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188 lines
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<title>25 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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<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>Transformation of forecasts for evaluating predictive performance in an epidemiological context</strong> -
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Forecast evaluation plays an essential role in the development cycle of predictive epidemic models and can inform their use for public health decision-making. Common scores to evaluate epidemiological forecasts are the Continuous Ranked Probability Score (CRPS) and the Weighted Interval Score (WIS), which are both measures of the absolute distance between the forecast distribution and the observation. They are commonly applied directly to predicted and observed incidence counts, but it can be questioned whether this yields the most meaningful results given the exponential nature of epidemic processes and the several orders of magnitude that observed values can span over space and time. In this paper, we argue that log transforming counts before applying scores such as the CRPS or WIS can effectively mitigate these difficulties and yield epidemiologically meaningful and easily interpretable results. We motivate the procedure threefold using the CRPS on log-transformed counts as an example: Firstly, it can be interpreted as a probabilistic version of a relative error. Secondly, it reflects how well models predicted the time-varying epidemic growth rate. And lastly, using arguments on variance-stabilizing transformations, it can be shown that under the assumption of a quadratic mean-variance relationship, the logarithmic transformation leads to expected CRPS values which are independent of the order of magnitude of the predicted quantity. Applying the log transformation to data and forecasts from the European COVID-19 Forecast Hub, we find that it changes model rankings regardless of stratification by forecast date, location or target types. Situations in which models missed the beginning of upward swings are more strongly emphasized while failing to predict a downturn following a peak is less severely penalized. We conclude that appropriate transformations, of which the natural logarithm is only one particularly attractive option, should be considered when assessing the performance of different models in the context of infectious disease incidence.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.23.23284722v1" target="_blank">Transformation of forecasts for evaluating predictive performance in an epidemiological context</a>
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<li><strong>Faecal shedding models for SARS-CoV-2 RNA amongst hospitalised patients and implications for wastewater-based epidemiology</strong> -
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The concentration of SARS-CoV-2 RNA in faeces is not well established, posing challenges for wastewater-based surveillance of COVID-19 and risk assessments of environmental transmission. We develop versatile hierarchical models for faecal RNA shedding and apply them to data collected in six studies. We find that the mean number of gene copies per mL of faeces is 1.9×10<sup>6</sup> (2.3×10<sup>5</sup>—2.0×10<sup>8</sup> 95% credible interval) amongst hospitalised patients. We find no evidence for a subpopulation of patients who do not shed RNA: limits of quantification can account for negative stool samples. Our models indicate that hospitalised patients represent the tail of the shedding profile with a half-life of 34 hours (28—43 95% credible interval), suggesting that wastewater-based surveillance signals are more indicative of incidence than prevalence and can be a leading indicator of clinical presentation. Shedding among inpatients cannot explain high RNA concentrations observed in wastewater, consistent with more abundant shedding during the early infection course. We show that the models generalise and can predict summary statistics of held-out clinical datasets. However, shedding prior to hospitalisation cannot be constrained due to lack of samples, and information on viral variants was not available.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.16.21253603v2" target="_blank">Faecal shedding models for SARS-CoV-2 RNA amongst hospitalised patients and implications for wastewater-based epidemiology</a>
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<li><strong>Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting</strong> -
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Many positive-strand RNA viruses, including all known coronaviruses, employ programmed -1 ribosomal frameshifting (-1 PRF) to regulate the translation of polycistronic viral RNAs. However, only a few host factors have been shown to regulate -1 PRF. Through a reporter-based genome-wide CRISPR/Cas9 knockout screen, we identified several host factors that either suppressed or enhanced -1 PRF of SARS-CoV-2. One of these factors is eukaryotic translation initiation factor 2A (eIF2A), which specifically and directly enhanced -1 PRF in vitro and in cells. Consistent with the crucial role of efficient -1 PRF in transcriptase/replicase expression, loss of eIF2A reduced SARS-CoV-2 replication in cells. Transcriptome-wide analysis of eIF2A-interacting RNAs showed that eIF2A primarily interacted with 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results revealed an unexpected role for eIF2A in modulating the translation of specific RNAs independent of its previously described role during initiation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.23.525275v1" target="_blank">Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed -1 ribosomal frameshifting</a>
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<li><strong>Preclinical efficacy, safety, and immunogenicity of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2</strong> -
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Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and a decrease in mortality rates. However, new variants of concern (VoCs) are continuously evolving, making the development of new accessible COVID-19 vaccines essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 VoCs formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice models induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralising activity against several variants and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.22.469117v6" target="_blank">Preclinical efficacy, safety, and immunogenicity of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2</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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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.22.23284880v2" 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>A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273</strong> -
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<b>Background</b> Omicron-containing bivalent boosters are available worldwide. Results of a large, randomized, active-controlled study are presented. <b>Methods</b> This phase 3, randomized, observer-blind, active-controlled trial in the United Kingdom evaluated the immunogenicity and safety of 50-μg doses of omicron-BA.1- monovalent mRNA-1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50-μg mRNA-1273 administered as boosters in individuals ≥16 years. Participants had previously received 2 doses of any authorized/approved Covid-19 vaccine with or without an mRNA vaccine booster. Safety and immunogenicity were primary objectives; immunogenicity was assessed in all participants, with analysis conducted based on prior infection status. Incidence of Covid-19 post-boost was a secondary (mRNA-1273.214) or exploratory (mRNA-1273.529) objective. <b>Results</b> In part 1 of the study, 719 participants received mRNA-1273.529 (n=362) or mRNA-1273 (n=357); in part 2, 2813 received mRNA-1273.214 (n=1418) or mRNA-1273 (n=1395). Median durations (months [range]) between the most recent Covid-19 vaccine and study boosters were similar in the mRNA-1273.529 (4.0 [1.5-8.9]) and mRNA-1273 (4.1 [3.0-5.6]) (part 1), and mRNA-1273.214 (5.5 [0.4-13.3] and mRNA-1273 (5.4 [0.2-10.6]) groups (part 2). Both mRNA-1273.529 and mRNA-1273.214 elicited superior neutralizing antibody responses against omicron BA.1 with geometric mean ratios (95% CI) of 1.68 (1.45-1.95) and 1.53 (1.41-1.67) compared to mRNA-1273 at Day 29 post-boost. Although the study was not powered to assess relative vaccine efficacy, the incidence rates/1000 person years (95% CI) of Covid-19 trended lower with mRNA-1273.529 (670.5 [528.3-839.3]) than mRNA-1273 (769.3 [615.4-950.1]) and mRNA-1273.214 (633.0 [538.1-739.7]) than mRNA-1273 (711.6 [607.5-828.5]). Sequence analysis in part 2 showed that this was driven by lower incidence of Covid-19 in the mRNA-1273.214 cohort with BA.2 and BA.4 sublineages but not BA.5 sublineages. All study boosters were well-tolerated. <b>Conclusion</b> The bivalent omicron BA.1 containing booster elicited superior neutralizing antibody responses against omicron BA.1 with acceptable safety results consistent with the BA.1 monovalent vaccine. Incidence rates for Covid-19 were numerically lower in participants who received mRNA-1273.214 compared to the original booster vaccine mRNA-1273, driven by the BA.2 and BA.4 sublineages.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.24.23284869v1" target="_blank">A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273</a>
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<li><strong>Multimodal characterization of antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection.</strong> -
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The human immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we utilize multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after BNT162b2 immunization. Our data reveal distinct subpopulations of CD8+ T cells which reliably appear 28 days after prime vaccination (7 days post boost). Using a suite of cross-modality integration tools, we define their transcriptome, accessible chromatin landscape, and immunophenotype, and identify unique biomarkers within each modality. By leveraging DNA-oligo-tagged peptide-MHC multimers and T cell receptor sequencing, we demonstrate that this vaccine-induced population is SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we also identify these CD8+ populations in scRNA-seq datasets from COVID-19 patients and find that their relative frequency and differentiation outcomes are predictive of subsequent clinical outcomes. Our work contributes to our understanding of T cell immunity, and highlights the potential for integrative and multimodal analysis to characterize rare cell populations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.24.525203v1" target="_blank">Multimodal characterization of antigen-specific CD8+ T cells across SARS-CoV-2 vaccination and infection.</a>
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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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<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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<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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🖺 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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<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>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>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>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>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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East 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>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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<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>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>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>: Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia<br/><b>Intervention</b>: Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>: Jiangsu Cancer Institute & Hospital; Nanjing Chest Hospital; The Affiliated BenQ Hospital of Nanjing Medical University; Zhongda Hospital; Central South University<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2</strong> - Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (M^(pro)) of SARS-CoV-2 as an example. We first…</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>Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling</strong> - Kruppel-like factor 2 (KLF2) has been linked with fibrosis and neutrophil-associated thromboinflammation; however, its role in COVID-19 remains elusive. We investigated the effect of disease microenvironment on the fibrotic potential of human lung fibroblasts (LFs) and its association with KLF2 expression. LFs stimulated with plasma from severe COVID-19 patients down-regulated KLF2 expression at mRNA/protein and functional level acquiring a pre-fibrotic phenotype, as indicated by increased…</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 evolution influences GBP and IFITM sensitivity</strong> - SARS-CoV-2 spike requires proteolytic processing for viral entry. A polybasic furin-cleavage site (FCS) in spike, and evolution toward an optimized FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmission. Here we show interferon-inducible restriction factors Guanylate-binding proteins (GBP) 2 and 5 interfere with furin-mediated spike cleavage and inhibit the infectivity of early-lineage isolates Wuhan-Hu-1 and VIC. By contrast, VOCs Alpha and Delta escape…</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>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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