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<title>08 June, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Emotional distress and affective knowledge representation one year after the Covid-19 outbreak</strong> -
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This study examines whether the detrimental effects of the COVID-19 pandemic on the affectivity of the population extend one year after the outbreak. In an online-mobile session, participants completed surveys (i.e. demographic characteristics, positive-negative affectivity, interoceptive awareness) and a similarity judgment task of triplets of emotional concepts, from which we derived 2D maps of their affective knowledge representation. Compared with pre-pandemic data derived from a comparable population, we report three main findings. First, we observed enhanced negative affectivity during the pandemic, but no changes in positive affectivity levels. Second, increased self-reported interoceptive awareness compared to pre-pandemic data, with greater attention to bodily sensations and adaptive aspects of interoceptive sensitivity. Furthermore, female participants reported higher scores than males on the questionnaire subscales of Emotional Awareness and Attention Regulation. Third, the effect of pandemic-related conditions is also apparent in the mental organization of emotional concepts, especially for female participants (i.e., reduced coherence in the organization of the concepts along the arousal dimension and more misclassification of concepts based on arousal) and participants who did not perform physical activity (a collapse of the arousal dimension). Some of the effects of the pandemic, thus, persist about a year after the outbreak. These results advise providing programs of psychological and emotional assistance throughout the pandemic beyond the outbreak, and that age-dependent gender differences should be accounted for to define tailored interventions. Physical activity might relieve pandemic-related stressors, so it should be promoted during particularly stressful periods for the population.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/gmazn/" target="_blank">Emotional distress and affective knowledge representation one year after the Covid-19 outbreak</a>
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<li><strong>Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</strong> -
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Since the publication of the genome of SARS-CoV-2, the causative agent of COVID-19, in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although effcient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in "divergent organisms". In order to improve the annotation of SARS-CoV-2 proteins, we used the HHpred protein annotation tool. To avoid "false positive predictions" as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs) belonging mainly to the "Rhodopsin family"; on the basis of the literature, we then show that specific G protein-coupled receptors (GPCRs) of this family are known to form ion channels; we emphasize this is consistent with a recent Cryo-EM structure of SARS-CoV-2 ORF3a suggesting that it can form a non-selective Ca2+-permeable cation channel; furthermore, we highlight that some of the GPCRs identified as sharing similarities with ORF3a are targeted by antibodies in patients with COVID-19 and Long-COVID, suggesting that these similarities may trigger some of the observed autoimmune responses. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543855v1" target="_blank">Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</a>
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</div></li>
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<li><strong>Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</strong> -
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<div>
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Sarcomeres are the basic contractile units within cardiac myocytes, and the collective shortening of sarcomeres aligned along myofibrils generates the force driving the heartbeat. The alignment of the individual sarcomeres is important for proper force generation, and misaligned sarcomeres are associated with diseases including cardiomyopathies and COVID-19. The actin bundling protein, -actinin-2, localizes to the Z-Bodies of sarcomere precursors and the Z-Lines of sarcomeres, and has been used previously to assess sarcomere assembly and maintenance. Previous measurements of -actinin-2 organization have been largely accomplished manually, which is time-consuming and has hampered research progress. Here, we introduce sarcApp, an image analysis tool that quantifies several components of the cardiac sarcomere and their alignment in muscle cells and tissue. We first developed sarcApp to utilize deep learning- based segmentation and real space quantification to measure -actinin-2 structures and determine the organization of both precursors and sarcomeres/myofibrils. We then expanded sarcApp to analyze M-Lines using the localization of myomesin and a protein that connects the Z-Lines to the M-Line (titin). sarcApp produces 33 distinct measurements per cell and 24 per myofibril that allow for precise quantification of changes in sarcomeres, myofibrils, and their precursors. We validated this system with perturbations to sarcomere assembly. Surprisingly, we found perturbations that affected Z-Lines and M-Lines differently, suggesting that they may be regulated independently during sarcomere assembly.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.11.523681v2" target="_blank">Independent regulation of Z-lines and M-lines during sarcomere assembly in cardiac myocytes revealed by the automatic image analysis software sarcApp</a>
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</div></li>
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<li><strong>Estimating the effectiveness of COVID-19 vaccination against COVID-19 hospitalisation and death: a cohort study based on the 2021 Census, England.</strong> -
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Objective: To estimate the effectiveness of COVID-19 vaccination against hospitalisation for COVID-19 and death involving COVID-19 in England using linked population level data sources including the 2021 Census. Design: Retrospective cohort study. Setting: England, 21 March 2021 to 20 March 2022. Participants: Individuals alive and aged 16+ on 21 March 2021, resident in England, enumerated in the 2021 Census as a usual resident, and able to link to an NHS number. A sample of 583,840 individuals was used for the analysis. Exposures: COVID-19 vaccination: first dose, second dose and third dose/first booster dose, with categories for time since each dose. Main outcome measures: Hospitalisation for COVID-19 or death involving COVID-19. An adjusted Cox proportional hazard model was used to estimate the hazard ratio for the outcomes for vaccinated participants for different doses and time since dose compared to unvaccinated individuals. Vaccine effectiveness was estimated as (1 minus hazard ratio)x 100%. A control outcome of non-COVID-19 death was also assessed. Results: Vaccine effectiveness against hospitalisation for COVID-19 was 52.1% (95% confidence interval 51.3% to 52.8%) for a first dose, 55.6% (55.2% to 56.1%) for a second dose and 77.6% (77.3% to 78.0%) for a third dose, with a decrease in vaccine effectiveness 3+ months after the third dose. Vaccine effectiveness against COVID-19 mortality was 58.7% (52.7% to 63.9%) for a first dose, 88.5% (87.5% to 89.5%) for a second dose and 93.2% (92.9% to 93.5%) for a third dose, with evidence of waning 3+ months after the second and third doses. For the second dose, which is the most comparable across the different time-periods, vaccine effectiveness was higher against COVID-19 hospitalisation but slightly lower against COVID-19 mortality in the Omicron dominant period than the period before the Omicron variant became dominant. Vaccine effectiveness against both COVID-19 hospitalisation and mortality was higher in general for mRNA vaccines than non mRNA vaccines, however this could be influenced by the different populations given each vaccine vector. Non-zero VE against non-COVID-19 mortality indicates that residual confounding may impact the results, despite the inclusion of up-to-date socio-demographic adjustments and various sources of health data, with possible frailty bias, confounding by indication and a healthy vaccinee effect observed. Conclusions: The vaccine effectiveness estimates show increased protection with number of doses and a high level of protection against both COVID-19 hospitalisation and mortality for the third/booster dose, as would be expected from previous research. However, despite the various sources of health data used to adjust the models, the estimates for different breakdowns and for non-COVID-19 mortality expose residual confounding by health status, which should be considered when interpreting estimates of vaccine effectiveness.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23290982v1" target="_blank">Estimating the effectiveness of COVID-19 vaccination against COVID-19 hospitalisation and death: a cohort study based on the 2021 Census, England.</a>
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<li><strong>Impact of CoronaVac on Covid-19 outcomes of elderly adults in a large and socially unequal Brazilian city: A target trial emulation study</strong> -
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Background: Although CoronaVac was the only Covid-19 vaccine adopted in the first months of the Brazilian vaccination campaign, randomized clinical trials to evaluate its efficacy in elderly adults were limited. In this study, we use routinely collected surveillance and SARS-CoV-2 vaccination and testing data comprising the population of the fifth largest city of Brazil to evaluate the effectiveness of CoronaVac in adults 60+ years old against severe outcomes. Methods: Using large observational databases on vaccination and surveillance data from the city of Fortaleza, Brazil, we defined a retrospective cohort including 324,302 eligible adults aged ≥ 60 years to evaluate the effectiveness of the CoronaVac vaccine. The cohort included individuals vaccinated between January 21, 2021, and August 31, 2021, who were matched with unvaccinated persons at the time of rollout following a 1:1 ratio according to baseline covariates of age, sex, and Human Development Index of the neighborhood of residence. Only Covid-19-related severe outcomes were included in the analysis: hospitalization, ICU admission, and death. Vaccine effectiveness for each outcome was calculated by using the risk ratio between the two groups, with the risk obtained by the Kaplan-Meier estimator. Results: We obtained 62,643 matched pairs for assessing the effectiveness of the two-dose regimen of CoronaVac. The demographic profile of the matched population was statistically representative of the population of Fortaleza. Using the cumulative incidence as the risk associated with each group, starting at day 14 since the receipt of the second dose, we found an 82.3% (95% CI 66.3 - 93.9) effectiveness against Covid-19-related death, 68.4% (95% CI 42.3 - 86.4) against ICU admission, and 55.8% (95% CI 42.7 - 68.3) against hospital admission. Conclusions: Our results show that, despite critical delays in vaccine delivery and limited evidence in efficacy trial estimates, CoronaVac contributed to preventing deaths and severe morbidity due to Covid-19 in elderly adults.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23291015v1" target="_blank">Impact of CoronaVac on Covid-19 outcomes of elderly adults in a large and socially unequal Brazilian city: A target trial emulation study</a>
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<li><strong>Upper limb functional recovery in chronic stroke patients after COVID-19-interrupted rehabilitation: An observational study</strong> -
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Background: Upper limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted, and outings restricted, due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we investigated whether these patients recovered upper limb function after resumption of outpatient rehabilitation. Methods: In this observational study, 43 chronic stroke hemiplegic patients with impaired upper extremity function were scored for limb function via Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 months and 3 months before and 3 months after rehabilitation interruption were examined retrospectively, and scores immediately after resumption of care and at 3 and 6 months after resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance was performed with time as a factor and the change in FMA-UE and ARAT scores as dependent variables and by setting statistical significance at 5%. Results: Time of evaluation significantly impacted total, part C, and part D of FMA-UE as well as total, pinch, and gross movement of ARAT. Post-hoc tests showed that the magnitude of change in limb function scores from immediately after resumption of rehabilitation to 3 months after resumption was significantly higher than the change from 3 months before to immediately after interruption for total, and part D of FMA-UE, and grip, and gross movement of ARAT (p<0.05). Conclusions: The results suggest that upper limb functional decline in chronic stroke patients, caused by the SARS-CoV-2 pandemic-related therapy interruption and outing restrictions, was resolved after approximately 3 months of resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with impaired upper limb function due to inactivity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.05.23290309v1" target="_blank">Upper limb functional recovery in chronic stroke patients after COVID-19-interrupted rehabilitation: An observational study</a>
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<li><strong>Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial</strong> -
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Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets.1-3 Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy.4 Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.5 In vitro, metformin has antiviral activity against RNA viruses including SARS-CoV-2.6,7 In the COVID-OUT phase 3, randomized, placebo-controlled trial of outpatient treatment of COVID-19, metformin had a 42% reduction in ER visits/hospitalizations/death through 14 days; a 58% reduction in hospitalizations/death through 28 days, and a 42% reduction in Long COVID through 10 months.8,9 Here we show viral load analysis of specimens collected in the COVID-OUT trial that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95%CI, -1.05 to -0.06, p=0.027) while there was no virologic effect for ivermectin or fluvoxamine vs placebo. The metformin effect was consistent across subgroups and with emerging data.10,11 Our results demonstrate, consistent with model predictions, that a safe, widely available,12 well-tolerated, and inexpensive oral medication, metformin, can be repurposed to significantly reduce SARS-CoV-2 viral load.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23290989v1" target="_blank">Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial</a>
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<li><strong>OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate.</strong> -
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Background: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study aimed to investigate if disease-modifying anti-rheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. Methods: A population-based cohort study was conducted with the approval of NHS England, using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP9s SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide, or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. Findings: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (Leflunomide: +20.7 percentage points), and monitoring tests (Blood Pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Substantial and consistent differences were observed in overall missed monitoring rates between several groups throughout the study. Interpretation: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions, and patient groups, highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups. Funding: None. Keywords COVID-19, electronic health records, general practice, primary health care, antirheumatic agents, methotrexate, azathioprine, leflunomide.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23290826v1" target="_blank">OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate.</a>
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<li><strong>Social genomics, cognition, and well-being during the COVID-19 pandemic</strong> -
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Introduction - Adverse psychosocial Adverse psychosocial exposure is associated with increased proinflammatory gene expression and reduced type-1 interferon gene expression, a profile known as the conserved transcriptional response to adversity (CTRA). Little is known about CTRA activity in the context of cognitive impairment, although chronic inflammatory activation has been posited as one mechanism contributing to late-life cognitive decline. Methods - We studied 171 community-dwelling older adults from the Wake Forest Alzheimers Disease Research Center who answered questions via a telephone questionnaire battery about their perceived stress, loneliness, well-being, and impact of COVID-19 on their life, and who provided a self-collected dried blood spot sample. Of those, 148 had adequate samples for mRNA analysis, and 143 were included in the final analysis, which including participants adjudicated as having normal cognition (NC, n = 91) or mild cognitive impairment (MCI, n = 52) were included in the analysis. Mixed effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. Results - In both NC and MCI groups, eudaimonic well-being (typically associated with a sense of purpose) was inversely associated with CTRA gene expression whereas hedonic well-being (typically associated with pleasure seeking) was positively associated. In participants with NC, coping through social support was associated with lower CTRA gene expression, whereas coping by distraction and reframing was associated with higher CTRA gene expression. CTRA gene expression was not related to coping strategies for participants with MCI, or to either loneliness or perceived stress in either group. Discussion - Eudaimonic and hedonic well-being remain important correlates of molecular markers of stress, even in people with MCI. However, prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. These results suggest that MCI can selectively alter biobehavioral interactions in ways that could potentially affect the rate of future cognitive decline and may serve as targets for future intervention efforts.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.31.23290618v2" target="_blank">Social genomics, cognition, and well-being during the COVID-19 pandemic</a>
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<li><strong>Data-driven recombination detection in viral genomes</strong> -
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Recombination is a key molecular mechanism for the evolution and adaptation of viruses. The first recombinant SARS-CoV-2 genomes were recognized in 2021; as of today, more than seventy SARS-CoV-2 lineages are designated as recombinant. In the wake of the COVID-19 pandemic, several methods for detecting recombination in SARS-CoV-2 have been proposed; however, none could faithfully reproduce manual analyses by experts in the field. We hereby present RecombinHunt, a novel, automated method for the identification of recombinant genomes purely based on a data-driven approach. RecombinHunt compares favorably with other state-of-the-art methods and recognizes recombinant SARS-CoV-2 genomes (or lineages) with one or two breakpoints with high accuracy, within reduced turn-around times and small discrepancies with respect to the expert manually-curated standard nomenclature. Strikingly, applied to the complete collection of viral sequences from the recent monkeypox epidemic, RecombinHunt identifies recombinant viral genomes in high concordance with manually curated analyses by experts, suggesting that our approach is robust and can be applied to any epidemic/pandemic virus. Although RecombinHunt does not substitute manual expert curation based on phylogenetic analysis, we believe that our method represents a breakthrough for the detection of recombinant viral lineages in pandemic/epidemic scenarios.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.05.543733v1" target="_blank">Data-driven recombination detection in viral genomes</a>
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<li><strong>Atypical Chemokine Receptor 1 (Ackr1)-deficient Mice Resist Lethal SARS-CoV-2 Challenge</strong> -
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High pro-inflammatory chemokine levels have been reported in blood and lung in patients with COVID-19. To investigate specific roles in pathogenesis, we studied the regulation of chemokine ligands and receptors in the lungs of 4-6-month-old wild type C57BL/6 mice infected with the MA10 mouse-adapted strain of SARS-CoV-2. We found that atypical chemokine receptor 1 (Ackr1, also known as Duffy antigen receptor for chemokines/DARC) was the most highly upregulated chemokine receptor in infected lung, where it localized to endothelial cells of veins and arterioles. In a screen of 7 leukocyte chemoattractant or chemoattractant receptor knockout mouse lines, Ackr1-/- mice were unique in having lower mortality after SARS-CoV-2 infection, particularly in males. ACKR1 is a non-signaling chemokine receptor that in addition to endothelium is also expressed on erythrocytes and Purkinje cells of the cerebellum. It binds promiscuously to both inflammatory CC and CXC chemokines and has been reported to control chemokine availability which may influence the shape of chemotactic gradients and the ability of leukocytes to extravasate and produce immunopathology. Of note, erythrocyte ACKR1 deficiency is fixed in sub-Saharan African populations where COVID-19 has been reported to result in low mortality compared to worldwide data. Our data suggest the possibility of a causal contribution of ACKR1 deficiency to low sub-Saharan COVID-19 mortality and identify ACKR1 as a possible drug target in the disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.05.543759v1" target="_blank">Atypical Chemokine Receptor 1 (Ackr1)-deficient Mice Resist Lethal SARS-CoV-2 Challenge</a>
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<li><strong>Widespread impact of immunoglobulin V gene allelic polymorphisms on antibody reactivity</strong> -
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The ability of human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V gene (IGV) allelic polymorphisms. However, previous studies have provided only a limited number of examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many IGV allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiment further demonstrates that paratope allelic mutations on both heavy and light chain often abolish antibody binding. We also illustrate the importance of minor IGV allelic variants with low frequency in several broadly neutralizing antibodies to SARS-CoV-2 and influenza virus. Overall, this study not only highlights the pervasive impact of IGV allelic polymorphisms on antibody binding, but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543969v1" target="_blank">Widespread impact of immunoglobulin V gene allelic polymorphisms on antibody reactivity</a>
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</div></li>
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<li><strong>Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies</strong> -
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SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) {beta} sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). In donors exhibiting sustained anti-S antibody titers (designated as "sustainers"), S-reactive T cell clonotypes detected immediately after 2nd vaccination polarized to follicular helper T (Tfh) cells, which was less obvious in "decliners". Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh cells upon vaccination contributes to the longevity of anti-S antibody titers.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543529v1" target="_blank">Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies</a>
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<li><strong>A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</strong> -
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Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/n3dyf/" target="_blank">A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</a>
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<li><strong>A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</strong> -
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The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/m4gpq/" target="_blank">A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</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>Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Extracorporeal photopheresis<br/><b>Sponsor</b>: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases<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 Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation<br/><b>Sponsors</b>: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of 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>Safety Study of COVID19 Vaccine on the Market</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant new coronavirus vaccine (CHO cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Diagnostic Test: SARS CoV-2 antigen tests<br/><b>Sponsors</b>: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)<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>Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19</strong> - <b>Conditions</b>: SARS-CoV Infection; COVID-19<br/><b>Interventions</b>: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo<br/><b>Sponsor</b>: University of Texas Southwestern 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>Pycnogenol® in Post-COVID-19 Condition</strong> - <b>Conditions</b>: Post COVID-19 Condition; Long COVID<br/><b>Interventions</b>: Drug: Pycnogenol®; Drug: Placebo<br/><b>Sponsor</b>: University of Zurich<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Bailing capsule<br/><b>Sponsor</b>: Second Affiliated Hospital, School of Medicine, Zhejiang 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>Evaluating Emetine for Viral Outbreaks (EVOLVE)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Emetine Hydrochloride; Drug: Placebo<br/><b>Sponsors</b>: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers 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>Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2373; Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant<br/><b>Sponsor</b>: Novavax<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07817883<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19)</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19<br/><b>Interventions</b>: Drug: AER002; Other: Placebo<br/><b>Sponsors</b>: Michael Peluso, MD; Aerium Therapeutics<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 to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug<br/><b>Sponsor</b>: Quratis Inc.<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>Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study</strong> - <b>Conditions</b>: Postural Orthostatic Tachycardia Syndrome; COVID-19; Post COVID-19 Condition; Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Individual tailored exercise<br/><b>Sponsors</b>: Karolinska Institutet; Karolinska University Hospital<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>Modifying Adiposity Through Behavioral Strategies to Improve COVID-19 Rehabilitation</strong> - <b>Conditions</b>: Post-COVID Conditions; Obesity<br/><b>Interventions</b>: Behavioral: 12-weeks of Weight Loss; Behavioral: 12-weeks of Weight Stability<br/><b>Sponsors</b>: VA Office of Research and Development; South Texas Veterans Health Care System; Baltimore Veterans Affairs Medical Center<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>SARS-CoV-2 infection impairs NK cell functions <em>via</em> activation of the LLT1-CD161 axis</strong> - CONCLUSION: We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.</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>DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature</strong> - DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also…</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>Failure of TRPC6 inhibition to prevent COVID-19 deterioration: more questions than answers</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis</strong> - Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite,…</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 Fluorescent Benzothiazolyl-Coumarin Hybrids as Anti-SARS-COVID-2 Agents Supported by Molecular Docking Studies: Design, Synthesis, X-ray Crystal Structures, DFT, and TD-DFT/PCM Calculations</strong> - This study revealed the design and preparation of new 3-(benzo[d]thiazol-2-yl)-2H-chromen-2-one derivatives 9a-h. The structures of the synthesized products were elucidated by their spectroscopic data and X-ray crystallography for compounds 9a and 9d. The prepared new compounds were measured for their fluorescence, and a good result indicated that the emission efficiency was decreased by increasing the electron-withdrawing groups from the unsubstituted compound 9a to the highly substituted…</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 dual nature of constraints on foreign worker participation in sports and physical activity in South Korea during COVID-19</strong> - This study provides a different understanding of the constraints imposed by the pandemic and the official and unofficial restrictions that accompanied it. It is an empirical effort demonstrating that the pandemic’s effects are not purely negative, but rather, also helped to produce positive and productive practices that draw upon both the inhibiting and enabling features of the constraints it triggered. Engaging with “productive power” in Foucault by considering constraints as practices that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A</strong> - Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial</strong> - CONCLUSION: In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.</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 efficient computational protocol for template-based design of peptides that inhibit interactions involving SARS-CoV-2 proteins</strong> - The RNA-dependent RNA polymerase (RdRp) complex of SARS-CoV-2 lies at the core of its replication and transcription processes. The interfaces between holo-RdRp subunits are highly conserved, facilitating the design of inhibitors with high affinity for the interaction interface hotspots. We, therefore, take this as a model protein complex for the application of a structural bioinformatics protocol to design peptides that inhibit RdRp complexation by preferential binding at the interface of 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>Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL<sup>pro</sup> and M<sup>pro</sup> proteases, and nsp14 guanine N7-methyltransferase</strong> - Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. SARS-CoV-2 main protease (M^(pro), 3CL^(pro)) and papain-like protease (PL^(pro)) are responsible for viral polyprotein cleavage-a process crucial for viral survival and replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2H)-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is a potent, covalent inhibitor of both the proteases and its potency was evaluated 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>One Week of Oral Camostat Versus Placebo in Non-Hospitalized Adults with Mild-to-Moderate COVID-19: A Randomized Controlled Phase 2 Trial</strong> - CONCLUSIONS: In a phase 2 study of non-hospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance nor time to symptom improvement, nor reduce hospitalizations or deaths. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT04518410.).</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 clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor</strong> - CONCLUSION: Emvododstat appears to be a strong CYP2D6 inhibitor. No drug-related treatment emergent adverse effects (TEAEs) were considered to be severe or serious.</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 PRMT5/WDR77 complex restricts hepatitis E virus replication</strong> - Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host…</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>Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors</strong> - Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword. Numerous studies have revealed the relationship between abnormal GSDMD activation and various inflammatory diseases, including sepsis, coronavirus disease 2019 (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>Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection</strong> - Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson’s disease and is used for treatment of Parkinson’s disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data…</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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