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<title>14 July, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</strong> -
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<div>
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The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
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🖺 Full Text HTML: <a href="https://osf.io/d3xat/" target="_blank">The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</a>
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</div></li>
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<li><strong>Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</strong> -
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<div>
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The government of Peru carried out extensive tracking of data for deaths and other public health parameters that allow analysis of potential efficacy of interventions used during the early years of the COVID-19 pandemic. Data from those sources for death seasonality, mobility trends, household composition and seropositivity rates, as well as Google community mobility trends, are provided here as can facilitate such analysis. Also, excess deaths as calculated from Peru’s National Death Information System (SINADEF) are compared with monthy summary data for excess deaths for the period 2020-2021 as reported by the World Health Organization.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/a9ex5/" target="_blank">Death Seasonality, Google Community Mobility Trends, Seropositivity Rates, Comparisons of SINADEF Data with WHO Summary Data, and other Data Items as Useful in Analysis of Excess Deaths During the COVID-19 Pandemic in Peru, 2020-2021</a>
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</div></li>
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<li><strong>Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2</strong> -
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SARS-CoV-2 has caused millions of infections worldwide since its emergence in 2019. Understanding how infection and vaccination induce mucosal immune responses and how they fluctuate over time is important, especially since they are key in preventing infection and reducing disease severity. We established a novel methodology for assessing SARS-CoV-2 cytokine and antibody responses at the nasal epithelium by using nasopharyngeal swabs collected longitudinally before and after either SARS-CoV-2 infection or vaccination. We then compared responses between mucosal and systemic compartments. We demonstrate that cytokine and antibody profiles differ markedly between compartments. Nasal cytokines show a wound healing phenotype while plasma cytokines are consistent with pro-inflammatory pathways. We found that nasal IgA and IgG have different kinetics after infection, with IgA peaking first. Although vaccination results in low nasal IgA, IgG induction persists for up to 180 days post-vaccination. This research highlights the importance of studying mucosal responses in addition to systemic responses to respiratory infections to understand the correlates of disease severity and immune memory. The methods described herein can be used to further mucosal vaccine development by giving us a better understanding of immunity at the nasal epithelium providing a simpler, alternative clinical practice to studying mucosal responses to infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.12.548630v1" target="_blank">Utility of nasal swabs for assessing mucosal immune responses towards SARS-CoV-2</a>
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</div></li>
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<li><strong>Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty</strong> -
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Background Licensed mRNA vaccines demonstrated initial effectiveness against COVID-19 but require booster doses to broaden the anti-SARS-CoV-2 response. There is an unmet need for novel highly immunogenic and broadly protective vaccines. We compared immunogenicity and tolerability of ARCT-154, a novel self-amplifying mRNA vaccine with the mRNA vaccine, Comirnaty. Methods We compared immune responses to ARCT-154 and Comirnaty booster doses in healthy 18-77-year-old Japanese adults initially immunised with two doses of mRNA COVID-19 vaccine (Comirnaty or Spikevax) then a third dose of Comirnaty at least 3 months previously. Neutralising antibodies were measured before and 28 days after booster vaccination. The primary objective was to demonstrate non-inferiority of the immune response against Wuhan-Hu-1 SARS-CoV-2 virus as geometric mean titre (GMT) ratios and seroresponse rates (SRR) of neutralising antibodies; key secondary endpoints included the immune response against the Omicron BA.4/5 variant and vaccine tolerability assessed using participant-completed electronic diaries. Findings Between December 13, 2022 and February 25, 2023 we enrolled 828 participants randomised 1:1 to receive ARCT-154 (n = 420) or Comirnaty (n = 408) booster doses. Four weeks after boosting, ARCT-154 induced higher Wuhan-Hu-1 neutralising antibodies GMTs than Comirnaty (5641 [95% CI: 4321-7363] and 3934 [2993-5169], respectively), a GMT ratio of 1.43 (95% CI: 1.26-1.63), with SRR of 65.2% (60.2-69.9) and 51.6% (46.4-56.8) meeting the non-inferiority criteria. Respective anti-Omicron BA.4/5 GMTs were 2551 (1687-3859) and 1958 (1281-2993), a GMT ratio of 1.30 (95% CI: 1.07-1.58), with SRR of 69.9% (65.0-74.4) and 58.0% (52.8-63.1), meeting the superiority criteria for ARCT-154 over Comirnaty. Booster doses of either ARCT-154 or Comirnaty were equally well-tolerated with no causally-associated severe or serious adverse events; 94.8% and 96.8% of ARCT-154 and Comirnaty vaccinees reported local reactions and 65.7% and 62.5% had solicited systemic adverse events. Events were mainly mild in severity, occurring and resolving within 3-4 days of vaccination. Interpretation Immune responses four weeks after an ARCT-154 booster dose in mRNA-immunised adults were higher than after a Comirnaty booster, meeting non-inferiority criteria against the prototype Wuhan-Hu-1 virus, and superiority criteria against the Omicron BA.4/5 variant.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.13.23292597v1" target="_blank">Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty</a>
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</div></li>
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<li><strong>Risk Factors for Admission into COVID-19 General Wards, Sub-Intensive and Intensive Care Units among SARS-CoV-2 Positive Subjects in the Municipality of Bologna, Italy</strong> -
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This is a retrospective cohort study aimed at identifying the risk factors for the hospitalization of patients with COVID-19 in the municipality of Bologna. A total of 32500 patients that tested positive for COVID-19 from February 28/2020 to October 13/2021 in the municipality of Bologna were included. The Kaplan-Meier method was used to estimate changes during time of ICU hospitalization for all patients as well as stratifying subjects by sex. A multi-state Cox9s proportional hazard model was fitted to investigate predictors of ICU and non-ICU hospitalization. Age, sex, calendar period of diagnosis, comorbidities and vaccination status of patients at the time of diagnosis were considered as candidate predictors. In general, male sex and advanced age resulted to be poor prognostic factors of COVID-19 outcomes. An exception was found for the over 80 age group which showed a decrease in the risk of ICU hospitalization compared to 70-79 (HR 0.57 95% CI 0.36 - 0.90 for DIAG->ICU; HR 0.40 95% CI 0.28 - 0.58 for HOSP->ICU). Having contracted the disease during the first wave was associated with a significant greater risk of hospitalization than during the second wave, while no difference in the risk of ICU admission was found between the second and third waves. Fully immunized patients showed a significant decrease in the risk of ICU and non-ICU hospitalization compared to the unvaccinated patients (HR 0.23 95% CI 0.16 - 0.31 for DIAG->HOSP; HR 0.10 95% CI 0.01 - 0.73 for DIAG->ICU). Chronic kidney failure and asthma were risk factors for non-ICU hospitalization. Diabetes and embolism were risk factors for both direct ICU and non-ICU hospitalization. The study of factors associated with a negative course of the COVID-19 disease allows to prevent fatal outcomes, establish priorities in the treatment of the disease and improve the management of hospital resources and the pandemic itself.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292559v2" target="_blank">Risk Factors for Admission into COVID-19 General Wards, Sub-Intensive and Intensive Care Units among SARS-CoV-2 Positive Subjects in the Municipality of Bologna, Italy</a>
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<li><strong>Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</strong> -
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<b>Background</b> Paediatric pneumococcal conjugate vaccination (PCV) has reduced adult PCV-serotype disease: PCV7 has greater indirect effects than PCV13. Ongoing surveillance is required to evaluate current vaccine usage and inform future vaccine deployment, particularly with respiratory infection epidemiology changing following SARS-CoV-2 emergence. <b>Methods and Findings</b> A retrospective cohort study, all adults >16 years admitted to three UK hospitals, 2006-2022, with pneumococcal disease. Medical records were reviewed for each clinical episode and serotype data were obtained from the UK Health Security Agency national reference laboratory. We identified 1,501 (40.3%) cases of invasive pneumococcal disease (IPD) with known serotype, 134 (3.6%) IPD cases without serotype data, and 2,084 (56.0%) non-IPD cases, which are typically missed in national surveillance. Disease incidence increased progressively from 2006-2020, followed by a sudden decline after COVID-19 emergence and then a gradual increase to pre-pandemic levels. Paediatric PCV7 introduction reduced adult PCV7 serotype IPD from 29.4% [24.1-35.4] of IPD in 2006-09 to 7.0% [3.7-12.7] in 2021-22. PCV13 introduction also decreased adult vaccine serotype IPD, but considerable residual adult disease remains, causing 34.3% [28.6-40.4] of IPD in 2006-09 and 21.7% [15.5-29.6] 9 in 2021-22, respectively. Serotype replacement diminished the benefits of PCV introduction: PCV20-13 and non-PCV serotypes represented 27.0% [21.9-32.9] and 9.3% [6.3-13.5] of disease in 2006-2009, and 39.5% [31.5-48.2] and 31.8% [24.4-40.2] in 2021-2022, respectively. Serotype shifts have resulted in increasing disease caused by serotype 3 and 8, and the re-emergence of serotype 19F and 19A. These serotype shifts occurred as clinical disease severity changed, and whilst the COVID-19 pandemic disrupted disease severity trends, these have now largely reverted to previous trajectories. Patient age trended upwards and although CURB65 severity decreased there were increased ICU admission rates. Overall, inpatient mortality decreased and hospitalisation duration remained stable. <b>Conclusions</b> After 17 years of PCV use, residual pneumococcal disease due to the vaccine serotypes among hospitalised adults remains. The sharp decline in pneumococcal disease during the COVID-19 pandemic has now reversed, with increasing cases due to vaccine serotypes, especially serotype 3. Around 68.2% of cases in 2022 were potentially covered by the recently licensed 20-valent PCV.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.30.23287917v2" target="_blank">Trends in serotype distribution and disease severity in adults hospitalised with Streptococcus pneumoniae infection in Bristol and Bath: a retrospective cohort study, 2006-2022</a>
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<li><strong>Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild-to-Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial</strong> -
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IMPORTANCE Treatment options for coronavirus disease 2019 (COVID-19) that can be used irrespective of risk factors for severe disease are warranted. OBJECTIVE To assess the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19. DESIGN The phase 3 part of a phase 2/3, double-blind, randomized, placebo controlled study conducted from February 10 to July 10, 2022. SETTING A multicenter study conducted at 92 institutions in Japan, Vietnam, and South Korea. PARTICIPANTS Patients (aged 12 to <70 years) with mild-to-moderate COVID-19 within 120 hours of positive viral testing. INTERVENTIONS Patients were randomized (1:1:1) to receive once-daily ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or placebo for 5 days. Among 1821 randomized patients, 1030 (347, 340, and 343 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were randomized in less than 72 hours of disease onset and assessed as the primary analysis population. MAIN OUTCOMES AND MEASURES The primary end point was the time to resolution of five COVID-19 symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness). Other end points included virologic efficacy and safety. RESULTS The mean age was 35.7, 35.3, and 34.7 years, and 193 (55.6%), 185 (54.4%), and 174 (50.7%) patients were men in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (intention-to-treat, primary analysis population). A significant difference (P=.04 with a Peto-Prentice generalized Wilcoxon test stratified by vaccination history) was observed in the primary end point between ensitrelvir 125 mg and placebo in the primary analysis population (difference in median, −24.3 hours; 95% confidence interval, −78.7 to 11.7). Viral RNA levels on day 4 and time to negative viral titer demonstrated significant reduction vs placebo. The incidence of adverse events was 44.2%, 53.6%, and 24.8% in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively. No treatment-related serious adverse events were reported. CONCLUSIONS AND RELEVANCE Treatment with ensitrelvir 125 mg demonstrated clinical and antiviral efficacy without new safety concerns. Generalizability to non-Asian populations should be confirmed. TRIAL REGISTRATION Japan Registry of Clinical Trials identifier: jRCT2031210350.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.11.23292264v1" target="_blank">Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild-to-Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial</a>
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<li><strong>Genetic Risk Factors for Severe and Fatigue Dominant Long COVID and Commonalities with ME/CFS Identified by Combinatorial Analysis</strong> -
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Background Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as ME/CFS that present with similar symptoms. Methods We used a combinatorial analysis approach to identify combinations of genetic variants significantly associated with the development of long COVID and to examine the biological mechanisms underpinning its various symptoms. We compared two subpopulations of long COVID patients from Sano Genetics9 Long COVID GOLD study cohort, focusing on patients with severe or fatigue dominant phenotypes. We evaluated the genetic signatures previously identified in an ME/CFS population against this long COVID population to understand similarities with other fatigue disorders that may be triggered by a prior viral infection. Finally, we also compared the output of this long COVID analysis against known genetic associations in other chronic diseases, including a range of metabolic and neurological disorders, to understand the overlap of pathophysiological mechanisms. Results Combinatorial analysis identified 73 genes that were highly associated with at least one of the long COVID populations included in this analysis. Of these, 9 genes have prior associations with acute COVID-19, and 14 were differentially expressed in a transcriptomic analysis of long COVID patients. A pathway enrichment analysis revealed that the biological pathways most significantly associated with the 73 long COVID genes were mainly aligned with neurological and cardiometabolic diseases. Expanded genotype analysis suggests that specific SNX9 genotypes are a significant contributor to the risk of or protection against severe long COVID infection, but that the gene-disease relationship is context dependent and mediated by interactions with KLF15 and RYR3. Comparison of the genes uniquely associated with the Severe and Fatigue Dominant long COVID patients revealed significant differences between the pathways enriched in each subgroup. The genes unique to Severe long COVID patients were associated with immune pathways such as myeloid differentiation and macrophage foam cells. Genes unique to the Fatigue Dominant subgroup were enriched in metabolic pathways such as MAPK/JNK signaling. We also identified overlap in the genes associated with Fatigue Dominant long COVID and ME/CFS, including several involved in circadian rhythm regulation and insulin regulation. Overall, 39 SNPs associated in this study with long COVID can be linked to 9 genes identified in a recent combinatorial analysis of ME/CFS patient from UK Biobank. Among the 73 genes associated with long COVID, 42 are potentially tractable for novel drug discovery approaches, with 13 of these already targeted by drugs in clinical development pipelines. From this analysis for example, we identified TLR4 antagonists as repurposing candidates with potential to protect against long term cognitive impairment pathology caused by SARS-CoV-2. We are currently evaluating the repurposing potential of these drug targets for use in treating long COVID and/or ME/CFS. Conclusion This study demonstrates the power of combinatorial analytics for stratifying heterogeneous populations in complex diseases that do not have simple monogenic etiologies. These results build upon the genetic findings from combinatorial analyses of severe acute COVID-19 patients and an ME/CFS population and we expect that access to additional independent, larger patient datasets will further improve the disease insights and validate potential treatment options in long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.13.23292611v1" target="_blank">Genetic Risk Factors for Severe and Fatigue Dominant Long COVID and Commonalities with ME/CFS Identified by Combinatorial Analysis</a>
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<li><strong>Exploring the use of preprints in dentistry</strong> -
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Objective: This study aims to assess the use, impact, and dissemination of preprints in dentistry. Methods: This is a meta-research study with a cross-sectional design. We included preprints published in dentistry, regardless of the year of publication. Searches were performed in the medRxiv.org and Preprints.org platforms and restricted to English. One researcher extracted the data, and another researcher verified data consistency. The following data were extracted: year of publication, country of the corresponding author, number of abstract and full-text views and downloads, Altmetric attention score, whether the preprint was mentioned in other servers such as Twitter and Publons, number of mentions in other servers, number of citations in the Dimensions database, and whether the preprint had already been published in a peer-reviewed journal. If already published, we extracted the journal9s impact factor (JCR 2021) and the number of citations in the Dimensions database. We conducted a descriptive analysis of the extracted characteristics and explored relationships between metrics using the Spearman correlation. Results: We identified 276 preprints. Most of the studies were published between 2020 and 2022 (n = 229), especially those from ten countries. The most-cited preprint and published article are the same study. Only the correlation between the number of preprint citations and peer-reviewed article citations in the Dimensions database showed a large positive association (Spearman9s rho = 0.5809). Conclusion: Preprints gained popularity over the last several years due to the COVID-19 pandemic and reached a larger audience, especially on platforms such as Twitter. Clinical Significance: Preprint publishing allows faster dissemination of science for the benefit of society.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.11.23292516v1" target="_blank">Exploring the use of preprints in dentistry</a>
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<li><strong>The role and influence of perceived experts in an anti-vaccine misinformation community</strong> -
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The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts in spreading anti-vaccine misinformation may be warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292568v1" target="_blank">The role and influence of perceived experts in an anti-vaccine misinformation community</a>
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<li><strong>Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation</strong> -
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<b> Background </b> Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. <b> Methods and Findings </b> We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α=0, as typically assumed) to one where symptoms always propagate (α=1). For parameters corresponding to three respiratory pathogens — seasonal influenza, pandemic influenza and SARS-CoV-2 — we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all levels of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. <b> Conclusions </b> Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292544v1" target="_blank">Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation</a>
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<li><strong>Quantifying the impact of hospital catchment area definitions on hospital admissions forecasts: COVID-19 in England, September 2020 - April 2021</strong> -
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Background. Defining healthcare facility catchment areas is a key step in predicting future healthcare demand in epidemic settings. Forecasts of hospitalisations can be informed by leading indicators measured at the community level. However, this relies on the definition of so-called catchment areas, or the geographies whose populations make up the patients admitted to a given hospital, and which are often not well-defined. Little work has been done to quantify the impact of hospital catchment area definitions on healthcare demand forecasting. Methods. We made forecasts of Trust-level hospital admissions using a scaled convolution of local cases (as defined by the hospital catchment area) and a delay distribution. Hospital catchment area definitions were derived from either simple heuristics (in which people are admitted to their nearest hospital or any nearby hospital) or historical admissions data (all emergency or elective admissions in 2019, or COVID-19 admissions), plus a marginal baseline definition based on the distribution of all hospital admissions. We evaluated predictive performance using each hospital catchment area definition using the Weighted Interval Score (WIS) and considered how this changed by the length of the predictive horizon, the date on which the forecast was made, and by location. We also considered the change, if any, on the relative performance of each definition in retrospective vs. real-time settings, or at different spatial scales. Results. The choice of hospital catchment area definition affected the accuracy of hospital admission forecasts. The definition based on COVID-19 admissions data resulted in the most accurate forecasts at both a 7- and 14-day horizon, and was one of the top two best-performing definitions across forecast dates and locations. The nearby heuristic also performed well, but less consistently than the COVID-19 data definition. The marginal distribution baseline, which did not include any spatial information, was the lowest-ranked definition. The relative performance of the definitions was larger when using case forecasts compared to future observed cases. All results were consistent across spatial scales of the catchment area definitions. Conclusions. Using catchment area definitions derived from context-specific data can improve local-level hospital admissions forecasts. Where context-specific data is not available, using catchment areas defined by carefully-chosen heuristics are a sufficiently-good substitute. There is clear value in understanding what drives local admissions patterns, and further research is needed to understand the impact of different catchment area definitions on forecast performance where case trends are more heterogeneous.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.12.23292451v1" target="_blank">Quantifying the impact of hospital catchment area definitions on hospital admissions forecasts: COVID-19 in England, September 2020 - April 2021</a>
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<li><strong>Using Short Messages to Encourage COVID-19 Prevention Behaviors</strong> -
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Controlling the spread of COVID-19 requires persuading the mass public to change their behavior in significant ways. Many efforts to encourage behavior change, such as public service announcements, social media posts, and billboards, involve short, persuasive appeals, yet the effectiveness of these messages is unknown. Here, we test whether short messages increase intentions to comply with public health guidelines. Research was conducted in the United States from March-July 2020. To identify promising messages, we conducted two pretests (total N = 1,596) where participants rated the persuasiveness of 56 unique messages: 31 based on the persuasion and social influence literature and 25 from a pool of 600 crowdsourced messages by online respondents. The four top-rated messages emphasized 1) civic responsibility to reciprocate the sacrifices of health care workers, 2) caring for the elderly and vulnerable, 3) a specific, sympathetic victim, and 4) limited health care system capacity. We then conducted three well-powered, pre-registered experiments (total N = 3,719) testing whether these four top-rated messages and a standard public health message based on language from the CDC increased intentions to comply with public health guidelines. In Study 1, we find the four messages and the standard public health message significantly outperformed a null control. In Studies 2 and 3, we compared the effects of persuasive messages to the standard public health message, finding that none consistently out-performed the standard public health message. Short messages can increase intentions to comply with public health guidelines, but short messages featuring persuasive techniques from the social science literature did not substantially outperform standard public health messages.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/g93zw/" target="_blank">Using Short Messages to Encourage COVID-19 Prevention Behaviors</a>
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<li><strong>Evaluating Twitter’s COVID-19 Vaccine Misinformation Removal Policy</strong> -
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Objectives. To assess the efficacy of Twitter’s March 1, 2021 COVID-19 vaccine misinformation removal policy. Methods. We collected over 400 million English-language tweets related to COVID-19 using more than 100 pertinent keywords from February 6, 2020, to December 15, 2022, comparing vaccine-related tweets and corresponding accounts before vs. after the implementation of Twitter’s interventions. We used a comparative interrupted time series analytic approach to compared the content of misinformative (>10% of tweets contain links to misinformative websites) to non-misinformative accounts. Results. We identified 7,084 misinformative accounts and 6,706,999 non-misinformative accounts. Misinformative accounts were 1.43 times more likely to persist (RR=1.43; 95% CI:1.41-1.45; P<0.001) and 30.16 times more likely to become more misinformative (RR=30.16; 95% CI: 28.48 - 31.95; P<0.001) compared to non-misinformative accounts. We did not detect a significant decrease in content from misinformative accounts (RR=0.03; 95% CI: 0.00 - 3.93; P=0.16) compared to pre-policy data; however, we did detect a significant decrease in content from non-misinformative accounts (RR=0.02; 95% CI: 0.00 - 0.32; P=0.005). We did not detect a significant difference between these two groups (RR=1.48; 95% CI: 0.01 - 398.61; P=0.89). Conclusion. Twitter’s vaccine misinformation removal policies do not appear to have been associated with a detectable reduction in content from misinformative, compared to non- misinformative, users or in more misinformative compared to less misinformative tweets. Public Health Implications. Our study highlights the necessity for external evaluations to ascertain the sufficiency of platforms’ self-regulatory measures to safeguard public health.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/cxg6y/" target="_blank">Evaluating Twitter’s COVID-19 Vaccine Misinformation Removal Policy</a>
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<li><strong>Endocytosis Inhibitors Block SARS-CoV-2 Pseudoparticle Infection of Mink Lung Epithelium</strong> -
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Both spill over and spill back of SARS-CoV-2 virus have been reported on mink farms in Europe and the United States. Zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback. The purpose of our study was to determine the SARS-CoV-2 entry mechanism using mink lung epithelial cell line (Mv1Lu) and to block entry with drug inhibitors. Mv1Lu cells were susceptible to SARS-CoV-2 viral pseudoparticle infection, validating them as a suitable disease model for COVID-19. Inhibitors of TMPRSS2 and of endocytosis, two pathways of viral entry, were tested to identify those that blocked infection. Dyngo4a, a small molecule endocytosis inhibitor, significantly reduced infection, while TMPRSS2 inhibitors had minimal impact, supporting the conclusion that the entry of the SARS-CoV-2 virus into Mv1Lu cells occurs primarily through endocytosis. The small molecule inhibitors that were effective in this study could potentially be used therapeutically to prevent SARS-CoV-2 infection in mink populations. This study will facilitate the development of therapeutics to prevent zoonotic transmission of SARS-CoV-2 variants to other animals, including humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.12.548725v1" target="_blank">Endocytosis Inhibitors Block SARS-CoV-2 Pseudoparticle Infection of Mink Lung Epithelium</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>Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine<br/><b>Sponsor</b>: PT Bio Farma<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>Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ivermectin Tablets; Drug: Colchicine 0.5 MG; Drug: Standared managment<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-2; Biological: SCTV01E<br/><b>Sponsor</b>: Sinocelltech 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>COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Standard implementation webinar and online training; Behavioral: Virtual facilitation<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Arkansas; University of South Carolina; National Institute on Minority Health and Health Disparities (NIMHD)<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>Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Resistance Training<br/><b>Sponsor</b>: Józef Piłsudski University of Physical Education<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multimodal Long Covid19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Other: Multimodal intervention in Long Covid19<br/><b>Sponsors</b>: Universidad de Magallanes; Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG; Clinical Hospital Dr. Lautaro Navarro Avaria<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>A Phase 1/2 Trial of COVID-19 Vaccine (COVIVAC)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVIVAC vaccine<br/><b>Sponsors</b>: Institute of Vaccines and Medical Biologicals, Vietnam; National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam<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>Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection; Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection<br/><b>Sponsor</b>: Clover Biopharmaceuticals AUS Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB002V14; Biological: LYB002V14A; Biological: LYB002CA<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<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>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>: COVID-19; Renal Insufficiency, Chronic<br/><b>Intervention</b>: Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>: Chinese PLA General Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001</strong> - <b>Conditions</b>: COVID-19; Vaccine Reaction<br/><b>Interventions</b>: Biological: LYB001; Biological: CoronaVac<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<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>Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Placebo; Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]<br/><b>Sponsor</b>: Hellenic Institute for the Study of Sepsis<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 Music Combined With Sports Games on Alleviating Psychological Stress, Anxiety and Mental Energy Among Adolescents During COVID-19 Pandemic in Lanzhou Gansu Province China</strong> - <b>Conditions</b>: Stress; Anxiety and Fear<br/><b>Interventions</b>: Behavioral: Music intervention only; Behavioral: Sports games intervention only; Behavioral: Music and sports games intervention<br/><b>Sponsor</b>: Wu Jiarun<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>: Drug: MBS-COV; Drug: Placebo<br/><b>Sponsor</b>: Oneness Biotech 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>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19; Functional MRI; Cognitive Impairment<br/><b>Interventions</b>: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases</strong> - Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed 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>SARS-CoV-2 main protease cleaves MAGED2 to antagonize host antiviral defense</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the global pandemic of COVID-19. SARS-CoV-2 genome encodes a main protease (nsp5, also called Mpro) and a papain-like protease (nsp3, also called PLpro), which are responsible for processing viral polyproteins to assemble a functional replicase complex. In this study, we found that Mpro of SARS-CoV-2 can cleave human MAGED2 and other mammalian orthologs at Gln-263. Moreover, SARS-CoV and MERS-CoV Mpro can also…</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>Effect of DMARDs on the immunogenicity of vaccines</strong> - Vaccines are important for protecting individuals at increased risk of severe infections, including patients undergoing DMARD therapy. However, DMARD therapy can also compromise the immune system, leading to impaired responses to vaccination. This Review focuses on the impact of DMARDs on influenza and SARS-CoV-2 vaccinations, as such vaccines have been investigated most thoroughly. Various data suggest that B cell depletion therapy, mycophenolate mofetil, cyclophosphamide, azathioprine 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>Characteristics of VOCs and Assessment of Emission Reduction Effect During the Epidemic Lockdown Period in Shenzhen Urban Area</strong> - To prevent disease spreading during the COVID-19 epidemic, Shenzhen adopted lockdown measures in March of 2022. This provided an opportunity to study the response of changes in anthropogenic volatile organic compounds (AVOCs) in Shenzhen to emission reduction and to evaluate the effectiveness of current emission reduction measures. This study analyzed the variety of AVOCs before, during, and after the epidemic lockdown based on the online observation data of pollutants at Lianhua Station in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Z-FA-FMK, a host cathepsin L protease inhibitor, as a potent and broad-spectrum antiviral therapy against SARS-CoV-2 and related coronaviruses</strong> - Even though the World Health Organization announced the end of the COVID-19 pandemic as a global public health emergency on May 5, 2023, SARS-CoV-2 continues to pose a significant health threat worldwide, resulting in substantial numbers of infections and fatalities. This study investigated the antiviral potential of Z-FA-FMK (FMK), a novel host cathepsin L protease inhibitor, against SARS-CoV-2 infection using both in vitro and in vivo models. In vitro assessments of FMK against a diverse set…</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>Isolation and characterization of Rhodococcus sp. GG1 for metabolic degradation of chloroxylenol</strong> - The coronavirus disease 2019 (COVID-19) pandemic has significantly increased the demand of disinfectant use. Chloroxylenol (para-chloro-meta-xylenol, PCMX) as the major antimicrobial ingredient of disinfectant has been widely detected in water environments, with identified toxicity and potential risk. The assessment of PCMX in domestic wastewater of Macau Special Administrative Region (SAR) showed a positive correlation between PCMX concentration and population density. An indigenous PCMX…</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>Neutralizing activity of Usnic acid and β-cyclodextrins complex against SARS-CoV-2 spike pseudovirus</strong> - The rapid spread of SARS-CoV-2 and its infection severity require an urgent development of antiviral agents. In this respect, Usnic acid (UA), a natural dibenzofuran derivative, exerts antiviral activity against several viruses, though presenting very low solubility and high cytotoxicity. Here, UA was complexed with β-cyclodextrins (β-CDs), a pharmaceutical excipient used to improve drug solubility. The cytotoxic activity, tested on Vero E6 cells, revealed no effect for β-CDs alone whereas…</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>Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors</strong> - Aim: Discovery of novel SARS-CoV-2 main protease (M^(pro)) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover M^(pro) inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 M^(pro) with IC(50) values of 0.4-3 μM. They were also…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of sulphonamide-tethered <em>N</em>-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease</strong> - SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel…</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 phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2</strong> - The 2’,5’- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened…</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>Mitochondria of lung venular capillaries mediate lung-liver crosstalk in pneumonia</strong> - Failure of the lung’s endothelial barrier underlies lung injury, which causes the high mortality Acute Respiratory Distress Syndrome (ARDS). Multiple organ failure predisposes to the mortality, but mechanisms are poorly understood. Here, we show that mitochondrial Uncoupling Protein 2 (UCP2), a component of the mitochondrial inner membrane, plays a role in the barrier failure. Subsequent lung-liver crosstalk mediated by neutrophil activation causes liver congestion. We intranasally instilled…</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>Cereals as a Source of Bioactive Compounds with Anti-Hypertensive Activity and Their Intake in Times of COVID-19</strong> - Cereals have phytochemical compounds that can diminish the incidence of chronic diseases such as hypertension. The angiotensin-converting enzyme 2 (ACE2) participates in the modulation of blood pressure and is the principal receptor of the virus SARS-CoV-2. The inhibitors of the angiotensin-converting enzyme (ACE) and the block receptors of angiotensin II regulate the expression of ACE2; thus, they could be useful in the treatment of patients infected with SARS-CoV-2. The inferior peptides from…</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>Recent advances in cholinergic mechanisms as reactions to toxicity, stress, and neuroimmune insults</strong> - This review presents recent studies of the chemical and molecular regulators of acetylcholine (ACh) signaling and the complexity of the small molecule and RNA regulators of those mechanisms that control cholinergic functioning in health and disease. The underlying structural, neurochemical, and transcriptomic concepts, including basic and translational research and clinical studies, shed new light on how these processes inter-change under acute states, age, sex, and COVID-19 infection; all of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of alpha-linolenic acid as a broad-spectrum antiviral against zika, dengue, herpes simplex, influenza virus and SARS-CoV-2 infection</strong> - Zika virus (ZIKV) has garnered global attention due to its association with severe congenital defects including microcephaly. However, there are no licensed vaccines or drugs against ZIKV infection. Pregnant women have the greatest need for treatment, making drug safety crucial. Alpha-linolenic acid (ALA), a polyunsaturated ω-3 fatty acid, has been used as a health-care product and dietary supplement due to its potential medicinal properties. Here, we demonstrated that ALA inhibits ZIKV…</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>Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy</strong> - The Transmembrane Protease Serine 2 (TMPRSS2) is a human enzyme which is involved in the maturation and post-translation of different proteins. In addition to being overexpressed in cancer cells, TMPRSS2 plays a further fundamental role in favoring viral infections by allowing the fusion of the virus envelope with the cellular membrane, notably in SARS-CoV-2. In this contribution, we resort to multiscale molecular modeling to unravel the structural and dynamical features of TMPRSS2 and its…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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