^(pro)C is known to stabilize its…</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>Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies</strong> - CONCLUSION: The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.</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 Enveloped Virus Surrogate Phi6 Infection Using Yeast-Derived Vacuoles</strong> - The periodic emergence of infectious disease poses a serious threat to human life. Among the causative agents, including pathogenic bacteria and fungi, enveloped viruses have caused global pandemics. In the last 10 years, outbreaks of severe acute respiratory syndrome coronavirus 2 disease, severe acute respiratory syndrome, and Middle East respiratory syndrome have all been caused by enveloped viruses. Among several paths of secondary transmission, inhalation of aerosols containing saliva with…</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>Valproate Coenzyme-A Conjugate Blocks Opening of Receptor Binding Domains in the Spike Trimer of SARS-CoV-2 through an Allosteric Mechanism</strong> - The receptor-binding domains (RBDs) of the SARS-CoV-2 spike trimer exhibit “up” and “down” conformations often targeted by neutralizing antibodies. Only in the “up” configuration can RBDs bind to the ACE2 receptor of the host cell and initiate the process of viral multiplication. Here, we identify a lead compound (3-oxo-valproate-coenzyme A conjugate or Val-CoA) that stabilizes the spike trimer with RBDs in the down conformation. Val-CoA interacts with three R408 residues, one from each RBD,…</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>Causal associations of tea intake with COVID-19 infection and severity</strong> - Tea ingredients can effectively inhibit SARS-CoV-2 infection at adequate concentrations. It is not known whether tea intake could impact the susceptibility to COVID-19 or its severity. We aimed to evaluate the causal effects of tea intake on COVID-19 outcomes. We performed Mendelian randomization (MR) analyses to assess the causal associations between tea intake (N = 441,279) and three COVID-19 outcomes, including SARS-CoV-2 infection (122,616 cases and 2,475,240 controls), hospitalized COVID-19…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron</strong> - The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that N protein can mediate RNA or DNA entering neighboring cells through ACE2-independent, receptor (STEAP2)-mediated endocytosis, and achieve gene expression. The effect is more pronounced for the N protein of wild-type SARS-CoV-2 than that of Omicron variant and other human coronaviruses. This effect is enhanced by RANTES (CCL5), a chemokine induced by N protein,…</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>6-Shogaol Exhibits Anti-viral and Anti-inflammatory Activity in COVID-19-Associated Inflammation by Regulating NLRP3 Inflammasomes</strong> - Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO…</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>Is the information on infection prevention measures against COVID-19 reaching the target audience? A cross-sectional survey among eating and drinking services in Tokyo, Japan</strong> - CONCLUSION: Current information dissemination methods for information on COVID-19 infection control may not successfully convey information or reach their target populations. This study indicates the need for specific expressions and layouts to effectively share information on COVID-19. Also, special means of communication must be established to cater to individuals aged 60 and above.</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>Bionics design of affinity peptide inhibitors for SARS-CoV-2 RBD to block SARS-CoV-2 RBD-ACE2 interactions</strong> - Coronavirus Disease 2019 (COVID-19), has already posed serious threats and impacts on the health of the population and the country’s economy. Therefore, it is of great theoretical significance and practical application value to better understand the process of COVID-19 infection and develop effective therapeutic drugs. It is known that the receptor-binding structural domain (SARS-CoV-2 RBD) on the spike protein of the novel coronavirus directly mediates its interaction with the host receptor…</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>Potential inhibitory properties of structurally modified quercetin/isohamnetin glucosides against SARS-CoV-2 Mpro; molecular docking and dynamics simulation strategies</strong> - Concerned organizations and individuals are fully engaged in seeking appropriate measures towards managing Severe Acute Respiratory Syndrome Coronavirus 2 (SAR-CoV-2) infection because of the unprecedented economic and health impact. SAR-CoV-2 Main protease (SARS-CoV-2 Mpro) is unique to the survival and viability of the virus. Therefore, inhibition of Mpro can block the viral propagation. Thirty (30) derivatives were built by changing the glucosides in the Meta and para position of quercetin…</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 inhibits spermatogenesis in the testes by inducing cellular senescence</strong> - Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown. Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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