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180 lines
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<title>21 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>Therapeutic Potential of Selective Medicinal Plants and Their Phytoconstituents Focusing the Prevention and Cure of COVID-19</strong> -
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<div>
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The spread of pandemic coronavirus disease-2019 has become a health emergency worldwide. Since the unprecedented outbreak, attention has been raised worldwide to develop and research for control options and treatments. Although several clinical trials are ongoing, no registered drugs or vaccines are available yet. As situation warrants for the exploration of a successful antiviral, there should be a search for the remedies in nature also. Medicinal plants and their metabolites have long been used as a treatment option for various life-threatening diseases with minimal or no side effects. Thus this review aims to summarize previous outcomes concerning the role of medicinal plants in treating several life-threatening diseases. Above all, this work intends to find the constituents of five selected medicinal plants and their possible working mechanisms in the management of COVID-19. Constituents of the presented medicinal plants possess excellent pharmacological properties, including significant antiviral and antimicrobial potential. Based on the traditional uses, pharmacological properties, and previous studies, these medicinal plants mentioned in this review can be considered as a possible therapeutic option for the management and treatment of COVID-19. However, further extensive researches and trials are suggested to discover specific effects and dosage for this pathogenic outbreak.
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🖺 Full Text HTML: <a href="https://osf.io/ekf8n/" target="_blank">Therapeutic Potential of Selective Medicinal Plants and Their Phytoconstituents Focusing the Prevention and Cure of COVID-19</a>
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</div></li>
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<li><strong>A robust Platform for Integrative Spatial Multi-omics Analysis to Map Immune Responses to SARS-CoV-2 infection in Lung Tissues</strong> -
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<div>
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The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid, and similar, but a robust platform for deep tissue characterisation of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterise and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.
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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/10.1101/2023.02.19.529128v1" target="_blank">A robust Platform for Integrative Spatial Multi-omics Analysis to Map Immune Responses to SARS-CoV-2 infection in Lung Tissues</a>
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</div></li>
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<li><strong>Genetic consequences of effective and suboptimal dosing with mutagenic drugs in a hamster model of SARS-CoV-2 infection</strong> -
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<div>
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Mutagenic antiviral drugs have shown promising results against multiple viruses, yet concerns have been raised about whether their use might promote the emergence of new and harmful viral variants. Here, we examine the genetic consequences of effective and suboptimal dosing of favipiravir and molnupiravir in the treatment of SARS-CoV-2 infection in a hamster model. We identify a dose-dependent effect upon the mutational load in a viral population, with molnupiravir having a greater potency than favipiravir per mg/kg of treatment. The emergence of de novo variants was largely driven by stochastic processes, with evidence of compensatory adaptation but not of the emergence of drug resistance or novel immune phenotypes. Effective doses for favipiravir and molunpiravir correspond to similar levels of mutational load. Combining both drugs had an increased impact on both efficacy and mutational load. Our results suggest the potential for mutational load to provide a marker for clinical efficacy.
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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/10.1101/2023.02.20.529243v1" target="_blank">Genetic consequences of effective and suboptimal dosing with mutagenic drugs in a hamster model of SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Bovine milk glycoproteins inhibit SARS-CoV-2 and influenza virus co-infection</strong> -
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The attachment of S1 subunit of spike (S) protein to angiotensin-converting enzyme 2 (ACE2) is the first and crucial step of SARS-CoV-2 infection. Although S protein and ACE2 are heavily glycosylated, the precise roles of glycans in their interactions are still unclear. Here, we profiled the glycopatterns of S1 subunit of SARS-CoV-2 and ACE2, and found that the galactosylated glycoforms were dominant in both S1 subunit and ACE2. Interestingly, S1 subunit exhibited the property of glycan-binding protein (GBP) and adhered to the ACE2 via binding to the galactosylated glycans on the ACE2. Our earlier findings demonstrated that the sialylated glycoproteins isolated from bovine milk potently inhibit and neutralize viral activity against influenza A virus (IAV). Importantly, we proved further that the galactosylated glycans on isolated glycoproteins bind to the glycan recognition domains of S1 subunit and competitively inhibit binding of S1 subunit to ACE2 and ultimately impede the entry of SARS-CoV-2 pseudovirus into host cells. We provided a potential protein drug that could be multiple simultaneous inhibitor for coronavirus and IAV co-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/10.1101/2023.02.20.529234v1" target="_blank">Bovine milk glycoproteins inhibit SARS-CoV-2 and influenza virus co-infection</a>
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</div></li>
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<li><strong>Antibody-mediated cell entry of SARS-CoV-2</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus-encoded spike protein and fusion between the viral and target cell membranes. We report here that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor-binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity. These receptor-like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc-gamma receptor I, a chimera of their antigen-binding fragment with the transmembrane domain of ACE2 or a membrane-bound B cell receptor, indicating that ACE2 and its specific interactions with the spike protein are dispensable for SARS-CoV-2 entry. These results suggest that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.20.529249v1" target="_blank">Antibody-mediated cell entry of SARS-CoV-2</a>
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</div></li>
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<li><strong>SARS-CoV-2 Protein Nsp2 Stimulates Translation Under Normal and Hypoxic Conditions</strong> -
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<div>
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When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A proteomic analysis of SARS-CoV-2/human proteins interaction revealed viral Nsp2 and initiation factor eIF4E2, but a role of Nsp2 in regulating translation is unknown. HEK293T cells stably expressing Nsp2 were tested for protein synthesis rates of synthetic and endogenous mRNAs known to be translated via cap- or IRES-dependent mechanism under normal and hypoxic conditions. Both cap- and IRES-dependent translation were increased in Nsp2-expressing cells under normal and hypoxic conditions, especially mRNAs that require high levels of eIF4F. This could be exploited by the virus to maintain high translation rates of both viral and cellular proteins, particularly in hypoxic conditions as may arise in SARS-CoV-2 patients with poor lung functioning.
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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/10.1101/2022.09.13.507829v4" target="_blank">SARS-CoV-2 Protein Nsp2 Stimulates Translation Under Normal and Hypoxic Conditions</a>
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</div></li>
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<li><strong>Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices</strong> -
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<div>
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The COVID-19 pandemic drastically increased food insecurity among U.S. households, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with U.S. caregivers of infants (<2 years) (N=319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feeding, and household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% white; 8% living in poverty). Results suggest that the COVID-19 pandemic had a greater negative impact on formula-feeding families, largely due to formula shortages and financial strain. We found 31% of formula-feeding families indicated they experienced various challenges to obtaining formula, citing the following top three reasons: formula was sold out (20%), had to travel to multiple stores (21%), or too expensive (8%). In response, 33% of formula-feeding families reported resorting to potentially harmful feeding practices such as diluting formula with extra water (12%) or cereal (10%), preparing smaller bottles (8%), or feeding left-over/expired formula (11%). Only 15% of breastfeeding families reported feeding difficulties directly as a result of the pandemic—15% were reluctant to obtain lactation support and 9% weaned early. In fact, 51% of breastfeeding families reported increased provision of human milk to infants due to perceived benefits for the infant’s immune system (37%), ability to work remotely/stay home (31%), or concerns about money (8%) or formula shortages (8%). To protect infants from malnutrition in future crises, our results underscore the need for policies to support breastfeeding families and ensure equitable access to infant formula.
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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/gx5qr/" target="_blank">Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices</a>
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</div></li>
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<li><strong>Omicron-Specific and Bivalent Omicron-Containing Vaccine Candidates Elicit Potent Virus Neutralisation in the Animal Model</strong> -
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<div>
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Background: Omicron variant (B.1.1.529) is able to escape from naturally acquired and vaccine-induced immunity, which mandates updating the current COVID-19 vaccines. Here, we investigated and compared the neutralising antibody induction of the ancestral variant-based BIV1-CovIran vaccine, the Omicron variant-based BIV1-CovIran Plus vaccine, and the novel bivalent vaccine candidate, BBIV1-CovIran, against the Omicron and ancestral Wuhan variants on the rat model. Methods: Viruses were isolated from a clinical specimen and virus characterisation performed. After inactivating the viral particles, the viruses were purified and formulated. Bivalent vaccines were a composition of 2.5 micrograms (5 micrograms total) or 5 micrograms (10 micrograms total) doses of each ancestral-based and Omicron-based monovalent vaccine. Subsequently, the potency of the monovalent and bivalent vaccines was investigated using the virus neutralisation test (VNT). Results: The group that received three doses of the Omicron-specific vaccine demonstrated neutralisation activity against the Omicron variant with a geometric mean titer of 337.8. However, three doses of the Wuhan variant-specific vaccine could neutralise the Omicron variant at a maximum of 1/32 serum dilution. The neutralisation activity of the Omicron-specific vaccine, when administered as the booster dose after two doses of the Wuhan variant-specific vaccine, was 100% against the Omicron variant and the Wuhan variant at 1/64 and 1/128 serum dilution, respectively. Three doses of 5 micrograms bivalent vaccine could effectively neutralise both variants at the minimum of 1/128 serum dilution. The 10 micrograms bivalent vaccine at three doses showed even higher neutralisation titers: geometric mean titer of 338.0 against Omicron and 445.7 against Wuhan). Conclusion: It is shown that the candidate bivalent vaccine could elicit a potent immune response against both Wuhan-Hu-1 and Omicron BA.1 variants. Therefore, we plan to evaluate the updated vaccine in the clinical trial setting.
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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/10.1101/2022.02.11.480131v2" target="_blank">Omicron-Specific and Bivalent Omicron-Containing Vaccine Candidates Elicit Potent Virus Neutralisation in the Animal Model</a>
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</div></li>
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<li><strong>Evaluation of primary allied healthcare in patients recovering from COVID-19: first results after six months follow-up in a Dutch nationwide prospective cohort study</strong> -
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Objectives: To report the recovery of patients receiving primary allied healthcare after a COVID-19 infection at a six-month follow-up, and to explore which patient characteristics are associated with the changes in outcomes between the baseline and six-month follow-up. Design: Prospective cohort study. Setting: Allied healthcare in Dutch primary care. Participants: 1,452 adult patients recovering from COVID-19 and receiving treatment from one or more primary care allied health professional(s) (i.e., dietitian, exercise therapist, occupational therapist, physical therapist and/or speech and language therapist). Results: For participation (USER-P range 0 to 100), estimated mean differences of at least 2.3 points were observed after six months. For HRQoL (EQ-VAS range 0 to 100), the mean increase was 12.31 at six months. Furthermore, significant improvements were found for fatigue (FSS range 1 to 7): the mean decrease was -0.7 at six months. For physical functioning (PROMIS-PF range 13.8 to 61.3), the mean increase was 5.9 at six months. Mean differences of -0.8 for anxiety (HADS range 0 to 21), and -1.5 for depression (HADS range 0 to 21), were found after six months. Having a worse baseline score, hospital admission and male sex were associated with greater improvement between the baseline and six-month follow-up, whereas age, BMI, comorbidities and smoking status were not associated with mean changes in any outcome measure. Conclusions: Patients recovering from COVID-19 who receive primary allied healthcare make progress in recovery, but still experience many limitations in their daily activities after six months. Our findings provide reference values to healthcare providers and healthcare policy-makers regarding what to expect from the recovery of patients who received health care from one or more primary care allied health professionals. Trial registration: Clinicaltrials.gov registry (NCT04735744).
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.03.22280639v2" target="_blank">Evaluation of primary allied healthcare in patients recovering from COVID-19: first results after six months follow-up in a Dutch nationwide prospective cohort study</a>
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<li><strong>Impact of the COVID-19 pandemic on the socioeconomic inequality of health behavior among Japanese adolescents: a two-year-repeated cross-sectional survey</strong> -
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Background: Although disparities in socioeconomic status in health behaviors have been highlighted globally, they are not well understood in Japanese adolescents. The purpose of this study was to clarify the changes in socioeconomic disparities in adolescents9 fundamental health behaviors, such as physical activity, screen time (ST), sleep, breakfast intake, and bowel movement before and during COVID-19. Methods: This was a repeated cross-sectional study which used data from the 2019 and 2021 National Sports-Life Survey of Children and Young in Japan. Data of 766 and 725 participants in 2019 and 2021, respectively, were analyzed. Favorable health behaviors were defined as daily moderate-to-vigorous physical activity (MVPA) of at least 60 minutes, ST of less than 2 hours, sleep of 8 to 10 hours, daily breakfast intake, and bowel movement frequency of at least once in every 3 days. We calculated the slope index of inequality (SII) and relative index of inequality (RII) in each health behavior for equivalent household income levels for assessing absolute and relative economic inequalities. Results: Compliance with MVPA and ST recommendation significantly declined from 20.1% and 23.0% in 2019 to 11.7% and 14.9% in 2021, respectively. The SII and RII increased in MVPA for income levels, but decreased in daily breakfast in 2019 to 2021. Although the widening and narrowing of the disparity was inconclusive for ST, it exacerbated for the higher income groups. Conclusions: Our study revealed widening of economic disparities in the achievement of recommended MVPA and narrowing of it in breakfast intake among adolescents before and during COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.11.22278499v2" target="_blank">Impact of the COVID-19 pandemic on the socioeconomic inequality of health behavior among Japanese adolescents: a two-year-repeated cross-sectional survey</a>
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<li><strong>Tracking and curating putative SARS-CoV-2 recombinants with RIVET</strong> -
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Identifying and tracking recombinant strains of SARS-CoV-2 is critical to understanding the evolution of the virus and controlling its spread. But confidently identifying SARS-CoV-2 recombinants from thousands of new genome sequences that are being shared online every day is quite challenging, causing many recombinants to be missed or suffer from weeks of delay in being formally identified while undergoing expert curation. We present RIVET - a software pipeline and visual platform that takes advantage of recent algorithmic advances in recombination inference to comprehensively and sensitively search for potential SARS-CoV-2 recombinants, and organizes the relevant information in a web interface that would help greatly accelerate the process identifying and tracking recombinants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.17.529036v1" target="_blank">Tracking and curating putative SARS-CoV-2 recombinants with RIVET</a>
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<li><strong>Mortality by cause of death in Brazil: effects of the COVID-19 pandemic and contribution to changes in life expectancy at birth</strong> -
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We investigate the consequences of the COVID-19 pandemic on other underlying causes of death in Brazil in 2020 and 2021. We estimate monthly age-standardized mortality rates for 2010-2021 and decompose those time series into three additive components: trend, seasonality, and remainder. Given the long-term trend and historical seasonal fluctuations, we assume that any impact from the pandemic will be left on the remainder. We also decompose the contributions of COVID-19 deaths (direct effect) and those from other causes (indirect effects) to the annual change in life expectancy at birth (e0) from 2017 to 2021. Broadly, the remainder mirrors the trajectory of pandemic waves. The impact of the COVID-19 pandemic on other causes of death was not limited to increases but also decreases. The direct effects of the pandemic reduced e0 by 1.89 years between 2019 and 2020 and 1.77 between 2020 and 2021. Indirect effects increased e0 by 0.44 between 2019 and 2020 and had virtually no impact on e0 between 2020 and 2021. Whether trajectories in mortality rates and annual gains in e0 will quickly return to pre-pandemic levels depends on governmental actions to mitigate the consequences of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.13.23285842v1" target="_blank">Mortality by cause of death in Brazil: effects of the COVID-19 pandemic and contribution to changes in life expectancy at birth</a>
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<li><strong>Protective effect of plasma neutralization from prior SARS-CoV-2 Omicron infection against BA.5 subvariant symptomatic reinfection</strong> -
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From December 2022 to January 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections caused by BA.5 and BF.7 subvariants of B.1.1.529 (Omicron) swept across mainland China. It is crucial to estimate the protective effect of the neutralizing antibodies generated by such mass infections against the next potential SARS-CoV-2 reinfection wave, especially if driven by CH.1.1 or XBB.1.5. Previously, we recruited and continuously followed a cohort of individuals that experienced Omicron BA.1, BA.2, and BA.5 breakthrough infections, as well as a control cohort with no history of SARS-CoV-2 infection. In the previously uninfected cohort, the total symptomatic infection rate surveyed during the outbreak was 91.6%, while the symptomatic reinfection rate was 32.9%, 10.5%, and 2.8% among individuals with prior Omicron BA.1, BA.2 and BA.5 infection, respectively, with median intervals between infections of 335, 225 and 94 days. Pseudovirus neutralization assays were performed in plasma samples collected from previously Omicron BA.1-infected individuals approximately 3 months before the outbreak. Results indicate a robust correlation between the plasma neutralizing antibody titers and the protective effect against symptomatic reinfection. The geometric mean of the 50% neutralizing titers (NT50) against D614G, BA.5, and BF.7 were 2.0, 2.5, and 2.3-fold higher in individuals without symptomatic reinfection than in those with symptomatic reinfection (p < 0.01). Low plasma neutralizing antibody titer (below the geometric mean of NT50) was associated with an enhanced cumulative risk of symptomatic reinfection, with a hazard ratio (HR) of 23.55 (95% CI: 9.23-60.06) against BF.7 subvariant. Importantly, neutralizing antibodies titers post one month after BF.7/BA.5 breakthrough infections against CH.1.1 and XBB.1.5 are similar to that against BF.7 from individuals with prior BA.1 infection while not experiencing a symptomatic BF.7/BA.5 reinfection (plasma collected 3 months before the outbreak), suggesting that the humoral immunity generated by the current BF.7/BA.5 breakthrough infection may provide protection against CH.1.1 and XBB.1.5 symptomatic reinfection wave for 4 months. Of note, the higher hACE2 binding of XBB.1.5 may reduce the protection period since the potential increase of infectivity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.14.527605v1" target="_blank">Protective effect of plasma neutralization from prior SARS-CoV-2 Omicron infection against BA.5 subvariant symptomatic reinfection</a>
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<li><strong>Speedy-PASEF: Analytical flow rate chromatography and trapped ion mobility for deep high-throughput proteomics</strong> -
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Increased throughput in proteomic experiments can improve accessibility of proteomic platforms, reduce costs and facilitate new approaches in systems biology and biomedical research. Here we propose Speedy-PASEF, a combination of analytical flow rate chromatography with ion mobility separation of peptide ions, data-independent acquisition and data analysis with the DIA-NN software suite, for conducting fast, high-quality proteomic experiments that require only moderate sample amounts. For instance, using a 500-l/min flow rate and a 3-minute chromatographic gradient, Speedy-PASEF quantified 5,211 proteins from 2 g of a mammalian cell-line standard at high quantitative accuracy and precision. We further used Speedy-PASEF to analyze blood plasma samples from a cohort of COVID-19 inpatients, using a 3-minute chromatographic gradient and alternating column regeneration on a dual pump system, for processing 398 samples per day. Speedy-PASEF delivered a comprehensive view of the COVID-19 plasma proteome, allowing classification of the patients according to disease severity and revealing plasma biomarker candidates. Speedy-PASEF thus facilitates acquisition of high-quality proteomes in large numbers.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.17.528968v1" target="_blank">Speedy-PASEF: Analytical flow rate chromatography and trapped ion mobility for deep high-throughput proteomics</a>
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<li><strong>Protocol for a cluster randomised controlled trial to evaluate the effectiveness of digital health interventions in improving non-communicable disease management during the pandemic in rural Pakistan</strong> -
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Background: The COVID-19 pandemic has revealed gaps in global health systems, especially in the low- and middle-income countries (LMICs). Evidence shows that patients with non-communicable diseases (NCDs) are at higher risk of contracting COVID-19 and suffering direct and indirect health consequences. Considering the future challenges such as environmental disasters and pandemics to the LMICs health systems, digital health interventions (DHI) are well poised to strengthen health care resilience. This study aims to implement and evaluate a comprehensive package of DHIs of integrated COVID-NCD care to manage NCDs in primary care facilities in rural Pakistan. Methods The study is designed as a pragmatic, parallel two-arm, multi-centre, cluster randomised controlled trial. We will randomise 30 primary care facilities in three districts of Punjab, where basic hypertension and diabetes diagnosis and treatment is provided, with a ratio of 1:1 between intervention and control. In each facility, we will recruit 50 patients who have uncontrolled hypertension. The intervention arm will receive training on an integrated COVID-NCD guideline, and will use a smartphone app-based telemedicine platform where patients can communicate with health providers and peer-supporters, along with a remote training and supervision system. Usual care will be provided in the control arm. Patients will be followed up for 10 months. Our primary indicator is systolic blood pressure measured at 10 months. A process evaluation guided by implementation science frameworks will be conducted to explore implementation questions. A cost-effectiveness evaluation will be conducted to inform future scale up in Pakistan and other LMICs. Discussion: Our study is one of the first randomised controlled trials to evaluate the effectiveness of DHIs to manage NCDs to strengthen health system resilience in LMICs. We will also evaluate the implementation process and cost-effectiveness to inform future scale-up in similar resource constrained settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.17.23286113v1" target="_blank">Protocol for a cluster randomised controlled trial to evaluate the effectiveness of digital health interventions in improving non-communicable disease management during the pandemic in rural Pakistan</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>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Manzi Guben granules<br/><b>Sponsors</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Pilates Exercises<br/><b>Sponsor</b>: Michele de Aguiar Zacaria<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>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>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Persuasive Appeal<br/><b>Sponsor</b>: University of Calgary<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>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AZD 1222<br/><b>Sponsors</b>: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health<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>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Double-Stranded RNA sodium salt; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<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>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-1558; Drug: STI-1558 placebo<br/><b>Sponsor</b>: Zhejiang ACEA 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>Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Biological: UC-MSCs<br/><b>Sponsor</b>: Shanghai East 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>CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: CONFIDENCE<br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health<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>The Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients</strong> - <b>Condition</b>: Health Education, COVID-19, Quarantine, Anxiety, Pandemic<br/><b>Intervention</b>: Other: health education intervention<br/><b>Sponsor</b>: University of Monastir<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>Study of Monoclonal Antibodies for Early Etiotropic Therapy for Coronavirus Infection Caused by the SARS-CoV-2 Virus</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: GamCoviMab<br/><b>Sponsor</b>: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation<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>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>To Evaluate the Safety, Efficacy,and Pharmacokinetics of Orally Administered Prolectin-M</strong> - <b>Conditions</b>: COVID-19; SARS CoV 2 Infection<br/><b>Intervention</b>: Drug: Prolectin-M<br/><b>Sponsor</b>: Bioxytran Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>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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<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>Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m<sup>6</sup><sub>2</sub>A and CD) regulations on patients with cancer and healthy individuals</strong> - The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. 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>P2X7 purinergic receptor: A potential target in heart diseases (Review)</strong> - The P2X7 purinergic receptor (P2X7R) is a non‑selective cation channel activated by high levels of adenosine triphosphate that are commonly present in serious conditions. Activation of this purinergic receptor is closely related to the development of various disease states including inflammatory and neurodegenerative disorders, orthopedic diseases and types of cancer. Accumulating evidence has shown that the P2X7R plays a crucial role in the development of various heart diseases. For example,…</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 OM-85 bacterial lysate: a new tool against SARS-CoV-2?</strong> - The emergence of SARS-CoV-2, a novel coronavirus, caused the global Coronavirus disease of 2019 (COVID-19) pandemic. Because SARS-CoV-2 mutates rapidly, vaccines that induce immune responses against viral components critical for target cell infection strongly mitigate but do not abrogate viral spread, and disease rates remain high worldwide. Complementary treatments are therefore needed to reduce the frequency and/or severity of SARS-CoV-2 infections. OM-85, a standardized lysate of 21 bacterial…</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>Renin-Angiotensin-Aldosterone Axis Inhibition Improves Outcome of Diabetic Patients with Chronic Hypertension and COVID-19: An Iranian Perspective</strong> - CONCLUSIONS: The current study suggests that ACE inhibitors and ARBs are associated with decreased mortality, ICU admission, and better ICU survival in the diabetic subgroup of hypertensive 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>Nanoscale Interaction Mechanisms of Antiviral Activity</strong> - Nanomaterials have now found applications across all segments of society including but not limited to energy, environment, defense, agriculture, purification, food medicine, diagnostics, and others. The pandemic and the vulnerability of humankind to emerging viruses and other infectious diseases has renewed interest in nanoparticles as a potential new class of antivirals. In fact, a growing body of evidence in the literature suggests nanoparticles may have activity against multiple viruses…</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 Investigational Anti-SARS-CoV-2 Agent Ensitrelvir “S-217622”: A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species</strong> - Lately, nitrogenous heterocyclic antivirals, such as nucleoside-like compounds, oxadiazoles, thiadiazoles, triazoles, quinolines, and isoquinolines, topped the therapeutic scene as promising agents of choice for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying ailment, the coronavirus disease 2019 (COVID-19). At the same time, the continuous emergence of new strains of SARS-CoV-2, like the Omicron variant and its multiple…</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>High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients</strong> - CONCLUSIONS: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.</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>Effect of chitooligosaccharide on the inhibition of SARS-CoV-2 main protease</strong> - CONCLUSION: This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.</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 dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses</strong> - Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CL^(pro)) and the papain-like protease, to generate non-structural proteins essential for the virus life cycle. Both proteases are recognized as promising drug targets for the development of anti-coronavirus…</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>Screen for Modulation of Nucleocapsid Protein Condensation Identifies Small Molecules with Anti-Coronavirus Activity</strong> - Biomolecular condensates formed by liquid-liquid phase separation have been implicated in multiple diseases. Modulation of condensate dynamics by small molecules has therapeutic potential, but so far, few condensate modulators have been disclosed. The SARS-CoV-2 nucleocapsid (N) protein forms phase-separated condensates that are hypothesized to play critical roles in viral replication, transcription, and packaging, suggesting that N condensation modulators might have anti-coronavirus activity…</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>Synthesis, X-ray crystal structure, Hirshfeld surface analysis and computational investigation into the potential inhibitory action of novel 6-(<em>p</em>-tolyl)-2-((<em>p</em>-tolyl)thio)methyl-7<em>H</em>-[1.2.4]triazolo[5,1-<em>b</em>][1,3,4]thiadiazine inhibits the main protease of COVID-19</strong> - In recent times, the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a worldwide pandemic. With over 71 million confirmed cases, even though the effectiveness and side effects of the specific drugs and vaccines approved for this disease are still limited. Scientists and researchers from all across the world are working to find a vaccine and a cure for COVID-19 by using large-scale drug discovery and analysis….</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 effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats</strong> - Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC). A total of 40 Sprague-Dawley male rats were randomly and equally…</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>Supporting and inhibiting factors of accepting COVID-19 booster vaccination in the elderly in north Jakarta, Indonesia</strong> - CONCLUSIONS: Most of the elderly displayed positive attitudes concerning booster shots, but it was discovered that some barriers need to be removed.</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>Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines</strong> - CONCLUSION: The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against omicron BA.1 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>The development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders</strong> - Pandemic and the globally applied restriction measures mainly affect vulnerable population groups, such as patients with opioid use disorders. Towards inhibiting SARS-Cov-2 spread, the medication-assisted treatment (MAT) programs follow strategies targeting the reduction of in-person psychosocial interventions and an increase of take-home doses. However, there is no available instrument to examine the impact of such modifications on diverse health aspects of patients under MAT. The aim of this…</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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