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178 lines
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<title>08 September, 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>The COVID-19 Mortality Paradox (Africa versus USA & Israel): An Egyptian Tale of Honor</strong> -
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The sum of the ongoing COVID-19 mortality in 55 African countries, including the elderly and patients suffering from multiple co-morbidities, were almost 4.5x lower than USA despite that over 4.2x more people live in Africa. Moreover, this similar mortality paradox is quite evident when you compare the heavily populated (over 216 millions), poorly vaccinated, poorly “mandated” Nigeria to the small (less than 10 millions), highly vaccinated and strictly mandated Israel to find almost 4x lower COVID mortality in Nigeria. In this perspective, I explain how this paradox evolved from a personal point of view gained from my academic, clinical and social experience while perfectly using the Egyptian immune-modulatory Kelleni’s protocol to manage pediatric, geriatric, pregnant and immune-compromised COVID-19 patients including many suffering multiple comorbidities since April 2020. It’s very unfortunate that SARS CoV-2 is still evolving and COVID-19 losses are undergoing, however in Africa, we enjoy a life free of anxiety or mandates, and this perspective represents an Egyptian medical tale of honor explaining how we trusted science through adopting early treatment using safe, effective and generic repurposed drugs that saved all COVID-19 patients unless a minority previously managed with the westerly adopted protocols.
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🖺 Full Text HTML: <a href="https://osf.io/5txdu/" target="_blank">The COVID-19 Mortality Paradox (Africa versus USA & Israel): An Egyptian Tale of Honor</a>
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</div></li>
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<li><strong>Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines</strong> -
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<b>Background:</b> Subvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. <b>Methods:</b> In this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-µg doses of mRNA-1273.815 monovalent (50-µg omicron XBB.1.5 spike mRNA) or mRNA-1273.231 bivalent (25-µg omicron XBB.1.5 and 25-µg omicron BA.4/BA.5 spike mRNAs) vaccines, administered as 5th doses, to adults who previously received a primary series and 3rd dose of an original mRNA coronavirus disease 2019 (Covid-19) vaccine, and a 4th dose of a bivalent (omicron BA.4/BA.5 and original SARS-CoV-2) vaccine. Interim safety and immunogenicity data 15 days post-vaccination are presented. <b>Results:</b> In April 2023, participants received mRNA-1273.815 (n=50) and mRNA-1273.231 (n=51). The median intervals from the prior dose of BA.4/BA.5-containing bivalent vaccine were 8.2 and 8.3 months for the mRNA-1273.815 and mRNA-1273.231 groups, respectively. Both vaccines increased neutralizing antibody (nAb) geometric mean titers against all variants tested at day 15 post-booster nAb compared to pre-booster levels. Geometric mean fold-rises from pre-booster titers after the monovalent booster were numerically higher against XBB.1.5, XBB.1.16 and SARS-CoV-2 (D614G) than those of the bivalent booster and were comparable against BA.4/BA.5 and BQ1.1 variants for both vaccines. The monovalent vaccine also elicited nAb responses against omicron XBB.2.3.2, EG.5.1, FL.1.5.1 and BA.2.86 that were similar to those against XBB.1.5 in a subset (n=20) of participants. The occurrence of solicited adverse reactions and unsolicited adverse events were overall similar to those previously reported for the original mRNA-1273 50-µg and omicron BA.4/BA.5-containing bivalent mRNA-1273 vaccines. <b>Conclusion:</b> In this interim analysis, XBB.1.5-containing monovalent and bivalent vaccines elicited potent neutralizing responses against variants of the omicron XBB-lineage (XBB.1.5, XBB.1.6, XBB.2.3.2, EG.5.1, and FL.1.5.1) as well as the recently emerged BA.2.86 variant. The safety profile of the XBB.1.5-containing vaccine was consistent with those of prior vaccines. These results overall indicate that the XBB.1.5-containing mRNA-1273.815 vaccine has the potential to provide protection against these emerging variants and support the Covid-19 vaccine update in 2023-2024 to a monovalent XBB.1.5-containing vaccine.
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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/10.1101/2023.08.22.23293434v2" target="_blank">Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines</a>
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</div></li>
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<li><strong>The public health impact of Paxlovid COVID-19 treatment in the United States</strong> -
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The antiviral drug Paxlovid has been shown to rapidly reduce viral load. Coupled with vaccination, timely administration of safe and effective antivirals could provide a path towards managing COVID-19 without restrictive non-pharmaceutical measures. Here, we estimate the population-level impacts of expanding treatment with Paxlovid in the US using a multi-scale mathematical model of SARS-CoV-2 transmission that incorporates the within-host viral load dynamics of the Omicron variant. We find that, under a low transmission scenario (Re~1.2) treating 20% of symptomatic cases with Paxlovid would be life and cost saving, leading to an estimated 0.26 (95% CrI:0.03, 0.59) million hospitalizations averted, 30.61 (95% CrI:1.69, 71.15) thousand deaths averted, and US$52.16 (95% CrI:2.62, 122.63) billion reduction in the US. Rapid and broad use of the antiviral Paxlovid could substantially reduce COVID-19 morbidity and mortality, while averting socioeconomic hardship.
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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/10.1101/2023.06.16.23288870v2" target="_blank">The public health impact of Paxlovid COVID-19 treatment in the United States</a>
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</div></li>
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<li><strong>SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant: Preclinical Study in Cynomolgus Macaques</strong> -
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<div>
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Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals; control (just 400 g poly(I:C) per head); low dose (30 g RBD and 400 g poly(I:C) per head); and high dose (150 g RBD and 400 g poly(I:C) per head), respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.21.508816v3" target="_blank">SARS-CoV-2 Sublingual Vaccine with RBD Antigen and Poly(I:C) Adjuvant: Preclinical Study in Cynomolgus Macaques</a>
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<li><strong>The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Fall 2023 vaccines in the United States</strong> -
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Objectives: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for Fall 2023 in adults ≥18 years over a 1-year analytic time horizon (September 2023-August 2024). Methods: A compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 in summer 2023. Numbers of symptomatic infections, COVID-19 related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA Fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech Fall 2023 vaccines were examined. Results: Base case results suggest the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to No Vaccine, yielding an ICER of $7,700 per QALY gained. Using a societal cost perspective, the ICER is $2,100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates and costs drive cost-effectiveness. With a relative vaccine effectiveness (rVE) of Moderna versus Pfizer-BioNTech of 5.1% for infection and 9.8% for hospitalization, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3,300 more deaths than the Pfizer-BioNTech vaccine. Limitations and Conclusions: As COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. Vaccine effectiveness of Fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, the Moderna Fall 2023 vaccine can be considered cost-effective relative to no vaccine.
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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/10.1101/2023.09.05.23295085v1" target="_blank">The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Fall 2023 vaccines in the United States</a>
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<li><strong>Hydroxychloroquine and Zinc ameliorate interleukin-6 associated hepato-renal toxicity induced by Aspergillus fumigatus in experimental models</strong> -
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<div>
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In Nigeria, immunocompromised persons, particularly those living with HIV, are at an increased risk of developing invasive pulmonary aspergillosis caused by Aspergillus fumigatus. Interestingly, this condition produces symptoms that can be easily mistaken for those of COVID-19. To better understand the pathophysiology of Aspergillosis and determine the therapeutic and toxic effects of Zinc and HCQ, this study examined liver and renal functions in experimental models. This experimental study included 28 Albino rats, assigned into 7 Groups (n= 4 each); designated A to G. Group A received the standardized rat chow and distilled water only. Group B received a moderate dose of HCQ only. Group C received A. fumigatus suspension (AFS) without any treatments. Group D simultaneously received AFS and a low dose of HCQ. Group E simultaneously received AFS and a moderate dose of HCQ. Group F simultaneously received AFS and a high dose of HCQ. Group G simultaneously received AFS and a moderate dose of HCQ and Zinc. Serum levels of interleukins (IL)-6 and 10, liver enzymes, and renal parameters were measured accordingly. The lungs, liver, and kidneys were excited and weighed. Significance was set at p< 0.05. Higher levels of serum alanine transaminase, creatinine, and urea and lower relative lung weight were observed in group C compared with other groups (p< 0.001). Higher IL-6 levels and IL-6/IL-10 ratio were also observed in group C compared with other groups (p> 0.05). In conclusion, this study revealed that HCQ and Zinc ameliorate oxidative stress and damage induced by A. fumigatus.
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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/10.1101/2023.09.05.556428v1" target="_blank">Hydroxychloroquine and Zinc ameliorate interleukin-6 associated hepato-renal toxicity induced by Aspergillus fumigatus in experimental models</a>
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<li><strong>The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells</strong> -
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The COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, and has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. The aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-PCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of -globin and {gamma}-globin mRNA accumulation. Inhibition of accumulation of {zeta}-globin and {varepsilon}-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.07.556634v1" target="_blank">The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells</a>
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<li><strong>The molecular reach of antibodies determines their SARS-CoV-2 neutralisation potency</strong> -
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Antibodies play crucial roles in health and disease and are invaluable tools for diagnostics, research, and therapy. Although antibodies bind bivalently, we lack methods to analyse bivalent binding. Here, we introduce a particle-based model and use it to analyse bivalent binding of SARS-CoV-2 RBD-specific antibodies in surface plasmon resonance assays. The method reproduces the monovalent on/off-rates and enables measurements of new parameters, including the molecular reach, which is the maximum antigen separation that supports bivalent binding. We show that the molecular reach (22-46 nm) exceeds the physical size of an antibody (15 nm) and that the variation in reach across 45 patient-isolated antibodies is the best correlate of viral neutralisation. Using the complete set of fitted parameters, the model predicts an emergent antibody binding potency that equals the neutralisation potency. This novel analytical method should improve our understanding and exploitation of antibodies and other bivalent molecules.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.06.556503v1" target="_blank">The molecular reach of antibodies determines their SARS-CoV-2 neutralisation potency</a>
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<li><strong>SARS-CoV-2 ORF7a mutation found in BF.5 and BF.7 sublineages impacts its functions</strong> -
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A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize type-I interferon (IFN-I) response and to downregulate Major Histocompatibility Complex-I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein resulting in changes in virus pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.06.556547v1" target="_blank">SARS-CoV-2 ORF7a mutation found in BF.5 and BF.7 sublineages impacts its functions</a>
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<li><strong>Japanese Encephalitis Virus: A pan-proteome analysis for aggregation propensities and in vitro validation with Capsid anchor and 2K peptide</strong> -
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Japanese encephalitis infection is a vector-borne disease caused by the flavivirus Japanese encephalitis virus (JEV). It is responsible for severe brain infections in humans worldwide. Given the ubiquitous nature of complications and tropism associated with Japanese encephalitis (JE) infection, a holistic understanding of its molecular mechanism is essential. The phenomenon of abnormal protein aggregation into pathogenic amyloids is now increasingly linked to multiple human diseases, also known as Amyloidosis. Most are neurodegenerative disorders, but amyloidosis is not restricted to a specific organ or tissue type. The overlap of viral protein aggregation with human pathologies remains limited, and it is gaining momentum, especially after the devastating Covid-19 pandemic. Therefore, in this study, we have examined the likelihood of aggregation for the entire collection of proteins in JEV. Multiple independent web server tools were employed to scan for potential amyloid-prone regions (APRs), and it was followed by in vitro validation using two JEV transmembrane domains, Capsid anchor, and 2K peptides. These synthetic viral peptides were introduced to artificial aggregation-inducing conditions and then analyzed using different dye-based assays and microscopy methods confirming amyloid-like fibril structure formation. We found these aggregates cytotoxic to human neuronal cell lines and membrane damaging to human blood-derived RBCs. The aggregation kinetics of both peptides is enhanced in the presence of artificial membrane models and seeds of self and diabetes hallmark protein Amylin. Our findings thereby strongly suggest the possibility of JEV protein aggregation playing a vital role in its pathogenesis, opening up a broad scope of future study. Also, the interplay between JEV protein aggregation and initiation/progression of other proteopathies is possible and needs further exploration.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.06.556571v1" target="_blank">Japanese Encephalitis Virus: A pan-proteome analysis for aggregation propensities and in vitro validation with Capsid anchor and 2K peptide</a>
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<li><strong>Immunogenicity and tolerability of a SARS-CoV-2 TNX-1800, a live recombinant poxvirus vaccine candidate, in Syrian Hamsters and New Zealand White Rabbits.</strong> -
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TNX-1800 is a preclinical stage synthetic derived live chimeric horsepox virus vaccine that comprises an engineered SARS-CoV-2 spike (S) gene expression cassette. The objectives of this study were to assess the immunogenicity and tolerability of TNX-1800 administration in Syrian golden hamsters and New Zealand white rabbits. Animals were vaccinated via percutaneous inoculation and evaluated for dose tolerance and immunogenicity at three different dose levels. The 28-day study data showed that the single percutaneous administration of three TNX-1800 vaccine dose levels was well tolerated in both hamsters and rabbits. For all dose levels, rabbits had more dermal observations than hamsters at the same dose levels. Vaccine-induced viral load four weeks post-dosing was below the detection level for both species.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.06.556620v1" target="_blank">Immunogenicity and tolerability of a SARS-CoV-2 TNX-1800, a live recombinant poxvirus vaccine candidate, in Syrian Hamsters and New Zealand White Rabbits.</a>
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<li><strong>Transmissibility, infectivity, and immune resistance of the SARS-CoV-2 BA.2.86 variant</strong> -
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In September 2023, the SARS-CoV-2 XBB descendants, such as XBB.1.5 and EG.5.1 (originally XBB.1.9.2.5.1), are predominantly circulating worldwide. Unexpectedly, however, a lineage distinct from XBB was identified and named BA.2.86 on August 14, 2023. Notably, BA.2.86 bears more than 30 mutations in the spike (S) protein when compared to XBB and the parental BA.2, and many of them are assumed to be associated with immune evasion. Although the number of reported cases is low (68 sequences have been reported as of 7 September 2023), BA.2.86 has been detected in several continents (Europe, North America and Africa), suggesting that this variant may be spreading silently worldwide. On 17 August 2023, the WHO designated BA.2.86 as a variant under monitoring. Here we show evidence suggesting that BA.2.86 potentially has greater fitness than current circulating XBB variants including EG.5.1. The pseudovirus assay showed that the infectivity of BA.2.86 was significantly lower than that of B.1.1 and EG.5.1, suggesting that the increased fitness of BA.2.86 is not due to the increased infectivity. We then performed a neutralization assay using XBB breakthrough infection sera to address whether BA.2.86 evades the antiviral effect of the humoral immunity induced XBB subvariants. The 50% neutralization titer of XBB BTI sera against BA.2.86 was significantly (1.4-fold) lower than those against EG.5.1. The sera obtained from individuals vaccinated with 3rd-dose monovalent, 4th-dose monovalent, 4th-dose BA.1 bivalent, and 4th-dose BA.5 bivalent mRNA vaccines exhibited very little or no antiviral effects against BA.2.86. Moreover, the three monoclonal antibodies (Bebtelovimab, Sotrovimab and Tixagevimab), which worked against the parental BA.2, did not exhibit antiviral effects against BA.2.86. These results suggest that BA.2.86 is one of the most highly immune evasive variants ever.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.07.556636v1" target="_blank">Transmissibility, infectivity, and immune resistance of the SARS-CoV-2 BA.2.86 variant</a>
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<li><strong>Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p</strong> -
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RNA viruses, such as respiratory syncytial virus and SARS-CoV-2, can generate viral circular RNAs (circRNAs), which may play important roles during viral infection. However, whether influenza A viruses have this ability to generate viral circRNAs remains unknown. In this study, we discovered that the negative-strand RNA of the H1N1 nucleoprotein (NP) gene can generate a circRNA, designated circNP37. Furthermore, we demonstrated that circNP37 positively regulated viral replication by competitively sponging host miR-361-5p which inhibited polymerase basic protein 2 (PB2) expression. These results were confirmed using in vivo experiments. Compared with wild-type virus, infection with circNP37 knockout virus resulted in a reduced viral load in the lungs. This study demonstrates, for the first time, the existence and biological function of H1N1-derived circNP37. These findings help us better understand the mechanisms of influenza virus replication and pathogenicity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.04.556164v1" target="_blank">Influenza A virus H1N1-derived circNP37 positively regulates viral replication by sponging host miR-361-5p</a>
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<li><strong>A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</strong> -
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During the COVID-19 pandemic, many countries and regions investigated the potential use of wastewater-based disease surveillance as an early warning system. Initially, methods were created to detect the presence of SARS-CoV-2 RNA in wastewater. Investigators have since conducted extensive studies to examine the link between viral concentration in wastewater and COVID-19 cases in areas served by sewage treatment plants over time. However, only a few reports have attempted to create predictive models for hospitalizations at county-level based on SARS-CoV-2 RNA concentrations in wastewater. This study implemented a linear mixed-effects model that observes the association between levels of virus in wastewater and county-level hospitalizations. The model was then utilized to predict short-term county-level hospitalization trends in 21 counties in California based on data from March 21, 2022, to May 21, 2023. The modeling framework proposed here permits repeated measurements as well as fixed and random effects. The model that assumed wastewater data as an input variable, instead of cases or test positivity rate, showed strong performance and successfully captured trends in hospitalizations. Additionally, the model allows for the prediction of SARS-CoV-2 hospitalizations two weeks ahead. Forecasts of COVID-19 hospitalizations could provide crucial information for hospitals to better allocate resources and prepare for potential surges in patient numbers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.14.23293945v2" target="_blank">A Mixed-Effects Model to Predict COVID-19 Hospitalizations Using Wastewater Surveillance</a>
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<li><strong>COVFlow: phylodynamics analyses of viruses from selected SARS-CoV-2 genome sequences</strong> -
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Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.17.496544v7" target="_blank">COVFlow: phylodynamics analyses of viruses from selected SARS-CoV-2 genome sequences</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>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>KAND567 Versus Placebo in Subjects Hospitalized With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: KAND567; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: Kancera AB<br/><b>Terminated</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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; Novavax<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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19.</strong> - <b>Condition</b>: Nervous System Diseases<br/><b>Interventions</b>: Drug: Tianeptine; Drug: Placebo<br/><b>Sponsors</b>: Military Institute od Medicine National Research Institute; ABM Industries<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service 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>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Pre-probiotic Supplementation for Post-covid Fatigue Syndrome</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo<br/><b>Sponsor</b>: University of Novi Sad, Faculty of Sport and Physical Education<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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<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 of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
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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>SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation 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>Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19</strong> - CONCLUSION: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.</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 Power of Molecular Dynamics Simulations and Their Applications to Discover Cysteine Protease Inhibitors</strong> - A large family of enzymes with the function of hydrolyzing peptide bonds, called peptidases or cysteine proteases (CPs), are divided into three categories according to the peptide chain involved. CPs catalyze the hydrolysis of amide, ester, thiol ester, and thioester peptide bonds. They can be divided into several groups, such as papain-like (CA), viral chymotrypsin-like CPs (CB), papain-like endopeptidases of RNA viruses (CC), legumain-type caspases (CD), and showing active residues of His,…</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>Investigating the Superiority of Chitosan/ D-alpha-tocopheryl Polyethylene Glycol Succinate Binary Coated Bilosomes in Promoting the Cellular Uptake and Anti-SARS-CoV-2 Activity of Polyphenolic Herbal Drug Candidate</strong> - The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 2³ full factorial…</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>Activation of Nrf2/ARE pathway by Anisodamine (654-2) for Inhibition of cellular aging and alleviation of Radiation-Induced lung injury</strong> - CONCLUSION: 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI.</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>Evidence of a Sjögren’s disease-like phenotype following COVID-1 19 in mice and human</strong> - CONCLUSION: Overall, our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD salivary glands were histologically indistinguishable from convalescent COVID-19 subjects.The results potentially implicate that SARS-CoV-2 could be an environmental trigger for SjD.</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>DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors</strong> - Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor…</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>Extracts of <em>Thesium chinense</em> inhibit SARS-CoV-2 and inflammation <em>in vitro</em></strong> - CONCLUSION: T. chinense can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.</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>Primary exposure to SARS-CoV-2 via infection or vaccination determines mucosal antibody-dependent ACE2 binding inhibition</strong> - CONCLUSIONS: Our study provides new insights into the relationship between antibody isotypes and neutralization by using a sensitive and high-throughput ACE2 binding inhibition assay. Key differences are highlighted between vaccination and infection at the mucosal level, showing that despite differences in the quantity of the response, post-infection and post-vaccination ACE2 binding inhibition capacity did not differ.</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>Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study</strong> - CONCLUSIONS: In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.</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>Unleashing the link between the relaxation of the COVID-19 control policy and residents’ mental health in China: the mediating role of family tourism consumption</strong> - CONCLUSION: Based on the findings, the study proposes that government and policymakers should strengthen mental health intervention, improve access to mental health counseling, stimulate economic development, expand the employment of residents, and track the mutation of the novel coronavirus.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response</strong> - Phosgene is widely used as an industrial chemical, and phosgene inhalation causes acute lung injury (ALI), which may further progress into pulmonary edema. Currently, an antidote for phosgene poisoning is not known. Alpha-1 antitrypsin (α1-AT) is a protease inhibitor used to treat patients with emphysema who are deficient in α1-AT. Recent studies have revealed that α1-AT has both anti-inflammatory and anti-SARS-CoV-2 effects. Herein, we aimed to investigate the role of α1-AT in phosgene-induced…</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>RNA-dependent RNA polymerase of SARS-CoV-2 regulate host mRNA translation efficiency by hijacking eEF1A factors</strong> - The RNA-dependent RNA polymerase (NSP12) of COVID-19 plays a significant role in the viral infection process, which promotes viral RNA replication by cooperating with NSP7 and NSP8, but little is known about its regulation on the function of host cells. We firstly found that overexpression of NSP12 had little effect on host mRNAs transcription. Using iCLIP technology, we found that NSP12 can bind a series of host RNAs with the conserved binding motif G(C/A/G)(U/G/A)UAG, especially ribosomal RNA….</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>Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19</strong> - CONCLUSION: Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.</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>Betacoronaviruses SARS-CoV-2 and HCoV-OC43 Infections in IGROV-1 Cell Line Require Aryl Hydrocarbon Receptor</strong> - AbstractThe emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronaviruses SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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