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188 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>29 October, 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>Streamlined DNA template preparation and co-transcriptional 5’ capped RNA synthesis enabled by solid-phase catalysis</strong> -
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<div>
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The success of SARS-CoV-2 mRNA vaccines demonstrated that rapid, large-scale manufacturing of synthetic mRNA is necessary for an effective and timely response to a pandemic. Innovations in areas such as template design and manufacturing processes are being implemented to facilitate more simple, cost-effective and scalable mRNA synthesis. In this study, for the first time, we demonstrate that the enzymatic steps in mRNA production (including DNA template linearization, RNA synthesis, 5' capping and methylation) can be carried out using enzymes immobilized to a solid support. Specifically, we demonstrate efficient IVT template DNA linearization using immobilized BspQI, where the linearized template DNA can be directly used in IVT without the need of purification. We also showed that immobilized T7 RNA polymerase, Faustovirus RNA capping enzyme (FCE), vaccinia cap 2'-O-methyltransfease (2'OMTase) and a novel FCE::T7RNAP fusion enable efficient enzymatic synthesis of Cap-1 RNA in a one-pot format. This solid-phase enzymatic platform may enable highly efficient, seamless and continuous mRNA synthesis workflows that minimizes sample loss and units of operation in biopharmaceutical manufacturing.
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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/10.1101/2023.10.28.564520v1" target="_blank">Streamlined DNA template preparation and co-transcriptional 5’ capped RNA synthesis enabled by solid-phase catalysis</a>
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</div></li>
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<li><strong>Exploring the Accuracy of Differentiation-Based Regressive Models in Disease Forecasting</strong> -
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Predictive models have been able to foresee outbreaks of mosquito-borne diseases such as malaria and map Ebola outbreaks. This has allowed health organizations to plan the amount of resources and the number of healthcare workers n eeded more effectively, on top of finding out other useful data such as the locations most vulnerable to the disease and the demographics most affected. It can therefore be assumed that predictive analytics can reduce the amount of economic and non-economic burden caused by other epidemics as well, with COVID-19 being an obvious example.
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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/10.1101/2023.10.26.23297654v1" target="_blank">Exploring the Accuracy of Differentiation-Based Regressive Models in Disease Forecasting</a>
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</div></li>
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<li><strong>Loneliness Online: Social media interaction decreased loneliness in young adults during recommended social isolation.</strong> -
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<div>
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The recent COVID-19 pandemic and periods of recommended social isolation has led to a rise in questions regarding the role of Social media as a mean of limiting feelings of loneliness. Loneliness is described as a disparity between an individual’s desired social relations and their present relations and while social media supports in building social connections, there is limited understanding of loneliness in relation to social media use, especially in the Middle East. Taking these contexts into consideration, the current study hypothesized that greater social media addiction, increased passive browsing, decreased interaction such as posting and tagging friends, and broadcasting such as status updates and going live would significantly increase loneliness in young adults during the pandemic in the UAE. In order to test this, data was collected online from 177 young adults in the UAE during recommended social isolation, and was analysed using hierarchical regression. Results indicated that only social media interaction significantly decreased feelings of loneliness amongst the participants. Browsing, broadcasting, and addiction however did not significantly impact levels of loneliness in young adults during recommended social isolation, which contradicts the majority of the past findings. The findings show that interactions with others on social media facilitate much needed connections, especially during a health emergency and recommended isolation.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/b549s/" target="_blank">Loneliness Online: Social media interaction decreased loneliness in young adults during recommended social isolation.</a>
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</div></li>
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<li><strong>Echocardiographic characterisation in severe Covid-19 with respiratory failure - an observational study.</strong> -
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Objective: We aimed to investigate cardiac effects of severe SARS-CoV-2 and the importance of echocardiography-assessment and biomarkers. Methods: This is an observational study of the first patients admitted to intensive care due to SARS-CoV-2-respiratory failure. Thirty-four underwent echocardiography of which twenty-five were included, compared to forty-four non-echo patients. Exclusion was based on absence of normofrequent sinus rhythm and/or mechanical respiratory support. Biomarkers were analysed on clinical indication. Results: Mortality was higher in the echo- compared to non-echo group (44 % vs. 16%, p<0.05). Right-sided parameters were not under significant strain. Tricuspid valve regurgitation velocity indicated how increased pulmonary pressure was associated with mortality (survivors: 2.51 +/- 0.01 m/s vs. non-survivors: 3.06 +/- 0.11 m/s, p<0.05), before multiple comparison-correction. Setting cut-off for pulmonary hypertension to 2.8 m/s generated p<0.01 using frequency distribution testing. Cardiac markers, high sensitivity cardiac troponin I and N-terminal pro brain natriuretic peptide, and D-dimer were higher in the echocardiography group. (hs-TnI (ng/L): echo : 133 +/- 45 vs. non-echo: 81.3 +/- 45, p<0.01; NT-proBNP (ng/L): echo: 2959 +/- 573 vs. non-echo: 1641 +/- 420, p<0.001; D-dimer (mg/L): echo: 16.1 +/- 3.7 vs. non-echo: 6.1 +/- 1.5, p<0.01) and non-survivor group (hs-TnI (ng/L): survivors: 59.1 +/- 21 vs. non-survivors: 211 +/- 105, p<0.0001; NT-proBNP (ng/L): survivors: 1310 +/- 314 vs. non-survivors: 4065 +/- 740, p<0.0001; D-dimer (mg/L): survivors: 7.2 +/- 1.5 vs. non-survivors: 17.1 +/- 4.8, p<0.01). Tricuspid regurgitation velocity was positively correlated with cardiac troponin I (r=0.93, r2=0.74, p<0.001). Conclusions: These results suggest there is no negative effect on cardiac function in critical SARS-CoV-2. Pulmonary pressure appears higher amongst non-survivors indicating pulmonary disease as the driver of mortality. Echocardiography was more commonly performed in the non-survivor group, and cardiac biomarkers as well as D-dimer was higher in the non-survivor group suggesting they carry negative prognostic values.
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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/10.1101/2023.10.27.23297666v1" target="_blank">Echocardiographic characterisation in severe Covid-19 with respiratory failure - an observational study.</a>
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</div></li>
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<li><strong>Mental health conditions and COVID-19 vaccine outcomes: a scoping review</strong> -
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Background: The COVID-19 pandemic has had a profound impact on the mental health of people worldwide. Mental health also impacts on physical health. In the context of viral illnesses, viral challenge studies have shown that indices of mental health are associated with susceptibility to viral infections, including coronaviruses. Research conducted during the pandemic has shown that people with a history of mental health conditions were at increased risk of infection, hospitalisation, and mortality. However, the relationship between mental health conditions and vaccine outcomes such as vaccine intentions, uptake, and vaccine breakthrough is not yet well-understood. Methods: We conducted a systematic search on the topics of COVID-19 vaccine intentions, vaccine uptake, and vaccine breakthrough, in relation to mental health conditions, in four databases: PubMed, MEDLINE, SCOPUS, and PsychINFO, as well as the publication lists of Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), OpenSAFELY, and QResearch. Inclusion criteria focus on studies reporting either of the aforementioned COVID-19 vaccine outcomes among people with mental health conditions. Results: Thirty-three out of 251 publications met our inclusion criteria for this review. Overall, the evidence is inconclusive regarding the level of intention to accept the COVID-19 vaccine among people with mental health conditions. However, people with mental health conditions were more likely to have lower uptake of the COVID-19 vaccine, compared to people without. Common barriers to COVID-19 vaccine uptake include concerns about the safety, effectiveness, and side effects of the vaccines. Limited evidence also suggests that vaccine breakthrough may be a particular risk for those with substance use disorder. Conclusions: Our findings revealed a possible intention-behaviour gap for receiving the COVID-19 vaccine among people with mental health conditions, yielding interventions to encourage vaccine uptake in this population. There is also the need to enhance our understanding of COVID-19 vaccine breakthrough in people with mental health conditions.
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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/10.1101/2023.10.27.23297663v1" target="_blank">Mental health conditions and COVID-19 vaccine outcomes: a scoping review</a>
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</div></li>
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<li><strong>ChineseCVD: first-in-world, web-based, Chinese-specific Cardiovascular Risk Calculator incorporating long COVID, COVID-19 vaccination, SGLT2i and PCSK9i treatment effects</strong> -
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Background: Web-based risk prediction tools for cardiovascular diseases are crucial for providing rapid risk estimates for busy clinicians, but there is none available specifically for Chinese subjects. This study developed ChineseCVD, first-in-world web-based Chinese-specific Cardiovascular Risk Calculator incorporating long COVID, COVID-19 vaccination, SGLT2i and PCSK9i treatment effects. Methods: Adult patients attending government-funded family medicine clinics in Hong Kong between 1st January 2000 and 31st December 2003 were included. The primary outcome was major adverse cardiovascular events (MACE) defined as a composite of myocardial infarction, heart failure, transient ischaemic attacks/ischaemic strokes, and cardiovascular mortality. Results: A total of 155,066 patients were used as the derivation cohort. Over a median follow-up of 16.1 (11.6-17.8) years, 31,061 (20.44%) had MACE. Cox regression identified male gender, age, comorbidities, cardiovascular medications, systolic and diastolic blood pressure, and laboratory test results (neutrophil-lymphocyte ratio, creatinine, ALP, AST, ALT, HbA1c, fasting glucose, triglyceride, LDL and HDL) as significant predictors of the above outcomes. ChineseCVD further incorporates the impact of smoking status, COVID-19 infection, number of COVID-19 vaccination doses, and modifier effects of newest medication classes of PCSK9i and SGLT2i. The calculator enables clinicians to demonstrate to patients how risks vary with different medications. Conclusions: The ChineseCVD risk calculator enables rapid web-based risk assessment for adverse cardiovascular outcomes, thereby facilitating clinical decision-making at the bedside or in the clinic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.27.23297656v1" target="_blank">ChineseCVD: first-in-world, web-based, Chinese-specific Cardiovascular Risk Calculator incorporating long COVID, COVID-19 vaccination, SGLT2i and PCSK9i treatment effects</a>
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</div></li>
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<li><strong>Complement dysregulation is a predictive and therapeutically amenable feature of long COVID</strong> -
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Background: Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID. Methods: We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID. Findings: Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785. Conclusions: These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID. Funding: This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297597v1" target="_blank">Complement dysregulation is a predictive and therapeutically amenable feature of long COVID</a>
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<li><strong>Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development</strong> -
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Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the toll-like receptors (TLRs), B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.26.564184v1" target="_blank">Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development</a>
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<li><strong>Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant</strong> -
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During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre- and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.26.564259v1" target="_blank">Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant</a>
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<li><strong>Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies</strong> -
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A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.26.564289v1" target="_blank">Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies</a>
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<li><strong>Eviction Moratorium Litigation: What Courts Said, and What Courts Missed</strong> -
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In 2020, federal, state, and local governments imposed eviction moratoriums to prevent mass homelessness and limit the spread of COVID-19. Landlords responded to this unprecedented action by filing lawsuits around the country. This Article analyzes the litigation. It examines the claims of landlords, defenses raised by the government, and how courts dealt with each of them. It also highlights the ways that courts misunderstand the rental market and devalue tenants. The Article shows that, before the Supreme Court intervened in mid-2021, most landlord suits failed, either because courts rejected their claims or governments ran out the clock, demonstrating that mass eviction moratoriums can protect the most vulnerable in times of crisis.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/zumw2/" target="_blank">Eviction Moratorium Litigation: What Courts Said, and What Courts Missed</a>
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<li><strong>Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</strong> -
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Background. Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with long-term kidney dysfunction are yet unexplored. Methods. In patients hospitalized with SARS-CoV2, we performed bulk RNA sequencing using peripheral blood mononuclear cells (PBMCs). We applied linear models accounting for technical and biological variability on RNA-Seq data accounting for false discovery rate (FDR) and compared the functional enrichment and pathway results to a historical sepsis-AKI cohort. Finally, we evaluated the association of these signatures with long-term trends in kidney function. Results. Of 283 patients, 106 had AKI. After adjustment for sex, age, mechanical ventilation, and chronic kidney disease (CKD), we identified 2635 significant differential gene expressions at FDR<0.05. Top canonical pathways were EIF2 signaling, oxidative phosphorylation, mTOR signaling, and Th17 signaling, indicating mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Comparison with sepsis associated AKI showed considerable overlap of key pathways (48.14%). Using follow-up estimated glomerular filtration rate (eGFR) measurements from 115 patients, we found that 164/2635 (6.2%) of the significantly differentiated genes were associated with overall decrease in long-term kidney function. The strongest associations were autophagy, renal impairment via fibrosis and cardiac structure/function. Conclusions. We show that AKI in SARS-CoV2 is a multifactorial process with mitochondrial dysfunction driven by ER stress whereas long-term kidney function decline is associated with cardiac structure and function, and immune dysregulation. Functional overlap with sepsis-AKI also highlights common signatures indicating generalizability in therapeutic approaches.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.25.23297469v2" target="_blank">Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection</a>
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<li><strong>Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data</strong> -
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Infections with SARS-CoV-2 and influenza are associated with acute and post-acute complications and sequelae of many organ systems (i.e., disease burden). It is important to understand the global disease burden that associates with and follows acute infection in order to establish preventive and therapeutic strategies and to reduce the use of health resources and improve patient health outcomes. To address these questions, we utilized the National Covid Cohort Collaborative, which is an integrated and harmonized data repository of electronic health record data in the USA. From this database, we included in analysis 346,648 eligible SARS-CoV-2-infected patients, 78,086 eligible influenza infected patients, and 146,635 uninfected controls. We describe the disease burden that extends over 2-3 months following infection, and we quantify the reduction of disease burden by treatment. We identify a burden of disease following medically attended influenza that is comparable to that of medically attended SARS-CoV-2 infection. However, in contrast to SARS-CoV-2, influenza acute infection and disease burden are not responsive to antiviral treatment and thus remain as an unmet medical need. Focusing therapeutic strategies solely on the short-term management of acute infection may also underestimate the extended health benefits of antiviral treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297626v2" target="_blank">Comparative Organ Disease Burden and Sequelae of Influenza and SARS-CoV-2 Infection: An Observational Study Using Real-World Data</a>
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<li><strong>Sort-Seq: immune repertoire-based scRNA-Seq systematization</strong> -
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The functional programs chosen by B and T cell clones fundamentally determine the architecture of immune response to distinct challenges. Advances in scRNA-Seq have improved our understanding of the diversity and stability of these programs, but it has proven difficult to link this information with known lymphocyte subsets. Here, we introduce Sort-Seq, an immune repertoire-based method that allows exact positioning of phenotypically defined lymphocyte subsets within scRNA-Seq data. Sort-Seq outperformed CITE-Seq for accurate mapping of the classical CD4+ T helper (Th) cell subsets (Th1, Th1-17, Th17, Th22, Th2a, Th2, and Treg), offering a more powerful approach to the surface phenotype-based scRNA-Seq classification of adaptive lymphocyte subpopulations. Using integrated scRNA-Seq, Sort-Seq, and CITE-Seq data from 122 donors, we provide a comprehensive Th cell scRNA-Seq reference map. Exploration of this dataset revealed the low plasticity and extreme sustainability of the Th17, Th22, Th2, and Th2a cell programs over years. We also develop Cultivation-based Antigen-specific T cell identificatoR in Replicates (CultivAToRR), which identified >80 SARS-CoV-2-specific CD4+ TCR{beta} clonotypes in a single donor across a wide frequency range. We complemented these results with frequency-based capturing of COVID-19-responsive clonotypes and screening against known SARS-CoV-2-specific TCRs. Positioning within the annotated scRNA-Seq map revealed functional subtypes of Th cell clones involved in primary and secondary responses against SARS-CoV-2. The ability to capture low-frequency antigen-specific T cell clones in combination with Sort-Seq-based scRNA-Seq annotation creates an integral pipeline that links challenge-responsive clones with their exact functional subtypes, providing a solid foundation for investigating T cell roles in healthy and pathological immune responses and vaccine development.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.24.563704v1" target="_blank">Sort-Seq: immune repertoire-based scRNA-Seq systematization</a>
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<li><strong>Cost-effectiveness analysis of COVID-19 booster doses and oral antivirals in the Indo-Pacific</strong> -
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Background: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. Methods: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using 3% discounting for ongoing costs and health benefits. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. Findings: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic ($25 United States Dollars) or middle-income reference price ($250 United States Dollars); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. Interestingly, the cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. Conclusions: Our results support that government funded COVID-19 booster programs continue to be cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of $250 USD per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.26.23297613v1" target="_blank">Cost-effectiveness analysis of COVID-19 booster doses and oral antivirals in the Indo-Pacific</a>
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</div></li>
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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>Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19; Coronavirus <br/><b>Interventions</b>: Device: eBAM Cov Testing <br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: EG-COVII <br/><b>Sponsors</b>: EyeGene Inc. <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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <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>Long COVID Brain Fog: Cognitive Rehabilitation Trial</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Impairment; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Speed of Processing Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: In-lab Brain Health Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Peer Mentoring <br/><b>Sponsors</b>: University of Alabama at Birmingham; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Paradoxical Response to Chest Wall Loading in Mechanically Ventilated Patients</strong> - <b>Conditions</b>: ARDS; COVID-19; Mechanical Ventilation Pressure High; Ventilator-Induced Lung Injury <br/><b>Interventions</b>: Diagnostic Test: Manual loading of the chest wall <br/><b>Sponsors</b>: HealthPartners Institute <br/><b>Withdrawn</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 Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment <br/><b>Sponsors</b>: Chinese University of Hong Kong <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>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro 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>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Inspiratory Muscle Training in People With Long COVID-19- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea 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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <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>COVID Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <br/><b>Active, not recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination</strong> - CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.</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>Neurotoxic effects of chloroquine and its main transformation product formed after chlorination</strong> - Pharmaceutical transformation products (TPs) generated during wastewater treatment have become an environmental concern. However, there is limited understanding regarding the TPs produced from pharmaceuticals during wastewater treatment. In this study, chloroquine (CQ), which was extensively used for treating coronavirus disease-19 (COVID-19) infections during the pandemic, was selected for research. We identified and fractionated the main TP produced from CQ during chlorine disinfection and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of Pan-Anti-SARS-CoV-2 Agents through Allosteric Inhibition of nsp14/nsp10 Complex</strong> - SARS-CoV-2 nsp14 functions both as an exoribonuclease (ExoN) together with its critical cofactor nsp10 and as an S-adenosyl methionine-dependent (guanine-N7) methyltransferase (MTase), which makes it an attractive target for the development of pan-anti-SARS-CoV-2 drugs. Herein, we screened a panel of compounds (and drugs) and found that certain compounds, especially Bi(III)-based compounds, could allosterically inhibit both MTase and ExoN activities of nsp14 potently. We further demonstrated…</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>Unraveling bioactive metabolites of mangroves as putative inhibitors of SARS-CoV-2 Mpro and RBD proteins: molecular dynamics and ADMET analysis</strong> - COVID-19 is a deadly pandemic caused by Corona virus leading to millions of deaths worldwide. Till today no medicine was available to cure this disease. This study selected 262 potential bioactive natural products derived from mangroves to inhibit the main protease (Mpro) and receptor-binding domain (RBD) protein of the COVID-19 virus. All the ligands were subjected to Adsorption Digestion Metabolism Excretion and Toxicity (ADMET) predictions and docking studies using AutodockVina. Among all the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of Co-Administered Omicron BA.4/BA.5 Bivalent COVID-19 and Quadrivalent Seasonal Influenza Vaccines in Israel during the 2022-2023 Winter Season</strong> - Vaccination against COVID-19 and influenza provides the best defense against morbidity and mortality. Administering both vaccines concurrently may increase vaccination rates and reduce the burden on the healthcare system. This study evaluated the immunogenicity of healthcare workers in Israel who were co-administered with the Omicron BA.4/BA.5 bivalent COVID-19 vaccine and the 2022-2023 quadrivalent influenza vaccine. SARS-CoV-2 neutralizing antibody titers were measured via microneutralization…</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>Longitudinal Analysis of SARS-CoV-2-Specific Cellular and Humoral Immune Responses and Breakthrough Infection following BNT162b2/BNT162b2/BNT162b2 and ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naive Healthcare Workers</strong> - Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13-15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate…</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>RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis</strong> - Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that induces diarrhea and death in neonatal piglets, resulting in substantial economic losses to the global swine industry. The mechanisms of PEDV infection and the roles of host factors are still under exploration. In this study, we used the ferroptosis pathway downstream target activator (1S,3R)-RSL3 compound as a starting point, combined with the interactions of N-acetylcysteine and deferoxamine, to elucidate the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacokinetic and Pharmacodynamic Analysis of the 3CL Protease Inhibitor Ensitrelvir in a SARS-CoV-2 Infection Mouse Model</strong> - The small-molecule antiviral drug ensitrelvir targets the 3C-like protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study evaluated its inhibitory effect on viral replication in a delayed-treatment mouse model and investigated the relationship between pharmacokinetic (PK) parameters and pharmacodynamic (PD) effects. SARS-CoV-2 gamma-strain-infected BALB/c mice were orally treated with various doses of ensitrelvir starting 24 h post-infection. Effectiveness was…</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>Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells</strong> - The utility of human neuroblastoma cell lines as in vitro model to study neuro-invasiveness and neuro-virulence of SARS-CoV-2 has been demonstrated by our laboratory and others. The aim of this report is to further characterize the associated cellular responses caused by a pre-alpha SARS-CoV-2 strain on differentiated SH-SY5Y and to prevent its cytopathic effect by using a set of entry inhibitors. The susceptibility of SH-SY5Y to SARS-CoV-2 was confirmed at high multiplicity-of-infection,…</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 Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry</strong> - Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed…</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>Extracellular Vesicles as a Translational Approach for the Treatment of COVID-19 Disease: An Updated Overview</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in the years 2020-2022. With a high prevalence, an easy route of transmission, and a long incubation time, SARS-CoV-2 spread quickly and affected public health and socioeconomic conditions. Several points need to be elucidated about its mechanisms of infection, in particular, its capability to evade the immune system and escape from neutralizing antibodies. Extracellular vesicles (EVs) are phospholipid…</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-Viral Activity of Bioactive Molecules of Silymarin against COVID-19 via In Silico Studies</strong> - The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection drove the global coronavirus disease 2019 (COVID-19) pandemic, causing a huge loss of human life and a negative impact on economic development. It is an urgent necessity to explore potential drugs against viruses, such as SARS-CoV-2. Silymarin, a mixture of herb-derived polyphenolic flavonoids extracted from the milk thistle, possesses potent antioxidative, anti-apoptotic, and anti-inflammatory properties. Accumulating…</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>Galangal-Cinnamon Spice Mixture Blocks the Coronavirus Infection Pathway through Inhibition of SARS-CoV-2 M<sup>Pro</sup>, Three HCoV-229E Targets; Quantum-Chemical Calculations Support In Vitro Evaluation</strong> - Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal-cinnamon mixture in the inhibition of SARS-CoV-2’s different protein targets. The potential antiviral effect of galangal-cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition…</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>Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States</strong> - Despite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and saturated (holo-bLf) forms, has been shown to exert broad-spectrum antiviral activity against many viruses. In this study, we evaluated the efficacy of both forms of bLf at 1 mg/mL against infection of…</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>PANoptosis: Mechanism and Role in Pulmonary Diseases</strong> - PANoptosis is a newly defined programmed cell death (PCD) triggered by a series of stimuli, and it engages three well-learned PCD forms (pyroptosis, apoptosis, necroptosis) concomitantly. Normally, cell death is recognized as a strategy to eliminate unnecessary cells, inhibit the proliferation of invaded pathogens and maintain homeostasis; however, vigorous cell death can cause excessive inflammation and tissue damage. Acute lung injury (ALI) and chronic obstructive pulmonary syndrome (COPD)…</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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