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176 lines
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<title>15 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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<li><strong>Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict</strong> -
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<div>
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The Covid-19 pandemic has decreased resilience, particularly the socio-psychological aspects of many families, including the Ajibarang Subdistrict. This can be seen from the many cases of domestic violence and child marriage occurring in this part of the Banyumas Regency. In order not to continue, this condition needs to be prevented immediately through counseling activities that are appropriate in material and right on target, for both women and men. In other words, counseling must be gender-responsive. In this case, Family Planning Cadres in the village and RW levels play a vital role in helping family planning counselors take preventive measures. Therefore, it would be interesting to study the gender responsivities of family planning counselors. This study aimed to gather information about (1) the phenomenon of family resilience in their area and (2) the gender responsivity of family resilience counseling conducted in the subdistrict. By applying a descriptive qualitative approach, this study gathered data through questionnaires and direct discussions. The data were analyzed using interactive methods. The results showed that during the Covid-19 pandemic, there were a large number of divorced and married children. While counseling was provided to address this issue, the target clients were mostly females. Among the many reasons, cadres only partially understood the concept of gender and never attended training for gender-perspective counseling.
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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/d3eak/" target="_blank">Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict</a>
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</div></li>
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<li><strong>Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses</strong> -
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<div>
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Differences in host ACE2 genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different Rhinolophus bat species, and show that these two spikes have different tropisms for Rhinolophus bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different Rhinolophus bat ACE2 proteins.
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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/10.1101/2023.04.13.536832v1" target="_blank">Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses</a>
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</div></li>
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<li><strong>A scoping review on the use and acceptability of preprints</strong> -
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<div>
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Background: Preprints are open and accessible scientific manuscript or report that has not been submitted to a peer reviewed journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The purpose of this scoping review was to explore the current evidence on the use and acceptability of preprints by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
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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/nug4p/" target="_blank">A scoping review on the use and acceptability of preprints</a>
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</div></li>
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<li><strong>The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review</strong> -
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<div>
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Background: “Vaccine hesitancy” (VH) has been described as a “threat to global health”, especially in the COVID-19 era. Research on VH indicates that the concerns of vaccine recipients with the balance of risks and benefits of COVID-19 vaccination, which involve safety and effectiveness considerations (hereafter “safety concerns”), are a leading driver of VH. However, what explains these concerns is underexplored. Goal: We conducted a qualitative umbrella review following PRISMA guidelines and informed by a critical perspective to examine how the safety concerns of COVID-19 vaccine recipients are addressed in the VH literature. Methods: We searched PubMed, the Epistemonikos COVID-19 platform (COVID-19 L. OVE), and the WHO Global Research on COVID-19 Database. We included 49 refereed reviews examining VH in any population involved with COVID-19 vaccination decisions for themselves or as caretakers, with no methodological, quality, temporal, or geographic restrictions, and were published in English, excluding those that authors did not identify as “systematic”. Two reviewers completed article screening and data extraction and synthesis. Thematic synthesis was used to identify themes and frequencies were calculated to assess the strength of support for themes. Disagreements were resolved through full team discussion. The protocol was registered with PROSPERO (ID CRD42022351489) and partially funded by a SSHRC grant (# 435-2022-0959). Findings: All reviews assumed that VH was a major barrier to ending the COVID-19 crisis. With vaccines assumed to be “safe and effective”, recipients’ safety concerns were downplayed. Evidence incompatible with “VH-as-a-problem”, whenever mentioned, was dismissed as “misinformation”. Informed consent was either not discussed or was presented as a potential threat to “vaccine confidence”. We observed no differences regardless of study population, methodology, or other study characteristics. Limitations are discussed. Conclusions: Neglecting or dismissing vaccine recipients’ safety concerns contributes to the problem that research on COVID-19 VH purports to address. It also undermines the implementation of informed consent, critical to ethical medical and public health research, policy, and practice. The scant attention to bioethical considerations in current COVID-19 VH research is concerning.
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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/r9xs7/" target="_blank">The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review</a>
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</div></li>
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<li><strong>SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</strong> -
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<div>
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SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on antigen presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. This downregulation of CIITA is independent of NSP5’s proteolytic activity, and rather, NSP5 delivers HDAC2 to the CIITA promoter via an IRF3-dependent mechanism. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 can limit MHC II expression, thereby delaying or weakening the subsequent adaptive immune response.
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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/10.1101/2023.02.10.528032v2" target="_blank">SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</a>
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</div></li>
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<li><strong>The airborne transmission of viruses causes tight transmission bottlenecks</strong> -
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<div>
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The transmission bottleneck describes the number of viral particles that found an infection in a new host. Previous studies have used genome sequence data to suggest that transmission bottlenecks for influenza and SARS-CoV-2 involve few viral particles, but the general principles underlying these bottlenecks are not fully understood. Here we show that, across a broad range of circumstances, tight transmission bottlenecks arise as a consequence of the physical process underlying airborne viral transmission. We use a mathematical model to describe the process of infectious particles being emitted by an infected individual and inhaled by others nearby. The extent to which exposure to particles translates into infection is determined by an effective viral load, which is calculated as a function of the epidemiological parameter R0. Across multiple scenarios, including those present at a superspreading event, our model suggests that the great majority of transmission bottlenecks involve few viral particles, with a high proportion of infections being caused by a single viral particle. Our results provide a physical explanation for previous inferences of bottleneck size and predict that tight transmission bottlenecks prevail more generally in respiratory virus transmission.
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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/10.1101/2023.04.14.536864v1" target="_blank">The airborne transmission of viruses causes tight transmission bottlenecks</a>
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</div></li>
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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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<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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<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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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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🖺 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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<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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🖺 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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<li><strong>Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab</strong> -
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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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🖺 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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<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>Sponsors</b>: Huazhong University of Science and Technology; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<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>Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19</strong> - <b>Condition</b>: Omicron Variant of COVID-19<br/><b>Intervention</b>: Drug: Nirmatrelvir/Ritonavir<br/><b>Sponsor</b>: Xiangao Jiang<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>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>To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<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>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>Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: PS23 heat-treated<br/><b>Sponsors</b>: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.<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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</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>Synthesis, cytotoxicity, and pharmacokinetic evaluations of niclosamide analogs for anti-SARS-CoV-2</strong> - Niclosamide, an oral anthelmintic drug, could inhibit SARS-CoV-2 virus replication through autophagy induction, but high cytotoxicity and poor oral bioavailability limited its application. Twenty-three niclosamide analogs were designed and synthesized, of which compound 21 was found to exhibit the best anti-SARS-CoV-2 efficacy (EC(50) = 1.00 μM for 24 h), lower cytotoxicity (CC(50) = 4.73 μM for 48 h), better pharmacokinetic, and it was also well tolerated in the sub-acute toxicity study in…</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>Characterization of the induction kinetics and antiviral functions of IRF1, ISG15 and ISG20 in cells infected with gammacoronavirus avian infectious bronchitis virus</strong> - Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics…</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>In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease</strong> - The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could…</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>AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity <em>In Vitro</em></strong> - SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp’s, making it essential for viral replication and has been successfully targeted…</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>Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis</strong> - Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely…</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>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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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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