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186 lines
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<title>26 July, 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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<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>Pandemic and student mental health: A cross-sectional and longitudinal analysis of mental health symptoms amongst university students and young adults after the first cycle of lockdown in the UK</strong> -
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Background Early COVID-19 research suggests a detrimental impact of the initial lockdown on young people’s mental health. Aims We investigated mental health amongst university students and young adults after the first UK lockdown and changes in symptoms over 6 months. Method 895 university students and 547 young adults not in higher education completed an online survey at T1 (July-September 2020). A subset of 201 university students also completed a 6-month follow-up survey at T2 (January-March 2021). Anxiety, depression, insomnia, substance misuse and suicide risk were assessed. Results At T1, ~40%, 25% and 33% of the participants reported moderate-severe anxiety and depression and substance misuse risk; clinically significant insomnia; and suicidal risk. Reduction in anxiety and depression were observed in participants reassessed at T2, but not in insomnia, substance misuse and suicidality. Student and non-student participants reported similar levels of mental health symptoms. Student status was not a significant marker of mental health symptoms, except for lower substance misuse risk. Cross-sectionally, greater symptoms across measures were consistently associated with younger age, pre-existing mental health condition(s), being a carer, worse-off financial status, increased sleep irregularity and difficulty since lockdown. Longitudinally, T2 symptoms were consistently associated with worse-off financial status and increased difficulty sleeping at T1. These associations however attenuated when baseline mental health symptoms were adjusted for in the models. Conclusions Mental health symptoms were prevalent in a large proportion of young people after the first UK lockdown. Risk factors identified may help characterise high-risk groups for enhanced support and inform interventions.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/w5k8e/" target="_blank">Pandemic and student mental health: A cross-sectional and longitudinal analysis of mental health symptoms amongst university students and young adults after the first cycle of lockdown in the UK</a>
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<li><strong>The Emotional Anatomy of Lockdown</strong> -
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Throughout the COVID-19 pandemic, policy makers have tried to balance the effectiveness of lockdowns (or stay-at-home orders) with their potential mental health costs. Yet, two years into the pandemic we lack solid evidence about the toll of lockdowns on daily emotional functioning, a key building block of mental health. Using data from two intensive longitudinal studies of 441 Australian participants, sampled at 14,511 occasions during COVID-19 lockdowns in 2021, we compared the degree, persistence, and regulation of people’s emotions on days in and out of lockdown. We found that the emotional toll of lockdowns was relatively mild: In lockdown, people experienced slightly more negative and slightly less positive emotion; returned to a mildly negative emotional state more quickly; and tended to use low-effort emotion regulation strategies. We conclude that people may be quite resilient to the psychological challenges posed by lockdowns.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hxatc/" target="_blank">The Emotional Anatomy of Lockdown</a>
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</div></li>
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<li><strong>Assessment of Canadian perinatal mental health services from the perspective of providers: Where can we improve?</strong> -
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Purpose: Perinatal mental health disorders are common, and rates have increased during the COVID-19 pandemic. It is unclear where providers may improve perinatal mental health care, particularly in countries lacking national guidelines, such as Canada. Methods: A cross-sectional survey of perinatal health providers was conducted to describe the landscape of perinatal mental health knowledge, screening, and treatment practices across Canada. Providers were recruited through listservs, social media, and snowball sampling. Participants completed an online survey that assessed their perinatal mental health training, service provision types, their patient wait times, and treatment barriers, and COVID-19 pandemic-related impacts. Results: A total of 435 providers completed the survey, including physicians, midwives, psychologists, social workers, nurses, and allied non-mental health professionals. Most (87.0%) did not have workplace mandated screening for perinatal mental illness but a third (66%) use a validated screening tool. Many (42%) providers stated their patients needed to wait more than 2 months for services. More than half (57.3%) reported they did not receive or were unsure if they received specialized training in perinatal mental health. Most (87.0%) indicated there were cultural, linguistic, and financial barriers to accessing services. Over two-thirds (69.0%) reported the COVID-19 pandemic reduced access to services. Conclusions: Survey findings reveal significant gaps in training, screening tool use, and timely and culturally safe treatment of perinatal mental health concerns. There is critical need for coordinated and nationally mandated perinatal mental health services in Canada to improve care for pregnant and postpartum people.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/cgy8b/" target="_blank">Assessment of Canadian perinatal mental health services from the perspective of providers: Where can we improve?</a>
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<li><strong>Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions</strong> -
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Background. We evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality.<br /><br />Methods. We used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening.<br /><br />Results. Models projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman’s lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman’s last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screeners<br /><br />Conclusions. Our independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.<br /><br />Funding. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O’Mahony is funded by Ireland’s Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily Burger receives salary support from the Norwegian Cancer Society.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.25.22278011v1" target="_blank">Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions</a>
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<li><strong>Transfer learning for Covid-19 detection in medical images</strong> -
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As of late, the Covid infection 2019 (COVID-19) has caused a pandemic sickness in more than 200 nations, therefore impacting billions of people. To control the spread of the coronavirus, it is crucial to detect infected individuals and ensure their complete isolation to prevent further infection. Chest X-rays and CT-scans have been proven to be very promising as signals of the infection can be clearly shown in lung areas. Transfer learning from ImageNet dataset has become the latent trend in medical imaging applications. However, there are major differences between ImageNet and medical imaging datasets. Therefore, the feasibility of transfer learning in medical applications remains questionable. This paper investigates the performance of five fine-tuned pre-trained models for chest x-rays and CT-scans classification in contrast with a deep CNN model built from scratch. DenseNet121, Resnet-50, Inception v2, Resnet101-V2 and VGG16 are selected and initialized with either random or pre-trained weights to classify augmented images into two classes: Covid and non-Covid. The performance evaluation proves the minuscule impact of training transfer learning models for good quality results, as all CNN models contribute almost equally to the classification and achieve considerable results in terms of precision, accuracy, recall and F1 score.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.25.22278017v1" target="_blank">Transfer learning for Covid-19 detection in medical images</a>
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<li><strong>McAN: an ultrafast haplotype network construction algorithm</strong> -
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Haplotype network is becoming popular due to its increasing use in analyzing genealogical relationships of closely related genomes. We newly proposed McAN, a minimum-cost arborescence based haplotype network con-struction algorithm, by considering mutation spectrum history (mutations in ancestry haplotype should be contained in descendant haplotype), node size (corresponding to sample count for a given node) and sampling time. McAN is two orders of magnitude faster than the state-of-the-art algorithms, making it suitable for analyzation of massive se-quences. Availability: Source code is written in C/C++ and available at https://github.com/Theory-Lun/McAN and https://ngdc.cncb.ac.cn/biocode/tools/BT007301 under the MIT license. The online web service of McAN is available at https://ngdc.cncb.ac.cn/ncov/online/tool/haplotype. SARS-CoV-2 dataset are available at https://ngdc.cncb.ac.cn/ncov/.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.23.501111v1" target="_blank">McAN: an ultrafast haplotype network construction algorithm</a>
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<li><strong>Poor sensitivity of iPSC-derived neural progenitors and glutamatergic neurons to SARS-CoV-2</strong> -
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COVID-19 is a respiratory disease affecting multiple organs including the central nervous system (CNS), with a characteristic loss of smell and taste. Although frequently reported, the neurological symptoms remain enigmatic. There is no consensus on the extent of CNS infection. Here, we derived human induced pluripotent stem cells (hiPSC) into neural progenitor cells (NPCs) and glutamatergic neurons to study their permissiveness to SARS-CoV-2 infection. Flow cytometry and western blot analysis indicated that NPCs and neurons do not express detectable levels of the SARS-CoV-2 receptor ACE2. We thus generated cells expressing ACE2 by lentiviral transduction to analyze in a controlled manner the properties of SARS-CoV-2 infection relative to ACE2 expression. Sensitivity of parental and ACE2 expressing cells was assessed with GFP- or luciferase- carrying pseudoviruses and with authentic SARS-CoV-2 Wuhan, D614G, Alpha or Delta variants. SARS-CoV-2 replication was assessed by microscopy, RT-qPCR and infectivity assays. Pseudoviruses infected only cells overexpressing ACE2. Neurons and NPCs were unable to efficiently replicate SARS-CoV-2, whereas ACE2 overexpressing neurons were highly sensitive to productive infection. Altogether, our results indicate that primary NPCs and glutamatergic neurons remain poorly permissive to SARS-CoV-2 across the SARS-CoV-2 variants inoculated, in the absence of ACE2 expression.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.25.501370v1" target="_blank">Poor sensitivity of iPSC-derived neural progenitors and glutamatergic neurons to SARS-CoV-2</a>
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<li><strong>Waning and boosting of functional humoral immunity to SARS-CoV-2</strong> -
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Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.22.501163v1" target="_blank">Waning and boosting of functional humoral immunity to SARS-CoV-2</a>
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<li><strong>Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19</strong> -
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T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.23.501235v1" target="_blank">Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19</a>
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<li><strong>The impact of surgical mask-wearing, contact tracing program, and vaccination on COVID-19 transmission in Taiwan from January 2020 to March 2022: a modelling study</strong> -
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The effectiveness of interventions such as public mask-wearing, contact tracing, and vaccination presents an important lesson for control of the further COVID-19 outbreaks without of whole country lockdowns and the restriction of individual movement. We simulated different scenarios of COVID-19 waves in Taiwan from 2020 to the beginning of March 2022 and considered the following interventions: travel restrictions, quarantine of infected individuals, contact tracing, mask-wearing, vaccination, and mass gathering restrictions. We propose an epidemiological compartmental model modified from the susceptible-exposed-infectious-removed (SEIR) model and derive a formula for the basic reproduction number (R0) describing its dependence on all investigated parameters. The simulation results are fitted with the official Taiwanese COVID-19 data. Thus, the results demonstrate that the fast introduction of the interventions and maintaining them at a high level are able the outbreak control without strict lockdowns. By estimation of the R0, it was shown that it is necessary to maintain on high implementation level of both non- and pharmaceutical intervention types to control the COVID-19 transmission. Our results can be useful as advice or recommendation for public health policies, and our model can be applied for other epidemiological simulation studies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22276025v2" target="_blank">The impact of surgical mask-wearing, contact tracing program, and vaccination on COVID-19 transmission in Taiwan from January 2020 to March 2022: a modelling study</a>
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<li><strong>Managing bed capacity and timing of interventions: a COVID-19 model considering behavior and underreporting</strong> -
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Introduction: At the start of the pandemic, the Philippine capital Metro Manila was placed under a strict lockdown termed Enhanced Community Quarantine (ECQ). When ECQ was eased to General Community Quarantine (GCQ) after three months, healthcare systems were soon faced with a surge of COVID-19 cases, putting most facilities at high or critical risk and prompting a return to a stricter policy. Methods: We developed a mathematical model considering behavior changes and underreporting to represent the first major epidemic wave in Metro Manila. Key parameters were fitted to the cumulative cases in the capital from March to September 2020. A bi-objective optimization problem was formulated that allows easing of restrictions at an earlier time and minimizes the necessary additional beds to ensure sufficient capacity in healthcare facilities once ECQ was lifted. Results: If behavior was changed one to four weeks earlier before GCQ, then the cumulative number of cases can be reduced by up to 55% and the peak delayed by up to four weeks. Increasing the reporting ratio during ECQ threefold may increase the reported cases by 23% but can reduce the total cases, including the unreported, by 61% on June 2020. If GCQ began on May 28, 2020, 48 beds should have been added per day to keep the capacity only at high-risk (75% occupancy). Among the optimal solutions, the peak of cases is lowest if ECQ was lifted on May 20, 2020 and with at least 56 additional beds per day. Conclusion: Since infectious diseases are likely to reemerge, the formulated model can be used as a decision support tool to improve existing policies and plan effective strategies that can minimize the socioeconomic impact of strict lockdown measures and ensure adequate healthcare capacity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.29.22273148v2" target="_blank">Managing bed capacity and timing of interventions: a COVID-19 model considering behavior and underreporting</a>
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<li><strong>The adverse impact of consecutive COVID-19 waves on mental health</strong> -
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Background: Although several studies documented the impact of COVID-19 on mental health, the long-term effects of COVID-19 on mental health remain unclear. Aims: To examine longitudinal changes in mental health prior to and during the consecutive COVID-19 waves in a well-established probability sample. Method: An online survey was completed by the participants of the COVID-19 add-on study at 4 timepoints (N1=1823, N2=788, N3=532, N4=383): pre-COVID period (2014/2015), 1st COVID-19 wave (April-May, 2020), 2nd COVID-19 wave (August-October, 2020) and 3rd COVID-19 wave (March-April, 2021). Data were collected via a set of validated instruments and analysed using latent growth models. Results: During the pandemic, we observed a significant increase in stress levels (slope=1.127, P<0.001) and depressive symptoms (slope=1.177, P<0.001). The rate of increase in stress levels (cov=2.167, P=0.002), but not in depressive symptoms (cov=0.558, P=0.10), was associated with the pre-pandemic mental health status of the participants. Further analysis revealed two opposing clusters of factors that influenced mental health: loneliness and COVID-19 showed a negative effect on emotionality, while higher resilience acted protectively. A greater increase in stress was observed in women and younger participants. Conclusions: The surge in stress levels and depressive symptoms persisted across all three consecutive COVID-19 waves. This surge is attributable to the effect of several risk factors including the status of mental health prior to the COVID-19 pandemic. Our findings have implications for strategies promoting resilience and addressing loneliness to mitigate the mental health impact of COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.25.21261094v3" target="_blank">The adverse impact of consecutive COVID-19 waves on mental health</a>
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<li><strong>Genomic epidemiology and phylodynamics for county-to-county transmission of SARS-CoV-2 in Minnesota, from 19A to Omicron</strong> -
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SARS-CoV-2 has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of the evolution and spread of pathogens and to inform policy decisions. Most efforts have focused on international or country-wide transmission, which are unable to highlight state-wide trends. We sequenced virus genomes from over 22,000 patients tested at Mayo Clinic Laboratories between 2020-2022 and leveraged detailed patient metadata to describe county-to-county spread in Minnesota. Our findings indicate that spread in the state was mostly dominated by viruses from Hennepin County, which contains the largest metropolis. For many counties, we found that state government restrictions eventually led to a decrease in the diversity of circulating viruses from other counties and that their complete removal in May of 2021 saw a drastic revert to levels at or greater than those observed during the months before. We also linked over 14,000 genomes with patient risk characteristics and infection-related phenotypes from the Mayo Clinic electronic health record. We found that the genetic relationship of Omicron viruses was structured by clinical outcomes when stratifying by patient risk factor and variant of concern. However, we were unable to identify nucleotide variants that drove this association.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.24.22277978v1" target="_blank">Genomic epidemiology and phylodynamics for county-to-county transmission of SARS-CoV-2 in Minnesota, from 19A to Omicron</a>
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<li><strong>Biomarkers and Outcomes in Hospitalized Covid-19 Patients: A Prospective Registry</strong> -
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ABSTRACT Objectives: To determine association of biomarkers high sensitivity C-reactive protein (hsCRP), D-dimer, interleukin-6 (IL-6), lactic dehydrogenase (LDH), ferritin and neutrophil-lymphocyte ratio (NLR) at hospital admission with clinical features and outcomes in Covid-19. Methods: Successive virologically confirmed Covid-19 patients hospitalized from April 2020 to July 2021 were recruited in a prospective registry. Details of clinical presentation, investigations, management and outcomes were recorded. All the biomarkers were divided into tertiles to determine associations with clinical features and outcomes. Numerical data are presented in median and interquartile range (IQR 25-75). Univariate and multivariate (age, sex, risk factor, comorbidity adjusted) odds ratio (OR) and 95% confidence intervals (CI) were calculated to determine association of deaths with each biomarker. Results: We identified 3036 virologically confirmed Covid-19 patients during the study period, 1215 were hospitalized and included in the present study. Men were 70.0%, aged >60y 44.8%, hypertension 44.8% diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5 days (IQR 4-7) and SpO2 95% (90-97). Total white cell count was 6.9x103/micro-litre, (5.0-9.8), neutrophils 79.2% (68.1-88.2) and lymphocytes 15.8% (8.7-25.5). Medians (IQR) for biomarkers were hsCRP 6.9 mg/dl (2.2-18.9), D-dimer 464 ng/dl (201-982), IL-6 20.1 ng/dl (6.5-60.4), LDH 284 mg/dl (220-396) and ferritin 351 mg/dl (159-676). Oxygen support at admission was in 38.6%, and non-invasive or invasive ventilatory support in 11.0% and 11.6% respectively. 173 (13.9%) patients died and 15 (1.2%) transferred to hospice care. For each biomarker, those in the second and third tertiles, compared to the first, had worse clinical and laboratory abnormalities, and greater oxygen and ventilatory support. Multivariate adjusted OR (95% CI) for deaths in second and third vs first tertiles, respectively, were for hsCRP 2.29(1.14-4.60) and 13.39(7.23-24.80); D-dimer 3.26(1.31-7.05) and 13.89(6.87-28.27); IL-6 2.61(1.31-5.18) and 10.96(5.88-20.43); ferritin 3.19(1.66-6.11) and 9.13(4.97-16.78); LDH 1.85(0.87-3.97) and 10.51(5.41-20.41); and NLR 3.34(1.62-6.89) and 17.52(9.03-34.00) (p<0.001). Conclusions: In Covid-19, high levels of biomarkers- hsCRP, D-dimer, IL-6, LDH, ferritin and NLR are associated with more severe illness and significantly greater in-hospital mortality. NLR, a simple, widely available and inexpensive investigation provides prognostic information similar to the more expensive biomarkers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.20.22277718v1" target="_blank">Biomarkers and Outcomes in Hospitalized Covid-19 Patients: A Prospective Registry</a>
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<li><strong>Reduced Olfactory Bulb Volume Accompanies Smelling Dysfunction After Mild SARS-CoV-2 Infection: The Hamburg City Health Study COVID Program</strong> -
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Background: Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain opaque. Olfactory bulb volumetry has been previously established as a promising surrogate marker of smelling function in multiple otorhinolaryngological diseases. In this work, we aimed to elucidate the correspondence between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment. Therefore, we conducted a large-scale magnetic resonance imaging (MRI)-based investigation of individuals recovered from mainly mild to moderate COVID-19. Methods: Data of 233 COVID-19 convalescents from the Hamburg City Health Study COVID Program were analyzed. Upon recruitment, patients underwent cranial MR imaging and assessment of neuropsychological testing. Automated olfactory bulb volumetry was performed on T2-weighted MR imaging data. Olfactory function was assessed longitudinally after recruitment and at follow-up via a structured questionnaire. Follow-up assessment included quantitative olfactometric testing with Sniffin Sticks. Group comparisons of olfactory bulb volume and olfactometric scores were performed between individuals with and without smelling impairment. The associations of olfactory bulb volume and neuropsychological as well as olfactometric scores were assessed via multiple linear regression. Results: Longitudinal assessment demonstrated a declining prevalence of olfactory dysfunction from 67.6% at acute infection, 21.0% at baseline examination (on average 8.31 +- 2.77 months post infection) and 17.5% at follow-up (21.8 +- 3.61 months post infection). Participants with post-acute olfactory dysfunction had a significantly lower olfactory bulb volume [mm3] at scan-time than normally smelling individuals (mean +- SD, baseline: 40.76 +- 13.08 vs. 46.74 +- 13.66, f=4.07, p=0.046; follow-up: 40.45 +- 12.59 vs. 46.55 +- 13.76, f=4.50, p=0.036). Olfactory bulb volume successfully predicted olfactometric scores at follow-up (r_sp = 0.154, p = 0.025). Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Conclusions: Our work demonstrates the association of smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Olfactory bulb volume was demonstrably lower in individuals with sustained smelling impairment and predicted smelling function longitudinally. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.24.22277973v1" target="_blank">Reduced Olfactory Bulb Volume Accompanies Smelling Dysfunction After Mild SARS-CoV-2 Infection: The Hamburg City Health Study COVID Program</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>Puerto Rico COVID-19 Vaccine Uptake Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Educational intervention<br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH); 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>A Study to Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br/><b>Sponsors</b>: BioNTech SE; 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>Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors<br/><b>Sponsor</b>: Central Hospital, Nancy, France<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>Beta-glucans for Hospitalised Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MC 3x3; Drug: Placebo<br/><b>Sponsors</b>: Concentra Educacion e Investigación Biomédica; Wohlstand Pharmaceutical<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Molnupiravir 200 mg<br/><b>Sponsors</b>: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth; Biological: Clover SCB-2019<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; University of Oxford<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>Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated; Biological: mRNA COVID-19 vaccine (Moderna); Biological: Viral Vector COVID-19 vaccine (AstraZeneca)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention</strong> - <b>Condition</b>: Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention<br/><b>Sponsor</b>: VA Office of Research and Development<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>Mineralocorticoid Use in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; ARDS<br/><b>Intervention</b>: Drug: Fludrocortisone Acetate 0.1 MG<br/><b>Sponsor</b>: Ain Shams University<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>Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/<br/><b>Sponsor</b>: Medical University of Lublin<br/><b>Suspended</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 of Immuno-bridging Between Different Manufacture Scales of Recombinant COVID-19 Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Pneumonia<br/><b>Intervention</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Combination Product: Delcetravir dry powder inhaler<br/><b>Sponsor</b>: Esfam Biotech Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physiotherapy for Persistent COVID-19 Disease Using Aerobic Exercise</strong> - <b>Conditions</b>: COVID-19; Genetic Predisposition to Disease<br/><b>Interventions</b>: Device: Experimental; Genetic: Control<br/><b>Sponsors</b>: Universidad Francisco de Vitoria; Universidad Rey Juan Carlos<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II/III Study of PIKA Recombinant SARS-CoV-2 Vaccine as a Booster Dose.</strong> - <b>Condition</b>: Covid-19 Vaccine<br/><b>Intervention</b>: Biological: PIKA COVID-19 vaccine<br/><b>Sponsor</b>: Yisheng Biopharma (Singapore) Pte. Ltd.<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression 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>Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior immune response to SARS-CoV-2</strong> - Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular…</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>Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression</strong> - The SARS-CoV-2 frameshifting element (FSE), a highly conserved mRNA region required for correct translation of viral polyproteins, defines an excellent therapeutic target against Covid-19. As discovered by our prior graph-theory analysis with SHAPE experiments, the FSE adopts a heterogeneous, length-dependent conformational landscape consisting of an assumed 3-stem H-type pseudoknot (graph motif 3_6), and two alternative motifs (3_3 and 3_5). Here, for the first time, we build and simulate, 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>Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding</strong> - Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X…</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 Omicron escapes mRNA vaccine booster-induced antibody neutralisation in patients with autoimmune rheumatic diseases: an observational cohort study</strong> - CONCLUSIONS: Striking antibody evasion manifested by the Omicron variant in patients with ARDs and current vaccine-induced immunity may not confer broad protection from Omicron breakthrough infection, highlighting the need for further research on vaccine effectiveness in patients with immune dysfunctions.</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>Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel</strong> - CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as…</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 impairs interferon production via NSP2-induced repression of mRNA translation</strong> - Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA…</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>Protease-Responsive Peptide-Conjugated Mitochondrial-Targeting AIEgens for Selective Imaging and Inhibition of SARS-CoV-2-Infected Cells</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to human health and lacks an effective treatment. There is an urgent need for both real-time tracking and precise treatment of the SARS-CoV-2-infected cells to mitigate and ultimately prevent viral transmission. However, selective triggering and tracking of the therapeutic process in the infected cells remains challenging. Here, we report a main protease (M^(pro))-responsive, mitochondrial-targeting, 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>Evaluation of the dual effects of antiviral drugs on SARS-CoV-2 receptors and the ACE2 receptor using structure-based virtual screening and molecular dynamics simulation</strong> - The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico medicine, repurposing is a quick and accurate way to screen US FDA-approved medications to find a therapeutic option for COVID-19 infection. Dual inhibitors possess dual inhibitory activity, which may be due to the inhibition of two different enzymes, and are considered better than combination therapy from the developmental and clinical perspectives. In this study, a molecular docking…</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>Targeting the Receptor-Binding Motif of SARS-CoV-2 with D-Peptides Mimicking the ACE2 Binding Helix: Lessons for Inhibiting Omicron and Future Variants of Concern</strong> - The COVID-19 pandemic continues to spread around the world, with several new variants emerging, particularly those of concern (VOCs). Omicron (B.1.1.529), a recent VOC with many mutations in the spike protein’s receptor-binding domain (RBD), has attracted a great deal of scientific and public interest. We previously developed two D-peptide inhibitors for the infection of the original SARS-CoV-2 and its VOCs, alpha and beta, in vitro. Here, we demonstrated that Covid3 and Covid_extended_1…</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>Unsymmetrical aromatic disulfides as SARS-CoV-2 Mpro inhibitors: Molecular docking, molecular dynamics, and ADME scoring investigations</strong> - COVID-19 pandemic caused by very severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) agent is an ongoing major global health concern. The disease has caused more than 452 million affected cases and more than 6 million death worldwide. Hence, there is an urgency to search for possible medications and drug treatments. There are no approved drugs available to treat COVID-19 yet, although several vaccine candidates are already available and some of them are listed for emergency use by 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>Severity, predictors and clinical correlates of post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study</strong> - BACKGROUND: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS.</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>Targeting ACLY efficiently inhibits SARS-CoV-2 replication</strong> - The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment…</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>Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation</strong> - COVID-19 which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has posed a worldwide pandemic and a major global public health threat. SARS-CoV-2 Nucleocapsid (N) protein plays a critical role in multiple steps of the viral life cycle and participates in viral replication, transcription, and assembly. The primary roles of N protein are to assemble with genomic RNA into the viral RNA-protein (vRNP) complex and to localize to the replication transcription complexes (RTCs)…</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>Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19</strong> - There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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