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190 lines
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<title>27 February, 2023</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>Children With Autism Spectrum Disorder in Times of COVID-19: Examining the Impact of the Pandemic on Emotional and Behavioral Problems and the Role of Parental Well-Being in Resilience</strong> -
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<div>
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This longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; Mage = 13 years) by measuring emotional and behavioral problems before and during the pandemic, and by comparing this change to a matched sample of children without ASD (n = 213; Mage = 16 years). Moreover, we examined whether indicators of parental well-being promoted resilience of children with ASD. Results showed that the mean change in problems did not differ between children with and without ASD. Importantly, some children showed an increase in problems, while others showed resilience. Parental well-being indicators were not related to resilience among children with ASD. The interindividual variability in responses, particularly among children with ASD, highlights the need for personalized support.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/h3s2u/" target="_blank">Children With Autism Spectrum Disorder in Times of COVID-19: Examining the Impact of the Pandemic on Emotional and Behavioral Problems and the Role of Parental Well-Being in Resilience</a>
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</div></li>
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<li><strong>Perceptions Matter: Quasi-Experimental Evidence on the Effects of Minimum Income on Objective and Subjective Financial Wellbeing in Spain</strong> -
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<div>
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This paper examines how minimum income schemes (MISs) affect households’ financial wellbeing and whether this effect differs across objective material conditions and households’ perceptions. Two reasons motivate this study. First, while the Covid-19 pandemic, the ecological transition and the cost-of-living crisis have all prompted a renewed interest in MISs, no consensus exists on how effective these schemes are in improving households’ financial wellbeing. Second, when evaluating MISs, the literature focuses on objective measures of financial wellbeing, namely monetary poverty. Yet, peoples’ perceptions of their own situation can be instrumental in affecting their health, productivity and decision-making and can reveal important information about adaptation mechanisms or spillovers to non-recipients. This examines the case study of Spain, a country that introduced a new MIS in 2020. The paper uses Eurostat survey data for the 2010-2022 period in a Synthetic Control Method analysis. The results show that, while the policy had no significant effect on objective financial wellbeing measures (i.e. the poverty rate, the poverty gap and mean income) for its first year and a half of existence, it did considerably improve subjective financial wellbeing after two years and a half, as it helped households feel less pessimistic about the evolution of their finances during the Covid-19 and cost-of-living crises. The paper discusses several mechanisms explaining this differentiated impact of the policy, such as its lagged rollout, the improvements made to the benefit from 2022 as well as anticipation, placebo and positive spillover effects of the MIS. The findings highlight the importance for practitioners to consider subjective measures when assessing income support schemes.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/wv7xt/" target="_blank">Perceptions Matter: Quasi-Experimental Evidence on the Effects of Minimum Income on Objective and Subjective Financial Wellbeing in Spain</a>
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</div></li>
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<li><strong>Application of comprehensive evaluation framework to Coronavirus Disease 19 studies: A systematic review of translational aspects of artificial intelligence in health care</strong> -
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<div>
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Background: Despite immense progress in artificial intelligence (AI) models, there has been limited deployment in healthcare environments. The gap between potential and actual AI applications is likely due to the lack of translatability between controlled research environments (where these models are developed) and clinical environments for which the AI tools are ultimately intended. Objective: We have previously developed the Translational Evaluation of Healthcare AI (TEHAI) framework to assess the translational value of AI models and to support successful transition to healthcare environments. In this study, we apply the TEHAI to COVID-19 literature in order to assess how well translational topics are covered. Methods: A systematic literature search for COVID-AI studies published between December 2019-2020 resulted in 3,830 records. A subset of 102 papers that passed inclusion criteria were sampled for full review. Nine reviewers assessed the papers for translational value and collected descriptive data (each study was assessed by two reviewers). Evaluation scores and extracted data were compared by a third reviewer for resolution of discrepancies. The review process was conducted on the Covidence software platform. Results: We observed a significant trend for studies to attain high scores for technical capability but low scores for the areas essential for clinical translatability. Specific questions regarding external model validation, safety, non-maleficence and service adoption received failed scores in most studies. Conclusions: Using TEHAI, we identified notable gaps in how well translational topics of AI models are covered in the COVID-19 clinical sphere. These gaps in areas crucial for clinical translatability could, and should, be considered already at the model development stage to increase translatability into real COVID-19 healthcare environments.
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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/10.1101/2023.02.23.23286374v1" target="_blank">Application of comprehensive evaluation framework to Coronavirus Disease 19 studies: A systematic review of translational aspects of artificial intelligence in health care</a>
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</div></li>
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<li><strong>Task shifting healthcare services in the post-COVID world: A scoping review</strong> -
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<div>
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Task shifting (TS) redistributes services from specialised to less-qualified providers. Need for TS was intensified during COVID-19 pandemic. We locate evidences of TS across all health conditions to answer: (A) What role has TS played in services delivery since the onset of the pandemic? (B) How has the pandemic impacted strategies of TS globally? We searched five databases in October 2022: Medline, CINHAL Plus, Elsevier, Global Health and Google Scholar. 35 citations were selected. Data was analysed thematically and reported as per PRSIMA-ScR. We used WHO health systems framework and emergent themes to discuss findings. TS was observed in countries of all income-levels. 63% (n=22) articles discussed what impact TS had in COVID-19 care, mental healthcare, care for HIV, sexual and reproductive health, nutrition and rheumatoid diseases. Others (n=13) highlight how pandemic altered TS strategies in mental healthcare, HIV services, hypertension and diabetes and emergency services. Studies varied in reporting TS; majority using terms “task shifting”, followed by “task sharing”, “task shifting and sharing” and “task delegation”. TS affected every block of health system. TS to non-specialists and non-healthcare staff improved services. Modifying roles through training and collaboration strengthened workforce. TS diagnostics increased access to medicines and technologies. Strategic leadership was key. Research on financing TS during pandemics is required. Stakeholders generally accepted TS. Shifting staff between programs led to unintended service incapacities. Pandemic affected strategies of TS. Training, providing care, follow-ups and consultations went digital. Virtually-delivered interventions improved outcomes. Accessibility to digital technology presented barriers.COVID-19 modified health-seeking behaviour. Patients preferred teleconsultations and online-symptom checkers. Organisations altered operating procedures and patient-flow pathways and added precautions to protect staff. Risks of spreading COVID-19 prompted facilities to reconsider TS. TS improved outcomes by filling workforce gaps and increasing access. We recommend TS to improve services delivery during the pandemic and beyond.
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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/10.1101/2023.02.26.23286301v1" target="_blank">Task shifting healthcare services in the post-COVID world: A scoping review</a>
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</div></li>
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<li><strong>Cellular and molecular heterogeneities and signatures, and pathological trajectories of fatal COVID-19 lungs defined by spatial single-cell transcriptome analysis</strong> -
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<div>
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Despite intensive studies during the last 3 years, the pathology and underlying molecular mechanism of coronavirus disease 2019 (COVID-19) remain poorly defined. Here, we examined postmortem COVID-19 lung tissues by spatial single-cell transcriptome analysis (SSCTA). We identified 18 major parenchymal and immune cell types, all of which are infected by SARS-CoV-2. Compared to the non-COVID-19 control, COVID-19 lungs have reduced alveolar cells (ACs), and increased innate and adaptive immune cells. Additionally, 19 differentially expressed genes in both infected and uninfected cells across the tissues mirror the altered cellular compositions. Spatial analysis of local infection rates revealed regions with high infection rates that are correlated with high cell densities (HIHD). The HIHD regions express high levels of SARS-CoV-2 entry-related factors including ACE2, FURIN, TMPRSS2, and NRP1, and co-localized with organizing pneumonia (OP) and lymphocytic and immune infiltration that have increased ACs and fibroblasts but decreased vascular endothelial cells and epithelial cells, echoing the tissue damage and wound healing processes. Sparse non-negative matrix factorization (SNMF) analysis of neighborhood cell type composition (NCTC) features identified 7 signatures that capture structure and immune niches in COVID-19 tissues. Trajectory inference based on immune niche signatures defined two pathological routes. Trajectory A progresses with primarily increased NK cells and granulocytes, likely reflecting the complication of microbial infections. Trajectory B is marked by increased HIHD and OP, possibly accounting for the increased immune infiltration. The OP regions are marked by high numbers of fibroblasts expressing extremely high levels of COL1A1 and COL1A2. Examination of single-cell RNA-seq data (scRNA-seq) from COVID-19 lung tissues and idiopathic pulmonary fibrosis (IPF) identified similar cell populations primarily consisting of myofibroblasts. Immunofluorescence staining revealed the activation of IL6-STAT3 and TGF-β-SMAD2/3 pathways in these cells, which likely mediate the upregulation of COL1A1 and COL1A2, and excessive fibrosis in the lung tissues. Together, this study provides an SSCTA atlas of cellular and molecular signatures of fatal COVID-19 lungs, revealing the complex spatial cellular heterogeneity, organization, and interactions that characterized the COVID-19 lung pathology.
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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/10.1101/2023.02.24.23286388v1" target="_blank">Cellular and molecular heterogeneities and signatures, and pathological trajectories of fatal COVID-19 lungs defined by spatial single-cell transcriptome analysis</a>
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</div></li>
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<li><strong>Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12-17 year-old adolescents</strong> -
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We previously demonstrated efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults in the SPECTRA phase 2/3 efficacy study. We extended the study to include 1278 healthy 12-17-year-old adolescents in Belgium, Colombia and the Philippines who received either two doses of SCB-2019 or placebo 21 days apart, to assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 and variants of concern, and safety and reactogenicity as solicited and unsolicited adverse events with a comparator group of young adults (18-25 years). In participants with no evidence of prior SARS-CoV-2 infection SCB-2019 immunogenicity in adolescents was non-inferior to that in young adults; respective geometric mean neutralizing titers (GMT) against prototype SARS-CoV-2 14 days after the second vaccination were 271 IU/mL (95% CI: 211-348) and 144 IU/mL (116-178). Most adolescents (1077, 84.3%) had serologic evidence of prior SAR-CoV-2 exposure at baseline; in these seropositive adolescents neutralizing GMTs increased from 173 IU/mL (135-122) to 982 IU/mL (881-1094) after the second dose. Neutralizing titers against Delta and Omicron BA SARS-CoV-2 variants were also increased, most notably in those with prior exposure. SCB-2019 vaccine was well tolerated with generally mild or moderate, transient solicited and unsolicited adverse events that were comparable in adolescent vaccine and placebo groups except for injection site pain - reported after 20% of SCB-2019 and 7.3% of placebo injections. SCB-2019 vaccine was highly immunogenic against SARS-CoV-2 prototype and variants in adolescents, especially in those with evidence of prior exposure, with comparable immunogenicity to young adults.
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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/10.1101/2023.02.22.23286317v1" target="_blank">Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12-17 year-old adolescents</a>
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</div></li>
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<li><strong>Safety of the NVX-CoV2373 COVID-19 Vaccine in Randomized Placebo-Controlled Clinical Trials</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: NVX-CoV2373 (Nuvaxovid™ or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7-90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged ≥18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials. Methods: All participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years). Findings: Pooled data from 49,950 participants (NVX-CoV2373, n=30,058; placebo, n=19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76%/systemic, 70%) than placebo recipients (29%/47%), and were mostly of mild-to-moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipients (6.28%/11.36%) than placebo recipients (0.48%/3.58%). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (0.91% and 0.07%, respectively) and placebo recipients (1.0% and 0.06%). Interpretation: To date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults.
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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/10.1101/2023.02.24.23285601v1" target="_blank">Safety of the NVX-CoV2373 COVID-19 Vaccine in Randomized Placebo-Controlled Clinical Trials</a>
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</div></li>
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<li><strong>Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection from a neurological reference center in Peru</strong> -
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Introduction: several cases of Guillain-Barre Syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge. Methods: A retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable. Results: 81 subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19,while AMAN pattern predominated (59.26%) in those without COVID-19 (p=<0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06 - 3.34), p=0.030, adjusted for age, sex, and neurophysiological subtype. Conclusions: The neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286287v1" target="_blank">Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection from a neurological reference center in Peru</a>
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</div></li>
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<li><strong>Comparing human and artificial intelligence in writing for health journals: an exploratory study</strong> -
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Aim and objectives: The aim was to contribute to the editorial principles on the possible use of Artificial Intelligence (AI)- based tools for scientific writing. The objectives included: A. Enlist the inclusion and exclusion criteria to test ChatGPT use in scientific writing B. Develop evaluation criteria to assess the quality of articles written by human authors and ChatGPT C. Compare prospectively written manuscripts by human authors and ChatGPT Design: Prospective exploratory study Intervention: Human authors and ChatGPT were asked to write short journal articles on three topics: 1) Promotion of early childhood development in Pakistan 2) Interventions to improve gender-responsive health services in low-and-middle-income countries, and 3) The pitfalls in risk communication for COVID-19. We content analyzed the articles using an evaluation matrix. Outcome measures: The completeness, credibility, and scientific content of an article. Completeness meant that structure (IMRaD) and organization was maintained. Credibility required that others work is duly cited, with an accurate bibliography. Scientific content required specificity, data accuracy, cohesion, inclusivity, confidentiality, limitations, readability, and time efficiency. Results: The articles by human authors scored better than ChatGPT in completeness and credibility. Similarly, human-written articles scored better for most of the items in scientific content except for time efficiency where ChatGPT scored better. The methods section was absent in ChatGPT articles, and a majority of references in its bibliography were unverifiable. Conclusions: ChatGPT generates content that is believable but may not be true. The creators of this powerful model must step up and provide solutions to manage its glitches and potential misuse. In parallel, the academic departments, editors, and publishers must expect a growing utilization of ChatGPT and similar tools. Disallowing ChatGPT as a co-author may not be enough on their part. They must adapt the editorial policies, use measures to detect AI-based writing, and stop its likely implications for human health and life.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286322v1" target="_blank">Comparing human and artificial intelligence in writing for health journals: an exploratory study</a>
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</div></li>
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<li><strong>A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023</strong> -
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In this work we estimate the incidence of COVID-19 in China using online indirect surveys (which preserve the privacy of the participants). The indirect surveys deployed collect data on the incidence of COVID-19, asking the participants about the number of cases, deaths, vaccinated, and hospitalized that they know. The incidence of COVID-19 (cases, deaths, etc.) is then estimated using a modified Network Scale-up Method (NSUM). Survey responses (100, 200 and 1,000, respectively) were collected from Australia, the UK, and China in January 2023. The estimates in Australia and the UK are compared with official data, showing that they are in the confidence intervals or rather close. Cronbach9s alpha values also indicate good confidence in the estimates. The estimates obtained in China are, among others, that 91% of the population is vaccinated, almost 80% had been infected in the last month, and almost 3% in the last 24 hours.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286167v1" target="_blank">A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023</a>
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</div></li>
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<li><strong>Quantifying the impact of SARS-CoV-2 temporal vaccination trends and disparities on disease control</strong> -
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SARS-CoV-2 vaccines were developed and distributed during a global crisis at unprecedented speed. Still, little is known about trends in vaccine uptake over time, their association with socioeconomic inequality, and the impact of these temporal trends on disease control. By analyzing data from dozens of countries, we examined vaccination rates across high and low socioeconomic (SES) groups, showing that socioeconomic disparities in the fraction of the population vaccinated exist at both national and sub-national levels. We also identified two distinct vaccination trends: one characterized by rapid initial roll-out, quickly reaching a plateau; and another trend that is sigmoidal and slow to begin. Informed by these patterns, we implemented an SES-stratified mechanistic model, finding profound differences across the two vaccination types in the burden of infections and deaths. The timing of initial roll-out has a more significant effect on transmission and deaths than the eventual level of coverage or the degree of SES disparity. Surprisingly, the speed of the roll-out is not associated with wealth inequality or GDP per capita of countries. While socioeconomic disparity should be addressed, accelerating the initial roll-out for all groups is a broadly accessible intervention and has the potential to minimize the burden of infections and deaths across socioeconomic groups.
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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/10.1101/2023.02.23.23286326v1" target="_blank">Quantifying the impact of SARS-CoV-2 temporal vaccination trends and disparities on disease control</a>
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</div></li>
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<li><strong>Moral dilemmas and trust in leaders during a global health crisis</strong> -
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Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non- utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others (‘instrumental harm’) reduces trust, while maximizing the welfare of everyone equally (‘impartial beneficence’) may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioral (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioral measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/mzswb/" target="_blank">Moral dilemmas and trust in leaders during a global health crisis</a>
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</div></li>
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<li><strong>Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</strong> -
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<div>
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Emerging variants of SARS-CoV-2 still threaten the effectiveness of currently deployed vaccines, and antivirals can prove to be an effective therapeutic option for attenuating it. The papain-like protease (PLpro) is an attractive target due to its sequence conservation and critical role in the replication and pathogenesis of SARS-CoV-2. PLpro also plays very important role in modulation of host immune responses by deubiquitinating (DUBs) or deISGylating host proteins. Thus, targeting PLpro serves as a two-pronged approach to abate SARS-CoV-2. Due to its structural and functional similarities with the host DUB enzymes, an in-house library of DUB inhibitors was constituted in this study. Five promising compounds exhibiting high binding affinities with the substrate binding site of PLpro were identified from a library of 81 compounds with in silico screening, docking, and simulation studies. Interestingly, lithocholic acid, linagliptin, teneligliptin, and flupenthixol significantly inhibited the proteolytic activity of PLpro. Each of these compounds abrogated in vitro replication of SARS-CoV-2 with EC50 values in the range of 5-21 micro M. In addition, crystal structure of SARS-CoV-2 PLpro and its complex with inhibitors have been determined that revealed their inhibitory mechanism. The findings of this study provide the proof-of-principle that the DUB inhibitors hold high potential as a new class of therapeutics against SARS-CoV-2. Additionally, this is the first study that has opened a new avenue towards not only targeting PLpro active site but also simultaneously directing towards restoration of antiviral immune response of the host for deterring SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.11.516107v2" target="_blank">Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies</a>
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<li><strong>Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</strong> -
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Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves rapidly and drug resistant strains have emerged. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning based on experimental data from knockout screens and a drug screen. As gold standard, we assembled perturbed genes reducing virus replication or protecting the host cells. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance with a balanced accuracy of 0.82 (knockout based classifier) and 0.71 (drugs screen based classifier), suggesting patterns of intrinsic data consistency. The predicted host dependency factors were enriched in sets of genes particularly coding for development, morphogenesis, and neural related processes. Focusing on development and morphogenesis-associated gene sets, we found {beta}-catenin to be central and selected PRI-724, a canonical {beta}-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in CPE development, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept may support focusing and accelerating the discovery of host dependency factors and the design of antiviral therapies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529833v1" target="_blank">Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</a>
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<li><strong>Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</strong> -
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During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529742v1" target="_blank">Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</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>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical 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>MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B<br/><b>Interventions</b>: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)<br/><b>Sponsors</b>: Medical Group Care, LLC; CSSi Life Sciences<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>Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution</strong> - <b>Condition</b>: SARS-CoV2 Infection<br/><b>Intervention</b>: Other: Hypertonic seawater solution<br/><b>Sponsor</b>: Larissa 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>Cognitive Rehabilitation for People With Cognitive Covid19</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Cognitive rehabilitation<br/><b>Sponsors</b>: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust<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>Exercise Intervention Using mHealth in Patients With Post-Acute COVID-19 Syndrome: a Randomized Clinical Trial</strong> - <b>Conditions</b>: Post-Acute COVID19 Syndrome; Long COVID; Post COVID-19 Condition<br/><b>Interventions</b>: Device: COVIDReApp Group; Other: Control Group<br/><b>Sponsor</b>: University of Cadiz<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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<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>Post COVID-19 REspiratory Mechanisms and the Efficacy of a Breathing Exercise Intervention for DYsregulated Breathing</strong> - <b>Conditions</b>: COVID-19; Respiratory Disease<br/><b>Intervention</b>: Other: Breathing techniques over 12 sessions / 6 weeks inc yoga<br/><b>Sponsor</b>: University of Nottingham<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1/2 Study to Assess the Safety and Immunogenicity of JCXH-221, an mRNA-based Broadly Protective COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19; Infectious Disease<br/><b>Interventions</b>: Biological: JCXH-221; Biological: Active Comparator; Other: Placebo<br/><b>Sponsors</b>: Immorna Biotherapeutics, Inc.; ICON plc<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nitriles: an attractive approach to the development of covalent inhibitors</strong> - Nitriles have broad applications in medicinal chemistry, with more than 60 small molecule drugs on the market containing the cyano functional group. In addition to the well-known noncovalent interactions that nitriles can perform with macromolecular targets, they are also known to improve drug candidates’ pharmacokinetic profiles. Moreover, the cyano group can be used as an electrophilic warhead to covalently bind an inhibitor to a target of interest, forming a covalent adduct, a strategy that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of the COVID-19 epidemic on medical product imports from china from outbreak to stabilization: Monthly panel data regression and instrumental variable test</strong> - This study conduct regressions of panal data with OLS and test with IV, empirically examines the COVID-19 epidemic’s impact on the import of medical products from China from the perspective of the importing countries, exporting country, and other trading partners, and analyzes the inter-temporal impact across different product categories. The empirical results reveal that, in importing countries, the COVID-19 epidemic increased the import of medical products from China. In China, as an exporting…</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>Exploration of SARS-CoV-2 Mpro Noncovalent Natural Inhibitors Using Structure-Based Approaches</strong> - With the emergence of antibody-evasive omicron subvariants (BA.2.12.1, BA.4, and BA.5), which can compromise the efficacy of vaccination, it is of utmost importance to widen the finite therapeutic options for COVID-19. Although more than 600 co-crystal complexes of Mpro with inhibitors have been revealed, utilizing them to search for novel Mpro inhibitors remains limited. Although there were two major groups of Mpro inhibitors, covalent and noncovalent inhibitors, noncovalent inhibitors were our…</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>Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro</strong> - The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC(50) values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV 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>Anti-Coronaviral Nanocluster Restrain Infections of SARS-CoV-2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation</strong> - Antivirals that can combat coronaviruses, including SARS-CoV-2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad-spectrum anti-coronavirus efficacy, which is difficult to achieve using a single small-molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS-CoV-2-like coronavirus of pangolin origin, is screened and a surface-functionalized gold…</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>Optimization of 5’UTR to evade SARS-CoV-2 Nonstructural protein 1-directed inhibition of protein synthesis in cells</strong> - Maximizing the expression level of therapeutic proteins in cells is the general goal for DNA/mRNA therapies. It is particularly challenging to achieve efficient protein expression in the cellular contexts with inhibited translation machineries, such as in the presence of cellular Nonstructural protein 1 (Nsp1) of coronaviruses (CoVs) that has been reported to inhibit overall protein synthesis of host genes and exogenously delivered mRNAs/DNAs. In this study, we thoroughly examined the sequence…</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 phase I/II safety and immunogenicity study of the Montanide-adjuvanted SARS-CoV-2 spike protein-RBD-Fc vaccine, AKS-452</strong> - CONCLUSION: These favorable safety and immunogenicity profiles of the candidate vaccine as demonstrated in this phase II study are consistent with those of the phase I study (ClinicalTrials.gov: NCT04681092) and suggest that a total of 90 µg received in 2 doses may offer a greater duration of cross-reactive neutralizing titers than when given in a single dose.</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 SARS-CoV-2 M<sup>pro</sup> inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2</strong> - COVID-19 caused by SARS-CoV-2 has continually been serious threat to public health worldwide. While a few anti-SARS-CoV-2 therapeutics are currently available, their antiviral potency is not sufficient. Here, we identify two orally available 4-fluoro-benzothiazole-containing small molecules, TKB245 and TKB248, which specifically inhibit the enzymatic activity of main protease (M^(pro)) of SARS-CoV-2 and significantly more potently block the infectivity and replication of various SARS-CoV-2…</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>Structural-based design of HD-TAC7 PROteolysis TArgeting chimeras (PROTACs) candidate transformations to abrogate SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for about 672 million infections and 6.85 million deaths worldwide. Upon SARS-CoV-2 infection, Histone deacetylases (HDACs) hyperactivate the pro-inflammatory response resulting in stimulation of Acetyl-Coenzyme A and cholesterol for viral entry. HDAC3 inhibition results in the anti-inflammatory activity and reduction of pro-inflammatory cytokines that may restrict COVID-19 progression. Here, we have designed 44…</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 immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial</strong> - CONCLUSION: Extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.</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>Sulforaphane is a reversible covalent inhibitor of 3-chymotrypsin-like protease of SARS-CoV-2</strong> - The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a major public health threat worldwide and emphasizes an urgent need for effective therapeutics. Recently, Ordonez et al. identified sulforaphane (SFN) as a novel coronavirus inhibitor both in vitro and in mice, but the mechanism of action remains elusive. In this study we independently discovered SFN for its inhibitory effect against SARS-CoV-2 using a…</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>Correction: Lee et al. The Synergistic Inhibition of Coronavirus Replication and Induced Cytokine Production by Ciclesonide and the Tylophorine-Based Compound Dbq33b. <em>Pharmaceutics</em> 2022, <em>14</em>, 1511</strong> - In the original publication […].</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 Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL<sup>pro</sup> Protein</strong> - Recent studies have shown that the peptide [des-Cys<sup>(11),Lys</sup>(12),Lys^(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PL^(pro) enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization,…</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>Saponins: Research Progress and Their Potential Role in the Post-COVID-19 Pandemic Era</strong> - In the post-COVID-19 pandemic era, the new global situation and the limited therapeutic management of the disease make it necessary to take urgent measures in more effective therapies and drug development in order to counteract the negative global impacts caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new infectious variants. In this context, plant-derived saponins-glycoside-type compounds constituted from a triterpene or steroidal aglycone and one or more sugar…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>Melastoma malabathricum</em> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection</strong> - Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment 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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