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<title>15 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>The state of e-commerce industry after Covid-19 pandemic and some development policies</strong> -
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The outbreak of the Covid-19 pandemic leads to e-commerce’s explosive growth with brands such as Shopee, Lazada, Tiki, Sendo and The Gioi Di Dong, etc. Since then, e-commerce activities have been going into practice in the life of every Vietnamese person and are constantly developing. The article presents the current situation of the e-commerce industry in recent years through discussion to analyze, evaluate and have a broader perspective on the development of e-commerce, thereby offering some development policies.
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🖺 Full Text HTML: <a href="https://osf.io/hy9e4/" target="_blank">The state of e-commerce industry after Covid-19 pandemic and some development policies</a>
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<li><strong>Pathology and Anticatalysis treatment of exacerbated COVID-19</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces various systemic coronavirus diseases 2019 (COVID-19). Its pathophysiologies involve 1 the angiotensin-converting enzyme 2 (ACE2) and toll-like receptor 4 (TLR4) pathway, 2 Neuropilins (NRPs) Pathway, 3 The sterile alpha motif (SAM) and histi-dine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway 4 Inflammasome ac-tivation pathways, 5 Cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) (cGAS–STING) signaling pathway, 6 Spike protein pathway, and 7 Immunological memory en-gram pathway. COVID-19 exacerbates immune-mediated diseases whose metabolisms use 1. ACE2, TLR4 in the brain, 2. SAMHD1 tetramerization and cGAS–STING-NLRP3 signaling, 3. inflammasome–spike protein–genetic activation, and 4. innate lymphoid cells (ILCs) with NRPs. Immune triad: Aspirin, Dapsone, and Dexamethasone to treat COVID-19 have worked harmoniously with modulating ILCs. Therefore, it is necessary to prescribe this triad to alleviate and block the pathologic course due to diverse and subsequent SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://osf.io/t9wjz/" target="_blank">Pathology and Anticatalysis treatment of exacerbated COVID-19</a>
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<li><strong>Sarbecoviruses of British Horseshoe Bats; Sequence Variation and Epidemiology</strong> -
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Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV-1 and 2. Despite the devastating impacts of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their original hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species (Rhinolophus hipposideros and R. ferrumequinum) present in Great Britain, collected in 2021-22 during the COVID-19 pandemic. One hundred and ninety seven R. hipposideros samples from 33 roost sites and 277 R. ferremequinum samples from 20 roost sites were tested. No coronaviruses were detected in any samples from R. ferrumequinum whereas 44% and 56% of individual and pooled (respectively) faecal samples from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive samples (and partial genomes from two more) using Illumina RNAseq on unenriched samples. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with >95% similarity, as previously reported European isolates from R. hipposideros. The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to high-risk GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros. Despite frequently sharing roost sites with R. ferrumequinum, no evidence of cross-species transmission was found.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.14.528476v1" target="_blank">Sarbecoviruses of British Horseshoe Bats; Sequence Variation and Epidemiology</a>
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<li><strong>Transcription regulation of SARS-CoV-2 receptor ACE2 by Sp1: a potential therapeutic target</strong> -
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Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of ACE2 expression may represent an effective tactic employed by SARS-CoV-2 to facilitate its own propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. By employing an array of 45 different luciferase reporters, we identify that the transcription factor Sp1 positively and HNF4 negatively regulate the expression of ACE2 at the transcriptional levels in HPAEpiC cells, a human lung epithelial cell line. SARS-CoV-2 infection promotes and inhibits the transcription activity of Sp1 and HNF4, respectively. The PI3K/AKT signaling pathway, which is activated by SARS-CoV-2 infection, is a crucial node for induction of ACE2 expression by increasing Sp1 phosphorylation, an indicator of its activity, and reducing HNF4 nuclear location. Furthermore, we show that colchicine could inhibit the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. Inhibition of Sp1 by either its inhibitor mithramycin A or colchicine reduces viral replication and tissue injury in Syrian hamsters infected with SARS-CoV-2. In summary, our study uncovers a novel function of Sp1 in regulating ACE2 expression and suggests that Sp1 is a potential target to reduce SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.14.528496v1" target="_blank">Transcription regulation of SARS-CoV-2 receptor ACE2 by Sp1: a potential therapeutic target</a>
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<li><strong>P-Selectin promotes SARS-CoV-2 interactions with platelets and the endothelium</strong> -
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COVID-19 causes a clinical spectrum of acute and chronic illness and host / virus interactions are not completely understood. To identify host factors that can influence SARS-CoV-2 infection, we screened the human genome for genes that, when upregulated, alter the outcome of authentic SARS-CoV-2 infection. From this, we identify 34 new genes that can alter the course of infection, including the innate immune receptor P-selectin, which we show is a novel SARS-CoV-2 spike receptor. At the cellular level expression of P-selectin does not confer tropism for SARS-CoV-2, instead it acts to suppress infection. More broadly, P-selectin can also promote binding to SARS-CoV-2 variants, SARS-CoV-1 and MERS, acting as a general spike receptor for highly pathogenic coronaviruses. P-selectin is expressed on platelets and endothelium, and we confirm SARS-CoV-2 spike interactions with these cells are P-selectin-dependent and can occur under shear flow conditions. In vivo, authentic SARS-CoV-2 uses P-selectin to home to airway capillary beds where the virus interacts with the endothelium and platelets, and blocking this interaction can clear vascular-associated SARS-CoV-2 from the lung. Together we show for the first time that coronaviruses can use the leukocyte recruitment system to control tissue localization, and this fundamental insight may help us understand and control highly pathogenic coronavirus disease progression.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.13.528235v1" target="_blank">P-Selectin promotes SARS-CoV-2 interactions with platelets and the endothelium</a>
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<li><strong>Propylene glycol inactivates respiratory viruses and prevents airborne transmission</strong> -
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Viruses are vulnerable as they transmit between hosts and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates influenza, SARS-CoV-2 and a broad range of other enveloped viruses, and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, aerosolized PG efficiently abolishes influenza and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels significantly below those well-tolerated by mammals. We present PG vapor as a first-in-class non-toxic airborne virucide, to prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.13.528349v1" target="_blank">Propylene glycol inactivates respiratory viruses and prevents airborne transmission</a>
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<li><strong>T-toxin virulence genes: unconnected dots in a sea of repeats</strong> -
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In 1970, the Southern Corn Leaf Blight epidemic ravaged US fields to great economic loss. The outbreak was caused by never-before-seen, super-virulent, Race T of the fungus Cochliobolus heterostrophus. The functional difference between Race T and O, the previously known, far less aggressive strain, is production of T-toxin, a host-selective polyketide. Super-virulence is associated with [~]1 Mb of Race T-specific DNA; only a fraction encodes T-toxin biosynthetic genes (Tox1). Tox1 is genetically and physically complex, with unlinked loci (Tox1A, Tox1B) genetically inseparable from breakpoints of a Race O reciprocal translocation that generated hybrid Race T chromosomes. Previously, we identified ten genes for T-toxin biosynthesis. Unfortunately, high depth, short-read sequencing placed these genes on four small, unconnected scaffolds surrounded by repeated A+T rich sequence, concealing context. To sort out Tox1 topology and pinpoint the hypothetical Race O translocation breakpoints corresponding to Race T-specific insertions, we undertook PacBio long-read sequencing which revealed Tox1 gene arrangement and the breakpoints. Six Tox1A genes are arranged as three small islands in a Race T-specific sea ([~]634 kb) of repeats. Four Tox1B genes are linked, on a large loop of Race T-specific DNA ([~]210 kb). The race O breakpoints are short sequences of race O-specific DNA; corresponding positions in race T are large insertions of race T-specific, A+T rich DNA, often with similarity to transposable (predominantly Gypsy) elements. Nearby, are Voyager Starship elements and DUF proteins. These elements may have facilitated Tox1 integration into progenitor Race O and promoted large scale recombination resulting in race T. ImportanceIn 1970 a corn disease epidemic ravaged fields in the US to great economic loss. The outbreak was caused by a never-before seen, super-virulent strain of the fungal pathogen Cochliobolus heterostrophus. This was a plant disease epidemic, however, the current COVID-19 pandemic of humans is a stark reminder that novel, highly virulent, pathogens evolve with devastating consequences, no matter what the host-animal, plant, or other organism. Long read DNA sequencing technology allowed in depth structural comparisons between the sole, previously known, much less aggressive, version of the pathogen and the super-virulent version and revealed, in meticulous detail, the structure of the unique virulence-causing DNA. These data are foundational for future analysis of mechanisms of DNA acquisition from a foreign source.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.06.527415v2" target="_blank">T-toxin virulence genes: unconnected dots in a sea of repeats</a>
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<li><strong>SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster</strong> -
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Bivalent mRNA vaccine boosters expressing Omicron BA.5 spike and ancestral D614G spike were introduced to attempt to boost waning antibody titers and broaden coverage against emerging SARS-CoV-2 lineages. Previous reports showed that peak serum neutralizing antibody (NAb) titers against SARS-CoV-2 variants following bivalent booster were similar to peak titers following monovalent booster. It remains unknown whether these antibody responses would diverge over time. We assessed serum virus-neutralizing titers in 41 participants who received three monovalent mRNA vaccine doses followed by bivalent booster, monovalent booster, or BA.5 breakthrough infection at one month and three months after the last vaccine dose or breakthrough infection using pseudovirus neutralization assays against D614G and Omicron subvariants (BA.2, BA.5, BQ.1.1, and XBB.1.5). There was no significant difference at one month and three months post-booster for the two booster cohorts. BA.5 breakthrough patients exhibited significantly higher NAb titers at three months against all Omicron subvariants tested compared against monovalent and bivalent booster cohorts. There was a 2-fold drop in mean NAb titers in the booster cohorts between one and three month time points, but no discernible waning of titers in the BA.5 breakthrough cohort over the same period. Our results suggest that NAb titers after boosting with one dose of bivalent mRNA vaccine are not higher than boosting with monovalent vaccine. Perhaps inclusion of D614G spike in the bivalent booster exacerbates the challenge posed by immunological imprinting. Hope remains that a second bivalent booster could induce superior NAb responses against emerging variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.13.528341v1" target="_blank">SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster</a>
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<li><strong>The relationship between controllability, optimal testing resource allocation, and incubation-latent period mismatch as revealed by COVID-19</strong> -
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The severe shortfall in testing supplies during the initial COVID-19 outbreak and ensuing struggle to manage the pandemic have affirmed the critical importance of optimal supply-constrained resource allocation strategies for controlling novel disease epidemics. To address the challenge of constrained resource optimization for managing diseases with complications like pre- and asymptomatic transmission, we develop an integro partial differential equation compartmental disease model which incorporates realistic latent, incubation, and infectious period distributions along with limited testing supplies for identifying and quarantining infected individuals. Our model overcomes the limitations of typical ordinary differential equation compartmental models by decoupling symptom status from model compartments to allow a more realistic representation of symptom onset and presymptomatic transmission. To analyze the influence of these realistic features on disease controllability, we find optimal strategies for reducing total infection sizes that allocate limited testing resources between `clinical9 testing, which targets symptomatic individuals, and `non-clinical9 testing, which targets non-symptomatic individuals. We apply our model not only to the original, delta, and omicron COVID-19 variants, but also to generically parameterized disease systems with varying mismatches between latent and incubation period distributions, which permit varying degrees of presymptomatic transmission or symptom onset before infectiousness. We find that factors that decrease controllability generally call for reduced levels of non-clinical testing in optimal strategies, while the relationship between incubation-latent mismatch, controllability, and optimal strategies is complicated. In particular, though greater degrees of presymptomatic transmission reduce disease controllability, they may increase or decrease the role of non-clinical testing in optimal strategies depending on other disease factors like transmissibility and latent period length. Importantly, our model allows a spectrum of diseases to be compared within a consistent framework such that lessons learned from COVID-19 can be transferred to resource constrained scenarios in future emerging epidemics and analyzed for optimality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.06.22281984v2" target="_blank">The relationship between controllability, optimal testing resource allocation, and incubation-latent period mismatch as revealed by COVID-19</a>
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<li><strong>Long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: a modelling study</strong> -
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Background Vaccines have reduced severe disease and death from COVID-19. However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated SARS-CoV-2 transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both original and variant-adapted vaccine products, in the presence of both continuing transmission of Omicron subvariants and considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is the most efficient strategy, although large numbers of hospitalisations and deaths can be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups is more effective than continuing primary vaccination into younger ages. These findings hold if even if virus drift results in a gradual reduction in vaccine effectiveness over time due to immune escape. In a worst-case scenario where a new variant emerges that is 10% more transmissible, as severe as Delta, and exhibits substantial further immune escape, demand on health services could be similar to that experienced during 2020. Conclusions Regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. The cost-effectiveness of boosting is difficult to assess given the ongoing uncertainty in the likelihood of future variants and their properties but focusing vaccination in the highest-risk cohorts remains the most efficient strategy to reduce morbidity and mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285743v1" target="_blank">Long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: a modelling study</a>
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<li><strong>Low Antibody Titers Demonstrate Significantly Increased Rate of SARS-CoV-2 Infection in a Highly Vaccinated Population from the National Basketball Association</strong> -
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SARS-CoV-2 antibody titers may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody titer and protection from infection was evaluated in 2,323 vaccinated individuals from the National Basketball Association who had antibody levels measured from 9/12/2021 to 12/31/2021. Cox-proportional hazards models were used to estimate risk of infection within 90-days of serologic testing by titer level (<250, 250-800, and >800 AU/mL) and individuals were censored on date of booster receipt. The cohort was 78.2% male, 68.1% aged ≤ 40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2,248 individuals not yet boosted at testing, those with titers <250 AU/mL (adj HR: 2.4; 95% CI: 1.5, 3.7) and 250-800 800 AU/mL (adj HR: 1.5; 95% CI: 0.98, 2.4) had greater infection risk compared to those with titers >800 AU/mL. Serologic titers could inform individual COVID-19 risk and booster scheduling.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.10.23285780v1" target="_blank">Low Antibody Titers Demonstrate Significantly Increased Rate of SARS-CoV-2 Infection in a Highly Vaccinated Population from the National Basketball Association</a>
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<li><strong>Ischemic stroke after COVID-19 bivalent vaccine administration in patients aged 65 years and older: analysis of nation-wide patient electronic health records in the United States</strong> -
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Importance: The Centers for Disease Control and Prevention (CDC) announced in January 2023 that they were investigating a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). Objective: To explore the relationship between Pfizer bivalent booster administration and IS in older patients in the United States and compare it to other COVID-19 vaccines. Design: A retrospective cohort study was conducted to compare hazard of IS among patients aged 65 years or over who received the Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster vaccine 1-21 and 22-42 days after vaccination. Setting: Patient data were collected from TriNetX, a cloud-based analytics platform that includes electronic health record data from over 90 million unique patients in the United States. Participants: Patients in the United States aged 65 years or over at the time of administration of a Pfizer bivalent (n = 43,216), Moderna bivalent (n = 4,267), or Pfizer/Moderna monovalent (n = 100,583) booster were included for analysis. Cohorts were propensity-score matched by demographic factors and risk factors for IS and severe COVID-19. Exposures: Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster administration. Main outcomes: The hazard ratio (HR) and 95% confidence interval (CI) for IS in the cohorts at 1-21 and 22-42 days after administration. Results: After matching, the Pfizer bivalent cohort included 4,267 patients, with an average age of 73.7 years (44.43% male, 76.59% white). The Moderna bivalent cohort included 4,267 patients, with an average age of 74.0 years (44.08% male, 77.39% white). There was no significant difference in the hazard of IS encounters between the Pfizer bivalent versus Moderna bivalent cohorts at 1-21- or 22-42-days post-administration: HR = 0.59 (0.31, 1.11), 0.73 (0.33, 1.60). The hazard for IS was lower in the Pfizer bivalent cohort than in the Pfizer/Moderna monovalent cohort at both timepoints: HR = 0.24 (0.19, 0.29), 0.25 (0.20, 0.31). Conclusions and relevance: Older adults administered the Pfizer bivalent booster had similar hazard for IS encounters compared to those administered the Moderna bivalent booster vaccine, but lower hazard than those administered the Pfizer/Moderna monovalent boosters.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.11.23285801v1" target="_blank">Ischemic stroke after COVID-19 bivalent vaccine administration in patients aged 65 years and older: analysis of nation-wide patient electronic health records in the United States</a>
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<li><strong>Impact of the COVID-19 pandemic on tuberculosis control in Indonesia: a nationwide analysis of programme data and health system vulnerabilities</strong> -
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Background There are limited measures of the impact of the COVID-19 pandemic on tuberculosis (TB) control in high-burden countries like Indonesia. Methods We analysed district-level data of reported TB cases, treatment and deaths, COVID-19 incidence and mortality, health care capacity, economic status, education level, and public health development index from all 514 districts in Indonesia. We compared data before (2016-2019) and during (2020-2021) the pandemic. Findings Compared to the preceding year (2019), in the first pandemic year (2020) the TB case notification declined by 31% (from median 172 [IQR 129-244] in 2019 to 119 [IQR 87-170] in 2020 per 100,000 population; 565,669 vs 393,323 cases, respectively); mortality increased by 8% (from median 4.2 [IQR 2.0-7.4] to 5.0 (IQR 3.1-7.5) per 100,000 population; 13,059 vs 14,148 deaths, respectively); and the overall proportion of cases who started treatment declined by 7% (from 98% to 91%). The second pandemic year (2021) saw a partial recovery of case notifications (median 142 [IQR 99-204]; 473,006) and deaths (4.1 [IQR 2.5-6.8]; 12,016), but a persistently reduced treatment coverage (84%). Reductions in TB notifications between districts were associated with higher COVID-19 incidence and fewer per capita GeneXpert machines for TB diagnosis. Likewise, reduced TB treatment coverage was associated with fewer per capita doctors, and increased reported TB deaths was associated with fewer per capita primary health centres, lower per capita domestic expenditure and higher education. Interpretation The COVID-19 pandemic significantly, yet unevenly, impacted the national TB control programme across Indonesia, with the greatest impacts in districts with the least resilient health systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285740v1" target="_blank">Impact of the COVID-19 pandemic on tuberculosis control in Indonesia: a nationwide analysis of programme data and health system vulnerabilities</a>
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<li><strong>Quantifying the rate and magnitude of the Omicron outbreak in China after sudden exit from ‘zero-COVID’ restrictions</strong> -
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In late 2022, China transitioned from a strict 9zero-COVID9 policy to rapidly abandoning nearly all interventions and data reporting. This raised great concern about the presumably-rapid but undisclosed spread of the SARS-CoV-2 Omicron variant in a very large population of very low pre-existing immunity. A quantitative understanding of the epidemic dynamics of COVID-19 during this period is urgently needed. Here, by modeling a combination of case count and survey data, we show that Omicron spread extremely fast, at a rate of 0.42/day (95% CrI: [0.35, 0.51]/day) after the full exit from zero-COVID policies on Dec. 7, 2022. Consequently, we estimate that the vast majority of the population (97%, 95% CrI: [95%, 99%]) was infected during December, with the nation-wide epidemic peaking on Dec. 23. Overall, our results highlight the extremely high transmissibility of the variant and the importance of proper design of intervention exit strategies to avoid large infection waves.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.10.23285776v1" target="_blank">Quantifying the rate and magnitude of the Omicron outbreak in China after sudden exit from ‘zero-COVID’ restrictions</a>
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<li><strong>Sustained systemic hyaluronan in COVID-19 patients, a 3D-lung model reveals mechanisms of overproduction counteracted by cortisone</strong> -
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Rationale: High levels of hyaluronan in lungs and blood associate with COVID-19 severity. However, the effects on systemic hyaluronan concentrations and the mechanisms involved in the pathological overproduction of hyaluronan upon SARS-CoV-2 infection remain incompletely characterized. Objectives: To determine how hyaluronan levels in blood of COVID-19 patients change over time and investigate SARS-CoV-2 impact on hyaluronan metabolism along with the effect of corticosteroid treatment. Methods: The concentrations of hyaluronan were measured in blood plasma from patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS 6-9), both during the acute and convalescent phases. Primary human bronchial epithelial cells isolated from healthy donors were differentiated into an in vitro 3D-lung model and used to study effects of SARS-CoV-2 infection and corticosteroids treatment on hyaluronan metabolism. Measurements and Main results: Compared to healthy controls, both patients with mild and severe COVID-19 showed elevated plasma hyaluronan concentrations, which increased with disease severity. A reduction was observed over time, but hyaluronan levels remained elevated for at least 12 weeks, especially in women. SARS-CoV-2 infection in the 3D-lung model showed upregulation of inflammatory genes, hyaluronan synthases and downregulation of hyaluronidases, which increased the overall hyaluronan concentration. Notably, several of these effects were counteracted by corticosteroid treatment. Conclusions: Overproduction of hyaluronan plays a role in the pathogenesis of COVID-19 and hyaluronan levels in blood remain elevated over time. The in vitro mechanism for the positive effects of corticosteroid treatment in COVID-19 suggests a combined action of reduced inflammation and counteraction of hyaluronan synthesis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.10.23285332v1" target="_blank">Sustained systemic hyaluronan in COVID-19 patients, a 3D-lung model reveals mechanisms of overproduction counteracted by cortisone</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Manzi Guben granules<br/><b>Sponsors</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Pilates Exercises<br/><b>Sponsor</b>: Michele de Aguiar Zacaria<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Persuasive Appeal<br/><b>Sponsor</b>: University of Calgary<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AZD 1222<br/><b>Sponsors</b>: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 nasal spray; Drug: Placebo Comparator<br/><b>Sponsor</b>: Huahui Health<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>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Double-Stranded RNA sodium salt; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VV116+SOC; Drug: SOC<br/><b>Sponsor</b>: Chengdu Zenitar Biomedical Technology Co., Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-1558; Drug: STI-1558 placebo<br/><b>Sponsor</b>: Zhejiang ACEA Pharmaceutical Co. Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo<br/><b>Sponsor</b>: Capital Medical University<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>Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Biological: UC-MSCs<br/><b>Sponsor</b>: Shanghai East Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: CONFIDENCE<br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients</strong> - <b>Condition</b>: Health Education, COVID-19, Quarantine, Anxiety, Pandemic<br/><b>Intervention</b>: Other: health education intervention<br/><b>Sponsor</b>: University of Monastir<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise Intervention Using mHealth in Patients With Post-Acute COVID-19 Syndrome: a Randomized Clinical Trial</strong> - <b>Conditions</b>: Post-Acute COVID19 Syndrome; Long COVID; Post COVID-19 Condition<br/><b>Interventions</b>: Device: COVIDReApp Group; Other: Control Group<br/><b>Sponsor</b>: University of Cadiz<br/><b>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><em>In silico</em> anti-SARS-CoV-2, antiplasmodial, antioxidant, and antimicrobial activities of crude extracts and homopterocarpin from heartwood of <em>Pterocarpus macrocarpus</em> Kurz</strong> - Natural products play an essential role in new drug discovery. In the present study, we determined the anti-SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2), antioxidant, antiplasmodial, and antimicrobial activities of Pterocarpus macrocarpus Kurz. heartwood and structurally characterized the bioactive compounds. P. macrocarpus Kurz. heartwood was macerated with n-hexane, ethyl acetate, and ethanol, respectively, for 7 days, three times. The compounds were isolated 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>A novel antiviral formulation containing caprylic acid inhibits SARS-CoV-2 infection of a human bronchial epithelial cell model</strong> - A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an…</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>Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3β,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology</strong> - Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where…</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 the SARS-CoV-2 main protease by a thiadiazolidinone derivative</strong> - No abstract</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>Nanozyme-Based Colorimetric SARS-CoV-2 Nucleic Acid Detection by Naked Eye</strong> - Fluorescence-based PCR and other amplification methods have been used for SARS-CoV-2 diagnostics, however, it requires costly fluorescence detectors and probes limiting deploying large-scale screening. Here, a cut-price colorimetric method for SARS-CoV-2 RNA detection by iron manganese silicate nanozyme (IMSN) is established. IMSN catalyzes the oxidation of chromogenic substrates by its peroxidase (POD)-like activity, which is effectively inhibited by pyrophosphate ions (PPi). Due to the large…</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>Remdesivir Use in Low Weight, Premature, and Renally Impaired Infants With SARS-CoV-2 Infection in Sheikh Khalifa Medical City, UAE: Case Series</strong> - Remdesivir possesses in vitro inhibitory effect against severe acute respiratory syndrome coronavirus 2 and the Middle East respiratory syndrome. It works by inhibiting severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase that is essential for viral replication. Remdesivir is approved by Food and Drug Administration for treating COVID-19 in hospitalized adult and pediatric patients aged 28 days and more and weighing 3 kg and more. This case series is describing two cases…</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>Can Internet penetration curb the spread of infectious diseases among regions?-Analysis based on spatial spillover perspective</strong> - Based on the outbreak of COVID-19, this paper empirically studied the impact of internet penetration on the incidence of class A and B infectious diseases among regions in spatial Dubin model, by using health panel data from 31 provinces in China from 2009 to 2018. The findings showed that: (1) The regional spillover effect of incidence of class A and B infectious diseases was significantly positive, and that is most obvious in the central regions. (2) Internet penetration not only has a…</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 comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic</strong> - Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all…</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>Stress adaptation signature into the functional units of spike, envelope, membrane protein and ssRNA of SARS-CoV-2</strong> - Pandemic coronavirus causes respiratory, enteric and sometimes neurological diseases. Proteome data of individual coronavirus strains were already reported. Here we investigated of SARS-CoV-2 ssRNA and protein of spike, envelope and membrane to determine stress adaptation profile. Thermodynamic properties, Physicochemical behaviour and, amino acid composition along with their RMSD value was analysed. Thermodynamic index of SARS-CoV2 spike, envelope and membrane ssRNA is unstable in higher…</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>Extensive blood transcriptome analysis reveals cellular signaling networks activated by circulating glycocalyx components reflecting vascular injury in COVID-19</strong> - CONCLUSIONS: Circulating glycocalyx components in COVID-19 have distinct biologic feedback effects on immune and endothelial cells and result in upregulation of key regulatory transcripts leading to further immune activation and more severe systemic inflammation. These consequences are most pronounced during the early hospital phase of COVID-19 before pulmonary failure develops. Elevated levels of circulating glycocalyx components may early identify patients at risk for microvascular injury 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>The evaluation of <em>in vitro</em> antichagasic and <em>anti</em>-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone</strong> - The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to…</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 review article on neuroprotective, immunomodulatory, and anti-inflammatory role of vitamin-D3 in elderly COVID-19 patients</strong> - Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting…</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>Multigenerational effects of microplastic fragments derived from polyethylene terephthalate bottles on duckweed Lemna minor: Size-dependent effects of microplastics on photosynthesis</strong> - The 2019 global coronavirus disease pandemic has led to an increase in the demand for polyethylene terephthalate (PET) packaging. Although PET is one of the most recycled plastics, it is likely to enter the aquatic ecosystem. To date, the chronic effects of PET microplastics (MPs) on aquatic plants have not been fully understood. Therefore, this study aimed to investigate the adverse effects of PET MP fragments derived from PET bottles on the aquatic duckweed plant Lemna minor through a…</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>Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 Main Protease</strong> - SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (M^(pro)) is an attractive target for antivirals. The clinically approved drug nirmatrelvir, and the clinical candidate ensitrelvir have so far showed great potential for treatment of viral infection. However, the broad use of antivirals is often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring M^(pro) polymorphisms that are close to the binding site of these antivirals….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison study of Beninese and Chinese herbal medicines in treating COVID-19</strong> - CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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