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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>04 September, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Knowledge and Quality of Life of Rural Older Adults during COVID-19 Pandemic</strong> -
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Background: The coronavirus (COVID-19) global pandemic negatively affected people’s way of life regardless of age, sex, or ethnicity. This infectious disease is particularly lethal among the elderly, with even higher fatality rates among this age group. Aim of the study: Assess knowledge and quality of life of rural older adults during COVID-19 pandemic. Subjects and Methods: Research design: A descriptive design was utilized. Setting: The study was conducted in a rural area Shobera el nakhla selected randomly from Sharkia Governorate, Egypt. Subjects: Purposive sample composed of 300 older adults aged ≥60 years. Tools of data collection: Three tools were used to collect the study data. Tool I: A structured interview sheet. Tool II: knowledge of the studied older adults about Covid-19. Tool III: WHO Quality of life instrument short form (THE WHOQOL-BREF). Results: among the studied older adults, 68.7% had inadequate knowledge and 51.3% had poor quality of life. Statistically significant relations were found between quality of life and illiteracy, insufficient monthly income, and unmarried status. Conclusion: two-third of older adults had inadequate knowledge and more than half of studied older adults had poor quality of life during covid-19 pandemic. Recommendation: Healthcare Providers should be aware that older individuals were particularly vulnerable to the effects of covid-19 on quality of life and explore strategies to minimize their suffering during the COVID-19 pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/e8w9m/" target="_blank">Knowledge and Quality of Life of Rural Older Adults during COVID-19 Pandemic</a>
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</div></li>
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<li><strong>The COVID-19 pandemic and fertility decline in Costa Rica: A brief plunge due to psychosocial and economic factors and a baby bust driven by migration decisions</strong> -
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The national birth registry shows a substantial baby bust in 2021 – the first full year plus nine months into the COVID-19 pandemic. The fertility of native Costa Rican women dropped by 13%. This decrease did not deviate from pre-existing fertility trends. A brief plunge in conceptions during the first full month of the pandemic (April 2020) decreased the fertility rate in January 2021 by as much as 24% for some groups. This plunge was a response to the hardships caused by pandemic mitigation measures as well as uncertainties and fears concerning the novel disease rather than to the physiological harm of the disease itself. The 2021 decrease in births among immigrant women (who contribute one-fifth of the birth rate) was 78% larger than among native women, driven mostly by pandemic-induced migration decisions. The data hint at a pandemic baby boom in low-SES communities and, especially, in families with several children.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/m749j/" target="_blank">The COVID-19 pandemic and fertility decline in Costa Rica: A brief plunge due to psychosocial and economic factors and a baby bust driven by migration decisions</a>
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<li><strong>High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions</strong> -
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Identifying protein environments at the virus-host cell interface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the virus behind the ongoing COVID-19 pandemic, uses the cell surface ACE2 protein as a major receptor, but the contribution of other cellular proteins in the entry process is unknown. To probe the microenvironment of SARS-CoV-2 Spike-ACE2 protein interactomes on human cells, we developed a photocatalyst-based viral-host protein microenvironment mapping platform (ViraMap) employing iridium photocatalysts conjugated to Spike for visible-light driven proximity labelling on host cells. Application of ViraMap on ACE2-expressing cells captured ACE2, the established co-receptor NRP1, as well as other proteins implicated in host cell entry and immunomodulation. We further investigated these enriched proteins via loss-of-function and over-expression in pseudotype and authentic infection models and observed that the Ig receptor PTGFRN and tyrosine kinase ligand EFNB1 can serve as SARS-CoV-2 entry factors. Our results highlight additional host targets that participate infection and showcase ViraMap for interrogating virus-host cell surface interactomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506438v1" target="_blank">High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions</a>
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<li><strong>The SARS-CoV-2 accessory protein Orf3a is not an ion channel, but does interact with trafficking proteins</strong> -
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The severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) and SARS-CoV-1 accessory protein Orf3a colocalizes with markers of the plasma membrane, endocytic pathway, and Golgi apparatus. Some reports have led to annotation of both Orf3a proteins as a viroporin. Here we show that neither SARS-CoV-2 nor SARS-CoV-1 form functional ion conducting pores and that the conductances measured are common contaminants in overexpression and with high levels of protein in reconstitution studies. Cryo-EM structures of both SARS-CoV-2 and SARS-CoV-1 Orf3a display a narrow constriction and the presence of a basic aqueous vestibule, which would not favor cation permeation. We observe enrichment of the late endosomal marker Rab7 upon SARS-CoV-2 Orf3a overexpression, and co-immunoprecipitation with VPS39. Interestingly, SARS-CoV-1 Orf3a does not cause the same cellular phenotype as SARS-CoV-2 Orf3a and does not interact with VPS39. To explain this difference, we find that a divergent, unstructured loop of SARS-CoV-2 Orf3a facilitates its binding with VPS39, a HOPS complex tethering protein involved in late endosome and autophagosome fusion with lysosomes. We suggest that the added loop enhances SARS-CoV-2 Orf3a ability to co-opt host cellular trafficking mechanisms for viral exit or host immune evasion.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506428v1" target="_blank">The SARS-CoV-2 accessory protein Orf3a is not an ion channel, but does interact with trafficking proteins</a>
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<li><strong>Plant production of high affinity nanobodies that block SARS-CoV-2 spike protein binding with its receptor, human angiotensin converting enzyme</strong> -
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Nanobodies (VHH antibodies), are small peptides that represent the antigen binding domain, VHH of unique single domain antibodies (heavy chain only antibodies, HcAb) derived from camelids. Here, we demonstrate production of VHH nanobodies against the SARS-CoV-2 spike proteins in the solanaceous plant Nicotiana benthamiana through transient expression and their subsequent detection verified through western blot. We demonstrate that these nanobodies competitively inhibit binding between the SARS-CoV-2 spike protein receptor binding domain and its human receptor protein, angiotensin converting enzyme 2 (ACE2). We present plant production of nanobodies as an economical and scalable alternative to rapidly respond to therapeutic needs for emerging pathogens in human medicine and agriculture.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.03.506425v1" target="_blank">Plant production of high affinity nanobodies that block SARS-CoV-2 spike protein binding with its receptor, human angiotensin converting enzyme</a>
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<li><strong>Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations</strong> -
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The COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here we demonstrate feasibility of a multiplexed platform (VaxArray) for efficient identity verification and concentration determination for both monovalent and multivalent mRNA formulations. A model system comprised of mRNA constructs for influenza hemagglutinin and neuraminidase was used to characterize the analytical performance metrics for a VaxArray mRNA assay. The assay presented herein had a time to result of less than 2 hours, required no PCR-based amplification nor extraction of mRNA from lipid nanoparticles, and exhibited high construct specificity that enabled application to the bivalent mixture. The sensitivity for influenza hemagglutinin and neuraminidase mRNA was sub-/mL, which is vaccine-relevant, and the average accuracy (%recovery) and precision were 104%{+/-}2%and 9%{+/-}2%, respectively.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.31.506088v1" target="_blank">Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations</a>
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<li><strong>TikTok Tourette’s: are we witnessing a rise in neurological conditions driven by adolescent social media use?</strong> -
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Perceptions of Tourette Syndrome (TS) and tic disorders are often driven by social media. During the COVID-19 pandemic, social media consumption greatly increased, particularly in the adolescent population. In parallel with increased social media consumption, there has also been an increase in tic severity and functional tic-like behavior (FTLB). Given that many of the tic videos posted on social media are misleading, perpetuate false beliefs about TS, or reinforce tic-like behaviors, there is increasing concern that these videos are driving the rapid increase in FTLBs. Several studies have reviewed newly presenting cases of FTLB and have found shared characteristics, including that a higher proportion of affected individuals are female, there is a low proportion with a history of childhood or family tics, and symptom onset is typically acute and develops in the teenage years. In addition, the quality of the tics seen in association with FTLB mirror many of the tics seen on popular social media channels, with higher rates of coprophenomena, tic attacks, and involvement of the trunk and extremities than is seen with typical tics. FTLBs are likely a specific subgroup of functional tics largely influenced by the portrayal of and growing popularity of functional tics posted on social media during the COVID-19 pandemic. However, several factors, including increased anxiety, social isolation, and social media use in general during the pandemic are likely also contributing factors to the surge of FTLBs seen recently. In this era of increased social media consumption, it will become increasingly important for clinicians to educate patients about where and how medical information is spread, to ensure the best possible diagnosis, treatment, and outcomes for patients.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/vs3tm/" target="_blank">TikTok Tourette’s: are we witnessing a rise in neurological conditions driven by adolescent social media use?</a>
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<li><strong>COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality</strong> -
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Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.
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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/10.1101/2022.09.02.22279398v1" target="_blank">COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality</a>
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<li><strong>Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)</strong> -
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Background: The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. Methods: We conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. Results: Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and moderate/severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted odds ratio 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). Conclusions: Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of moderate/severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.01.22279473v1" target="_blank">Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)</a>
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<li><strong>Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA</strong> -
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Background: Because circulating DNA (cirDNA) are mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNA Methods: We used the synergistic analytical information provided by specifically quantifying DNA by qPCR, and analyzing fragment size analysis by shallow WGS, and capillary electrophoresis to unequivocally study the following: the in vitro kinetics of cell derived genomic high molecular weight (gHMW) DNA degradation in serum; the production of extracellular DNA and NET markers such as neutrophil elastase (NE) and myeloperoxidase (MPO) by ex vivo activated neutrophils; in vitro NET degradation in serum. We also performed an in vivo study in knockout mice, and an in vitro study of gHMW DNA degradation, to elucidate the role of NE and MPO in effecting DNA degradation and fragmentation. We then compared the NET associated markers and fragmentation size profiles of cirDNA in plasma obtained from patients with inflammatory diseases found to be associated with NET formation and high levels of cirDNA (COVID-19, N= 28; systemic lupus erythematosus, N= 10; metastatic colorectal cancer, N= 10; and from healthy individuals, N= 114). Results: Our studies reveal that: gHMW DNA degradation in serum results in the accumulation of mono-N DNA (81.3% of the remaining DNA following 24H incubation in serum corresponded to mono-N DNA); ex vivo NET formation, as demonstrated by a concurrent 5-, 5- and 35-fold increase of NE, MPO, and cell-free DNA (cfDNA) concentration in PMA-activated neutrophil culture supernatant, leads to the release of high molecular weight DNA that degrades down to mono-N in serum; NET mainly in the form of gHMW DNA generate mono-N cirDNA (2% and 41% of the remaining DNA after 2 hours in serum corresponded to 1-10 kbp fragments and mono-N, respectively) independent of any cellular process when degraded in serum; NE and MPO may contribute synergistically to NET autocatabolism, resulting in a 25-fold decrease in total DNA concentration and a DNA fragment size profile similar to that observed from cirDNA following 8h incubation with both NE and MPO; the cirDNA size profile of NE KO mice significantly differed from that of the WT, suggesting NE involvement in DNA degradation; and a significant increase in the levels of NE, MPO and cirDNA was detected in plasma samples from lupus, COVID-19 and mCRC, showing a high correlation with these inflammatory diseases, while no correlation of NE and MPO with cirDNA was found in HI. Conclusions: Our work thus describes the mechanisms by which NET and cirDNA are linked, by demonstrating that NET are a major source of mono-N cirDNA independent of apoptosis, and thus establishing a new paradigm of the mechanisms of cirDNA release in normal and pathological conditions, as well as demonstrating a link between immune response and cirDNA.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.01.506266v1" target="_blank">Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA</a>
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<li><strong>Novel monoclonal antibodies showing broad neutralizing activity for SARS-CoV-2 variants including Omicrons BA.5 and BA.2.75</strong> -
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We identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506305v1" target="_blank">Novel monoclonal antibodies showing broad neutralizing activity for SARS-CoV-2 variants including Omicrons BA.5 and BA.2.75</a>
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<li><strong>SARS-CoV-2 nucleocapsid protein inhibits the stress response through RNA-binding domain N2b</strong> -
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The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding - prevented PKR activation, inhibited {beta}-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Observations made for the N protein of human coronavirus 229E suggests that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506332v1" target="_blank">SARS-CoV-2 nucleocapsid protein inhibits the stress response through RNA-binding domain N2b</a>
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<li><strong>White-tailed deer (Odocoileus virginianus) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern</strong> -
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The spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans into white-tailed deer (WTD) and its ability to transmit from deer-to-deer raised concerns about the role of WTD in the epidemiology and ecology of the virus. In the present study, we conducted a comprehensive investigation to assess the prevalence, genetic diversity, and evolution of SARS-CoV-2 in WTD in the State of New York (NY). A total of 5,462 retropharyngeal lymph node (RPLN) samples collected from free-ranging hunter-harvested WTD during the hunting seasons of 2020 (Season 1, September-December 2020, n=2,700) and 2021 (Season 2, September-December 2021, n=2,762) were tested by SARS-CoV-2 real-time RT-PCR. SARS-CoV-2 RNA was detected in 17 samples (0.6%) from Season 1 and in 583 (21.1%) samples from Season 2. Hotspots of infection were identified in multiple confined geographic areas of NY. Sequence analysis of SARS-CoV-2 genomes from 164 samples demonstrated the presence multipls SARS-CoV-2 lineages as well as the co-circulation of three major variants of concern (VOCs) (Alpha, Gamma, and Delta) in WTD. Our analysis suggests the occurrence of multiple spillover events (human-to-deer) of the Alpha and Delta lineages with subsequent deer-to-deer transmission of the viruses. Detection of Alpha and Gamma variants in WTD long after their broad circulation in humans in NY suggests that WTD may serve as a wildlife reservoir for VOCs no longer circulating in humans. Thus, implementation of continuous surveillance programs to monitor SARS-CoV-2 dynamics in WTD are warranted, and measures to minimize virus transmission between humans and animals are urgently needed.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506368v1" target="_blank">White-tailed deer (Odocoileus virginianus) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern</a>
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<li><strong>COVID-19 disruptions of food systems and nutrition services in Ethiopia: Evidence of the impacts and policy responses</strong> -
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Background: Since its first case of COVID-19 on March 13, 2020 and Ethiopia has exerted efforts to curb the spread of the Coronavirus disease 2019 (COVID-19) without imposing a nationwide lockdown. Globally, COVID-19 related disruptions and mitigation measures have impacted livelihoods and food systems, nutrition, as well as access and use of health services. Objective: To develop a comprehensive understanding of the impacts of the COVID-19 pandemic on food security and maternal and child nutrition and health services and to synthesize lessons from policy responses to the COVID-19 pandemic in Ethiopia. Methods: We conducted a review of literature and 8 key informant interviews across government agencies, donors, and non-governmental organizations (NGOs), to map the impacts of the COVID-19 pandemic on the food and health systems in Ethiopia. We summarized policy responses and identified recommendations for future actions related to the COVID-19 pandemic and other future emergencies. Results: The impacts of the COVID-19 pandemic were felt across the food system. Disruptions were noted in inputs supply due to travel restrictions and closed borders restricting trade, reduced in-person support by agriculture extension workers, income losses, increases in food prices, and the reduction in food security and consumption of less diverse diets. Maternal and child health services were disrupted due to fear of contacting COVID-19, diversion of resources, and lack of personal protective equipment. Disruptions eased over time due to the expansion of social protection, through the Productive Safety Net Program, and the increased outreach and home service provision by the health extension workers. Conclusion: Ethiopia experienced disruptions to food systems and expanded existing social protection and public health infrastructure and leveraged partnerships with non-state actors. Nevertheless, vulnerabilities and gaps remain and there is a need for a long-term strategy that considers the cyclical nature of COVID-19 cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.31.22279432v1" target="_blank">COVID-19 disruptions of food systems and nutrition services in Ethiopia: Evidence of the impacts and policy responses</a>
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<li><strong>Spatial analysis of COVID-19 booster vaccine uptake in Scotland, and projection of future distributions</strong> -
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Vaccine hesitancy is one of the critical challenges for the implementation of a successful vaccination strategy. Rates of vaccine hesitancy and refusal vary substantially across different socioeconomic groups, and can result in those considered most vulnerable to disease having the lowest levels of uptake. Widespread coverage of COVID-19 vaccination is of particular importance as prevalence remains high, in effort to reduce overall burden from serious disease. Scotland9s COVID-19 vaccination programme has progressed to booster vaccinations, however uptake is falling across successive doses, and there is concern that some vulnerable individuals will not have sustained protection. To this end we analyse uptake in Scotland9s first (starting September 2021) booster dose round, as a benchmark for future rounds. We fit a machine learning model to explain variation in uptake across Scotland at fine population scales. The model is able to estimate a neighbourhood9s booster uptake with high precision using its population structure and relative deprivation alone, without any knowledge of geographic location. This is indicative of a strong relationship between increasing local deprivation and falling uptake, and specifically in those failing to return for a booster, despite getting a first dose. Geographically, this manifests as clusters of lower uptake, coinciding with communities with higher deprivation. With an upcoming booster rollout in Autumn 2022, we use first booster uptake as a baseline, to generate a set of plausible distributions for future uptake, if nationwide uptake were to fall. We make the core assumption that as uptake falls, trends with respect to deprivation will persist. Projected uptake declines more rapidly in clusters of more deprived neighbourhoods. If these projected distributions were to manifest, gaps in immunity would emerge in more deprived communities, which have historically had the highest rates of COVID-19 hospitalisation and mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279415v1" target="_blank">Spatial analysis of COVID-19 booster vaccine uptake in Scotland, and projection of future distributions</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>Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran; Faculty of Medicine Universitas Udayana<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 Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-1 on D0; Biological: SCTV01E-1 on D28; Biological: SCTV01E-1 on D150; Biological: SCTV01E on D0; Biological: SCTV01E on D28; Biological: SCTV01E on D150; Biological: SCTV01E-1 on D120; Biological: SCTV01E on D120<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>A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Diagnostic Test: the LIT test<br/><b>Sponsors</b>: Gazi University; Oxford MediStress<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>Efficacy and Safety of ES16001 in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ES16001 40 mg; Drug: ES16001 80 mg; Drug: ES16001 160 mg; Drug: Placebo<br/><b>Sponsor</b>: Genencell 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>Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)<br/><b>Sponsors</b>: The Aurum Institute NPC; Coalition for Epidemic Preparedness Innovations<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 Protection After Transplant - Sanofi GSK (CPAT-SG) Study</strong> - <b>Conditions</b>: COVID-19; Kidney Transplant<br/><b>Intervention</b>: Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); PPD; Johns Hopkins University; Sanofi Pasteur, a Sanofi Company<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 COVID-19 Vaccine, AdCLD-CoV19-1</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Intervention</b>: Biological: AdCLD-CoV19-1<br/><b>Sponsors</b>: International Vaccine Institute; Cellid 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>Smartphone Intervention for Overdose and COVID-19</strong> - <b>Conditions</b>: Substance Use Disorders; Overdose; COVID-19<br/><b>Intervention</b>: Device: iThrive WI Intervention<br/><b>Sponsors</b>: University of Wisconsin, Madison; National Institute on Drug Abuse (NIDA)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19; Influenza<br/><b>Interventions</b>: Drug: CIC Vaccine; Drug: qNIV Vaccine; Drug: SARS-CoV-2 rS Vaccine; Drug: Influenza Vaccine<br/><b>Sponsor</b>: Novavax<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Assess Efficacy and Safety of Treamid for Patients With Reduced Exercise Tolerance After COVID-19</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Lung Fibrosis<br/><b>Interventions</b>: Drug: Treamid; Drug: Treamid twice a day; Drug: Treamid once a day; Drug: Placebo<br/><b>Sponsor</b>: PHARMENTERPRISES LLC<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>Self-proning and Repositioning in COVID-19 Outpatients at Risk of Complicated Illness</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pneumonia; Proning; Hospitalization; Death; Outpatient; Complication<br/><b>Intervention</b>: Other: Self-proning<br/><b>Sponsors</b>: Unity Health Toronto; Applied Health Research Centre<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>Effects of Immulina TM Supplements With PASC Patients</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Interventions</b>: Dietary Supplement: Immulina TM; Dietary Supplement: Placebo<br/><b>Sponsors</b>: University of Mississippi Medical Center; National Institute of General Medical Sciences (NIGMS)<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>Evaluation of Clinical Performance and Usability of iStatis COVID-19 Ag Rapid Test at POC</strong> - <b>Conditions</b>: COVID-19 Virus Infection; COVID-19; Coronavirus Disease-19; COVID-19 Pandemic; SARS-CoV-2 Infection<br/><b>Interventions</b>: Diagnostic Test: iStatis COVID-19 Ag Rapid Test; Diagnostic Test: “COVID-19 RT-PCR Test EUA Number: EUA200011, Company: Laboratory Corporation of America (”Labcorp")<br/><b>Sponsor</b>: bioLytical Laboratories<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>Resilience Intervention for Health Professionals COVID-19</strong> - <b>Condition</b>: Mental Health Wellness 1<br/><b>Intervention</b>: Other: Mindfulness-based Intervention<br/><b>Sponsor</b>: Universidad de Monterrey<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>Addressing Post-COVID-19 Musculoskeletal Symptoms</strong> - <b>Conditions</b>: Telemedicine; Musculoskeletal Disease; SARS-CoV-2; Pain; COVID-19; Exercise<br/><b>Interventions</b>: Other: Multicomponent exercise program; Other: Tele-health primary care rehabilitation program<br/><b>Sponsor</b>: Universidad Europea de Madrid<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>Semi-selective plasma filtration applied to the treatment of acquired thrombotic thrombocytopenic purpura following bnt162b2 administration</strong> - Following the widespread use of anti SARS-CoV-2 vaccines, there have been reports of thrombocytopenia developing after the administration of different types of vaccine. We report a case of a 63-year-old male who developed neurological symptoms after receiving the second dose of the bnt162b2 vaccine. Blood tests performed upon admission to the Emergency Department revealed severe thrombocytopenia and microangiopathic hemolytic anemia. ADAMTS13 activity was undetectable and antibody titer was…</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>Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection</strong> - Host cell proteases such as TMPRSS2 are critical determinants of SARS-CoV-2 tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes 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>Dipeptidylpeptidase (DPP)-4 inhibitor therapy increases circulating levels of anti-inflammatory soluble frizzle receptor protein (sFRP)-5 which is decreased in severe COVID-19 disease</strong> - Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide…</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>Retro-2 alters Golgi structure</strong> - Retro-2 directly interacts with an ER exit site protein, Sec16A, inhibiting ER exit of a Golgi tSNARE, Syntaxin5, which results in rapid re-distribution of Syntaxin5 to the ER. Recently, it was shown that SARS-CoV-2 infection disrupts the Golgi apparatus within 6-12 h, while its replication was effectively inhibited by Retro-2 in cultured human lung cells. Yet, exactly how Retro-2 may influence ultrastructure of the Golgi apparatus have not been thoroughly investigated. In this study, we…</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 Pathogenesis of African Trypanosomiasis</strong> - African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</strong> - Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure…</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>Cotton flower metabolites inhibit SARS-CoV-2 main protease</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading globally for over two years, causing serious contagious disease and incalculable damage. The introduction of vaccines has slowed the spread of SARS-CoV-2 to some extent, but there remains a need for specific and effective treatment. The high chemical diversity and safety profiles of natural products make them a potential source of effective anti-SARS-CoV-2 drugs. Cotton plant is one of the most important economic 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>Lipocalin-2 is an essential component of the innate immune response to Acinetobacter baumannii infection</strong> - Acinetobacter baumannii is an opportunistic pathogen and an emerging global health threat. Within healthcare settings, major presentations of A. baumannii include bloodstream infections and ventilator-associated pneumonia. The increased prevalence of ventilated patients during the COVID-19 pandemic has led to a rise in secondary bacterial pneumonia caused by multidrug resistant (MDR) A. baumannii. Additionally, due to its MDR status and the lack of antimicrobial drugs in the development…</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>Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction</strong> - The Toll-like receptor (TLR)7- and TLR9-dependent signaling cascade is responsible for production of a large amount of alpha interferon by plasmacytoid dendritic cells upon viral infection. Here, we show that Middle East respiratory syndrome coronavirus (MERS-CoV) accessory protein ORF4b has the most potential among the MERS-CoV accessory proteins to inhibit the TLR7/9-signaling-dependent alpha interferon production. ORF4b protein, which has a bipartite nuclear localization signal, was found to…</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>Human ACE2 Peptide-Attached Plasmonic-Magnetic Heterostructure for Magnetic Separation, Surface Enhanced Raman Spectroscopy Identification, and Inhibition of Different Variants of SARS-CoV-2 Infections</strong> - The emergence of Alpha, Beta, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for several million deaths up to now. Because of the huge amount of vaccine escape mutations in the spike (S) protein for different variants, the design of material for combating SARS-CoV-2 is very important for our society. Herein, we report on the design of a human angiotensin converting enzyme 2 (ACE2) peptide-conjugated plasmonic-magnetic…</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>Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway</strong> - Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional…</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>Blood-brain Barrier Damage is Pivotal for SARS-CoV-2 Infection to the Central Nervous System</strong> - Transsynaptic transport is the most accepted proposal to explain the SARS-CoV-2 infection of the CNS. Nevertheless, emerging evidence shows that neurons do not express the SARS-CoV-2 receptor ACE2, which highlights the importance of the blood-brain barrier (BBB) in preventing virus entry to the brain. In this study, we examine the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) and the cytokine profile in cerebrospinal fluids (CSF) from two patients with a brain tumor and COVID-19. To…</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>Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs</strong> - Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Docking Study of Several Seconder Metabolites from Medicinal Plants as Potential Inhibitors of COVID-19 Main Protease</strong> - CONCLUSION: Our results obtained from docking studies suggest that pycnamine should be examined in vitro to combat 2019-CoV. Moreover, pycnamine might be a promising lead compound for anti-CoV drugs.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>Withania somnifera</em> (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy</strong> - Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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