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188 lines
51 KiB
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<title>24 December, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Epidemiological Risk in Italy Increases During the Cold Season and Heatwaves: Considerations for Health Policies During COVID-19 and Future Crises.</strong> -
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Objectives. This paper aims to investigate the interaction between SARS-CoV-2 and historical seasonal and environmental mortality factors to assess its real impact on public health in Italy. Study design. The study is longitudinal retrospective. Methods. The relationship between the number of deaths in the period 2015-2019 and the average monthly temperatures was investigated. The excess deaths and confirmed deaths from COVID-19 in 2020, 2021, and 2022 were examined to estimate the impact of the COVID-19 crisis and its relationships with temperatures. Parametric and non-parametric tests were used for the scope based on the distributive nature of the data. Effect size and statistical surprise (measured by S-values) were evaluated separately. Results. Cold months lead to a considerable and surprising increase in epidemiological risk and mortality in Italy from 2015 to 2019 (+45,000 annual deaths, SD = 4,700, S = 21). COVID-19 crisis has further aggravated this scenario during 2020 (+115,000) and 2021 (+63,000, S > 52). Mortality was boosted by low average minimum temperatures, although the death curve rose moderately during the four warmest months (Spearman r = -0.75, 95% CI = [-0.87; -0.56], S = 23). COVID-19 deaths also showed a pronounced seasonality, although the latter was decreasing over time (Spearman r = -0.85, 95% CI = [-0.92; -0.70], S = 20). Monthly excess deaths during COVID-19 were extremely high and surprising (+4,200, IQR = [2,800; 8,000], Wilcoxon signed rank test S = 28) but didn’t show a clear seasonality during 2021 and 2022. Overall COVID-19 mortality was strongly and surprisingly correlated with regional latitude (Spearman r = 0.86, 95% CI = [0.68; 0.94], S = 20). Discrepancies between COVID-19 and excess deaths during 2021 and 2022 suggest seasonal estimation errors and/or unexpected interactions between epidemiological variables, including coinfections (e.g., COVID-19 and seasonal flu), comorbidities, cold-induced risk factors but also reduced risk factors (e.g., due to pandemic-related health countermeasures), summer heat waves, and decreases in the most exposed population. Conclusions. Based on these findings, it can be concluded that: i) the epidemiological risk in Italy is seasonal and geographically dependent since cold seasons and low temperatures lead to higher mortality, ii) COVID-19’s impact on public health is strongly influenced by both environmental/seasonal and virological factors, iii) temperatures’ increase due to climate change is able to create summer mortality peaks. Future research should investigate the interrelation between all these epidemiological variables at the causal level. Keywords. COVID-19, epidemiology, Italy, mortality, public health, risk factors, seasonality, temperature.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/f9x5h/" target="_blank">Epidemiological Risk in Italy Increases During the Cold Season and Heatwaves: Considerations for Health Policies During COVID-19 and Future Crises.</a>
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</div></li>
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<li><strong>Contact-number-driven virus evolution: a multi-level modeling framework for the evolution of acute or persistent RNA virus infection</strong> -
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<div>
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Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as and SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.g., borna disease virus) can be maintained in nonhuman populations, and why the persistent viruses evolved has been rarely explored. Here, using a multi-level modeling approach including both individual-level virus infection dynamics and population-scale transmission, we consider virus evolution based on the host environment, specifically, the effect of the contact history of infected hosts. We found that, with a highly dense contact history, viruses with a high virus production rate but low accuracy are likely to be optimal, resulting in a short infectious period with a high peak viral load. In contrast, with a low-density contact history, viral evolution is toward low virus production but high accuracy, resulting in long infection durations with low peak viral load. Our study sheds light on the origin of persistent viruses and why acute viral infections but not persistent virus infection tends to prevail in human society.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.22.521662v1" target="_blank">Contact-number-driven virus evolution: a multi-level modeling framework for the evolution of acute or persistent RNA virus infection</a>
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</div></li>
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<li><strong>Evaluation of Covid-19 antigen rapid diagnostic tests for self-testing in Lesotho and Zambia</strong> -
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Background The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (BRCCH-EDCTP COVID-19 Initiative) was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region. Methods A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 11 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants’ understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed. Results Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.6% (404/414, 95% CI: 95.6-99.8) and 99.8% (1116/1118, 95% CI: 99.4-100) respectively. Conclusion Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.21.22283827v1" target="_blank">Evaluation of Covid-19 antigen rapid diagnostic tests for self-testing in Lesotho and Zambia</a>
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</div></li>
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<li><strong>Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 Omicron sub-lineages</strong> -
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<div>
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The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1 and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1 and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1 and XBB variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.22.521201v1" target="_blank">Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 Omicron sub-lineages</a>
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<li><strong>Calculation and meaning of “excess mortality”: A comparison of Covid- and pre-Covid mortality data in 31 Eurostat countries from 1965 to 2021.</strong> -
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Determining ″excess mortality″ makes it possible to compare the burden of disasters between countries and over time, and thus also to evaluate the success of mitigation measures. However, the debate on Covid-19 has exposed that calculations of excess mortalities vary considerably depending on the method and its specification. Moreover, it is often unclear what exactly is meant by ″excess mortality″. We define excess mortality as the excess over the number of deaths that would have been expected counter-factually, i.e. without the catastrophic event in question. That is, we include all normally occurring flu and heat waves, which are excluded by some authors with the consequence that they almost always record low expected values and correspondingly high excess mortality rates. Based on this definition, we use a very parsimonious calculation method that is easy to understand even for laypersons, namely the linear extrapolation of death figures from previous years to determine the excess mortality during the Covid-19 pandemic. But unlike other literature on this topic, we first evaluated and optimised the specification of our method using a larger historical data set in order to identify and minimise estimation errors and biases. The result shows that the excess mortality rates continuously published by international statistical offices — OECD and Eurostat — are often inflated and would have exhibited considerable excess mortalities in many countries and periods before Covid-19, if this value had already been of public interest at that time. It also reveals that mortality rates already fluctuated strongly in the past and that in a third of the countries studied, individual values from the past exceed the current fluctuations due to the Covid-19 pandemic. Three conclusions can be drawn from this study and its findings: 1) All calculation methods for current figures should first be evaluated against past figures. 2) The definition of excess mortality used should be made explicit. 3) Statistical offices should provide more realistic estimates.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283850v1" target="_blank">Calculation and meaning of “excess mortality”: A comparison of Covid- and pre-Covid mortality data in 31 Eurostat countries from 1965 to 2021.</a>
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<li><strong>Unbiased single cell spatial analysis localises inflammatory clusters of immature neutrophils-CD8 T cells to alveolar progenitor cells in fatal COVID-19 lungs</strong> -
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Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we developed a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method revealed a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and cytotoxic CD8 T cells, was found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings provide new insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.21.22283654v1" target="_blank">Unbiased single cell spatial analysis localises inflammatory clusters of immature neutrophils-CD8 T cells to alveolar progenitor cells in fatal COVID-19 lungs</a>
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<li><strong>How to Run Behavioural Experiments Online: Best Practice Suggestions for Cognitive Psychology and Neuroscience</strong> -
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The combination of a replication crisis, global COVID-19 pandemic, and recent technological advances have accelerated the on-going transition of research in cognitive psychology and neuroscience to the online realm. When participants cannot be tested in-person, data of acceptable quality can still be collected online. While online research offers many advantages, numerous pitfalls may hinder researchers in addressing their questions appropriately, potentially resulting in unusable data and misleading conclusions. Here, we present a cost-benefit analysis of conducting online studies in cognitive psychology and neuroscience, coupled with detailed best practice suggestions that span the range from initial study design to the final interpretation of data. These suggestions offer a critical look at issues regarding recruitment of typical and (sub)clinical samples, their comparison, and the importance of context- dependency in each part of a study. We illustrate our suggestions by means of a recent online experiment investigating cognitive working memory skills in adults with the learning disorder dyslexia.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/nt67j/" target="_blank">How to Run Behavioural Experiments Online: Best Practice Suggestions for Cognitive Psychology and Neuroscience</a>
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<li><strong>Implications OF ORAL Health Policy consequent Covid19</strong> -
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COVID 19 virus rearrange the priorities of the global society regarding oral health to systemic health . Oral Health Policy and Epidemiology (OHPE) is the connection of dentistry, medicine, and public health which increase the perspective and impact of global and community health practice and policy through education, research, and leadership. Dental faculties and students, with community stakeholders and oral health professionals, drive collaborative, interdisciplinary, and innovative approaches to achieve oral health equity and wellbeing for all. Global vision for oral health policy is fully integrated in general health and based on primary health care, with emphasis on promotion on oral health and prevention of oral disease . This policy is a framework contribute to a program strategy of public health to guarantee the access to fundamental rights .
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🖺 Full Text HTML: <a href="https://osf.io/9upf2/" target="_blank">Implications OF ORAL Health Policy consequent Covid19</a>
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<li><strong>Monkeypox Post COVID19: Knowledge, Worrying, and Vaccine Adoption of the Arabic General Population</strong> -
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Abstract: Background: The outbreak of monkeypox was designated a global public health emergency by the World Health Organization on July 23, 2022. There have been more reported 60000 cases worldwide, most of which are in places where monkeypox has never been seen due to the travel of people who have the virus. This research aims to evaluate the Arabic general population on monkeypox disease, fears, and vaccine adoption after the WHO proclaimed a monkeypox epidemic and to compare these attitudes to those of the COVID-19 pandemic. Methods: This cross-sectional study was performed in some Arabic countries (Syria, Egypt, Qatar, Yemen, Jordan, Sudan, Algeria, and Iraq) between August 18 and September 7, 2022 to examine the Arabic people perspectives on monkeypox disease, fears, and vaccine adoption and to compare these attitudes to those of the COVID-19 pandemic. The inclusion criteria were the general public residing in Arabic nations and older than 18. This questionnaire has 32 questions separated into three sections: sociodemographic variables, prior COVID-19 exposure, and COVID-19 vaccination history. The second portion assesses knowledge and anxieties about monkeypox, while the third section includes the generalized anxiety disorder (GAD7) scale. Logistic regression analysis were performed to compute the adjusted odds ratios (aOR), and their confidence intervals (95%CI) using STATA (version 17.0) Results: A total of 3665 respondents from 17 Arabic countries were involved in this study. Almost two third (n= 2427, 66.2%) of participants expressed more worried about COVID -19 than monkeypox diseases. Regarding the major cause for concern about monkeypox, 39.5% of participants attributed their anxiety they or a member of their family may contract the illness, while 38.4% were concerned about another worldwide pandemic of monkeypox. According to the GAD 7 score, 71.7% of respondents showed very low anxiety toward monkeypox. 43.8% of the participants scored poor levels of knowledge about monkeypox disease. Participants with previous COVID-19 infection showed greater acceptance to receive the monkeypox vaccine 1.206 times than those with no previous infection. A higher concern for the monkeypox than COVID-19 was shown by the participants who perceived monkeypox as dangerous and virulent 3.097 times than those who didn’t. Participants who have a chronic disease (aOR: 1.32; 95%CI: 1.09-1.60); participants worried about monkeypox (aOR: 1.21; 95%CI: 1.04-1.40); and perceived monkeypox as a dangerous and virulent disease (aOR: 2.25; 95%CI: 1.92-2.65); and excellent knowledge level (aOR: 2.28; 95%CI: 1.79-2.90) have emerged as significant predictors. Conclusion: Our study reported that three fourth of the participants were more concerned about COVID-19 than monkeypox disease. As well, most of the participants have inadequate levels of knowledge regarding monkeypox disease. Hence immediate action should be taken to address this problem. Consequently, it is crucial to learn about monkeypox and spread information about its prevention.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.20.22283750v1" target="_blank">Monkeypox Post COVID19: Knowledge, Worrying, and Vaccine Adoption of the Arabic General Population</a>
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<li><strong>Glyco-engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues</strong> -
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Immunoglobulin M (IgM) is the largest antibody isotype with unique features like extensive glycosylation and oligomerization. Major hurdles in characterizing its properties are difficulties in the production of well-defined multimers. Here we report the expression of two SARS-CoV-2 neutralizing monoclonal antibodies in glycoengineered plants. Isotype switch from IgG1 to IgM resulted in the production of pentameric IgMs, comprising of correctly assembled 21 human protein subunits. All four recombinant monoclonal antibodies carried a highly reproducible human-type N-glycosylation profile, with a single dominant N-glycan species at each glycosite. Both pentameric IgMs exhibited increased antigen binding and virus neutralization potency, up to 390-fold, compared to the parental IgG1. Collectively, the results may impact on the future design of vaccines, diagnostics and antibody-based therapies and emphasize the versatile use of plants for the expression of highly complex human proteins with targeted posttranslational modifications.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.22.521646v1" target="_blank">Glyco-engineered pentameric SARS-CoV-2 IgMs show superior activities compared to IgG1 orthologues</a>
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<li><strong>Stay away, Santa: Children’s beliefs about the impact of COVID-19 on real and fictional beings</strong> -
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The COVID-19 pandemic has forced children to reckon with the causal relations underlying disease transmission. What are children’s theories of how COVID-19 is transmitted? And how do they understand the relation between COVID-19 susceptibility and the need for disease-mitigating behavior? We explored these questions in the context of children’s beliefs about supernatural beings, like Santa and the Tooth Fairy. Because these beings cannot be observed, children’s beliefs about the impact of COVID-19 on them must be based on their underlying theories of disease transmission and prevention rather than on experience. In Summer of 2020, N = 218 U.S. children between the ages of 3 and 10 (M = 81.2 months) were asked to rate supernatural beings’ susceptibility to COVID-19, and the extent to which these beings should engage in disease-mitigating behaviors, such as social distancing and mask wearing. Many children believed supernatural beings were susceptible to COVID-19. However, children rated the need for supernatural beings to engage in disease-mitigating behaviors as higher than the beings’ disease susceptibility, indicating a disconnect between their conceptions of the causal relations between disease-mitigating behavior and disease prevention. Children’s belief that a particular supernatural being could be impacted by COVID-19 was best predicted by the number of human-like properties they attributed to it, regardless of the child’s age. Together, these findings suggest that although young children fail to appreciate specific pathways of disease transmission, they nonetheless understand disease as a bodily affliction, even for beings whose bodies have never been observed.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/dj37h/" target="_blank">Stay away, Santa: Children’s beliefs about the impact of COVID-19 on real and fictional beings</a>
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<li><strong>Wastewater genomic surveillance captures early detection of Omicron in Utah</strong> -
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Wastewater-based epidemiology has emerged as a powerful public health tool to trace new outbreaks, detect trends in infection and provide an early warning of COVID-19 community spread. Here, we investigated the spread of SARS-CoV-2 infections across Utah by characterizing lineages and mutations detected in wastewater samples. We sequenced over 1,200 samples from 32 sewersheds collected between November 2021 and March 2022. Wastewater sequencing confirmed the presence of Omicron (B.1.1.529) in Utah in samples collected on November 19, 2021, up to ten days before its corresponding detection via clinical sequencing. Analysis of diversity of SARS-CoV-2 lineages revealed Delta as the most frequently detected lineage during November, 2021 (67.71%), but it started declining in December, 2021 with the onset of Omicron (B.1.1529) and its sub-lineage BA.1 (6.79%). Proportion of Omicron increased to ~58% by January 4th 2022 and completely displaced Delta by February 7th, 2022. Wastewater genomic surveillance revealed the presence of Omicron sub-lineage BA.3, a lineage that is yet to be identified from clinical surveillance in Utah. Interestingly, several Omicron-defining mutations began to appear in early November, 2021 and increased in prevalence across sewersheds from December to January. Our study suggests that tracking epidemiologically relevant mutations is critical in detecting emerging lineages in the early stages of an outbreak. Wastewater genomic epidemiology provides an unbiased representation of community-wide infection dynamics and is an excellent complementary tool to SARS-CoV-2 clinical surveillance, with the potential of guiding public health action and policy decisions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.24.22282643v2" target="_blank">Wastewater genomic surveillance captures early detection of Omicron in Utah</a>
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<li><strong>Molecular stratification of hospitalized COVID19 patients points to FGFR and SHC4-signaling in ARDS</strong> -
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A minority of people infected with SARS-CoV-2 will develop severe COVID-19 disease requiring invasive respiratory support associated with high mortality. To understand the molecular mechanisms underlying severe pathology, we conducted an unsupervised stratification of the circulating proteome that identified six endophenotypes (EPs) among 731 SARS-CoV-2 PCR-positive hospitalized participants in the Biobanque Québécoise de la COVID-19, with varying degrees of disease severity and times to intensive care unit (ICU) admission. One endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death. Clinical features of EP6 included increased levels of C-reactive protein, D-dimers, elevated neutrophils, and depleted lymphocytes. Proteomic, metabolomic, and genomic characterization supported a role for neutrophil-associated procoagulant activity in severe COVID-19 ARDS that is inversely correlated with sphinghosine-1 phosphate plasma levels. Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with severe COVID-19. Mechanical ventilation in EP6 was associated with alterations in lipoprotein metabolism. Importantly, a prognostic model solely based on clinical laboratory measurements was developed and validated on 631 patients that generalizes the EPs to new patients and creates new opportunities for automated identification of high-risk groups in the clinic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.02.22281834v3" target="_blank">Molecular stratification of hospitalized COVID19 patients points to FGFR and SHC4-signaling in ARDS</a>
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<li><strong>A probabilistic approach for the study of epidemiological dynamics of infectious diseases: basic model and properties</strong> -
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The dynamics of epidemiological phenomena associated to infectious diseases have long been modelled with different approaches. However, recent pandemic events exposed many areas of opportunity to improve over the existing models. We develop a model based on the idea that transitions between epidemiological stages are alike sampling processes. Such processes may involve more than one subset of the pop- ulation (e.g. infection), or they may be mostly dependent on time intervals defined by infectious or clinical criteria. The resulting modelling scheme is robust, easy to implement, and can readily lend itself for extensions aimed at answering questions that emerge from close examination of data trends, such as those emerging from the COVID-19 pandemic, and other infectious diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278844v2" target="_blank">A probabilistic approach for the study of epidemiological dynamics of infectious diseases: basic model and properties</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/10.1101/2022.07.24.22277973v2" 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>A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156.</strong> - <b>Condition</b>: COVID 19<br/><b>Interventions</b>: Biological: Placebo; Biological: AZD5156; Biological: AZD7442 (EVUSHELD™)<br/><b>Sponsor</b>: AstraZeneca<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>101-PGC-005 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: 101-PGC-005; Drug: Dexamethasone<br/><b>Sponsor</b>: 101 Therapeutics<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients</strong> - <b>Condition</b>: Coronavirus Disease 2019(COVID-19)<br/><b>Intervention</b>: Biological: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Booster Study in Healthy Adults in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Moderna; Biological: Novavax<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<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>Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: N-acetyl cysteine<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Baldachin<br/><b>Sponsor</b>: University Hospital Inselspital, Berne<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly; Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled; Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<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>Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above（Negative Antibody Against COVID-19）</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: GST-HG171/Ritonavir; Drug: Placebo<br/><b>Sponsor</b>: Fujian Akeylink Biotechnology 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 PhaseⅡ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Placebo (normal saline)<br/><b>Sponsor</b>: Sinocelltech 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>The COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID-19</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: 6-Week Self-Management Group<br/><b>Sponsor</b>: University of Washington<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>ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening</strong> - <b>Condition</b>: Depression and Anxiety Symptoms Related to the COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Internet-based Cognitive Behavioral Therapy<br/><b>Sponsor</b>: Linkoeping University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Intervention</b>: Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)<br/><b>Sponsors</b>: Laboratorio Pablo Cassara S.R.L.; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Supportive Psychotherapy<br/><b>Sponsor</b>: Indonesia University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Graphene spectrum light wave therapy room<br/><b>Sponsors</b>: Southeast University, China; Hohhot First Hospital<br/><b>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>Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for SARS-CoV-2. The full-length membrane form of ACE2 (memACE2) undergoes ectodomain shedding to generate a shed soluble form (solACE2) that mediates SARS-CoV-2 entry via receptor-mediated endocytosis. Currently, it is not known how the physiological regulation of ACE2 shedding contributes to the etiology of COVID-19 in vivo. The present 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>Cyclophilin D-mediated angiotensin II-induced NADPH oxidase 4 activation in endothelial mitochondrial dysfunction that can be rescued by gallic acid</strong> - Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2…</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 epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2</strong> - Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes…</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 D614G mutation redirects SARS-CoV-2 spike to lysosomes and suppresses deleterious traits of the furin cleavage site insertion mutation</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress occurs by lysosomal exocytosis. We show that the Spike D614G mutation enhances Spike trafficking to lysosomes, drives Spike-mediated reprogramming of lysosomes, and reduces cell surface Spike expression by ~3-fold. D614G is not a human-specific adaptation. Rather, it is an adaptation to the earlier furin cleavage site insertion (FCSI) mutation that occurred at the genesis of SARS-CoV-2. While advantageous to the virus, furin…</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>Biogenic nanosilver-fabricated endotracheal tube to prevent microbial colonization in a veterinary hospital</strong> - COVID-19 patients have often required prolonged endotracheal intubation, increasing the risk of developing ventilator-associated pneumonia (VAP). A preventive strategy is proposed based on an endotracheal tube (ETT) modified by the in situ deposition of eucalyptus-mediated synthesized silver nanoparticles (AgNPs). The surfaces of the modified ETT were embedded with AgNPs of approximately 28 nm and presented a nanoscale roughness. Energy dispersive X-ray spectroscopy confirmed the presence 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>Visualization of early RNA replication kinetics of SARS-CoV-2 by using single molecule RNA-FISH</strong> - SARS-CoV-2 infection has caused a major global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of plus stranded genomic and subgenomic RNAs (gRNA and sgRNA) starting from the RNA from the first virus that enters the cell. We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA in infected cells and carried out a time…</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 of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2</strong> - Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development. In this study, to generate SARS-CoV-2 VLPs…</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>Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process</strong> - Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca^(2+)…</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>Structural Characteristics of Heparin Binding to SARS-CoV-2 Spike Protein RBD of Omicron Sub-Lineages BA.2.12.1, BA.4 and BA.5</strong> - The now prevalent Omicron variant and its subvariants/sub-lineages have led to a significant increase in COVID-19 cases and raised serious concerns about increased risk of infectivity, immune evasion, and reinfection. Heparan sulfate (HS), located on the surface of host cells, plays an important role as a co-receptor for virus-host cell interaction. The ability of heparin and HS to compete for binding of the SARS-CoV-2 spike (S) protein to cell surface HS illustrates the therapeutic potential 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>Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells</strong> - SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary…</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>Neutralizing Antibody and T-Cell Responses against SARS-CoV-2 Wild-Type and Variants of Concern in Chronic Obstructive Pulmonary Disease Subjects after ChAdOx-1/ChAdOx-1 Homologous Vaccination: A Preliminary Study</strong> - Data on immunogenicity of adenovirus-vectored vaccine in chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, we aimed to determine the humoral and cellular immune responses after homologous ChAdOx-1 vaccination in subjects with COPD. COPD subjects and age- and sex-matched healthy elderly receiving ChAdOx-1 homologous vaccination were included. The levels of neutralizing antibodies (NAb) and specific CD4 and CD8 T-cell responses against SARS-CoV-2 wild-type (WT) 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>Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants</strong> - Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory…</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 Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of <em>Lactobacillus sakei</em> Probio65</strong> - In the three years since the first outbreak of COVID-19 in 2019, the SARS-CoV-2 virus has continued to be prevalent in our community. It is believed that the virus will remain present, and be transmitted at a predictable rate, turning endemic. A major challenge that leads to this is the constant yet rapid mutation of the virus, which has rendered vaccination and current treatments less effective. In this study, the Lactobacillus sakei Probio65 extract (P65-CFS) was tested for its safety 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>Engagement of the G3BP2-TRIM25 Interaction by Nucleocapsid Protein Suppresses the Type I Interferon Response in SARS-CoV-2-Infected Cells</strong> - The nucleocapsid (N) protein contributes to key steps of the SARS-CoV-2 life cycle, including packaging of the virus genome and modulating interactions with cytoplasmic components. Expanding knowledge of the N protein acting on cellular proteins and interfering with innate immunity is critical for studying the host antiviral strategy. In the study on SARS-CoV-2 infecting human bronchial epithelial cell line s1(16HBE), we identified that the N protein can promote the interaction between…</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 Immunogenicity and Clinical Protection of SARS-CoV-2 S1 and N Antigens in Syrian Golden Hamster</strong> - The novel coronavirus (SARS-CoV-2) epidemic continues to be a global public crisis affecting human health. Many research groups are developing different types of vaccines to suppress the spread of SARS-CoV-2, and some vaccines have entered phase III clinical trials and have been rapidly implemented. Whether multiple antigen matches are necessary to induce a better immune response remains unclear. To address this question, this study tested the immunogenicity and protective effects of a…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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