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182 lines
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<title>14 July, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Emotion Regulation and Disordered Eating in Youths: Two Daily-Diary Studies</strong> -
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Disordered eating cognitions and behaviors in childhood and adolescence have been identified as precursors for the development of eating disorders. Another important contributor to eating disorder risk is maladaptive emotion regulation. However, while the regulation of negative affect has been the focus of much research, the literature on the role of positive emotion regulation in eating pathology is extremely limited. The present study extends previous research by examining the regulation of both positive and negative affect in disordered eating using two waves of a daily diary design. Every evening for 21 days, 139 youths (8-15 years) reported their use of rumination, dampening, and disordered eating cognitions and behaviors. One year later, during the onset of the COVID-19 pandemic, 115 of these youths were followed-up. As predicted, higher levels of rumination and dampening were found to be associated with a higher frequency of weight concerns and restrictive eating behaviors on person-level (both Waves) and day-level (Wave 2). Further, a higher frequency of rumination at Wave 1 predicted increases in the frequency of restrictive eating behaviors one year later. Our findings underline the importance of examining regulation of both positive and negative emotion in order to understand eating disorder risk.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/jzn5q/" target="_blank">Emotion Regulation and Disordered Eating in Youths: Two Daily-Diary Studies</a>
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<li><strong>SHAME, GUILT AND FEAR AS PREDICTORS OF TRAUMATIC EXPERIENCES RELATED TO COVID-19 PANDEMIC</strong> -
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<div>
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Objective: The general objective of the current study was to investigate the role of shame, guilt and fear activations related to stressful experiences related to COVID-19 in predicting post-traumatic stress symptoms severity. Methods: We focused on 72 participants recruited in Lombardy region (Italy) from June 2021 to February 2022. Primary outcome measures were intrusion, avoidance, hyperarousal and global traumatic stress scores related to the most stressful experience related to COVID-19 pandemic. Results: Using multiple linear models, the most consistent result was that the emotions of shame and fear related to stressful experiences related to COVID-19 predicted traumatic symptoms severity. More specifically, while shame predicted in a more consistent way intrusivity, hyperarousal and avoidance subscales. Conclusion: Globally, the present findings suggest the importance of shame in the maintenance of post-traumatic symptoms related to COVID-19 experiences. These results support of the changes introduced with DSM-V in PTSD theoretical framework underscoring a range of self-related appraisals and emotions beyond the classic fear/life threat activations. Future research should provide analysis of neural correlates and biomarkers combined with the presence of psychometric measures indicating if the level of emotion activated would allow for a more robust neural and epigenetic discernment of traumatic symptoms.
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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://psyarxiv.com/prg52/" target="_blank">SHAME, GUILT AND FEAR AS PREDICTORS OF TRAUMATIC EXPERIENCES RELATED TO COVID-19 PANDEMIC</a>
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</div></li>
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<li><strong>Resuming Social Contact After Months of Contact Restrictions: Social Traits Moderate Associations Between Changes in Social Contact and Well-Being</strong> -
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<div>
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Humans possess a need for social contact. Satisfaction of this need benefits well-being, whereas deprivation is detrimental. However, how much contact people desire is not universal, and evidence is mixed on individual differences in the association between contact and well-being. This preregistered longitudinal study (N = 190) examined changes in social contact and well-being (life satisfaction, depressivity/anxiety) in Germany during pervasive contact restrictions, which exceed lab-based social deprivation. We analyzed how changes in personal and indirect contact and well-being during the first COVID-19 lockdown varied with social traits (e.g., affiliation, extraversion). Results showed that affiliation motive, need to be alone, and social anxiety moderated the resumption of personal contact under loosened restrictions as well as associated changes in life satisfaction and depressivity/anxiety.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rmq8e/" target="_blank">Resuming Social Contact After Months of Contact Restrictions: Social Traits Moderate Associations Between Changes in Social Contact and Well-Being</a>
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</div></li>
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<li><strong>Structural basis for the enhanced infectivity and immune evasion of Omicron subvariants</strong> -
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The Omicron variants of SARS-CoV-2 have recently become the globally dominant variants of concern in the COVID-19 pandemic. At least five major Omicron sub-lineages have been characterized: BA.1, BA.2, BA.3, BA.4 and BA.5. They all possess over 30 mutations on the Spike (S) protein. Here we report the cryo-EM structures of the trimeric S proteins from the five subvariants, of which BA.4 and BA.5 share the same mutations of S protein, each in complex with the surface receptor ACE2. All three receptor binding domains of S protein from BA.2 and BA.4/BA.5 are up, while the BA.1 S protein has two up and one down. The BA.3 S protein displays increased heterogeneity, with the majority in the all up RBD state. The differentially preferred conformations of the S protein are consistent with their varied transmissibilities. Analysis of the well defined S309 and S2K146 epitopes reveals the underlie immune evasion mechanism of Omicron subvariants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.13.499586v1" target="_blank">Structural basis for the enhanced infectivity and immune evasion of Omicron subvariants</a>
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</div></li>
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<li><strong>Comparison of the 2021 COVID-19 Roadmap Projections against Public Health Data in England</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Control and mitigation of the COVID-19 pandemic in England has relied on a combination of vac- cination and non-pharmaceutical interventions (NPIs). Some of these NPIs are extremely costly (economically and socially), so it was important to relax these promptly without overwhelming already burdened health services. The eventual policy was a Roadmap of four relaxation steps throughout 2021, taking England from lock-down to the cessation of all restrictions on social interaction. In a series of six Roadmap documents generated throughout 2021, models assessed the potential risk of each relaxation step. Here we show that the model projections generated a reliable estimation of medium-term hospital admission trends, with the data points up to September 2021 generally lying within our 95% prediction intervals. The greatest uncertainties in the modelled scenarios came from vaccine efficacy estimates against novel variants, and from assumptions about human behaviour in the face of changing restrictions and risk.
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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/10.1101/2022.03.17.22272535v2" target="_blank">Comparison of the 2021 COVID-19 Roadmap Projections against Public Health Data in England</a>
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<li><strong>Cross-GWAS coherence test at the gene and pathway level</strong> -
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Proximal genetic variants are frequently correlated, implying that the corresponding effect sizes detected by genome-wide association studies (GWAS) are also not independent. Methods already exist to account for this when aggregating effects from a single GWAS across genes or pathways. Here we present a rigorous yet fast method for detecting genes with coherent association signals for two traits, facilitating cross-GWAS analyses. To this end, we devised a new significance test for the covariance of datapoints not drawn independently but with a known inter-sample covariance structure. We show that the distribution of its test statistic is a linear combination of chi2 distributions with positive and negative coefficients. The corresponding cumulative distribution function can be efficiently calculated with Davies9 algorithm at high precision. We apply this general framework to test for dependence between SNP-wise effect sizes of two GWAS at the gene level. We extend this test to detect also gene-wise causal links. We demonstrate the utility of our method by uncovering potential shared genetic links between the severity of COVID-19 and (1) being prescribed class M05B medication (drugs affecting bone structure and mineralization), (2) rheumatoid arthritis, (3) vitamin D (25OHD), and (4) serum calcium concentrations. Our method detects a potential role played by chemokine receptor genes linked to TH1 versus TH2 immune response, a gene related to integrin beta-1 cell surface expression, and other genes potentially impacting the severity of COVID-19. Our approach will be useful for similar analyses involving datapoints with known auto-correlation structures.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.16.21257289v4" target="_blank">Cross-GWAS coherence test at the gene and pathway level</a>
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</div></li>
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<li><strong>Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques</strong> -
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Pulmonary immunity against SARS-CoV-2 infection has not been well studied. This study investigated the distribution of immune cells int the lungs of 8 rhesus macaques experimentally infected with SARS-CoV-2, and euthanized 11-14 days later. Using immunohistochemistry, inducible bronchus-associated lymphoid tissue was found in all animals. The inducible bronchus-associated lymphoid tissues were composed of B cells, T cells, and follicular dendritic cells with evidence of lymphocyte priming and differentiation. This suggests local immunity plays an important role in the SARS-CoV-2 infection. Further study of local immunity in the lung would benefit our understanding of SARS-CoV-2 pathogenesis and could lead to new interventions to control the SARS-CoV-2 infection and disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.12.499813v1" target="_blank">Inducible Bronchus-Associated Lymphoid Tissue in SARS-CoV-2 Infected Rhesus Macaques</a>
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<li><strong>Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2</strong> -
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The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS2) affected the geriatric population. Among research models, Golden Syrian hamsters (GSH) are one of the most representative to study SARS2 pathogenesis and host responses. However, animal studies that recapitulate the effects of SARS2 in the human geriatric population are lacking. To address this gap, we inoculated 14 months old GSH (resembling people over 60 years old) with a prototypic ancestral strain of SARS2 and studied the effects on virus pathogenesis, virus shedding, and respiratory and gastrointestinal microbiome changes. SARS2 infection led to high vRNA loads in the nasal turbinates (NT), lungs, and trachea as well as higher pulmonary lesions scores later in infection. Dysbiosis throughout SARS2 disease progression was observed in the pulmonary microbial dynamics with the enrichment of opportunistic pathogens (Haemophilus, Fusobacterium, Streptococcus, Campylobacter, and Johnsonella) and microbes associated with inflammation (Prevotella). Changes in the gut microbial community also reflected an increase in multiple genera previously associated with intestinal inflammation and disease (Helicobacter, Mucispirillum, Streptococcus, unclassified Erysipelotrichaceae, and Spirochaetaceae). Influenza A virus (FLUAV) pre-exposure resulted in slightly more pronounced pathology in the NT and lungs early on (3 dpc), and more notable changes in lungs compared to the gut microbiome dynamics. Similarities among aged GSH and the microbiome in critically ill COVID-19 patients, particularly in the lower respiratory tract, suggest that GSHs are a representative model to investigate microbial changes during SARS2 infection. The relationship between the residential microbiome and other confounding factors, such as SARS2 infection, in a widely used animal model, contributes to a better understanding of the complexities associated with the host responses during viral infections.
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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/10.1101/2022.07.13.499851v1" target="_blank">Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2</a>
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<li><strong>Public-private partnership to rapidly strengthen and scale COVID-19 response in Western Kenya</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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INTRODUCTION: In Africa almost half of healthcare services are delivered through private sector providers. These are often underused in national public health responses. In line with our previous HIV experience and to support and accelerate the public sectors COVID-19 response, we initiated a public-private project (PPP) in Kisumu County, Kenya. In this manuscript we demonstrate this PPP9s performance, using COVID-19 testing as an aggregator and with semi-real time digital monitoring tools for rapid scaling of COVID-19 response. METHODS: COVID-19 diagnostic testing formed the basis for a PPP between KEMRI, Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities: COVID-Dx. COVID-Dx was implemented from June 01, 2020, to March 31, 2021 in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the Kenyan MoH COVID-19 case definition. Samples were rapidly transported by motorbike and tested using RT-PCR at the central reference laboratory in KEMRI. Healthcare workers in participating facilities collected patient clinical data using a digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboards with all relevant stakeholders through their mobile phones. Statistical analyses were performed using Stata 16 to inform project processes. RESULTS: Nine private facilities participated in the project. A detailed patient trajectory was developed from case identification to result reporting, all steps supported by a semi-real time digital dashboard. A total of 4,324 PCR tests for SARS-CoV-2 (16%) were added to the public response, identifying 425 positives. Geo-mapped and time-tagged information on incident cases was depicted on Google maps dashboards and fed back to policymakers for informed rapid decision-making. Preferential COVID-19 testing was performed on health workers at risk, with 1,009 tested (43% of all County health workforce). CONCLUSION: We demonstrate feasibility of rapidly increasing the public health sector response to a COVID-19 epidemic outbreak in an African setting. Our PPP intervention in Kisumu, Kenya was based on a joint testing strategy and demonstrated that semi-real time digitalization of patient trajectories in the healthcare system can gain significant efficiencies, linking public and private healthcare efforts, increasing transparency, support better quality health services and informing policymakers to target interventions. This PPP has since scaled to 33 facilities in Kisumu and subsequently to 84 sites in 14 western Kenyan Counties.
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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/10.1101/2021.08.31.21262891v4" target="_blank">Public-private partnership to rapidly strengthen and scale COVID-19 response in Western Kenya</a>
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</div></li>
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<li><strong>Early life adversity, dispositional mindfulness, and longitudinal stress experience during the COVID-19 pandemic</strong> -
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Experiencing severe or prolonged stressors in early life is associated with increased risk for mental and physical disorders in adulthood. Further, individuals who experienced early life stress (ELS) may use dysfunctional coping strategies like stress-related eating, in contrast to more beneficial stress buffering mechanisms e.g. based on mindfulness. Whether these mechanisms contribute to increased levels of perceived stress and symptoms of mental disorders in individuals with ELS in times of crisis is yet unclear. As part of a larger project, we assessed changes in perceived stress and psychopathological symptoms in a sample of N=102 participants (81% female; meanage=23.49, SDage= 7.11, range 18–62) from October/December 2019 (prior to the Covid-19 pandemic) to April/June 2020 (after the German government introduced Covid-19 related restrictions). Additionally, we assessed ELS and dispositional mindfulness. Perceived stress and depression significantly increased while anxiety levels decreased. No significant change was observed for somatization. ELS and dispositional mindfulness were not associated with change scores, but with perceived stress and psychopathological symptoms at both assessments. The increase in perceived stress during the pandemic in a majority of participants demonstrates the impact of the pandemic in the general population.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/5kt6z/" target="_blank">Early life adversity, dispositional mindfulness, and longitudinal stress experience during the COVID-19 pandemic</a>
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<li><strong>BNT162b2 effectiveness against Delta & Omicron variants in teens by dosing interval and duration</strong> -
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Background and Objectives Two- and three-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccine effectiveness (VE) against SARS-CoV-2 infection, including Delta and Omicron variants, was assessed among adolescents in two Canadian provinces where first and second doses were spaced longer than the manufacturer specified 3-week interval. Methods Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection among 12-17-year-olds in Quebec and British Columbia, Canada between September 5, 2021 (epi-week 36), and April 30, 2022 (epi-week 17). Delta-dominant and Omicron-dominant periods spanned epi-weeks 36-47 and 51-17, respectively. VE was assessed from 14 days and explored by interval between first and second doses, time since second dose, and with administration of a third dose. Results Median first-second dosing-interval was ~8 weeks and second-third dosing-interval was ~29-31 weeks. Median follow-up post-second dose was ~10-11 weeks for Delta-dominant and ~21-22 weeks for Omicron-dominant periods, and ~2-7 weeks post-third dose. VE against Delta was ≥90% to at least the 5th month post-second dose. VE against Omicron declined from ~65-75% at 2-3 weeks to ≤50% by the 3rd month post-vaccination, restored to ~65% shortly following a third dose. VE exceeded 90% against Delta regardless of dosing-interval but appeared improved against Omicron with ≥8 weeks between first and second doses. Conclusion In adolescents, two BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly-waning VE against Omicron. Longer interval between first and second doses and a third dose improved Omicron protection. Updated vaccine antigens, increased doses and/or dosing-intervals may be needed to improve adolescent VE against immunological-escape variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276790v3" target="_blank">BNT162b2 effectiveness against Delta &amp; Omicron variants in teens by dosing interval and duration</a>
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<li><strong>Longitudinal change in adolescent depression and anxiety symptoms from before to during the COVID-19 pandemic: A collaborative of 12 samples from 3 countries</strong> -
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Published paper can be found at https://doi.org/10.1111/jora.12781. This study aimed to examine changes in depression and anxiety symptoms from before to during the first six months of the COVID-19 pandemic in a sample of 1,339 adolescents from three countries (9-18 years old, 59% female). We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression symptoms increased significantly (median increase=28%), whereas anxiety symptoms remained stable overall. The most negative mental health impacts were reported by multiracial adolescents and those under ‘lockdown’ restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents’ mental health during the pandemic.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hn7us/" target="_blank">Longitudinal change in adolescent depression and anxiety symptoms from before to during the COVID-19 pandemic: A collaborative of 12 samples from 3 countries</a>
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<li><strong>Mapping SARS-CoV-2 antigenic relationships and serological responses</strong> -
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During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at spike positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron BA.1) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.28.477987v2" target="_blank">Mapping SARS-CoV-2 antigenic relationships and serological responses</a>
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<li><strong>Urban pandemic response: survey results describing the experiences from twenty-five cities during the COVID-19 pandemic.</strong> -
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Since first being detected in Wuhan, China in late December 2019, the COVID-19 pandemic has demanded a response from all levels of government. While the role of local governments in routine public health functions is well understood, and the response to the pandemic has highlighted the importance of involving local governments in the response to and management of large, multifaceted challenges, their role in pandemic response remains more opaque. Accordingly, to better understand how local governments in cities were involved in the response to the COVID-19 pandemic, we conducted a survey involving cities in the Partnership for Healthy Cities to: (i) understand which levels of government were responsible, accountable, consulted, and informed regarding select pandemic response activities; (ii) document when response activities were implemented; (iii) characterize how challenging response activities were; and (iv) query about future engagement in pandemic and epidemic preparedness. Twenty-five cities from around the world completed the survey and we used descriptive statistics to summarize the urban experience in pandemic response. Our results show that national authorities were responsible and accountable for a majority of the activities considered, but that local governments were also responsible and accountable for key activities – especially risk communication and coordinating with community-based organizations and civil society organizations. Further, most response activities were implemented after COVID-19 had been confirmed in a city, many pandemic response activities proved to be challenging for local authorities, and nearly all local authorities envisioned being more engaged in pandemic preparedness and response following the COVID-19 pandemic. This descriptive research represents an important contribution to an expanding evidence base focused on improving the response to the ongoing COVID-19 pandemic, as well as future outbreaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.12.22277559v1" target="_blank">Urban pandemic response: survey results describing the experiences from twenty-five cities during the COVID-19 pandemic.</a>
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<li><strong>Efficient Tracing of the SARS-CoV-2 Omicron Variants in Santa Barbara County Using a Rapid Quantitative Reverse Transcription PCR Assay</strong> -
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The recent emergence of the SARS-CoV-2 Omicron variant is associated with a dramatic surge of cases around the globe in late 2021 and early 2022. The numerous mutations in this variant, particularly in the Spike protein, enhance its transmission, increase immune evasion, and limit treatment with monoclonal antibodies. Identifying a community9s introduction to a novel SARS-CoV-2 variant with new clinical features related to treatment options and infection control needs is imperative to inform decisions by clinicians and public health officials, and traditional sequencing techniques often take weeks to result. Here, we describe a quantitative reverse transcription PCR assay (RT-qPCR) to accurately and precisely detect the presence of the Omicron sublineages BA.1/BA1.1 and BA.2 viral RNA from patient samples in less than four hours. The assay uses primers targeting the BA.1/BA1.1 unique mutations N211del, L212I, and L214 insertion EPE in the Spike protein gene, and the BA.2 specific mutations T19I and L24/P25/P26 deletion in the Spike protein gene. Using this assay, we detected 169 cases of Omicron, 164 BA.1/BA1.1 and 5 BA.2, from 270 residual SARS-CoV-2 positive samples collected for diagnostic purposes from Santa Barbara County (SBC) between December 2021 to February 2022. The RT-qPCR results show concordance with whole viral genome sequencing. Our observations indicate that Omicron was the dominant variant in SB County and is likely responsible for the surge of cases in the area during the sampling period. Using this inexpensive and accurate test, the rapid detection of Omicron in patient samples allowed clinicians to modify treatment strategies and public health officers to enhance contact tracing strategies. This RT-qPCR assay offers an alternative to current variant-specific detection approaches, provides a template for the fast design of similar assays, and allows the rapid, accurate, and inexpensive detection of Omicron variants in patient samples. It can also be readily adapted to new variants as they emerge in the future.
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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/10.1101/2022.07.12.22277554v1" target="_blank">Efficient Tracing of the SARS-CoV-2 Omicron Variants in Santa Barbara County Using a Rapid Quantitative Reverse Transcription PCR Assay</a>
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</div></li>
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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>Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors<br/><b>Sponsor</b>: Central Hospital, Nancy, France<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<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>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<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>Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Full Intervention; Other: Enhanced Usual Care<br/><b>Sponsors</b>: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)<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 Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, Inc.<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>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut 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>Topical Antibacterial Agents for Prevention of COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV2 Infection<br/><b>Interventions</b>: Drug: Neosporin; Other: Vaseline<br/><b>Sponsors</b>: Yale University; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Drug: Placebo; Drug: Experimental drug<br/><b>Sponsor</b>: Medesis Pharma SA<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>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<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 Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Rehabilitation<br/><b>Interventions</b>: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer<br/><b>Sponsor</b>: Medical University of Bialystok<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>Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention</strong> - <b>Condition</b>: Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention<br/><b>Sponsor</b>: VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mineralocorticoid Use in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; ARDS<br/><b>Intervention</b>: Drug: Fludrocortisone Acetate 0.1 MG<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Dysglycemia<br/><b>Interventions</b>: Drug: Insulin; Drug: Subcutaneous Insulin<br/><b>Sponsor</b>: Benha 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>A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Combination Product: Delcetravir dry powder inhaler<br/><b>Sponsor</b>: Esfam Biotech Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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</ul>
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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>Opaganib in Coronavirus Disease 2019 Pneumonia: Results of a Randomized, Placebo-Controlled Phase 2a Trial</strong> - CONCLUSIONS: In this proof-of-concept study, hypoxic, hospitalized patients receiving oral opaganib had a similar safety profile to placebo-treated patients, with preliminary evidence of benefit for opaganib as measured by supplementary oxygen requirement and earlier hospital discharge. These findings support further evaluation of opaganib in this population.</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>Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation</strong> - Excessive inflammation and coagulation contribute to high morbidity and mortality in sepsis. Many studies have indicated the role of piperlongumine (PL) in anti-inflammation, but its effect on coagulation remains uncertain. Here, we explore whether PL could moderate coagulation indicators and alleviate lung inflammation during sepsis. RAW264.7 cells were induced by lipopolysaccharide (LPS) and treated with PL. Inflammatory and coagulation indicators, cell function and signaling, were evaluated…</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>Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although…</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>Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2</strong> - The outbreak of the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 triggered a global pandemic where control is needed through therapeutic and preventive interventions. This study aims to identify natural compounds that could affect the fusion between the viral membrane (receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein) and the human cell receptor angiotensin-converting enzyme 2. Accordingly, we performed the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults</strong> - Introduction: Each year, a disproportionate number of the total seasonal influenza-related hospitalizations (90%) and deaths (70%) occur among adults who are >65 years old. Inflammasome activation has been shown to be important for protection against influenza infection in animal models but has not yet been demonstrated in humans. We hypothesized that age-related dysfunction (immunosenescence) of the inflammasome may be associated with poor influenza-vaccine response among older adults. Methods:…</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 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available, or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enzyme Nanoscale Interactions with Manganese Zinc Sulfide Give Insight into Potential Antiviral Mechanisms and SARS-CoV-2 Inhibition</strong> - Recent interest in nanomedicine has skyrocketed because of mRNA vaccine lipid nanoparticles (LNPs) against COVID-19. Ironically, despite this success, the innovative nexus between nanotechnology and biochemistry, and the impact of nanoparticles on enzyme biochemical activity is poorly understood. The studies of this group on zinc nanoparticle (ZNP) compositions suggest that nanorod morphologies are preferred and that ZNP doped with manganese or iron can increase activity against model enzymes…</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>Allosteric Binders of ACE2 Are Promising Anti-SARS-CoV-2 Agents</strong> - The COVID-19 pandemic has had enormous health, economic, and social consequences. Vaccines have been successful in reducing rates of infection and hospitalization, but there is still a need for acute treatment of the disease. We investigate whether compounds that bind the human angiotensin-converting enzyme 2 (ACE2) protein can decrease SARS-CoV-2 replication without impacting ACE2’s natural enzymatic function. Initial screening of a diversity library resulted in hit compounds active in an…</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>Cancer vaccine strategies using self-replicating RNA viral platforms</strong> - The development and success of RNA-based vaccines targeting SARS-CoV-2 has awakened new interest in utilizing RNA vaccines against cancer, particularly in the emerging use of self-replicating RNA (srRNA) viral vaccine platforms. These vaccines are based on different single-stranded RNA viruses, which encode RNA for target antigens in addition to replication genes that are capable of massively amplifying RNA messages after infection. The encoded replicase genes also stimulate innate immunity,…</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>CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation</strong> - CONCLUSIONS: This study demonstrates that SARS-CoV-2-activated platelets produce EVs to enhance thromboinflammation via CLEC5A and TLR2, and highlight the importance of CLEC5A and TLR2 as therapeutic targets to reduce the risk of ARDS in COVID-19 patients.</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>Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity</strong> - CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.</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>Rational identification of small molecules derived from 9,10-dihydrophenanthrene as potential inhibitors of 3CL<sup>pro</sup> enzyme for COVID-19 therapy: a computer-aided drug design approach</strong> - Small molecules such as 9,10-dihydrophenanthrene derivatives have remarkable activity toward inhibition of SARS-CoV-2 3CL^(pro) and COVID-19 proliferation, which show a strong correlation between their structures and bioactivity. Therefore, these small compounds could be suitable for clinical pharmaceutical use against COVID-19. The objective of this study was to remodel the structures of 9,10-dihydrophenanthrene derivatives to achieve a powerful biological activity against 3CL^(pro) 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>The Pharmacological Mechanism of Xiyanping Injection for the Treatment of Novel Coronavirus Pneumonia (COVID-19): Based on Network Pharmacology Strategy</strong> - CONCLUSION: Xiyanping injection may inhibit the release of various inflammatory factors by inhibiting intracellular pathways such as MAPK and TNF. It acts on protein targets such as HSP90AA1 and plays a potential therapeutic role in COVID-19. Thus, compound III may be treated as a potential new drug for the treatment of COVID-19 and the Xiyanping injection may treat patients with COVID-19 infection.</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>Comparative Computational Analysis of Dirithromycin and Azithromycin in Search for a Potent Drug against COVID-19 caused by SARS-CoV-2: Evidence from molecular docking and dynamic simulation</strong> - Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit…</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>N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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