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186 lines
53 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>22 October, 2022</title>
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div.column{display: inline-block; vertical-align: top; width: 50%;}
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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>Psychological Distress and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study</strong> -
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<div>
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Background and Objectives: During the COVID-19 pandemic, Chinese international students (CISs) experienced increased distress associated with a combination of unique and universal stressors, among which discrimination against Chinese is especially harmful. Therefore, studying correlates of distress among CISs, including the association between discrimination and distress and factors intensifying or attenuating this link, may yield important insights into prevention and intervention efforts. Design: We adopted a cross-sectional self-report design. Methods: Our study compared depression and anxiety between CISs (N = 381) and Chinese students in Chinese colleges (CSCCs; N = 306) and examined correlates of distress including the association between discrimination and distress as well as moderators on this link within CISs. Results: Compared to CSCCs, CISs reported greater depression and anxiety. Depression was associated with being female, older, non-heterosexual, increased discrimination, decreased self- esteem, coping flexibility, perceived social support, and satisfaction with online learning. Anxiety was associated with being female, heterosexual, in undergraduate years, increased discrimination, decreased self-esteem, subjective socioeconomic status, coping flexibility, and satisfaction with online learning. High perceived social support and being heterosexual weakened the association between discrimination and distress (anxiety and depression). Conclusions: Our study underscored the impact of the pandemic and related discrimination on CISs and highlighted individual differences that may warrant attention.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/mtk7w/" target="_blank">Psychological Distress and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study</a>
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</div></li>
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<li><strong>Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 regions sequences</strong> -
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Background: Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. Methods: We included asymptomatic subjects with no previous COVID-19 infection or vaccination; patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using a Illumina MiSeq platform. Results: We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Conclusions: Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease.
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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/10.1101/2022.10.20.513136v1" target="_blank">Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 regions sequences</a>
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<li><strong>SARS-CoV-2 nsp3-4 suffice to form a pore shaping replication organelles</strong> -
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Coronavirus replication is associated with the remodeling of cellular membranes resulting in the formation of double-membrane vesicles (DMVs). Recently, a pore spanning DMV was identified as a putative portal for viral RNA transcription and replication products providing a novel target for antiviral intervention. However, the exact components and the structure of the SARS-CoV-2 pore remain to be determined. Here, we investigate the structure of DMV pores by in situ cryo-electron tomography combined with subtomogram averaging. We reveal non-structural proteins (nsp) 3 and 4 as minimal components forming a DMV spanning pore and show that nsp3 Ubl1-Ubl2 domains are critical for inducing membrane curvature and DMV formation. Altogether, SARS-CoV-2 nsp3-4 has a dual role by driving the biogenesis of replication organelles and forming DMV-spanning replicopores.
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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/10.1101/2022.10.21.513196v1" target="_blank">SARS-CoV-2 nsp3-4 suffice to form a pore shaping replication organelles</a>
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<li><strong>A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses</strong> -
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<div>
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T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus rapid evolution, which leads to new variants with immune escape capacity. In this study, we used the Omicron variant as a model organism and took a systems approach to evaluate the impact of mutations on CD8+ T cell immunogenicity. We computed an immunogenicity potential score for each SARS-CoV-2 peptide antigen from the ancestral strain and Omicron, capturing both antigen presentation and T cell recognition probabilities. By comparing ancestral vs. Omicron immunogenicity scores, we reveal a divergent and heterogeneous landscape of impact for CD8+ T cell recognition of mutated targets in Omicron variants. While T cell recognition of Omicron peptides is broadly preserved, we observed mutated peptides with deteriorated immunogenicity that may assist breakthrough infection in some individuals. We then combined our scoring scheme with an in-silico mutagenesis, to characterise the position- and residue-specific theoretical mutational impact on immunogenicity. While we predict many escape trajectories from the theoretical landscape of substitutions, our study suggests that Omicron mutations in T cell epitopes did not develop under cell-mediated pressure. Our study provides a generalisable platform for fostering a deeper understanding of existing and novel variant impact on antigen-specific vaccine- and/or infection-induced T cell immunity.
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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/10.1101/2022.10.21.513200v1" target="_blank">A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses</a>
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<li><strong>RandomRibo: A Novel Tool for Transcript-Level Translation Elongation Velocity Determinant Identification at Single Codon Resolution</strong> -
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<div>
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Cells have evolved the process of translational regulation to rapidly fine-tune protein expression to suit intracellular needs. Ribosome velocity during translation elongation is a key contributor to typical protein expression, as abnormal regulation of it can give rise to disease states. Ribosomes travel along mRNA transcripts with varying speeds, with regions of high movement to increase efficiency as well as pause site regions to allow for processes such as co-translational folding. Having a comprehensive understanding of why ribosomal movement undergoes such positional fluctuation gives researchers critical, molecular-level insight into disease states. However, previous methods cannot offer precise information at the single transcript level due to the high amounts of noise present in Ribo-seq data and simple measures of determinants, rendering them unable to analyze a variety of disease states affecting the translation of specific genes. In this study, I present the software RandomRibo, the first computational tool to identify translation velocity determinants for individual transcripts by incorporating (1) Bayesian wavelet thresholding with double exponential priors to denoise ribosome profiling data, (2) nascent chain alpha helix propensity and electrostatic force algorithms to better model interactions with the ribosome exit tunnel, and (3) Random Forest Regression models to capture the non-linear relationships between translation velocity and its determinants. I demonstrate RandomRibo’s capabilities by applying its algorithms to different cell lines and cellular states to corroborate previous observations and establish novel hypotheses regarding the mechanisms of SARS-CoV-2 Nonstructural protein 1 (Nsp1).
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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://osf.io/ey63f/" target="_blank">RandomRibo: A Novel Tool for Transcript-Level Translation Elongation Velocity Determinant Identification at Single Codon Resolution</a>
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<li><strong>T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Many people experiencing long COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). However, whether virus-specific adaptive immunity is affected in Neuro-PASC patients remains poorly understood. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated humoral and cellular responses toward SARS-CoV-2 Nucleocapsid protein at an average of 6 months post-infection compared to healthy COVID convalescents. Neuro-PASC patients also had enhanced virus-specific production of IL-6 from and diminished activation of CD8+ T cells. Furthermore, the severity of cognitive deficits or quality of life disturbances in Neuro-PASC patients were associated with a reduced diversity of effector molecule expression in T cells but elevated IFN-γ production to the C-terminal domain of Nucleocapsid protein. Proteomics analysis showed enhanced plasma immunoregulatory proteins and reduced pro-inflammatory and antiviral response proteins in Neuro-PASC patients compared with healthy COVID convalescents, which were also correlated with worse neurocognitive dysfunction. These data provide new insight into the pathogenesis of long COVID syndrome and a framework for the rational design of predictive biomarkers and therapeutic interventions. Keywords: COVID-19 immunity, T cell memory, Neuro-PASC, long COVID, immunoregulation, proteomics
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</p>
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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/10.1101/2021.08.08.21261763v4" target="_blank">T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID</a>
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<li><strong>Global landscape of the host response to SARS-CoV-2 variants reveals viral evolutionary trajectories</strong> -
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A series of SARS-CoV-2 variants of concern (VOCs) have evolved in humans during the COVID-19 pandemic: Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic and genomic analyses during infection to understand the molecular responses driving VOC evolution. We discovered VOC-specific differences in viral RNA and protein expression levels, including for N, Orf6, and Orf9b, and pinpointed several viral mutations responsible. An analysis of the host response to VOC infection and comprehensive interrogation of altered virus-host protein-protein interactions revealed conserved and divergent regulation of biological pathways. For example, regulation of host translation was highly conserved, consistent with suppression of VOC replication in mice using the translation inhibitor plitidepsin. Conversely, modulation of the host inflammatory response was most divergent, where we found Alpha and Beta, but not Omicron BA.1, antagonized interferon stimulated genes (ISGs), a phenotype that correlated with differing levels of Orf6. Additionally, Delta more strongly upregulated proinflammatory genes compared to other VOCs. Systematic comparison of Omicron subvariants revealed BA.5 to have evolved enhanced ISG and proinflammatory gene suppression that similarly correlated with Orf6 expression, effects not seen in BA.4 due to a mutation that disrupts the Orf6-nuclear pore interaction. Our findings describe how VOCs have evolved to fine-tune viral protein expression and protein-protein interactions to evade both innate and adaptive immune responses, offering a likely explanation for increased transmission in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.19.512927v1" target="_blank">Global landscape of the host response to SARS-CoV-2 variants reveals viral evolutionary trajectories</a>
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<li><strong>Impact of COVID-19 related social isolation on behavioral outcomes in young adults.</strong> -
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Social isolation strongly affects our emotions and behavior. Worldwide, individuals experienced prolonged periods of isolation during the first wave of the COVID-19 pandemic when authorities imposed restrictions to reduce the spread of the virus. In this study, we investigated the effects of social isolation on emotional and behavioral outcomes in young adults from Lombardy, Italy, a global hotspot of COVID-19. We leverage baseline (pre-social isolation) and follow-up (mid-or post isolation) data collected from young adults enrolled in the ongoing, longitudinal PHIME study. At baseline, 167 participants completed the ASEBA questionnaires (ASR/YSR) by weblink or in person; 65 completed the ASR between 12-18 weeks after the onset of restrictions. Using the sign test and multiple linear regression models, we examined differences in ASR scores between baseline and follow-up adjusting for sex, age, pre-pandemic IQ (Kaufman Brief Intelligence Tests; K-BIT 2), and time with social restrictions (weeks). Further, we examined interactions between sex and time in social isolation. Participants completed the ASR after spending an average of 14 weeks in social isolation (range 12-18 weeks). Thought Problems increased between baseline and follow-up (median difference 1.0; 1st., 3rd quartile: -1.0, 4.0; p=0.049). Among males, a longer time with social isolation (≥ 14 weeks) was associated with increased rule-breaking behaviors of 2.8 points. These results suggest the social isolation related to COVID-19 adversely impacted mental health. In particular, males seem to externalize their condition. These findings might help future interventions and treatment to minimize the consequences of social isolation experience in young adults.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.20.22280791v1" target="_blank">Impact of COVID-19 related social isolation on behavioral outcomes in young adults.</a>
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<li><strong>Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021</strong> -
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Background: Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. Methods: Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. Results: We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. Conclusions: During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.20.22281327v1" target="_blank">Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021</a>
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<li><strong>Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: Data from a Multisite Cohort Study</strong> -
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Purpose: Evaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 (COVID-19) pandemic using data from a prospective nationwide cohort: the Adolescent Brain Cognitive DevelopmentSM Study. Method: 9,270 youth ages 11.5-13.0 years old completed a pre-pandemic assessment of past- month alcohol and drug use in 2018-2019, then up to seven during-pandemic assessments between May 2020 and May 2021. We compared the prevalence of substance use among same- age youth across these eight timepoints. Results: Pandemic-related decreases in the prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% pre- pandemic, p<.001). Pandemic-related increases in inhalant use and prescription drug misuse were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021 (0.2% vs. 0% pre-pandemic, p<.001). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from pre- pandemic levels in May 2021 (0.5% vs. 0.2% pre-pandemic, p=.09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families. Conclusions: Among youth ages 11.5-13.0 years old, rates of alcohol use remained dramatically reduced in May 2021 relative to pre-pandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite partial restoration of pre- pandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/jhma5/" target="_blank">Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: Data from a Multisite Cohort Study</a>
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<li><strong>Evidence of a Sjogrens disease-like phenotype following COVID-19</strong> -
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Objectives: Sjogrens Disease (SjD) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth resulting from the secretory dysfunction of the exocrine glands. SARS-CoV-2 may trigger the development or progression of autoimmune diseases, as evidenced by increased autoantibodies in patients and the presentation of cardinal symptoms of SjD. The objective of the study was to determine whether SARS-CoV-2 induces the signature clinical symptoms of SjD. Methods: The ACE2-transgenic mice were infected with SARS-CoV-2. SJD profiling was conducted. COVID-19 patient sera were examined for autoantibodies. Clinical evaluations of convalescent COVID-19 subjects, including minor salivary gland (MSG) biopsies, were collected. Lastly, monoclonal antibodies generated from single B cells of patients were interrogated for ACE2/spike inhibition and nuclear antigens. Results: Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) with anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. Sera of COVID-19 patients showed an increase in ANA, anti-SSA/Ro52, and anti-SSB/La. The male patients showed elevated levels of anti-SSA/Ro52 compared to female patients, and female patients had more diverse ANA patterns. Minor salivary gland biopsies of convalescent COVID-19 subjects showed focal lymphocytic infiltrates in four of six subjects, and 2 of 6 subjects had focus scores >2. Lastly, we found monoclonal antibodies produced in recovered patients can both block ACE2/spike interaction and recognize nuclear antigens. Conclusion: Overall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects. The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.20.22281265v1" target="_blank">Evidence of a Sjogrens disease-like phenotype following COVID-19</a>
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<li><strong>Efficacy of Linear Regression Modelling of SARS-CoV-2 cases based on local wastewater surveillance</strong> -
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In the ongoing SARS-CoV-2 pandemic, there is a need for new strategies for surveillance and identification of arising infection waves. Reported cases of new infections based on individual testing are soon deemed inaccurate due to ever changing regulations and limited testing capacity. Wastewater based epidemiology is one promising solution that can be broadly applied with low efforts in comparison to current large-scale testing of individuals. Here, we are combining local wastewater data from the city of Dresden (Germany) along with reported cases and vaccination data from a central database (Robert-Koch-Institute) with virus variant information to investigate the correlation of virus concentrations in the wastewater and reported SARS-CoV-2 cases. In particular, we compared Linear Regression and Machine Learning (ML) models, which are both revealing an existing correlation of virus particles in wastewater and reported cases. Our findings demonstrate that the different virus variants of concern (Alpha, Delta, BA.1, and BA.2) contribute differently over time and parameters vary between variants, as well. By comparing the Linear Regression and ML-based models, we observed that ML can achieve a good fit for training data, but Linear Regression is a more robust tool, especially for new virus variants. We hereby conclude that deriving the rate of new infections from local wastewater by applying Linear Regression may be a robust approximation of tracing the state of the pandemic for practitioners and policy makers alike.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.20.22281303v1" target="_blank">Efficacy of Linear Regression Modelling of SARS-CoV-2 cases based on local wastewater surveillance</a>
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<li><strong>Socioeconomic inequalities of Long COVID: findings from a population-based survey in the United Kingdom</strong> -
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Objective To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the socioeconomic inequalities in Long COVID by sex and occupational groups. Design We analysed data from the COVID-19 Infection Survey conducted by the Office for National Statistics between 26/04/2020 and 31/01/2022. This is the largest and nationally representative survey of COVID-19 in the UK and provides uniquely rich, contemporaneous, and longitudinal data on occupation, health status, COVID-19 exposure, and Long COVID symptoms. Setting Community-based longitudinal survey of COVID-19 in the UK. Participants We included 201,799 participants in our analysis who were aged between 16 and 64 years and had a confirmed SARS-CoV-2 infection. Main outcome measures We used multivariable logistic regression models to estimate the risk of Long COVID at least 4 weeks after acute SARS-CoV-2 infection by deciles of index of multiple deprivation (IMD) and adjusted for a range of demographic and spatiotemporal factors. We further examined the modifying effects of socioeconomic deprivation by sex and occupational groups. Results A total of 19,315 (9.6%) participants reported having Long COVID symptoms. Compared to the least deprived IMD decile, participants in the most deprived decile had a higher adjusted risk of Long COVID (11.4% vs 8.2%; adjusted OR: 1.45; 95% confidence interval [CI]: 1.33, 1.57). There were particularly significantly higher inequalities (most vs least deprived decile) of Long COVID in healthcare and patient facing roles (aOR: 1.76; 1.27, 2.44), and in the education sector (aOR: 1.62; 1.26, 2.08). The inequality of Long COVID was higher in females (aOR: 1.54; 1.38, 1.71) than males (OR: 1.32; 1.15, 1.51). Conclusions Participants living in the most socioeconomically deprived areas had a higher risk of Long COVID. The inequality gap was wider in females and certain public facing occupations (e.g., healthcare and education). These findings will help inform public health policies and interventions in adopting a social justice and health inequality lens.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.19.22281254v1" target="_blank">Socioeconomic inequalities of Long COVID: findings from a population-based survey in the United Kingdom</a>
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<li><strong>Safety and effectiveness of COVID-19 mRNA vaccination and risk factors for hospitalisation caused by the omicron variant in 0.8 million adolescents: A nationwide cohort study in Sweden</strong> -
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Background Real-world evidence on the safety and effectiveness of COVID-19 vaccination against severe disease caused by the omicron variant among adolescents is sparse. In addition, evidence on risk factors for severe COVID-19 disease, and whether vaccination is similarly effective in such risk groups, is unclear. Methods and findings Nationwide registers were used to examine the safety and effectiveness of COVID-19 mRNA vaccination against COVID-19 hospitalisation, and risk factors for COVID-19 hospitalisation in adolescents. The safety analysis included all individuals in Sweden born between 2003-2009 (aged 11.3-19.2 years) given at least one dose of mRNA vaccine (N=645,355), and never vaccinated controls (N=199,022). Outcomes evaluated included all hospitalisations until 5 June 2022. The vaccine effectiveness (VE) against COVID-19 hospitalisation and associated risk factors was evaluated in adolescents given two doses of mRNA vaccine (N=501,945), as compared to never vaccinated controls (N=170,083), during an omicron predominant period (1 January 2022 to 5 June 2022). The safety analysis showed that COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse events resulting in hospitalisation. During follow-up, 1.69% of the vaccinated individuals were hospitalised compared to 1.71% of the controls (P=0.29). In the VE analysis, there were 21 cases (0.004%) of COVID-19 hospitalisation among 2-dose recipients and 26 cases (0.015%) among controls, resulting in an estimated VE of 75% (95% CI, 54-86, P<0.001). Strong risk factors for COVID-19 hospitalisation included previous infections (odds ratio [OR], 14.3, 95% CI, 7.7-26.6, P<0.001), and cerebral palsy/development disorders (OR, 12.0, 95% CI, 6.4-22.6, P<0.001), with similar estimates of VE in these subgroups as in the total cohort. The number needed to vaccinate with two doses to prevent one case of COVID-19 hospitalisation was 9,007 in the total cohort and 1,031 in those with previous infections or developmental disorders. None of the individuals hospitalised due to COVID-19 died within 30 days. Conclusions In this nationwide study, COVID-19 mRNA vaccination was not associated with an increased risk of any serious adverse event in adolescents. Two doses were associated with a lower risk of COVID-19 hospitalisation during the omicron predominant period, especially among those with certain predisposing conditions who should be prioritized for vaccination. However, COVID-19 hospitalisation among general adolescents was extremely rare, and additional doses in this population may not be warranted at this stage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.19.22281286v1" target="_blank">Safety and effectiveness of COVID-19 mRNA vaccination and risk factors for hospitalisation caused by the omicron variant in 0.8 million adolescents: A nationwide cohort study in Sweden</a>
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<li><strong>Uptake of COVID-19 vaccines among healthcare workers within primary healthcare facilities, Entebbe municipality Uganda</strong> -
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Background: Routine vaccination is an essential highly successfully public health intervention in the prevention of infectious diseases that greatly depends on high coverage, and health care workers (HCWs) who play a pivotal role in ensuring the high uptake of vaccines in the population. COVID-19 vaccines have been proven efficacious, and vaccination campaigns have been ongoing, however, there is a perceived high vaccine hesitancy among health care workers in Uganda. This study describes the level and determinants of uptake of COVID-19 vaccines among HCWs in Entebbe municipality, Uganda. Materials and methods: We conducted a health facility based cross-sectional study among HCWs from private and government health facilities in Entebbe municipality between July 2021 and August 2021. Structured questionnaires were used, and data were analysed using Stata version 12. We defined uptake as having received at least the first doze of COVID 19 vaccine or completed the two dozes. Results: The level of vaccine uptake was 65.6%with higher uptake among males than females. HCWs aged 30-39 years were 2.7 times more likely to have been vaccinated than those less than 30 years (OR 2.72, 95% CI: 1.26-5.88, P-value <0.01), and the odds of having been vaccinated were 4 times higher among health workers above 40 years (OR 4.29, 95% CI 1.50-12.24, P-value < 0.01). Additionally, the odds of having been vaccinated were 4 times higher among health care workers that participated in COVID-19 vaccine related activities (OR 4.18, 95% CI 2.16-8.10, p-value <0.001). Healthcare workers (98%) had confidence in the vaccines although 45% of those that were not vaccinated felt that the vaccines were ineffective. Conclusion. Vaccine uptake among HCWs was relatively high compared to the WHO recommended uptake of 70% by mid-2022, although some HCWs were still hesitant. The convenience of vaccination services was an important factor in vaccine uptake. Hence, governments should endeavour to improve access to vaccination both for HCWs and the public.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.20.22281300v1" target="_blank">Uptake of COVID-19 vaccines among healthcare workers within primary healthcare facilities, Entebbe municipality Uganda</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>Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell); Biological: Inactivated COVID-19 vaccine (Vero Cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; First Affiliated Hospital Bengbu Medical College<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics 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>COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Tri-City COVID Attitudes Study<br/><b>Sponsor</b>: University of Kansas Medical Center<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>JT001 (VV116) for the Treatment of COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH<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>Boost Intentions and Facilitate Action to Promote Covid-19 Booster Take-up</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine<br/><b>Sponsor</b>: University of California, Los Angeles<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>Effects of Prompt to Bundle Covid-19 Booster and Flu Shot</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle<br/><b>Sponsor</b>: University of California, Los Angeles<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>Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms<br/><b>Sponsor</b>: University of California, Los Angeles<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>Respiratory Muscles After Inspiratory Muscle Training After COVID-19</strong> - <b>Conditions</b>: COVID-19; Diaphragm Injury<br/><b>Intervention</b>: Device: Inspiratory Muscle Training (IMT)<br/><b>Sponsors</b>: RWTH Aachen University; Philipps University Marburg Medical Center<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 Simulation Education on Nursing Students</strong> - <b>Conditions</b>: COVID-19 Pandemic; Simulation of Physical Illness<br/><b>Interventions</b>: Behavioral: Simulation training; Other: Control Group<br/><b>Sponsor</b>: Mehmet Akif Ersoy University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial</strong> - <b>Conditions</b>: COVID-19; Immunodeficiency<br/><b>Interventions</b>: Drug: Paxlovid 5 days; Drug: Paxlovid 10 days; Drug: Tixagevimab and Cilgavimab<br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; University Hospital, Geneva<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>COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<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>COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability</strong> - <b>Conditions</b>: Sars-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Device: Rapid SARS-CoV-2 Antigen Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: V-01/V-01-B5; Biological: V-01-351/V-01-B5; Biological: V-01<br/><b>Sponsor</b>: Livzon Pharmaceutical Group Inc.<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploratory Clinical Study to Evaluation of the Safety and Immunogenicity of Bivalent Vaccine V-01D-351</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: V-01D-351; Biological: CoronaVac<br/><b>Sponsor</b>: Livzon Pharmaceutical Group Inc.<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Biological: AdCLD-CoV19-1 OMI (Part A); Biological: AdCLD-CoV19-1 OMI (Part B); Other: Placebo (Part B)<br/><b>Sponsor</b>: Cellid Co., Ltd.<br/><b>Active, not 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>Therapeutic use of calpeptin in COVID-19 infection</strong> - This perspective considers the benefits of the potential future use of the cell permeant calpain inhibitor, calpeptin, as a drug to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent work has reported calpeptin’s capacity to inhibit entry of the virus into cells. Elsewhere, several drugs, including calpeptin, were found to be able to inhibit extracellular vesicle (EV) biogenesis. Unsurprisingly, because of similarities between viral and EV release mechanisms,…</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 ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1</strong> - ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Post COVID-19 neuropsychiatric complications and therapeutic role for TNF-α inhibitors: a case series study</strong> - CONCLUSIONS: To our knowledge, this report is the first case series study that suggests TNF inhibitors in the treatment of post-COVID-19 syndrome, especially neuropsychological complications. However, future studies should evaluate the best therapeutic options for this syndrome.</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>Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases</strong> - Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block…</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>Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases</strong> - CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potent inhibition of diverse Omicron sublineages by SARS-CoV-2 fusion-inhibitory lipopeptides</strong> - The emergence and rapid spreading of SARS-CoV-2 variants of concern (VOCs) have posed a great challenge to the efficacy of vaccines and therapeutic antibodies, calling for antivirals that can overcome viral evasion. We recently reported that SARS-CoV-2 fusion-inhibitory lipopeptides, IPB02V3 and IPB24, possessed the potent activities against divergent VOCs, including Alpha, Beta, Gamma, Delta, and the initial Omicron strain (B.1.1.529); however, multiple Omicron sublineages have emerged 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>Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature</strong> - Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body’s defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress,…</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>Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2</strong> - SARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combined Molnupiravir and Nirmatrelvir Treatment Improves the Inhibitory Effect on SARS-CoV-2 in Rhesus Macaques</strong> - The periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have each recently been approved as monotherapy for use in high risk COVID-19 patients. As preclinical data are only available for rodent and ferret models, 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>Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection</strong> - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro…</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 systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases</strong> - CONCLUSION: IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.</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>Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19</strong> - The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. 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>SARS-CoV-2 Vaccination in Kidney Transplant Recipients-Stratified Analysis of the Humoral Immune Response</strong> - CONCLUSIONS: Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft…</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>Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients co-morbidly affected by type 2 diabetes</strong> - CONCLUSIONS: The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those co-morbid patients. This article is protected by…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DNA damage contributes to age-associated differences in SARS-CoV-2 infection</strong> - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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