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192 lines
53 KiB
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<title>27 April, 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>Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</strong> -
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The role of the Huanan Seafood Market in the early SARS-CoV-2 outbreak remains unclear. Recently the Chinese CDC released data from deep sequencing of environmental samples collected from the market after it was closed on January-1-2020 (Liu et al, 2023). Prior to this release, Crits-Christoph et al (2023) analyzed data from a subset of the samples. Both studies concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species, and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al (2023). However, the number of SARS-CoV-2 reads is not consistently correlated with reads mapping to any non-human susceptible species. For instance, 14 samples have >20% of their chordate mitochondrial material from raccoon dogs, but only one of these samples contains any SARS-CoV-2 reads, and that sample only has 1 of ~200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.25.538336v1" target="_blank">Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market</a>
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<li><strong>A systematic review of the prevalence of persistent gastrointestinal symptoms and incidence of new gastrointestinal illness after acute SARS-CoV-2 infection</strong> -
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It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as post-COVID syndrome. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illness following acute SARS-CoV-2 infection. We searched scientific literature using MedLine, SCOPUS, Embase, Europe PubMed Central, medRxiv and Google Scholar from December 2019 to October 2022. Two reviewers independently identified 28 eligible articles which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptom of any nature and duration was 10.7%, compared to 4.9% in healthy controls. For six studies at a low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1% with a median follow-up time of 13 weeks. We also identified the presence of functional gastrointestinal disorders in historically SARS-CoV-2 exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal symptoms, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.26.23289142v1" target="_blank">A systematic review of the prevalence of persistent gastrointestinal symptoms and incidence of new gastrointestinal illness after acute SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)</strong> -
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Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, brain-fog, and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. Methods/Design: A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Discussion: Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.25.23289110v1" target="_blank">Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)</a>
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<li><strong>Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA</strong> -
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Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Our results indicate that no sampled wildlife were positive for SARS-CoV-2. This finding is surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American’s wildlife populations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.25.538264v1" target="_blank">Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA</a>
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<li><strong>Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice</strong> -
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As the COVID-19 pandemic transitions to endemic, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD-specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activity in vitro than mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.25.538294v1" target="_blank">Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice</a>
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<li><strong>Remote Aerosol SARS-CoV-2 Transmission from Clinical COVID Patients to Rodent Sentinels</strong> -
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We performed studies investigating the feasibility of human to animal (H2A) model system to test whether patient generated respiratory bioaerosols hold infective capacity when traversing long distance airborne transport within the built environment. South African patients, clinically confirmed by facemask sampling to be exhaling SARS-CoV-2 genomic sequence, were recruited and housed for multiple days in a clinical ward with a uniquely designed building ventilation system continuously channeling exhaust airflow to individual microisolator animal caging units located proximal but segregated from clinic space (University of Pretoria AIR facility).
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🖺 Full Text HTML: <a href="https://osf.io/cre2w/" target="_blank">Remote Aerosol SARS-CoV-2 Transmission from Clinical COVID Patients to Rodent Sentinels</a>
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<li><strong>Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</strong> -
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We describe several regression models to predict severe outcomes in COVID-19 and challenges present in complex observational medical data. We demonstrate best practices for data curation, cross-validated statistical modelling, and variable selection emphasizing recent Bayesian methods. The study follows a retrospective observational cohort design using multicentre records across National Health Service (NHS) trusts in southwest England, UK. Participants included hospitalised adult patients positive for SARS-CoV 2 during March to October 2020, totalling 843 patients (mean age 71, 45% female, 32% died or needed ICU stay), split into training (n=590) and validation groups (n=253). Models were fit to predict severe outcomes (ICU admission or death within 28-days of admission to hospital for COVID-19, or a positive PCR result if already admitted) using demographic data and initial results from 30 biomarker tests collected within 3 days of admission or testing positive if already admitted. Cross-validation results showed standard logistic regression had an internal validation median AUC of 0.74 (95% Interval [0.62,0.83]), and external validation AUC of 0.68 [0.61, 0.71]; a Bayesian logistic regression (with horseshoe prior) internal AUC of 0.79 [0.71, 0.87], and external AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median internal AUC of 0.79 [0.78, 0.80], and external AUC of 0.67 [0.65, 0.69]. We illustrate best-practices protocol for conventional and Bayesian prediction modelling on complex clinical data and reiterate the predictive value of previously identified biomarkers for COVID-19 severity assessment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.16.22279985v4" target="_blank">Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort</a>
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<li><strong>Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022</strong> -
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SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread, and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020-2022 and use Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest introduction into Minnesota was to Hennepin County from a domestic source around January 22, 2020; six weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota, and eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International (MSP) airport) totaling 45 (out of 107) over the two-year period. Southern Minnesota counties were most common for domestic introductions with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (n=772) over the two-year period. We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases or major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have impact on virus diversity across each individual county.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.24.22277978v3" target="_blank">Genomic epidemiology reveals the dominance of Hennepin County in transmission of SARS-CoV-2 in Minnesota from 2020-2022</a>
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<li><strong>Variability in excess deaths across countries with different vulnerability during 2020-2023</strong> -
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Importance: Excess deaths provide estimates of total impact of major crises, such as the COVID-19 pandemic. Objective: To evaluate excess deaths trajectories during 2020-2023 across countries with accurate death registration and population age structure data; and to assess how excess death patterns and trajectories correlate with economic indicators of vulnerability overall and in different age strata. Methods: Data were used from the Human Mortality Database on 34 countries. Excess deaths were calculated for 2020-2023 (to 2/26/2023) using 2017-2019 as baseline reference, with weekly expected death calculations and adjustment for 5 age strata. Countries were divided into less and more vulnerable; the latter had per capita nominal GDT<$30,000, Gini>0.35 for income inequality and/or at least 2.5% of their population living in poverty. Results: Excess deaths (as proportion of expected deaths, p% ) were strongly inversely correlated with per capita GDP (r=-0.61), strongly correlated with proportion living in poverty (r=0.65) and modestly correlated with income inequality (r=0.42). The 17 less vulnerable countries had 201,471 excess deaths versus 2,005,380 among the 17 more vulnerable countries. The USA would have had 1.50 million fewer deaths if it had the performance of Sweden, 1.13 million fewer deaths if it had the performance of Finland, and 0.93 million fewer deaths if it had the performance of France. Excess deaths started deviating in the two groups after the first wave when correlational patterns with the 3 economic indicators also started to emerge. Between-country heterogeneity diminished over time within each of the two groups. Less vulnerable countries had mean p%=-0.4% and 0.9% in 0-64 and >65 year-old strata while more vulnerable countries had mean p%=8.3% and 9.0%, respectively. Certain countries performed substantially worse (USA, Canada, Chile, UK) or better (France, Poland, Slovenia) in the non-elderly than in the elderly. Usually lower death rates were seen in children 0-14 years old during 2020-2023 versus pre-pandemic years. Conclusion: While the pandemic hit some countries earlier than others, country vulnerability dominated eventually the cumulative impact. Half of the analyzed countries witnessed no substantial excess deaths versus pre-pandemic levels, while the other half suffered major death tolls.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23289066v1" target="_blank">Variability in excess deaths across countries with different vulnerability during 2020-2023</a>
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<li><strong>Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach</strong> -
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Background: Sketching the major portraits of the COVID-19 epidemic when variants of the pathogen emerge is critical to inform the dynamics of disease transmission, reproduction (i.e., the average counts of individuals of secondary infections generated by an index individual infected by the virus) strength of the pathogen, and countermeasure strategies. Multiple approaches, including log-linear, EpiEstim (an R package generally utilized to estimate the evolution traits of epidemics), and near-log-linear techniques, have been exploited to evaluate the principal parameters such as basic and effective reproduction numbers of an epidemic outbreak. Objective: This study focuses on the kink corner (i.e., sharp alternation of direction of the transmission curve) presenting differentiated log-quadratic traits where more infectious variants of viruses emerge at the diminishing transmission phase of an infectious disease. Methods: A novel log-quadratic trending framework was proposed to project potentially unidentified cases (i.e., forward imputing approximately one week ahead) of COVID-19 around the kink, where the transmission of the pandemic initially lowered and accelerated subsequently, and exercised with the updated framework of classic EpiEstim and Log-linear model. I first compared the performance near the kink using the proposed technique versus the two traditional models taking into account a variety of levels of transmissibility, data distribution (Weibull, Gamma, and Lognormal distributions), and reporting rates (0.2, 0.4, 0.6, 0.8 and 1.0 respectively). Thereafter I utilized the revised framework on the outbreak data of four settings including Bulgaria, Japan, Poland, and South Korea from June to August 2022. Results: The proposed framework reduced the estimation bias versus traditional EpiEstim and log-linear methods near the kink. The coverage estimates of 95% confidence intervals improved. The proposed forward-imputation method implied generally a consistent ascending trend of effective reproduction number estimation applying to a precipitous transition from diminishing to diverging scenarios versus the irregular zigzagging outcomes in classic methods when more contagious variants of the virus were present in the absence of effective vaccines. Conclusions: The log-quadratic correction accounting for transmissibility, data distribution, reporting rates, sliding windows, and generation intervals improved the basic and effective reproduction numbers estimation at the kink corner versus the classic EpiEstim and log-linear models by refined amendment of curve fitting. This is of concern when essentially the fundamental transmission traits of a pandemic alter expeditiously and countermeasures are needed at the earlier variant phases of the transiting climax with the advancement of the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23289029v1" target="_blank">Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach</a>
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<li><strong>Aerosol Jet Printing Enabled Dual-Function Electrochemical and Colorimetric Biosensor for SARS-CoV-2 Detection</strong> -
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An aerosol jet printing enabled dual-function biosensor for the sensitive detection of pathogens using SARS-CoV-2 RNA as an example has been developed. A CRISPR-Cas13: guide-RNA complex is activated in the presence of a target RNA, leading to the collateral trans-cleavage of ssRNA probes that contain a horseradish peroxidase (HRP) tag. This, in turn, catalyzes the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) by HRP, resulting in a color change and electrochemical signal change. The colorimetric and electrochemical sensing protocol does not require complicated target amplification and probe immobilization and exhibits a detection sensitivity in the femtomolar range. Additionally, our biosensor demonstrates a wide dynamic range of 5 orders of magnitude. This low-cost aerosol inkjet printing technique allows for an amplification-free and integrated dual-function biosensor platform, which operates at physiological temperature and is designed for simple, rapid, and accurate point-of-care (POC) diagnostics in either low-resource settings or hospitals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.20.23288904v1" target="_blank">Aerosol Jet Printing Enabled Dual-Function Electrochemical and Colorimetric Biosensor for SARS-CoV-2 Detection</a>
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<li><strong>Immune signature of patients with cardiovascular disease - in-depth immunophenotyping predicts increased risk for a severe course of COVID-19</strong> -
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Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients. Approach and Results: We prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4<sup>+</sup> T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16<sup>+</sup> monocytes, innate lymphoid cells, and CD8<sup>+</sup> T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8<sup>+</sup> T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission. Conclusion: Acute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23288921v1" target="_blank">Immune signature of patients with cardiovascular disease - in-depth immunophenotyping predicts increased risk for a severe course of COVID-19</a>
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<li><strong>Anxiety due to Long COVID is partially driven by activation of the tryptophan catabolite (TRYCAT) pathway</strong> -
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This study examines whether activation of the tryptophan catabolite (TRYCAT) pathway is associated with anxiety symptoms due to Long COVID. We selected 90 participants, 60 Long COVID patients and 30 individuals without any symptoms following acute CIVID-19 infection. Using cluster analysis and the Hamilton Anxiety Rating scale (HAMA) score, the pure HAMA anxiety score, serum tryptophan (TRP) and kynurenine (KYN), the KYN/TRP ratio (all measured during Long COVID), and oxygen saturation (SpO2) (measured during the acute phase of COVID-19), we were able to classify Long COVID patients into two distinct clusters with an adequate silhouette cohesion and separation index (0.58): cluster 1 (n=61) and cluster 2 (n=29). Cluster 2 patients had lower SpO2 and TRP levels, as well as higher KYN, KYN/TRP ratio, and HAMA scores than cluster 1. Regression analysis revealed that the KYN/TRP ratio explained 14.4% of the variance in the HAMA score (F=14.81, df=1/88, p=0.001). In addition, regression analysis revealed that SpO2 partially explained the variance in serum TRP (r=0.396, p=0.005), KYN/TRP ratio (r=-0.248, p=0.018), and the HAMA score (r=-0.279, p=0.008). The current data imply that decreased SpO2 during the acute phase of COVID-19 infection is predictive of anxiety caused by Long COVID. Our data reveal that around 32% of Long COVID patients have elevated IDO activity in association with elevated anxiety.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23288115v1" target="_blank">Anxiety due to Long COVID is partially driven by activation of the tryptophan catabolite (TRYCAT) pathway</a>
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<li><strong>Is Covid-19 Mortality “Like the Flu”? A Cumulative Death Rates Comparison</strong> -
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It has been common both to make and to resist comparisons that equate the Covid-19 pandemic to influenza. We take the comparison between Covid-19 and flu seriously by asking how many years of influenza and pneumonia deaths are needed for cumulative deaths to those two causes to equal the cumulative toll of the Covid-19 pandemic between March 2020 and February 2023 – that is, three years of pandemic deaths. We find that in one state alone – Hawaii – three years of Covid-19 mortality is equivalent to influenza and pneumonia mortality in the three years preceding the Covid-19 pandemic. For all other states, at least nine years of flu and pneumonia are needed to match Covid-19; for the United States as a whole, seventeen years are needed; and for four states, more than 21 years (the maximum observable) are needed. These results provide an easy-to-understand calibration of flu as a heuristic for Covid-19, and vice versa.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.24.23289045v1" target="_blank">Is Covid-19 Mortality “Like the Flu”? A Cumulative Death Rates Comparison</a>
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<li><strong>Increased consumption despite fewer occasions: A longitudinal analysis of COVID-19 lockdown effects on soft drink consumption in England</strong> -
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We examined the impact of a COVID-19 lockdown in England on the frequency of consumption occasions and amount of soft drinks consumed. Beverage consumption is strongly associated with specific, often social, consumption situations (e.g., going out). We reasoned that lockdown would affect consumption behaviour because it removed typical soft drink consumption situations. Specifically, we hypothesised that soft drink consumption occasions and amount would be reduced during lockdown compared to before and after lockdown, especially in typical soft drink consumption situations. In two surveys (Dec. 2020 and May 2021) among the same participants (N = 211, N = 160; consuming soft drinks at least once/week), we assessed the frequency of soft drink and water consumption occasions before, during, and after the November/December 2020 lockdown, across typical soft drink and water drinking situations. This presents a detailed picture of the situations in which participants drink soft drinks and water, and how this was affected by a lockdown. We also assessed the daily amount of soft drinks and water consumed in each period, and perceived habitualness of drinking soft drinks and water. As predicted, participants reported fewer occasions of drinking soft drinks during lockdown compared to before and after, especially in typical soft drink consumption situations. Unexpectedly, however, the daily amount of soft drinks consumed increased during lockdown, compared to before and after, especially among participants with stronger perceived habitualness of soft drink consumption. Exploratory analyses suggest that during lockdown, participants increased their soft drink consump¬¬tion at home. Water consumption, on the other hand, was not systematically affected by the lockdown. These findings suggest that even if some typical consumption situations disappear, consumption may be hard to disrupt if the behaviour is rewarding.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/wdx5k/" target="_blank">Increased consumption despite fewer occasions: A longitudinal analysis of COVID-19 lockdown effects on soft drink consumption in England</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>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>: Omicron Variant of COVID-19<br/><b>Intervention</b>: Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>: Xiangao Jiang<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 Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-1283.222; Biological: mRNA-1273.222<br/><b>Sponsor</b>: ModernaTX, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: RD-X19; Device: Sham<br/><b>Sponsor</b>: EmitBio Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation<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>Postoperative Sugammadex After COVID-19</strong> - <b>Conditions</b>: General Anesthesia; COVID-19<br/><b>Interventions</b>: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg<br/><b>Sponsor</b>: Korea University Ansan 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>A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azeliragon; Drug: Placebo<br/><b>Sponsor</b>: Salim S. Hayek<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>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of Post-COVID-19</strong> - <b>Condition</b>: Post-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>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>Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)<br/><b>Sponsor</b>: Azienda Socio Sanitaria Territoriale di Lecco<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 Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>: Mackay Memorial Hospital; Bened Biomedical 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>A Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<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>Effect of Telerehabilitation Practice in Long COVID-19 Patients</strong> - <b>Conditions</b>: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care<br/><b>Sponsor</b>: Indonesia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech Co., Ltd<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>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus Medical Center<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>Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: abatacept infusion; Drug: Placebo group<br/><b>Sponsor</b>: University of Minnesota<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 Study of Silmitasertib (CX-4945) in Healthy Subject</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: CX-4945<br/><b>Sponsor</b>: Senhwa Biosciences, Inc.<br/><b>Active, not recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Well-Defined Heparin Mimetics Can Inhibit Binding of the Trimeric Spike of SARS-CoV-2 in a Length-Dependent Manner</strong> - The emergence of new SARS-CoV-2 variants and the dangers of long-covid necessitate the development of broad-acting therapeutics that can reduce viral burden. SARS-CoV-2 employs heparan sulfate (HS) as an initial cellular attachment factor, and therefore, there is interest in developing heparin as a therapeutic for SARS-CoV-2. Its use is, however, complicated by structural heterogeneity and the risk of causing bleeding and thrombocytopenia. Here, we describe the preparation of well-defined…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>Cichorium intybus</em> L. “hairy” roots as a rich source of antioxidants and anti-inflammatory compounds</strong> - The present study aimed to determine the bioactive profile of various extracts of Cichorium intybus L. “hairy” roots. In particular, the total content of flavonoids as well as the reducing power, antioxidant and anti-inflammatory activity of the aqueous and ethanolic (70%) extracts were evaluated. The total content of flavonoids the ethanolic extract of the dry “hairy” root reached up to 121.3 mg (RE)/g, which was twofold greater than in the aqueous one. A total of 33 diverse polyphenols were…</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>Ethanol vapor inhalation treatment inhibits lethal respiratory viral infection with Influenza A</strong> - Ethanol (EtOH) effectively inactivates enveloped viruses in vitro, including influenza and SARS-CoV-2. Inhaled EtOH vapor may inhibit viral infection in mammalian respiratory tracts, but this has not yet been demonstrated. Here we report that unexpectedly low EtOH concentrations in solution, approximately 20% (v/v), rapidly inactivate influenza A virus (IAV) at mammalian body temperature (37°C) and are not toxic to lung epithelial cells upon apical exposure. Furthermore, brief exposure to 20%…</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 Exchange Proteins Directly Activated by cAMP (EPAC) as a Strategy for Broad-Spectrum Antiviral Development</strong> - The recent SARS-CoV-2 and mpox outbreaks have highlighted the need to expand our arsenal of broad-spectrum antiviral agents for future pandemic preparedness. Host-directed antivirals are an important tool to accomplish this as they typically offer protection against a broader range of viruses than direct-acting antivirals and have a lower susceptibility to viral mutations that cause drug resistance. In this study, we investigate the Exchange Protein Activated by cAMP (EPAC) as a target for…</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>Curcumin attenuates hydroxychloroquine-mediated apoptosis and oxidative stress via the inhibition of TRPM2 channel signalling pathways in a retinal pigment epithelium cell line</strong> - CONCLUSION: HCQ-mediated overload Ca^(2+) influx and retinal oxidative toxicity were induced in an ARPE19 cell line through the stimulation of TRPM2, although they were attenuated by treatment with CRC. Hence, CRC may be a potential therapeutic antioxidant for TRPM2 activation and HCQ treatment-induced retinal oxidative injury and apoptosis.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel pseudonucleosides and sulfamoyl-oxazolidinone <em>β</em>-<em>D</em>-glucosamine derivative as anti-COVID-19: design, synthesis, and <em>in silico</em> study</strong> - New pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl β-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and β-D-glucosamine hydrochloride in five steps; (protection, acetylation, removal of the Boc group, sulfamoylation, and cyclization). Further, novel glycosylated sulfamoyloxazolidin-2-one is prepared in three steps; carbamoylation, sulfamoylation, and intramolecular cyclization. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RAAS inhibition and beyond-cardiovascular medications in patients at risk of or affected by COVID-19</strong> - The COVID-19 pandemic led to an enormous burden on healthcare systems worldwide. Causal therapy is still in its infancy. Contrary to initial views that the use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) may increase the risk for a deleterious disease course, it has been shown that these agents may actually be beneficial for patients affected by COVID-19. In this article, we provide an overview of the three most commonly used classes of drugs in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein</strong> - Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus</strong> - Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for…</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>Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains</strong> - CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.</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>Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2</strong> - Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC(50) = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC(50))….</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>Hemoptysis after COVID-19 and the importance of differential diagnosis: Birt-Hogg-Dubé syndrome</strong> - Birt-Hogg-Dubé syndrome is a genodermatosis of autosomal dominant inheritance characterized by mutations in the folliculin (FLCN) gene. There is an inappropriate inhibition/activation of a protein, the foliculin, which may cause tumor lesions in skin, renal and lung lesions; they could have more risk of developing pneumothorax compared to the normal population. A 38-year-old male patient with bronchial asthma who consulted for hemoptysis three weeks after recovery from COVID-19 infection. A…</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>Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19</strong> - The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory…</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>Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions</strong> - The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ’combination…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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