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180 lines
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<title>20 August, 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>Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</strong> -
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<div>
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Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune responses, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform’s true impact on human health.
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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/10.1101/2022.03.16.484616v2" target="_blank">Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</a>
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</div></li>
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<li><strong>Disrupted chromatin architecture in olfactory sensory neurons: A missing link from COVID-19 infection to anosmia</strong> -
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<div>
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We tackle here genomic mechanisms of a rapid onset and recovery from anosmia - a useful diagnostic indicator for early-stage COVID-19 infection. On the basis of earlier observed specifics of olfactory receptors (ORs) regulation in the mice chromatin structures, we hypothesized that the disruption of OR function can be caused by chromatin reorganization taking place upon SARS-CoV-2 infection. We reconstructed the chromatin ensembles of ORs obtained from COVID-19 patients and control samples using our original computational framework for the whole-genome chromatin ensemble 3D reconstruction. We have also developed here a new procedure for the analysis of fine structural hierarchy in local, megabase scale, parts of chromosomes containing the OR genes and corresponding epigenetic factors. We observed structural modifications in COVID-19 patients on different levels of chromatin organization, from alteration of the whole genome structure and chromosomal intermingling to reorganization of contacts between the chromatin loops at the level of topologically associating domains. While complementary data on known regulatory elements point to pathology-associated changes within the overall picture of chromatin alterations, further investigation using additional epigenetic factors mapped on 3D reconstructions with improved resolution will be required for better understanding of anosmia caused by SARS-CoV-2 infection.
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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/10.1101/2022.08.19.504545v1" target="_blank">Disrupted chromatin architecture in olfactory sensory neurons: A missing link from COVID-19 infection to anosmia</a>
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</div></li>
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<li><strong>Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cells in recovered COVID-19 pregnant women</strong> -
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<div>
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Pregnancy is a complex phenomenon during which women undergo immense immunological change throughout this period. Having an infection with the SARS-CoV-2 virus leads to an additional burden on the highly stretched immune response. Some studies suggest that age-matched pregnant women are more prone to SARS-CoV-2 infection compared with normal healthy (non-pregnant) women, while alternative evidence proposed that pregnant women are neither susceptible nor develop severe symptoms. This discrepancy in different findings regarding the immune responses of pregnant women infected with the SARS-CoV-2 virus is not well understood. In this study, we investigated how SARS-CoV-2 viral infection could modulate the immune landscape during the active infection phase and recovery in pregnant females. Using flow cytometry, we identified that intermediate effector CD8+ T cells were increased in pregnant women who had recovered from COVID-19 as opposed to those currently infected. Similarly, an increase in CD4+ T helper cells (early or late) during the recovered phase was observed during the recovery phase compared with infected pregnant women or healthy pregnant women, whilst infected pregnant women had a reduced number of late effector CD4+ T cells. CD3+CD4-CD8-NKT cells that diminished during active infection in contrast to healthy pregnant women were a significant increase in recovered COVID-19 recovered pregnant women. Further, our single-cell RNA sequencing data revealed that infection of SARS-CoV-2 had changed the gene expression profile of monocytes, CD4+ effector cells and antibody-producing B cells in convalescent as opposed to healthy pregnant women. Additionally, several genes with cytotoxic function, interferon signalling type I & II, and pro- and anti-inflammatory functions in natural killer cells and CD8+ cytotoxic T cells were compromised in recovered patients compared with healthy pregnant women. Overall, our study highlights that SARS-CoV-2 infection deranged the adaptive immune response in pregnant women and could be implicated in pregnancy complications in ongoing pregnancies.
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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/10.1101/2022.08.18.504053v1" target="_blank">Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cells in recovered COVID-19 pregnant women</a>
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</div></li>
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<li><strong>Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic has resulted in extensive surveillance of the genomic diversity of SARS-CoV-2. Sequencing data generated as part of these efforts can also capture the diversity of the SARS-CoV-2 virus populations replicating within infected individuals. To assess this within-host diversity of SARS-CoV-2 we quantified low frequency (minor) variants from deep sequence data of thousands of clinical samples collected by a large urban hospital system over the course of a year. Using a robust analytical pipeline to control for technical artefacts, we observe that at comparable viral loads, specimens from patients hospitalized due to COVID-19 had a greater number of minor variants than samples from outpatients. Since individuals with highly diverse viral populations could be disproportionate drivers of new viral lineages in the patient population, these results suggest that transmission control should pay special attention to patients with severe or protracted disease to prevent the spread of novel variants.
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</p>
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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.medrxiv.org/content/10.1101/2022.08.17.22278898v1" target="_blank">Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance</a>
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</div></li>
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<li><strong>Relative contributions of vaccination and previous infection to population-level SARS-CoV-2 immunity over time: a simulation modelling study</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Population-level immunity to SARS-CoV-2 directly impacts the incidence of COVID-19 morbidity and mortality. Understanding how this immunity is likely to change over time in the context of future vaccination schedules and emerging SARS-CoV-2 variants is critical to inform pandemic policy. This study simulates population-level COVID-19 immunity (including relative contributions of vaccination and previous infection) in Victoria, Australia over 18 months using an agent-based model and logistic regression equations that predict immunity and waning following vaccination and/or infection. Previous infection was found to drive most immunity against infection even with ongoing regular vaccination, however a greater proportion of overall immunity against mortality was accounted for by vaccination. Although previous infection appears to be driving a substantial component of population-level COVID-19 immunity currently, improved vaccines providing longer lasting (and better sterilizing) immunity are likely to be a critical component of the future pandemic response given the risks associated with SARS-CoV-2 infection.
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</p>
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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.medrxiv.org/content/10.1101/2022.08.18.22278963v1" target="_blank">Relative contributions of vaccination and previous infection to population-level SARS-CoV-2 immunity over time: a simulation modelling study</a>
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</div></li>
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<li><strong>Demographic and Outcome Characteristics of Children Hospitalized with Acute COVID-19 versus Multisystem Inflammatory Syndrome in Children in Canada</strong> -
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Direct comparisons of pediatric hospitalizations for acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. While there were more hospitalizations and deaths from acute COVID-19 amongst Canadian children between March 2020-May 2021, MIS-C cases were more severe, requiring more intensive care and vasopressor support.
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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/10.1101/2022.08.18.22278939v1" target="_blank">Demographic and Outcome Characteristics of Children Hospitalized with Acute COVID-19 versus Multisystem Inflammatory Syndrome in Children in Canada</a>
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</div></li>
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<li><strong>Loss of Control Eating and COVID 19 Factors</strong> -
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<div>
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Loss-of-control eating (LOCE) is the perceived inability to stop eating once one has started or feeling unable to resist eating onset. LOCE has been found to be highly driven by mood, and particularly negative mood. However, it has been indicated that LOCE pathology increased during the coronavirus disease 2019 (COVID-19) pandemic, evincing a need to understand the unique factors and concerns that may contribute to LOCE during COVID-19. Given that COVID-19 has also been associated with significant increase in stressors across multiple domains, such as fear of contracting the virus, an effect exists of the pandemic on both positive and negative mood, and those fears could arguably in turn effect a relationship between mood and LOCE. In addition, it was hypothesized that daily protective strategies meant to prevent contagion may be associated with LOCE. A sample of n = 109 adults from the United States completed an online diary study over the course of ten days regarding their daily LOCE, positive and negative mood, and protective behaviors against contagion. Data were analyzed both within- and between-subjects with a Bayesian method to examine the direct relationships between predictors and LOCE. Participants indicated their illness fear beliefs at a baseline assessment, which was hypothesized to predict LOCE directly between subjects and have a cross-level interactive effect on predictors within-subjects. Negative mood was associated with LOCE at both levels, and positive mood and protective behaviors did not reveal significant direct associations with LOCE, nor did illness fear beliefs. However, an interactive effect between illness fear beliefs and with within-subject positive mood was found, such that when illness fear beliefs were low, positive mood had a significant inverse association with LOCE. Findings and implications are discussed.
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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/ta659/" target="_blank">Loss of Control Eating and COVID 19 Factors</a>
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</div></li>
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<li><strong>Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: A Multisite, Longitudinal, Prospective Cohort Study</strong> -
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<div>
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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 a prospective, longitudinal, nationwide cohort: the Adolescent Brain Cognitive DevelopmentSM Study. Method: 9,270 youth ages 11-12 years old completed up to seven assessments between May 2020 and May 2021, reporting on past-month use of alcohol and drugs. The prevalence of use was compared to that at pre-pandemic assessments completed in 2018-2019, adjusting for the age-related increases in substance use expected over time. 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 11-12 year-olds, 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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</div>
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<div class="article-link article-html-link">
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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: A Multisite, Longitudinal, Prospective Cohort Study</a>
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</div></li>
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<li><strong>Public attitudes to social care in Wales following the COVID-19 pandemic</strong> -
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Background. The COVID-19 pandemic has shone further light on some of the challenges facing social care in Wales, as in many countries, and looks to have exacerbated a crisis that was already extant. This has led to the intensification of longer-standing arguments that social reform is necessary and that the pandemic presents an added impetus and opportunity for reform. Methods. An online survey was completed by 2569 respondents between February 11th and March 11th, 2022. Additionally, online focus groups were conducted with a sample of 14 participants. The inclusion criteria were adults aged 18 years and over living in Wales. Results. Four-in-ten of those who felt that they or someone in their household or close family needed social care during the past two years did not receive or make use of it. The pandemic was cited as a major reason why many of those who may have needed social care didn’t access it Satisfaction with social care was variable, with approximately one-third either very or quite dissatisfied, and a little over half either very or quite satisfied with social care services for themselves or a household or close family member. Discussion. Social care policymakers and providers should seek to understand and address what people feel are the main barriers to accessing or using social care, including increasing provision for those who need it, encouraging and enabling those who feel they need social care to apply, consider broadening the eligibility criteria where appropriate, and simplifying the application process.
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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/7jnca/" target="_blank">Public attitudes to social care in Wales following the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape</strong> -
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Consecutive waves of SARS-CoV-2 infection have been driven in part by the repeated emergence of variants with mutations that confer resistance to neutralizing antibodies Nevertheless, prolonged or repeated antigen exposure generates diverse memory B-cells that can produce affinity matured receptor binding domain (RBD)-specific antibodies that likely contribute to ongoing protection against severe disease. To determine how SARS-CoV-2 omicron variants might escape these broadly neutralizing antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection pressure by a collection of 40 broadly neutralizing antibodies from individuals with various SARS-CoV-2 antigen exposures. Notably, pre-existing substitutions in the BA.1 and BA.2 spikes facilitated acquisition of resistance to many broadly neutralizing antibodies. Specifically, selection experiments identified numerous RBD substitutions that did not confer resistance to broadly neutralizing antibodies in the context of the ancestral Wuhan-Hu-1 spike sequence, but did so in the context of BA.1 and BA.2. A subset of these substitutions corresponds to those that have appeared in several BA.2 daughter lineages that have recently emerged, such as BA.5. By including as few as 2 or 3 of these additional changes in the context of BA.5, we generated spike proteins that were resistant to nearly all of the 40 broadly neutralizing antibodies and were poorly neutralized by plasma from most individuals. The emergence of omicron variants has therefore not only allowed SARS-CoV-2 escape from previously elicited neutralizing antibodies but also lowered the genetic barrier to the acquisition of resistance to the subset of antibodies that remained effective against early omicron variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.17.504313v1" target="_blank">Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape</a>
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</div></li>
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<li><strong>Ancestral lineage of SARS-CoV-2 is more stable in human biological fluids than Alpha, Beta and Omicron variants of concern</strong> -
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<div>
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SARS-CoV-2 is a zoonotic virus which was first identified in 2019, and has quickly spread worldwide. The virus is primarily transmitted through respiratory droplets from infected persons; however, the virus-laden excretions can contaminate surfaces which can serve as a potential source of infection. Since the beginning of the pandemic, SARS-CoV-2 has continued to evolve and accumulate mutations throughout its genome leading to the emergence of variants of concern (VOCs) which exhibit increased fitness, transmissibility, and/or virulence. However, the stability of SARS-CoV-2 VOCs in biological fluids has not been thoroughly investigated so far. The aim of this study was to determine and compare the stability of different SARS-CoV-2 strains in human biological fluids. Here, we demonstrate that the ancestral strain of Wuhan-like lineage A was more stable than the Alpha VOC B.1.1.7, and the Beta VOC B.1.351 strains in human liquid nasal mucus and sputum. In contrast, there was no difference in stability among the three strains in dried biological fluids. Furthermore, we also show that the Omicron VOC B.1.1.529 strain was less stable than the ancestral Wuhan-like strain in liquid nasal mucus. These studies provide insight into the effect of the molecular evolution of SARS-CoV-2 on environmental virus stability, which is important information for the development of countermeasures against SARS-CoV-2.
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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/10.1101/2022.08.17.504362v1" target="_blank">Ancestral lineage of SARS-CoV-2 is more stable in human biological fluids than Alpha, Beta and Omicron variants of concern</a>
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<li><strong>Fertility recovery despite the COVID-19 pandemic in Finland?</strong> -
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Finland’s increase in births, recorded in the months following the first two waves of the COVID-19 pandemic, was among the strongest. We assess whether the fertility increase in Finland occurred because of or despite the pandemic, or both, by investigating the country’s fertility trends by women’s region of residence, age group, and parity. While the country as a whole was modestly hit by the pandemic in 2020, the capital region Helsinki-Uusimaa faced more severe restrictions. We used aggregate register data until September 2021 to assess monthly fertility. In 2020 and 2021, the relative annual increases in fertility were strongest among women aged 30–34 and 35–49. In 2021, but not in 2020, fertility increased most in Helsinki-Uusimaa, and across all parities. Model-based estimates provided tentative support for an overall pandemic fertility boost for the time period until September 2019. We conclude that the unusual fertility increases in 2021 in Finland broadly follow from pre-existing trends where the country recovers from its all-time low fertility, but do not exclude the possibility of an additional boost from the pandemic itself. The study highlights the importance of carefully considering existing fertility trends when studying fertility responses to the pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/fxwe3/" target="_blank">Fertility recovery despite the COVID-19 pandemic in Finland?</a>
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<li><strong>A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</strong> -
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Viruses are dependent on interactions with host factors in order to efficiently establish an infection and replicate. Targeting such interactions provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking, and has previously been shown to be important for HPV infection. Here we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits SARS-CoV-2 infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection, and strongly reduced flavivirus infection, which are completely dependent on receptor mediated endocytosis for their entry. In conclusion, we have identified a novel pan-viral inhibitor that efficiently target a broad range of RNA viruses.
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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/10.1101/2022.08.18.504268v1" target="_blank">A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</a>
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<li><strong>SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model</strong> -
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<div>
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Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.
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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/10.1101/2022.08.19.504551v1" target="_blank">SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model</a>
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<li><strong>A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</strong> -
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The unfolding of the COVID-19 pandemic has been very difficult to predict using mathematical models for infectious diseases. While it has been demonstrated that variations in susceptibility have a damping effect on key quantities such as the incidence peak, the herd-immunity threshold and the final size of the pandemic, this complex phenomenon is almost impossible to measure or quantify, and it remains unclear how to incorporate it for modeling and prediction. In this work we show that, from a modeling perspective, variability in susceptibility on an individual level is equivalent with a fraction theta of the population having an ``artificial99 sterilizing immunity. Given that this new parameter theta can be estimated, we also derive formulas for R0, the herd-immunity threshold and the final size of the pandemic. In the particular case of SARS-CoV-2, there is by now undoubtedly variable susceptibility due to waning immunity from both vaccines and previous infections, and our findings may be used to greatly simplify models. If such variations were also present prior to the first wave, as indicated by a number of studies, these findings can help explain why the magnitude of the initial waves of SARS-CoV-2 was relatively low, compared to what one may have expected based on standard models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.08.21260175v2" target="_blank">A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SIM0417; Drug: Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>: University of Manitoba<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>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<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>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo<br/><b>Sponsors</b>: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora<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>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital<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>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>: LumiraDx UK Limited<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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<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 of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<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>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>: University Vila Velha<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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., Ltd.<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>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International University<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>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<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>UNAIR Inactivated COVID-19 Vaccine Phase 3</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<br/><b>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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<ul>
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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>Computational Design of Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein</strong> - The ongoing pandemic of COVID-19 caused by SARS-CoV-2 has become a global health problem. There is an urgent need to develop therapeutic drugs, effective therapies, and vaccines to prevent the spread of the virus. The virus first enters the host cell through the interaction between the receptor binding domain (RBD) of spike protein and the peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2). Therefore, blocking the binding of RBD and ACE2 is a promising strategy to inhibit the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico identification of novel SARS-CoV-2 main protease and non-structural protein 13 (nsp13) inhibitors through consensus docking and free binding energy calculations</strong> - CONCLUSION: In conclusion, the analysis of the results identified that the phytochemicals demonstrated enhanced binding capacities, compared to the FDA-approved database.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">.</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>Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study</strong> - Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: A virtual screening of ZINC natural products on SARS-CoV-2 nsp12’s druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. Results: ZINC03977803 was…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody feedback regulation of memory B cell development in SARS-CoV-2 mRNA vaccination</strong> - Feedback inhibition of humoral immunity by antibodies was initially documented in guinea pigs by Theobald Smith in 1909, who showed that passive administration of excess anti-Diphtheria toxin inhibited immune responses ¹ . Subsequent work documented that antibodies can enhance or inhibit immune responses depending on antibody isotype, affinity, the physical nature of the antigen, and engagement of immunoglobulin (Fc) and complement (C’) receptors ^(2, 3) . However, little is known about how…</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 Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019</strong> - Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems 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>Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein</strong> - Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors which…</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 effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2</strong> - Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%-0.005% (10-50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha,…</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>Holistic care of patients with diabetic foot ulcers during the COVID-19 era: integration of Henderson’s Need Theory</strong> - The COVID-19 pandemic has inhibited the practice of diabetic foot ulcer care, particularly in the community. Comprehensive theory-based nursing care is needed to prevent further complications. Unfortunately, a study combining theory with nursing care in diabetic foot ulcer care has not been explored. When caring for patients with diabetic foot ulcers, who are also at increased risk of severe complications from COVID-19, it is important to take a holistic view of the patient and consider all of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of a promising inhibitor from <em>Illicium verum</em> (star anise) against the main protease of SARS-CoV-2: insights from the computational study</strong> - SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (M^(pro)) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has…</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>UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b</strong> - Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome…</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>Antimicrobial peptides: Defending the mucosal epithelial barrier</strong> - The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SEMgsa: topology-based pathway enrichment analysis with structural equation models</strong> - CONCLUSIONS: SEMgsa is a novel yet powerful method for identifying enrichment with regard to gene expression data. It takes into account topological information and exploits pathway perturbation statistics to reveal biological information. SEMgsa is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph .</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 spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2)…</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>Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum</strong> - The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee’s serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE(490), exhibited ultrabright fluorescence due to the rigidity…</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>Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents</strong> - Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung, but notably in the LDLN, where the extent of…</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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