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<title>23 November, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses</strong> -
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Humans display vast clinical variability upon SARS-CoV-2 infection, partly due to genetic and immunological factors. However, the magnitude of population differences in immune responses to SARS-CoV-2 and the mechanisms underlying such variation remain unknown. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells from 222 healthy donors of various ancestries stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces a weaker, but more heterogeneous interferon-stimulated gene activity than influenza A virus, and a unique pro-inflammatory signature in myeloid cells. We observe marked population differences in transcriptional responses to viral exposure that reflect environmentally induced cellular heterogeneity, as illustrated by higher rates of cytomegalovirus infection, affecting lymphoid cells, in African-descent individuals. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell proportions on population differences in immune responses, with genetic variants having a narrower but stronger effect on specific loci. Additionally, natural selection has increased immune response differentiation across populations, particularly for variants associated with SARS-CoV-2 responses in East Asians. We document the cellular and molecular mechanisms through which Neanderthal introgression has altered immune functions, such as its impact on the myeloid response in Europeans. Finally, colocalization analyses reveal an overlap between the genetic architecture of immune responses to SARS-CoV-2 and COVID-19 severity. Collectively, these findings suggest that adaptive evolution targeting immunity has also contributed to current disparities in COVID-19 risk.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.22.517073v1" target="_blank">Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses</a>
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<li><strong>Modeling COVID-19 in different countries as sequences of SI waves</strong> -
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The COVID-19 pandemic has been a huge challenge worldwide for many institutions, researchers, national health organizations, and the pharmaceutical industry. As natural scientists and engineers, we attempted to contribute by calculating models and analyzing data to keep track of the pandemic. While a frequent goal is to predict the next pandemic wave by considering all influencing parameters, we examined methods to calculate a model course of the entire pandemic. This is done by reconstructing the course of infections into multiple model waves that sum up into a pandemic model that is close to the real course. The model wave parameters are varied by an algorithm, such as the Excel solver, to minimize the difference between the real and model courses. By reconstructing the course of infections using the commonly known SIR model, we found that the calculated model parameters were ambiguous and difficult to interpret. In contrast, we found that sequenced SI model waves provide an astonishing precise digital representation of the pandemic course. Until November 2022, we found between six and 16 waves (depending on the country) in each of the 14 countries investigated. The calculated parameters are easy to interpret and are comparable between different waves and countries. These wave parameters may be correlated with the virus types and measures in each country by other researchers. New waves are detectable early as they show a certain deviation from the actual model wave. After the maximum of the last real wave, the model indicates the further procedure for the pandemic course.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.22.22282631v1" target="_blank">Modeling COVID-19 in different countries as sequences of SI waves</a>
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<li><strong>One-day preoperative systemic treatment regimen outcompetes five-day regimen in potentially resectable esophageal squamous cancer</strong> -
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Introduction The current standard-of-care treatment for locally advanced esophageal squamous cell carcinoma (ESCC) is preoperative chemoradiotherapy.1 However, most ESCC patients in China are from economically underdeveloped areas 2. The shortage of medical resources exhaust the willingness of such patients to receive radiotherapy. Therefore, neoadjuvant chemotherapy alone is a preferred option in Eastern Asia. The one-day platinum plus paclitaxel (pla/pac) regimen is commonly used in China, while the five-day platinum plus 5-fluorouracil (5FU-based) regimen is preferred in other countries.3 Especially in the context of the COVID-19 pandemic, how to deliver timely and effective treatment for cancer patients has become a huge challenge.4 Fortunately, The effectiveness of immunochemotherapy is encouraging. We compared the effectiveness among the one-day immunochemotherapy regimen, the one-day chemotherapy regimen and the five-day chemotherapy regimen in locally advanced ESCC patients treated with preoperative systemic treatment (POST). Methods We retrospectively analyzed locally advanced ESCC patients who had received POST from January 2012 to September 2021 at the Department of Thoracic Surgery, Guangdong Provincial Peoples9 Hospital. The clinical and follow-up data were collected and analyzed according to 3 regimens including 5FU-based regimen which contains docetaxel+platinum+5-FU and platinum+5-FU regimens (5FU-based group), pla/pac regimen and pla/pac plus PD-1 inhibitor regimen (pla/pac/ICI). Complete response and partial response were defined as the objective response rate (ORR) per RECIST1.1 5. Categorical and continuous variables were analyzed by Chi-square and One-way ANOVA respectively, and overall survival (OS) was assessed using Kaplan-Meier analysis. Statistical analysis was performed using SPSS v26 (Inc, Chicago, Illinois) and R, and a P value less than 0.05 was considered statistically significant. Results A total of 395 POST-treated ESCC patients were enrolled, including 72 in the 5FU-based group, 168 in the pla/pac group, and 155 in the pla/pac/ICI group, and the mean follow-up time were 32.2, 44.2 and 14.3 months, respectively. There was no statistical difference in the baseline data among the three groups except POST cycles (Table). As shown in the Figure 1A, the pla/pac/ICI group had the greatest benefit, with an ORR of 63.2% (P < 0.05) and a surgery conversion rate of 85.2% (P < 0.05). Moreover, the ypT0 or ypTis rate in the pla/pac/ICI group was significantly higher than that in 5FU-based and pla/pac groups. Furthermore, pla/pac/ICI group acquired a better short-term OS than the other groups (one-year OS: pla/pac/ICI 93.6% vs. pla/pac 87.4% vs. 5FU-based 70.5%, Figure 1B). Discussion The COVID-19 pandemic has caused considerable consumption of medical resourse and cancer patients bear the brunt of delays in the interruption of medical care during the long treatment period4. Thus, it is urgent to deliver more effective and time-saving treatment. In this study, we demonstrated that the one-day pla/pac/IC group regimen has obvious clinical advantage over one-day pla/pac and five-day 5FU-based regimen in terms of radiological/pathological tumor response, as well as long-term overall survival. Taken both time cost and efficacy into consideration, the one-day pla/pac/IC regimen migth be a more favorable option in treating locally advanced ESCC. Despite exciting results, patients treated with immunotherapy shoulder great financial burden. Our results showed that there were no significant differences in the surgical conversion rate and response rate between one-day pla/pac and five-day 5FU-based group. Furthermore, the pla/pac group showed better survival benefits than 5FU-based group. The one-day pla/pac regimen might be an better alternative until affordable immunotherapy could benefit the whole population. Conclusion In the context of the COVID-19 pandemic, one-day immunochemotherapy should be considered because it may yield higher response rates, bring better overall survival as well as significantly reduce the risk of treatment interruption. If immunotherapy is not available, the 1-day pla/pac regimen is also an effective and timely alternative.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282548v1" target="_blank">One-day preoperative systemic treatment regimen outcompetes five-day regimen in potentially resectable esophageal squamous cancer</a>
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<li><strong>Susceptibility-Weighted Magnetic Resonance Imaging Highlights Brain Alterations in COVID Recovered Patients.</strong> -
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The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID-recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of the brain when compared to healthy controls (HCs). Hence, we performed our investigations on susceptibility-weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID, has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed an unpaired two-sample t-test over the pre-processed SWI volumes of both groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in the anterior cingulate gyrus and midbrain, which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of the SWI modality for analysis of post-COVID symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282600v1" target="_blank">Susceptibility-Weighted Magnetic Resonance Imaging Highlights Brain Alterations in COVID Recovered Patients.</a>
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<li><strong>Cost of In-patient Management of Covid-19 Patients in a Tertiary Hospital in Kuwait</strong> -
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Background: Among the GCC countries affected by COVID-19 infections, Kuwait was impacted with 658,520 cases and 2,563 deaths as reported by WHO on September 30, 2022. However, the impact of the COVID-19 epidemic on the economy of Kuwait especially in health sector is unknown. Objective: The aim of this study is to determine the total cost of COVID-19 in-patient management in Kuwait. Method: Retrospective design was employed in this study. A total 485 Covid-19 patients admitted to a tertiary hospital assigned to manage Covid-19 cases was randomly selected for this study from 1st May to 31st September 2021. Data on sociodemographic, length of stay (LOS), discharge status and comorbidity were obtained from the patients9 medical records. Among others, data on cost in this study cover administration, utility, pharmacy, radiology, laboratory, nursing, and ICU costs. The unit cost per admission was imputed using a step-down costing method with three levels of cost centers. The unit cost was multiplied by the individual patient’s length of stay to obtain the cost of care per patient per admission. Findings: The mean cost of Covid-19 inpatient per episode of care was KD 2,216 (SD=2,018) equals to US$ 7,344 (SD=6,688) with the average length of stay of 9.4 (SD=8.5) days per admission. The total treatment costs of Covid-19 inpatient (n=485) were estimated to be KD 1,074,644 (US$ 3,561,585), in which the physician and nursing care cost were the largest share of costs (42.1%) with KD 452,154 (US$ 1,498,529). The second- and third-largest costs were intensive care (20.6%) of KD 221,439 (US$ 733,893) and laboratory costs (10.2%) of KD 109,264 (US$ 362,123). The average cost for severe Covid-19 patient was KD 4,626 (US$ 15,332), which is almost three times higher than the non-severe patients of KD 1,544 (US$ 5,117). Conclusion: The cost of managing Covid-19 cases is substantial. The cost information can assist hospital managers and policymakers in designing more efficient interventions, especially for the management of high-risk groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282601v1" target="_blank">Cost of In-patient Management of Covid-19 Patients in a Tertiary Hospital in Kuwait</a>
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<li><strong>Inability to work following COVID-19 vaccination among healthcare workers - an important aspect for future booster vaccinations</strong> -
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Background COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections, especially among highly exposed healthcare workers (HCWs). However, vaccine-related inability to work among HCWs could overstrain healthcare systems. Methods This study examined sick leave and intake of pro re nata (PRN) medication after the first, second and third COVID-19 vaccination in HCWs. Subgroup analyses were performed for different vaccines, gender, healthcare professions, and for HCWs aged at least 30 years. Data was collected by using an electronic questionnaire. Findings Among 1,704 HCWs enrolled, in total 595 (34·9%) HCWs were on sick leave following at least one COVID 19 vaccination, leading to a total number of 1,550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273 the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. Interpretation A considerable number of HCWs have been on sick leave after COVID-19 vaccination, staff absences increase with each additional dose, depend on the vaccine, and vary between HCWs9 gender, and profession. In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to post-vaccination inability to work, which could acutely overload healthcare systems and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282594v1" target="_blank">Inability to work following COVID-19 vaccination among healthcare workers - an important aspect for future booster vaccinations</a>
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<li><strong>Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic</strong> -
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The COVID-19 pandemic has taken a devastating toll around the world. Since January 2020, the World Health Organization estimates 14.9 million excess deaths have occurred globally. Despite this grim number quantifying the deadly impact, the underlying factors contributing to COVID-19 deaths at the population level remain unclear. Prior studies indicate that demographic factors like proportion of population older than 65 and population health explain the cross-country difference in COVID-19 deaths. However, there has not been a holistic analysis including variables describing government policies and COVID-19 vaccination rate. Furthermore, prior studies focus on COVID-19 death rather than excess death to assess the impact of the pandemic. Through a robust statistical modeling framework, we analyze 80 countries and show that actionable public health efforts beyond just the factors intrinsic to each country are necessary to explain the cross-country heterogeneity in excess death.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282563v1" target="_blank">Do Public Health Efforts Matter? Explaining Cross-Country Heterogeneity in Excess Death During the COVID-19 Pandemic</a>
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<li><strong>Temporal Associations of Plasma Levels of the Secreted Phospholipase A2 Family and Mortality in Severe COVID-19</strong> -
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Previous research suggests that group IIA secreted phospholipase A<sub>2</sub> (sPLA<sub>2</sub>-IIA) plays a role in and predicts severe COVID-19 disease. The current study reanalyzed a longitudinal proteomic data set to determine the temporal (days 0, 3 and 7) relationship between the levels of several members of a family of sPLA<sub>2</sub> isoforms and the severity of COVID-19 in 214 ICU patients. The levels of six secreted PLA<sub>2</sub> isoforms, sPLA<sub>2</sub>-IIA, sPLA<sub>2</sub>-V, sPLA<sub>2</sub>-X, sPLA<sub>2</sub>-IB, sPLA<sub>2</sub>-IIC, and sPLA<sub>2</sub>-XVI, increased over the first 7 ICU days in those who succumbed to the disease. sPLA<sub>2</sub>-IIA outperformed top ranked cytokines and chemokines as predictors of patient outcome. A decision tree corroborated these results with day 0 to day 3 kinetic changes of sPLA<sub>2</sub>-IIA that separated the death and severe categories from the mild category and increases from day 3 to day 7 significantly enriched the lethal category. In contrast, there was a time-dependent decrease in sPLA<sub>2</sub>-IID and sPLA<sub>2</sub>-XIIB in patients with severe or lethal disease, and these two isoforms were at higher levels in mild patients. Taken together, proteomic analysis revealed temporal sPLA2 patterns that reflect the critical roles of sPLA<sub>2</sub> isoforms in severe COVID-19 disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282595v1" target="_blank">Temporal Associations of Plasma Levels of the Secreted Phospholipase A2 Family and Mortality in Severe COVID-19</a>
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<li><strong>Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels</strong> -
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With the emergence of SARS-CoV-2 variants that eluded immunity from vaccines and prior infections, vaccine shortages and their effectiveness pose unprecedented challenges for governments to expand booster vaccination programs. Fractionation of vaccine doses might be an effective strategy to help society to face these challenges, which may have comparable efficacies in contrast with the standard doses. In this study, we analyzed the relationship between in-vitro neutralization levels and the observed efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines using data from 13 studies from vaccination and convalescent cohorts. We further projected efficacies for fractional doses based on 51 studies included in our systematic review. By comparing with the convalescent level, vaccine efficacy increases from 8.8% (95% CI: 1.4%, 16.1%) to 71.8% (95% CI: 63.0%, 80.7%) against asymptomatic infection, and from 33.6% (95% CI: 23.6%, 43.6%) to 98.6% (95% CI: 97.6%, 99.7%) against symptomatic infection, respectively, along with the mean neutralization level from 0.1 to 10 folds of convalescent level. And mRNA vaccines provide the strongest protection, and decrease slowly for fractional dosing between 50% and 100% dosage. Our results are consistent with studies for immune protection from COVID-19 infection. Based on our study, we expect that fractional dose vaccination could provide a partial immunity for SARS-CoV-2 virus. Fractional doses of vaccines could be a viable vaccination strategy compared to full-dose vaccination and deserves further exploration.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282613v1" target="_blank">Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels</a>
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<li><strong>Mortality associated with different influenza subtypes in France between 2015-2019</strong> -
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Background: High levels of excess mortality during periods of active influenza circulation in France were observed in the years preceding the COVID-19 pandemic. Some of the factors that affect the rates of influenza associated mortality are influenza vaccination coverage levels in different population groups and practices for testing for influenza and related use of antiviral medications for various illness episodes (including pneumonia hospitalizations) during periods of active influenza circulation in the community. Methods: Data on sentinel ILI surveillance and sentinel virological surveillance in France were combined in a framework of a previously developed regression model to estimate the number of deaths associated with the circulation of the major influenza subtypes (A/H3N2, A/H1N1, B/Yamagata and B/Victoria) in France between 2015-2019. Results: Between week 3, 2015 and week 2, 2020, there were on average 15403 (95% CI (12591,18229)) annual influenza-associated deaths, of which 60.3% (49.9%,71.9%) were associated with influenza A/H3N2, and 29.5% (13.3%,45.5%) were associated with influenza B/Yamagata. During weeks when levels of ILI consultation in mainland France were above 50 per 100,000 persons, 7.9% (6.5%,9.4%) of all deaths in France were influenza-associated. Conclusions: High rates of influenza-associated mortality in France prior to the COVID-19 pandemic suggest that boosting influenza vaccination coverage in different population groups and testing for influenza in respiratory illness episodes (including pneumonia hospitalizations) during periods of active influenza (particularly influenza A/H3N2) circulation in combination with the use of antiviral medications is needed to mitigate the impact of influenza epidemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282612v1" target="_blank">Mortality associated with different influenza subtypes in France between 2015-2019</a>
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<li><strong>Survey Examination of Resilience, Psychological, and Relational Well-Being during COVID-19: A Developmental and Cross-Cultural Dataset</strong> -
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The datasets include relevant psychological and demographic variables relating to people’s relationships, perceptions, and reactions to the Covid-19 pandemic. Participants were recruited from the United States (N = 396), China (N = 156), and Iran (N = 248). Participants were directed to an online survey that assessed their psychological well-being, affective states, factors related to life satisfaction, and their experiences with the Covid-19 pandemic. For the United States, participants were separated by developmental stage (e.g., young adults between 18 and 35 years old and older adults who were 55 years old or older). Participants from China and Iran were 18 years old or older. Participants from the United States also provided qualitative data in the form of a text-box response where they described their reactions to the Covid-19 pandemic. These data may be relevant for researchers who want to investigate cross-cultural or developmental differences in people’s psychological states, perceptions, and reactions in the beginning phases of the Covid-19 pandemic.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/k4jfa/" target="_blank">Survey Examination of Resilience, Psychological, and Relational Well-Being during COVID-19: A Developmental and Cross-Cultural Dataset</a>
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<li><strong>The Hazards of Daily Stressors: Comparing the Experiences of Sexual and Gender Minority Young Adults to Cisgender Heterosexual Young Adults during the COVID-19 Pandemic</strong> -
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Some individuals may be at greater risk for encountering stressors in daily life than others, especially those with minority identities. Initial evidence shows that the disparities between cisgender heterosexual (CH) individuals and sexual and gender minority (SGM) individuals on stress-related experiences may be exacerbated by the COVID-19 pandemic. We examined the daily stressors experienced by undergraduate students during the COVID-19 pandemic (stressor exposure), the association between the experience of daily stress and same-day negative mood (stressor reactivity), and whether these varied between undergraduate students with SGM identities and their CH counterparts using a 14-day daily diary design. We did not find significant differences between SGM and CH groups on stressor exposure or stressor reactivity. One common feature of daily diary data is right censoring, which is when some individuals do not experience specific events during the study duration. We used multilevel survival analysis, which accounts for right censored data, to examine group differences in the risks of stressor exposure. We discuss the statistical issues involved when right-censored cases are not taken into consideration in studies of stressor exposure and propose multilevel survival analysis as one solution to move the field towards more accurately understanding whether and when SGM individuals are at greater risk for stressors.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2d7bm/" target="_blank">The Hazards of Daily Stressors: Comparing the Experiences of Sexual and Gender Minority Young Adults to Cisgender Heterosexual Young Adults during the COVID-19 Pandemic</a>
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<li><strong>In-depth characterization of the Syrian hamster as translational model for COVID-19 in humans</strong> -
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The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the importance of having proper tools and models to study the pathophysiology of emerging infectious diseases to test therapeutic protocols, assess changes in viral phenotype and evaluate the effect of viral evolution. This study provides a comprehensive characterization of the Syrian hamster (Mesocricetus auratus) as an animal model for SARS-CoV-2 infection, using different approaches (description of clinical signs, viral replication, receptor profiling and host immune response) and targeting four different organs (lungs, intestine, brain and PBMCs). Our data showed that both male and female hamsters are susceptible to the infection and develop a disease similar to the one observed in patients with COVID-19, including moderate to severe pulmonary lesions, inflammation and recruitment of the immune system in lungs and at systemic level. However, all animals recovered within 14 days without developing the severe pathology seen in humans, and none of them died. We found faint evidence for intestinal and neurological tropism associated with absence of lesions and a minimal host response in intestines and brains, highlighting another crucial difference with the multi-organ impairment of severe COVID-19. When comparing male and female hamsters, it was observed that males sustained higher viral shedding and replication in lungs, suffered from more severe symptoms and histopathological lesions and triggered higher pulmonary inflammation. Overall, these data confirm the Syrian hamster as being a suitable model for mild-moderate COVID-19 and reflect sex-related differences in the response against the virus observed in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.22.517339v1" target="_blank">In-depth characterization of the Syrian hamster as translational model for COVID-19 in humans</a>
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<li><strong>Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice</strong> -
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Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir, an orally available inhibitor of the 3- chymotrypsin-like cysteine protease, has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.22.517465v1" target="_blank">Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice</a>
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<li><strong>Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</strong> -
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Random genetic drift in the population-level dynamics of an infectious disease outbreak results from the randomness of inter-host transmission and the randomness of host recovery or death. The strength of genetic drift has been found to be high for SARS-CoV-2 due to superspreading, and this is expected to substantially impact the disease epidemiology and evolution. Noise that results from the measurement process, such as biases in data collection across time, geographical areas, etc., can potentially confound estimates of genetic drift as both processes contribute “noise” to the data. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude. Corrections taking into account epidemiological dynamics (susceptible-infected-recovered or susceptible-exposed-infected-recovered models) do not explain the discrepancy. Moreover, the levels of genetic drift that we observe are higher than the estimated levels of superspreading found by modeling studies that incorporate data on actual contact statistics in England. We discuss how even in the absence of superspreading, high levels of genetic drift can be generated via community structure in the host contact network. Our results suggest that further investigations of heterogeneous host contact structure may be important for understanding the high levels of genetic drift observed for SARS-CoV-2 in England.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.21.517390v1" target="_blank">Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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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>A comparative in-vitro study on antimicrobial efficacy of on-market alcohol-based hand washing sanitizers towards combating microbes and its application in combating Covid-19 global outbreak</strong> - The coronavirus disease 2019 (COVID-19) outbreak has created endless social, economic, and political fear in the global human population. Measures employed include frequent washing hands and using alcohol-based hand sanitisers and hand rubs as instant hand hygiene products. Due to the need to mitigate the pandermic, there is an increase in the local production of alcohol-based hand sanitisers, whose quality and efficacy against germs and the virus are questionable. Therefore, the current study…</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 role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis</strong> - BACKGROUND: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics</strong> - BACKGROUND: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics.</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>Reactogenicity and immunogenicity of the intradermal administration of BNT162b2 mRNA vaccine in healthy adults who were primed with an inactivated SARS-CoV-2 vaccine</strong> - Because of the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), safe and effective vaccines are urgently required. The shortage of effective vaccines is a major challenge in many developing countries. We studied intradermal (ID) fractional dose BNT162b2 mRNA (Comirnaty®, Pfizer-BioNTech) as a booster dose in healthy adults who were previously immunized with an inactivated SARS-CoV-2 vaccine. This is a retrospective cohort study that included healthy adults who 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>Statin Therapy in COVID-19: Inhibition of NETosis</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>Infliximab as a potential treatment for COVID-19</strong> - INTRODUCTION: : As the third year of the SARS-CoV-2 pandemic approaches, COVID-19 continues to cause substantial morbidity and mortality due to waning vaccine efficacy and the emergence of new, highly contagious subvariants and better therapies are urgently needed.</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 of phytochemicals in Qingfei Paidu decoction for the treatment of coronavirus disease 2019 by targeting the virus-host interactome</strong> - Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of COVID-19 by targeting the virus-host interactome and verifying the antiviral activities of its active components in vitro. Key active components and targets were identified by…</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>Antcin A, a phytosterol regulates SARS-CoV-2 spike protein-mediated metabolic alteration in THP-1 cells explored by the <sup>1</sup> H-NMR-based metabolomics approach</strong> - The mechanism of SARS-CoV-2 spike protein-mediated perturbations of metabolic pathways and modulation of antcin A, a steroid-like compound isolated from Taiwanofungus camphoratus, are not studied. Here, we investigated the metabolic alteration by SARS-CoV-2 spike protein and the regulatory effect of antcin A on SARS-CoV-2 spike protein-induced metabolic changes in the Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) using proton nuclear magnetic resonance (¹ H-NMR) 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>A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins</strong> - We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses,…</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>Discovering new potential inhibitors to SARS-CoV-2 RNA dependent RNA polymerase (RdRp) using high throughput virtual screening and molecular dynamics simulations</strong> - RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active…</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>S-allylmercapto-N-acetylcysteine ameliorates pulmonary fibrosis in mice via Nrf2 pathway activation and NF-κB, TGF-β1/Smad2/3 pathway suppression</strong> - Pulmonary fibrosis (PF) is a chronic lung disease characterised by alveolar inflammatory injury, alveolar septal thickening, and eventually fibrosis. Patients with severe Coronavirus Disease 2019 (COVID-19) may have left a certain degree of pulmonary fibrosis. PF is commonly caused by oxidative imbalance and inflammatory damage. S-allylmercapto-N-acetylcysteine (ASSNAC) exhibits anti-oxidative and anti-inflammatory effects in other diseases. However, the pharmacodynamics of ASSNAC remain unclear…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Anti-Spike IgG Antibody and ACE2 Receptor Binding Inhibition Levels among Breakthrough Stage Veteran Patients</strong> - SARS-CoV-2 mRNA vaccines have been critical to curbing pandemic COVID-19; however, a major shortcoming has been the inability to assess levels of protection after vaccination. This study assessed serologic status of breakthrough infections in vaccinated patients at a Veterans Administration medical center from June through December 2021 during a SARS-CoV-2 delta variant wave. Breakthrough occurred mostly beyond 150 days after two-dose vaccination with a mean of 239 days. Anti-SARS-CoV-2 spike…</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 glycyrrhizic acid preparation treating comorbid liver injury in COVID-19: A systematic review</strong> - Background: No specific drug for COVID-19 has been found, and many studies have found that different degrees of liver injury often occurred after infection with COVID-19. Glycyrrhizic acid preparation (GAP) has been frequently used clinically, often combined with conventional treatments such as antiviral therapy, to improve the prognosis of COVID-19 and patients’ liver function. Aims: To critically review and analyze clinical evidence on the efficacy and safety of GAP in the treatment of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein</strong> - The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against 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>Masitinib analogues with the <em>N</em>-methylpiperazine group replaced - A new hope for the development of anti-COVID-19 drugs</strong> - Masitinib is an orally acceptable tyrosine kinase inhibitor that is currently investigated under clinical trials against cancer, asthma, Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis. A recent study confirmed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity of masitinib through inhibition of the main protease (M^(pro)) enzyme, an important pharmacological drug target to block the replication of the coronavirus. However, due to the adverse…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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