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182 lines
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<title>22 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19</strong> -
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Rationale: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a muco-trapping monoclonal antibody would provide a more effective and convenient treatment for COVID-19. Objective: We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements of IN-006 in nasal fluid and serum. Results: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and were graded mild to moderate in severity. Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 microgram/gram of nasal fluid at 30 minutes after dosing and 5.4 microgram/gram at 22 hours. Mean serum levels in the multiple dose cohort peaked at 0.55 microgram/mL at 3 days after the final dose. Conclusions IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above its inhibitory concentration. These data support further clinical development of IN-006.
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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/10.1101/2022.08.17.22278748v1" target="_blank">A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19</a>
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</div></li>
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<li><strong>Effectiveness of fourth dose COVID-19 vaccine against the Omicron variant compared to no vaccination</strong> -
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In response to enhanced immune evasion properties of the Omicron SARS-CoV-2 variant and waning COVID-19 vaccine effectiveness (VE), several jurisdictions have rolled out fourth dose vaccination programs. Using a system of logistic regression equations and VE estimates for a fourth dose relative to a third dose reported in an Israeli study, we estimated absolute vaccine effectiveness for third and fourth doses of mRNA COVID-19 vaccine (c.f. no vaccination) against Omicron, by clinical outcome. We found that a fourth dose restores or even enhances protection conferred by a third dose at the same time since vaccination.
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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/10.1101/2022.08.17.22278807v1" target="_blank">Effectiveness of fourth dose COVID-19 vaccine against the Omicron variant compared to no vaccination</a>
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</div></li>
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<li><strong>Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources</strong> -
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Objectives This study aimed to monitor use of COVID-19 vaccines and incidence rates of pre-specified adverse events of special interest (AESI) of COVID-19 vaccines prior to and after COVID-19 vaccination. This study was not aimed to test a specific hypothesis. Design A retrospective cohort study including subjects from January 1, 2020 to October 31st, 2021, or latest availability of data. Setting Primary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, Spain Participants Individuals with complete data for the year preceding enrolment or those born at the start of observation time. The cohort comprised 25,720,158 subjects. Interventions First and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine. Main outcome measures 29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells palsy, chilblain-like lesions death, erythema multiforme, Guillain Barre Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE) Results 12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare: less than 10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia. Conclusion We showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278894v1" target="_blank">Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources</a>
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</div></li>
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<li><strong>Cryo-EM structures and binding of mouse ACE2 to SARS-CoV-2 variants of concern</strong> -
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<div>
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Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. Mice are well adapted to human environments, frequently come in contact with humans, are used widely as infection models, and may act as reservoirs for SARS-CoV-2. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of variants of concern (VOC). Previous studies have developed mouse-adapted variants and have identified some determinants of binding. Here we report the cryo-EM structures of mouse ACE2 bound to Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants that are able to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein to enable the binding to mouse ACE2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.19.504450v1" target="_blank">Cryo-EM structures and binding of mouse ACE2 to SARS-CoV-2 variants of concern</a>
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</div></li>
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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 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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🖺 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 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 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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<div>
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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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🖺 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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<div>
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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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🖺 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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<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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🖺 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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<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>Wearing the face mask affects our social attention over space</strong> - Recent studies suggest that covering the face inhibits the recognition of identity and emotional expressions. However, it might also make the eyes more salient, since they are a reliable index to orient our social and spatial attention. This study investigates (1) whether the pervasive interaction with people with face masks fostered by the COVID-19 pandemic modulates the processing of spatial information essential to shift attention according to other’s eye-gaze direction (i.e., gaze-cueing…</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>Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern</strong> - The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron were noticed in immunized and recovered individuals, therefore development of new treatments against VOC infections are urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein 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>Identification of potent inhibitors of SARS-CoV-2 infection by combined pharmacological evaluation and cellular network prioritization</strong> - Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6710 clinical and preclinical compounds targeting 2183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure,…</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>NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration</strong> - In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also…</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>Small Molecules Targeting SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Several variants of SARS-CoV-2 have emerged worldwide. These variants show different transmissibility infectivity due to mutations in the viral spike (S) glycoprotein that interacts with the human angiotensin-converting enzyme 2 (hACE2) receptor and facilitates viral entry into target cells. Despite the effective SARS-CoV-2 vaccines, we still need to identify selective…</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>Playing for Resilience in a Pandemic; Exploring the Role of an Online Board Game in Recognising Resources</strong> - In the current climate of Covid-19 and world-wide social distancing, the mental health toll has been widely reported, with an expectation that the negative impact will last beyond the lockdowns. Facing the prospect of an unknown future and continuing challenges, resilience is both topical and necessary. With a call for digitally delivered interventions to help people affected by the pandemic, this study explores how playing an online positive psychology-informed board game supported people to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The cross-talk of lung and heart complications in COVID-19: Endothelial cells dysfunction, thrombosis, and treatment</strong> - The pandemic respiratory illness SARS-CoV-2 has increasingly been shown to be a systemic disease that can also have profound impacts on the cardiovascular system. Although associated cardiopulmonary sequelae can persist after infection, the link between viral infection and these complications remains unclear. There is now a recognized link between endothelial cell dysfunction and thrombosis. Its role in stimulating platelet activation and thrombotic inflammation has been widely reported….</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>Buffer or boost? the role of openness to experience and knowledge sharing in the relationship between team cognitive diversity and members’ innovative work behavior</strong> - Although literature frequently argues that diversity stimulates innovative work behavior, theoretical perspectives and empirical findings on this relationship remain inconsistent. Based on self-category theory, this study aims to comprehensively investigate when and how team cognitive diversity benefits or inhibits innovative work behavior. We introduced a new context of research (i.e., virtual teams) during COVID-19 and tested a moderated mediation model using a two-wave survey of 238 employees…</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>Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion</strong> - The global emergence of coronavirus disease 2019 (COVID-19) has caused substantial human casualties. Clinical manifestations of this disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and hyperinflammation. In face of the urgent demand for effective drugs to treat COVID-19, we have searched for candidate compounds using in silico approach followed by experimental validation. Here we identified celastrol, a pentacyclic triterpene isolated from…</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>Virtual screening and molecular dynamics simulation for identification of natural antiviral agents targeting SARS-CoV-2 NSP10</strong> - New variations of SARS-CoV-2 continue to emerge in the global pandemic, which may be resistant to at least some vaccines in COVID-19, indicating that drug and vaccine development must be continuously strengthened. NSP10 plays an essential role in SARS-CoV-2 viral life cycle. It stimulates the enzymatic activities of NSP14-ExoN and NSP16-O-MTase by the formation of NSP10/NSP14 and NSP10/NSP16 complexes. Inhibiting NSP10 can block the binding of NSP10 to NSP14 and NSP16. This study has identified…</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>Major severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccine-associated adverse effects; benefits outweigh the risks</strong> - INTRODUCTION: Since its emergence, there have been huge efforts to design vaccines against coronavirus disease 2019 (COVID-19) to inhibit its interpersonal spread. Global vaccine development and vaccination of the population are the most promising cost-effective methods for overcoming the epidemic. However, following reports of post-vaccination thromboembolic adverse effects, there have been raising concerns about the safety profile of the COVID-19 vaccine.</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>Potential medicinal plants involved in inhibiting 3CL<sup>pro</sup> activity: A practical alternate approach to combating COVID-19</strong> - At present, a variety of vaccines have been approved, and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019 (COVID-19). However, no standardized treatment has yet been approved by the World Health Organization. The virally encoded chymotrypsin-like protease (3CL^(pro)) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which facilitates the replication of SARS-CoV in the host cells, is one potential pharmacological target for…</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>Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro</strong> - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) helicase NSP13 plays a conserved role in the replication of coronaviruses and has been identified as an ideal target for the development of antiviral drugs against SARS-CoV-2. Here, we identify a novel NSP13 helicase inhibitor punicalagin (PUG) through high-throughput screening. Surface plasmon resonance (SPR)-based analysis and molecular docking calculation reveal that PUG directly binds NSP13 on the interface of domains 1A 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>Novel hit of DPP-4Is as promising antihyperglycemic agents with dual antioxidant/anti-inflammatory effects for type 2 diabetes with/without COVID-19</strong> - DPP-4Is are well recognized therapy for type 2 diabetes. In spite of sharing a common mode of action, the chemical diversity among members of DPP-4Is raised the question whether structural differences may result in distinguished activities. DPP-4Is were recently explored as drug repurposing means for treatment of SARS-CoV-2 due to the urgent need for small molecule drugs for controlling infections. The use of DPP-4Is was not correlated with adverse COVID-19-related consequences among 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>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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