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<title>14 April, 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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<ul>
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<li><strong>SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes</strong> -
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<div>
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Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.
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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/10.1101/2023.04.12.536671v1" target="_blank">SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes</a>
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</div></li>
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<li><strong>The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study</strong> -
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<div>
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Aims: The postpartum/postnatal period is widely acknowledged as a time when mothers require greater levels of support from multiple sources. However, stay-at-home orders commonly known as “lockdown” deployed in some countries to limit COVID-19 transmission reduced access to support. In England, many postpartum mothers navigated household isolation under intensive mothering and expert parenting culture. Examining the impact of lockdown may reveal strengths and weaknesses in current policy and practice, revealing opportunities to improve maternal experience and wellbeing. Subject and Methods: We conducted an online focus group involving 20 mothers living in London, England, with “lockdown babies,” following up on our earlier survey on social support and maternal wellbeing. We thematically analysed focus group transcripts, and identified key themes around Lockdown Experience and Determinants of Lockdown Experience. Results: Participants raised some positives of lockdown, including fostering connections and protection from external expectations, but also raised many negatives, including social isolation, institutional abandonment, and intense relationships within the household. Potential reasons behind variations in lockdown experience include physical environments, timing of birth, and number of children. Our findings reflect how current systems may be “trapping” some families into the male-breadwinner/female-caregiver family model, while intensive mothering and expert parenting culture may be increasing maternal stress and undermining responsive mothering. Conclusions: Facilitating partners to stay at home during the postpartum period and establishing peer/community support instead of reliance on professionals may promote positive postpartum maternal experience and wellbeing.
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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/r7enw/" target="_blank">The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study</a>
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</div></li>
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<li><strong>Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model</strong> -
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<div>
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Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.
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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/10.1101/2023.04.12.536590v1" target="_blank">Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model</a>
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</div></li>
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<li><strong>SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition</strong> -
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<div>
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A significant proportion of patients with SARS-CoV-2 infection develop lingering symptoms for months, even years after their infection, a condition now known as Post-COVID Condition (PCC). The underlying pathophysiology of PCC is not known. The wide spectrum of symptoms encompassing various organ systems and the detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be associated with aberrant immune response to the viral antigens. Here, we studied the antibody and B cell responses to the spike protein and the RBD domain in PCC patients who experienced mild COVID-19 disease during the early stages of COVID-19 pandemic in the pre-vaccination era. Our results suggest that the immune responses to the spike antigen may be altered in those who develop PCC.
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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/10.1101/2023.04.13.535896v1" target="_blank">SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition</a>
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</div></li>
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<li><strong>Resolving a Guanine-Quadruplex Structure in the SARS-CoV-2 Genome through Circular Dichroism and Multiscale Molecular Modeling.</strong> -
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<div>
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The genome of SARS-CoV-2 coronavirus is made up of a single-stranded RNA fragment that can assume a specific second-ary structure, whose stability can influence the virus ability to reproduce. Recent studies have identified putative guanine quadruplex sequences in SARS-CoV-2 genome fragments that are involved in coding for both structural and non-structural proteins. In this contribution, we focus on a specific G-rich sequence referred as RG-2, which codes for the non-structural protein 10 (Nsp10) and assumes a parallel guanine-quadruplex (G4) arrangement. We provide the secondary structure of the RG-2 G4 at atomistic resolution by molecular modeling and simulation, validated by the superposition of experimental and calculated electronic circular dichroism spectrum. Through both experimental and simulation approaches, we have demon-strated that pyridostatin (PDS), a widely recognized G4 binder, can bind to and stabilize RG-2 G4 more strongly than RG-1, another G4 forming sequence that was previously proposed as a potential target for antiviral drug candidates. Overall, this study highlights RG-2 as a valuable target to inhibit the translation and replication of SARS-CoV-2 paving the way towards original therapeutic approaches against emerging RNA viruses.
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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/10.1101/2023.04.13.536758v1" target="_blank">Resolving a Guanine-Quadruplex Structure in the SARS-CoV-2 Genome through Circular Dichroism and Multiscale Molecular Modeling.</a>
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</div></li>
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<li><strong>PROSPECTS AND CHALLENGES OF E-LEARNING (A REVIEW DURING COVID-19 PANDEMIC)</strong> -
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<div>
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In the past few years, e-learning is emerging as a global platform in the continuation of studies. E-learning has revolutionized the entire education system by providing flexibility and easy access to lectures anytime and anywhere, especially during covid-19 pandemic after which face-to-face learning was no longer possible. Although people were aware about e-learning and its usage but it got more prominent after COVID-19 pandemic. So, e-learning became a necessity for continuing education. This present study attempts to analyze the difficulties, benefits, and drawbacks of both educators and students by implementing these technologies as well as alternative solutions. This study discusses numerous prospects made possible by the COVID-19 pandemic and emphasizes the requirement for developing suitable methods to handle such an unanticipated crisis in the future. The problems faced by learners were a poor internet connection, a lack of electricity, a lack of interest, and a lack of desire. This study also suggests the government take the lead in assisting students who have limited access to the internet and technology, which are essential for participation in online classes, while also encouraging students to participate more actively in e-learning, particularly in context of the serious pandemic. To this purpose, various suggestions have been offered that could help academic institutions overcome these challenges and preserve academic quality during turbulent times.
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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/un5g8/" target="_blank">PROSPECTS AND CHALLENGES OF E-LEARNING (A REVIEW DURING COVID-19 PANDEMIC)</a>
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</div></li>
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<li><strong>Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background During the pandemic period, healthcare systems were substantially reorganized for managing COVID-19 cases. The corresponding changes on the standard care of persons with chronic diseases and the potential consequences on their outcomes remain insufficiently documented. This observational study investigates the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR), in particular in those not hospitalized for COVID-19. Methods We conducted a cohort study using the French national health data system which contains all healthcare consumptions in France. Incident persons with end stage kidney disease between January 1, 2015 and December 31, 2020 who received a kidney transplant were included and followed-up from their transplantation date to December 31, 2021. The survival of KTR during the pre-pandemic and pandemic periods was investigated using Cox models with time-dependent covariates, including vaccination and hospitalization events. Findings There were 10,637 KTR included in the study, with 324 and 430 deaths observed during the pre-pandemic (15,115 person-years of follow-up) and pandemic periods (14,657 person-years of follow-up), including 127 deaths observed among the 659 persons with a COVID-19-related hospitalization. In multivariable analyses, the risk of death during the pandemic period was similar to that observed during the pre-pandemic period (hazard ratio (HR) [95% confidence interval]: 0.92 [0.77-1.11]), while COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]). In addition, pre-emptive kidney transplantation was associated with a lower risk of death (HR: 0.71 [0.56-0.89]), as well as a third vaccine dose (HR: 0.42 [0.30-0.57]), while age, diabetes and cardiovascular diseases were associated with higher risks of death. Interpretation Considering persons living with a kidney transplant with no severe COVID-19-related hospitalization, the pandemic period was not associated with a higher risk of death.
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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/10.1101/2023.04.05.23288113v2" target="_blank">Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</a>
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</div></li>
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<li><strong>Should Health Communication During the SARS-CoV-2 Pandemic Emphasize Self- or Other-Focused Impacts of Mitigation Behaviors? Insights from Two Message Matching Studies</strong> -
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<div>
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Mask-wearing, social distancing, and vaccination remain effective ways to mitigate the spread of COVID-19. Yet, many hesitate to enact some or all these preventive behaviors. We created three persuasive messages—framed to promote benefits to either 1) oneself, 2) close-others, or 3) distant-others—to determine whether the effectiveness of these messages varied based on personality differences (specifically independent/interdependent self-construal and chronic construal level). In two online experiments (N = 862), we measured individual differences and showed participants one of the three messages. Consistent interactions between interdependent self-construal and message conditions showed that those high in interdependent self-construal responded most positively to the self-focused messages promoting mask-wearing, social distancing, and COVID-19 vaccination. Those low in interdependent self-construal responded most negatively to the self-focused messages. Although no interaction effect was observed for independent self-construal, and inconsistent evidence emerged for construal level, other-focused messages performed either better or equally well to the self-focused messages for most participants and may thus be promising for future public health communication efforts.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2ysn5/" target="_blank">Should Health Communication During the SARS-CoV-2 Pandemic Emphasize Self- or Other-Focused Impacts of Mitigation Behaviors? Insights from Two Message Matching Studies</a>
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</div></li>
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<li><strong>Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Little data exists to guide the treatment of persistent COVID-19 in immunocompromised patients. We have employed a unique protocol combining tixegavimab/cilgavimab, and short-term combination antivirals including remdesivir. Methods: A retrospective single-center analysis of persistent COVID-19 in immunocompromised patients. Response was assessed by symptom resolution, declining C-reactive protein (CRP) levels and increasing SARS-CoV-2-PCR cycle-threshold (Ct) values. Results: Fourteen patients were included, including 2 kidney transplant recipients, 11 with B-cell lymphoproliferative disease, treated with anti-CD20 or ibrutinib, and 1 with rheumatoid arthritis, treated with anti-CD20. Median Ct-value was 27 (interquartile range (IQR):24-32). All patients received tixegavimab/cilgavimab and a 5-day course of remdesivir. Eleven also received nirmaltrevir/ritonavir and one received molnupiravir. Median follow-up was 45 days (IQR:12-89). Eleven patients had complete responses including symptom resolution, decrease in CRP, and increase in Ct values (all with either a negative PCR or Ct value>30 on day 4-16). Three patients had a partial response with relapses requiring re-admission. One had died, and two responded to prolonged antiviral treatments. Conclusions: A combination of monoclonal antibodies with antivirals has led to complete resolution of persistent COVID-19 in most severely-immunocompromised patients. Controlled studies will further direct the treatment of these patients, while more effective antivirals are urgently needed.
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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/10.1101/2023.04.07.23288144v1" target="_blank">Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab</a>
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</div></li>
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<li><strong>The COVID-19 vaccination campaign in Switzerland and its impact on disease spread</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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We analyse infectious disease case surveillance data stratified by region and age group to estimate COVID-19 spread and gain an understanding of the impact of introducing vaccines to counter the disease in Switzerland. The data used in this work is extensive and detailed and includes information on weekly number of cases and vaccination rates by age and region. Our approach takes into account waning immunity. The statistical analysis allows us to determine the effects of choosing alternative vaccination strategies. Our results indicate greater uptake of vaccine would have led to fewer cases with a particularly large effect on undervaccinated regions while an alternative distribution scheme ignoring age would affect the vulnerable population at the time (the elderly) and is less ideal.
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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/10.1101/2023.04.06.23288251v1" target="_blank">The COVID-19 vaccination campaign in Switzerland and its impact on disease spread</a>
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</div></li>
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<li><strong>A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Vaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.
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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/10.1101/2023.04.11.23288409v3" target="_blank">A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</a>
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</div></li>
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<li><strong>A gene-expression module in circulating immune cells is associated with cell migration during immune diseases.</strong> -
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<div>
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Circulating immune cells are critical mediators of the response to inflammation upon recruitment to the tissue but how gene expression state influences recruitment is not well known. Here we report the longitudinal single-cell transcriptome profiling of blood mononuclear cells in patients undergoing kidney transplantation rejection. We identify a gene expression module which is associated to transcriptional regulation, homing and early activation in multiple cell types. The circulating cells expressing this module are reduced in patients undergoing graft rejection. This reduction was confirmed in a pig model of acute kidney transplantation rejection. In connection with this, the module expression drastically increased in the kidney grafts undergoing rejection indicating a preferential recruitment of cells highly expressing this module. We identify the receptor CXCR4 within the module and its ligand CXCL12 expressed in the graft as a likely recruitment mechanism between circulating cells and the tissue. We then explore publicly available transcriptomics data in circulating cells and show that this module is generally expressed in healthy individuals and more importantly is associated with the response to infection, including SARS Covid-19. Moreover, we find that module expression is predictive of immune mediated diseases. In summary, we find a gene expression module in circulating immune cells which enables preferential recruitment to inflamed tissues to mediate effector function.
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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/10.1101/2023.04.11.536347v1" target="_blank">A gene-expression module in circulating immune cells is associated with cell migration during immune diseases.</a>
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</div></li>
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<li><strong>A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The extent to which dengue virus has been circulating in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection; the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform a dengue seroprevalence survey which is currently being conducted in Ghana by the Drug for Neglected disease initiative, utilizing samples previously collected fora SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.
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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/10.1101/2023.04.07.23288282v1" target="_blank">A simulation-based method to inform serosurvey designs for estimating dengue force of infection using existing blood samples</a>
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</div></li>
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<li><strong>Development of Accurate Long-lead COVID-19 Forecast</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Coronavirus disease 2019 (COVID-19) will likely remain a major public health burden; accurate forecast of COVID-19 epidemic outcomes several months into the future is needed to support more proactive planning. Here, we propose strategies to address three major forecast challenges, i.e., error growth, the emergence of new variants, and infection seasonality. Using these strategies in combination we generate retrospective predictions of COVID-19 cases and deaths 6 months in the future for 10 representative US states. Tallied over >25,000 retrospective predictions through September 2022, the forecast approach using all three strategies consistently outperformed a baseline forecast approach without these strategies across different variant waves and locations, for all forecast targets. Overall, probabilistic forecast accuracy improved by 64% and 38% and point prediction accuracy by 133% and 87% for cases and deaths, respectively. Real-time 6-month lead predictions made in early October 2022 suggested large attack rates in most states but a lower burden of deaths than previous waves during October 2022 - March 2023; these predictions are in general accurate compared to reported data. The superior skill of the forecast methods developed here demonstrate means for generating more accurate long-lead forecast of COVID-19 and possibly other infectious diseases.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.14.22282323v2" target="_blank">Development of Accurate Long-lead COVID-19 Forecast</a>
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</div></li>
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<li><strong>A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Vaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.
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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/10.1101/2023.04.11.23288409v2" target="_blank">A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK</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>Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Standard of Care + Quinine Sulfate; Drug: Standard of Care<br/><b>Sponsors</b>: Universitas Padjadjaran; National Research and Innovation Agency of Indonesia; Prodia Diacro Laboratories P.T.<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>Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Biological: MSC-derived exosomes<br/><b>Sponsor</b>: Huazhong University of Science and Technology<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 Nasal Treatment for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Optate; Drug: Placebo<br/><b>Sponsor</b>: Indiana University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ropeginterferon alfa-2b; Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation<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>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>: COVID19 Testing<br/><b>Interventions</b>: Behavioral: FABI tailored COVID-19 testing pamphlet; Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>: Texas Woman’s 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>Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual<br/><b>Sponsor</b>: Universität Duisburg-Essen<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: PF-07817883; Drug: Placebo<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>: China-Japan Friendship Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>: COVID-19; Diagnostic Test<br/><b>Intervention</b>: Device: Lollipop<br/><b>Sponsor</b>: University of Wisconsin, Madison<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>Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination</strong> - <b>Conditions</b>: Vaccine Refusal; COVID-19<br/><b>Interventions</b>: Behavioral: Informational Video; Behavioral: Altruistic Video; Behavioral: Individualistic Video<br/><b>Sponsor</b>: Sir Mortimer B. Davis - Jewish General 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>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Interventions</b>: Drug: Testofen; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: RDC Clinical Pty 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>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>: Healthy; COVID-19; Distress, Emotional<br/><b>Interventions</b>: Behavioral: RASMUS Resilience Training; Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>: Medical University Innsbruck<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>Rehabilitation Treatment of Patients With COVID-19</strong> - <b>Conditions</b>: Rehabilitation; Pneumonia, Viral; COVID-19; Quality of Life<br/><b>Interventions</b>: Other: exercises; Other: massage<br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University; MEDSI Clinical Hospital 1, ICU<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>Addressing Vaccine Acceptance in Carceral Settings Through Community Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: ADVANCE Steering Committee interventions<br/><b>Sponsors</b>: Yale University; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently posed a serious threat to global public health. Harringtonine (HT), as a small-molecule antagonist, has antiviral activity against a variety of viruses. There is evidence that HT can inhibit the SARS-CoV-2 entry into host cells by blocking the Spike protein and transmembrane protease serine 2 (TMPRSS2). However, the molecular mechanism underlying the inhibition effect of HT is largely elusive. Here, docking and all-atom…</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>Neutralization of the new coronavirus by extracting their spikes using engineered liposomes</strong> - The devastating COVID-19 pandemic motivates the development of safe and effective antivirals to reduce morbidity and mortality associated with infection. We developed nanoscale liposomes that are coated with the cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Lentiviral particles pseudotyped with the spike protein of SARS-CoV-2 were constructed and used to test the virus neutralization potential of the engineered liposomes. Under…</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>3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents</strong> - Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity. It was found that GSK3β inhibition by…</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>Sphingosine Kinases Promote Ebola Virus Infection and Can Be Targeted to Inhibit Filoviruses, Coronaviruses, and Arenaviruses Using Late Endocytic Trafficking to Enter Cells</strong> - Entry of enveloped viruses in host cells requires the fusion of viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. These viral fusion proteins need to be triggered by host factors, and for some viruses, this event occurs inside endosomes and/or lysosomes. Consequently, these ‘late-penetrating viruses’ must be internalized and delivered to entry-conducive intracellular vesicles. Because endocytosis and vesicular trafficking…</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>Low Peripheral B-Cell Counts in Patients With Systemic Rheumatic Diseases Due to Treatment With Belimumab and/or Rituximab Are Associated With Low Antibody Responses to Primary COVID-19 Vaccination</strong> - Background: Immunosuppressive agents inhibit COVID-19 vaccine antibody (Ab) responses in patients with systemic rheumatic diseases. Rituximab may fully block Ab responses when B cells become undetected. The effect of detected but low number of B cells due to treatment with a B-cell agent (belimumab and/or rituximab) has not been established. Purpose: We sought to examine whether there is an association between a low number of B cells due to treatment with belimumab and/or rituximab and impaired…</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>Impulsive Neural Control to Schedule Antivirals and Immunomodulators for COVID-19</strong> - New SARS-CoV-2 variants escaping the effect of vaccines are an eminent threat. The use of antivirals to inhibit the viral replication cycle or immunomodulators to regulate host immune responses can help to tackle the viral infection at the host level. To evaluate the potential use of these therapies, we propose the application of an inverse optimal neural controller to a mathematical model that represents SARS-CoV-2 dynamics in the host. Antiviral effects and immune responses are considered as…</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-SARS-CoV-2 Activity of <em>Ampelozizyphus amazonicus</em> (Saracura-Mirá): Focus on the Modulation of the Spike-ACE2 Interaction by Chemically Characterized Bark Extracts by LC-DAD-APCI-MS/MS</strong> - Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents. Ampelozizyphus amazonicus is popularly used in the Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of A. amazonicus, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful…</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>Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application</strong> - The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of Papaver somniferum L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine…</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>Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19: A Computational Molecular Docking and Dynamic Simulation Approach</strong> - Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit…</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>Exploring the Potential Medicinal Benefits of <em>Ganoderma lucidum</em>: From Metabolic Disorders to Coronavirus Infections</strong> - Ganoderma lucidum is a medicinal mushroom that has been traditionally used in Chinese medicine for centuries. It has been found to have a wide range of medicinal properties, including antioxidant, anti-inflammatory, and immune-boosting effects. Recent research has focused on the potential benefits of G. lucidum in treating metabolic disorders such as diabetes and obesity, as well as its possible role in preventing and treating infections caused by the coronavirus. Triterpenoids are a major group…</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 Signaling Pathway of the ADP Receptor P2Y<sub>12</sub> in the Immune System: Recent Discoveries and New Challenges</strong> - P2Y(12) is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y(12) has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y(12) is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies…</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>COVID-19 and Diarylamidines: The Parasitic Connection</strong> - As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of “post-COVID-19 syndrome” and associated…</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>Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection</strong> - The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3’ to 5’ exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions…</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 Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations</strong> - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents….</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>Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir</strong> - The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site. Individual monomers, however, have very low or…</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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