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<title>12 January, 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>ADAPTIVE TIME LOCATION SAMPLING FOR COMPASS, A SARS-COV-2 PREVALENCE STUDY IN FIFTEEN DIVERSE COMMUNITIES IN THE UNITED STATES</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVPN 5002 (COMPASS) study aimed to estimate the prevalence of SARS-CoV-2 (active SARS-CoV-2 or prior SARS-CoV-2 infection) in children and adults attending public venues in 15 socio-demographically diverse communities in the United States. To protect against potential challenges in implementing traditional sampling strategies, time-location sampling (TLS) using complex sampling involving stratification, clustering of units, and unequal probabilities of selection was used to recruit individuals from neighborhoods in selected communities. The innovative design adapted to constraints such as closure of venues; changing infection hotspots; and uncertain policies. Recruitment of children and the elderly raised additional challenges in sample selection and implementation. To address these challenges, the TLS design adaptively updated both the sampling frame and the selection probabilities over time using information acquired from prior weeks. Although the study itself was specific to COVID-19, the strategies presented in this paper could serve as a case study that can be adapted for performing rigorous population-level inferences in similar settings and could help inform rapid and effective responses to future global public health challenges.
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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/10.1101/2023.01.10.23284400v1" target="_blank">ADAPTIVE TIME LOCATION SAMPLING FOR COMPASS, A SARS-COV-2 PREVALENCE STUDY IN FIFTEEN DIVERSE COMMUNITIES IN THE UNITED STATES</a>
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</div></li>
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<li><strong>Exosome based multivalent vaccine: achieving potent immunization, broaden reactivity and T cell response with nanograms of proteins without any adjuvant.</strong> -
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<div>
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Exosome based vaccines represent an interesting opportunity in the pandemic time we live. Compared to the available vaccines, an exosome-based vaccine may answer to the need of efficacy and increased safety. Here, we used exosomes to deliver a “cocktail” protein-based vaccine, in which two independent viral proteins are delivered using the exosome membrane as carrier. Cells were engineered to express either SARS-CoV-2 Delta spike (StealthTM X-Spike, STX-S) or nucleocapsid (StealthTM X-Nucleocapsid, STX-N) protein on the surface and facilitate their trafficking to the exosomes. When administered as single product, both STX-S and STX-N induced a strong immunization with the production of a potent humoral and cellular immune response. Interestingly, these effects are obtained with administration of nanograms of protein and without adjuvant. Therefore, we developed a multivalent low dose vaccine, namely STX-S+N, using a teeter-toother dose approach of STX-S and STX-N. In two independent animal models (mouse and rabbit), administration of STX-S+N resulted in increased antibody production, potent neutralizing antibodies with cross-reactivity to other VOC and strong T-cell response. Importantly, no competition in immune response was observed. Our data show that our exosome platform has an enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation, and for therapeutics by enabling cell and tissue specific targeting.
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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/10.1101/2023.01.10.523356v1" target="_blank">Exosome based multivalent vaccine: achieving potent immunization, broaden reactivity and T cell response with nanograms of proteins without any adjuvant.</a>
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</div></li>
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<li><strong>Genetic determinants of severe COVID-19 in young Asian and Middle Eastern patients</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we use whole exome sequencing to characterize the genetic landscape of severe COVID-19 in a well phenotyped cohort of otherwise healthy, young adults (N=55; mean age 34.1 ± SD 5.0 years) representing 16 countries in Asia, the Middle East, and North Africa. Our findings show enrichment of rare, likely deleterious missense and truncating variants in interferon-mediated and bacterial infection-susceptibility genes, when compared to control, mildly affected, or asymptomatic COVID-19 patients (N = 25), or to general populations representing Asia and the Middle East. Genetic variants tended to associate with mortality, intensive care admission, and ventilation support. Our findings confirm the association of interferon pathway genes with severe COVID-19 and highlight the importance of extending genetic studies to diverse populations given implications for pan-ethnic therapeutic and genetic screening options.
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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/10.1101/2023.01.11.23284427v1" target="_blank">Genetic determinants of severe COVID-19 in young Asian and Middle Eastern patients</a>
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</div></li>
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<li><strong>Effectiveness of an eHealth Intervention for Reducing Psychological Distress and Increasing COVID-19 Knowledge and Protective Behaviors among Ethnoracially Diverse Sexual and Gender Minority Adults: A Quasi-experimental Study (#SafeHandsSafeHearts)</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Purpose: Lesbian, gay, bisexual, transgender, queer, and other persons outside of heteronormative and cisgender identities (LGBTQ+) and ethnic/racial minority populations are at heightened vulnerability amid the Covid-19 pandemic. Systemic marginalization and resulting adverse social determinants of health contribute to health disparities among these populations that result in more severe consequences due to Covid-19 and the public health measures to control it. We developed and tested a tailored online intervention (#SafeHandsSafeHearts) to support ethnoracially diverse LGBTQ+ individuals in Toronto, Canada amid the pandemic. Methods: We used a quasi-experimental pre-test post-test design to evaluate the effectiveness of a 3-session, peer-delivered eHealth intervention in reducing psychological distress and increasing Covid-19 knowledge and protective behaviors. Individuals ≥18-years-old, resident in Toronto, and self-identified as sexual or gender minority were recruited online. Depressive and anxiety symptoms, Covid-19 knowledge and protective behaviors were assessed at baseline, 2-weeks postintervention, and 2-months follow-up. We used generalized estimating equations and zero-truncated Poisson models to evaluate the effectiveness of the intervention on the four primary outcomes. Results: From March to November 2021, 202 participants (median age, 27 years [Interquartile rage: 23-32]) were enrolled in #SafeHandsSafeHearts. Over half (54%, n=110) identified as cisgender lesbian or bisexual women or women who have sex with women, 26.2% (n=53) cisgender gay or bisexual men or men who have sex with men, and 19.3% (n=39) transgender or nonbinary individuals. The majority (75.7%, n=143) were Black and other people of color. The intervention led to statistically significant reductions in the prevalence of clinically significant depressive and anxiety symptoms, and increases in Covid-19 protective behaviors from baseline to postintervention. Conclusion: We demonstrated the effectiveness of a brief, peer-delivered eHealth intervention for ethnoracially diverse LGBTQ+ communities in reducing psychological distress and increasing protective behaviors amid the Covid-19 pandemic. Implementation through community-based health services with trained peer educators supports feasibility, acceptability, and the importance of engaging ethnoracially diverse LGBTQ+ communities in pandemic response preparedness. This trial is registered with ClinicalTrials.gov, number NCT04870723.
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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/10.1101/2023.01.09.23284380v1" target="_blank">Effectiveness of an eHealth Intervention for Reducing Psychological Distress and Increasing COVID-19 Knowledge and Protective Behaviors among Ethnoracially Diverse Sexual and Gender Minority Adults: A Quasi-experimental Study (#SafeHandsSafeHearts)</a>
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</div></li>
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<li><strong>Interleukin-1 receptor antagonist gene (IL1RN) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2</strong> -
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<div>
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Objective. To explore the regulation of the inflammatory response in acute SARS-CoV-2 infection, we examined effects of single nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory IL1 receptor antagonist (IL1Ra), on the cytokine release syndrome and mortality. Methods. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021 at NYU Langone Tisch Hospital. CTA and TTG haplotypes formed from three SNVs (rs419598, rs315952, rs9005) and the individual SNVs of the IL1RN gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. Results. Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 to 1.00); 0.052), with the most pronounced effect observed between the ages of 55-74 [5.5% vs. 18.4%, p<0.001]. Conclusion. The IL1RN haplotype CTA, and sequence variant of rs419598 are associated with attenuation of the cytokine release syndrome and decreased mortality in males with acute SARS CoV2 infection. The data suggest that IL1RN modulates the COVID 19 cytokine release syndrome via endogenous anti inflammatory mechanisms.
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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/10.1101/2023.01.09.23284348v1" target="_blank">Interleukin-1 receptor antagonist gene (IL1RN) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2</a>
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</div></li>
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<li><strong>Bayesian sequential approach to monitor COVID-19 variants through positivity rate from wastewate</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Trends in COVID-19 infection have changed throughout the pandemic due to myriad factors, including changes in transmission driven by social behavior, vaccine development and uptake, mutations in the virus genome, and public health policies. Mass testing was an essential control measure for curtailing the burden of COVID-19 and monitoring the magnitude of the pandemic during its multiple phases. However, as the pandemic progressed, new preventive and surveillance mechanisms emerged. Implementing vaccine programs, wastewater (WW) surveillance, and at-home COVID-19 tests reduced the demand for mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. This paper proposes a sequential Bayesian approach to estimate the COVID-19 positivity rate (PR) using SARS-CoV-2 RNA concentrations measured in WW through an adaptive scheme incorporating changes in virus dynamics. PR estimates are used to compute thresholds for WW data using the CDC thresholds for low, substantial, and high transmission. The effective reproductive number estimates are calculated using PR estimates from the WW data. This approach provides insights into the dynamics of the virus evolution and an analytical framework that combines different data sources to continue monitoring the COVID-19 trends. These results can provide public health guidance to reduce the burden of future outbreaks as new variants continue to emerge. The proposed modeling framework was applied to the City of Davis and the campus of the University of California Davis.
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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/10.1101/2023.01.10.23284365v1" target="_blank">Bayesian sequential approach to monitor COVID-19 variants through positivity rate from wastewate</a>
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</div></li>
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<li><strong>Vaccine effectiveness against SARS-CoV-2 Delta and Omicron infection and infectiousness within households in the Netherlands between July 2021 and August 2022.</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Introduction. We aimed to estimate vaccine effectiveness against infection (VE-infection) and infectiousness (VE- infectiousness) in a household setting during Delta and Omicron. Knowing these effects can aid policy makers in deciding which groups to prioritize for vaccination. Methods. Participants with a positive SARS-CoV-2 test were asked about COVID-19 vaccination status and SARS-CoV-2 testing of their household members one month later. VE-infection and VE-infectiousness was estimated using GEE logistic regression adjusting for age and vaccination status, calendar week and household size. Results. 3,409 questionnaires concerning 4,123 household members were included. During the Delta-period, VE-infection of primary series was 47% (95% CI: -27%-78%) and VE-infectiousness of primary series was 70% (95% CI: 28%-87%). During the Omicron-period, VE-infection was -36% (95% CI: -88%-1%) for primary series and -30% (95% CI: -80%-6%) for booster vaccination. The VE-infectiousness was 45% (95% CI: -14%-74%) for primary series and 64% (95% CI: 31%-82%) for booster vaccination. Discussion. Our study shows that COVID-19 vaccination is effective against infection with SARS-CoV-2 Delta and against infectiousness of SARS-CoV-2 Delta and Omicron. Estimation of VE against infection with SARS-CoV-2 Omicron was limited by several factors. Our results support vaccination for those in close contact with vulnerable people to prevent transmission.
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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/10.1101/2023.01.10.23284386v1" target="_blank">Vaccine effectiveness against SARS-CoV-2 Delta and Omicron infection and infectiousness within households in the Netherlands between July 2021 and August 2022.</a>
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</div></li>
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<li><strong>A cross sectional survey examining the association of clinician characteristics with perceived changes in cervical cancer screening and colposcopy practice during the COVID-19 pandemic</strong> -
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<b>Background</b>: The COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed method study we explored perceived pandemic-related practice changes to cervical cancer screenings and colposcopies.
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</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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<b>Methods</b>: In 2021, a national sample of 1,251 clinicians completed surveys, including 675 clinicians who performed colposcopy; a subset (n=55) of clinicians completed qualitative interviews.
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</p>
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Results: Nearly half of all clinicians reported they were currently performing fewer cervical cancer screenings (47%) and colposcopies (44% of those who perform the procedure) than before the pandemic. About one-fifth (18.6%) of colposcopists reported performing fewer LEEPs than prior to the pandemic. Binomial regression analyses indicated that older, non-White, internal medicine and family medicine clinicians (compared to OB-GYNs), and those practicing in community health centers (compared to private practice) had higher odds of reporting reduced screening. Among colposcopists, males, internal medicine physicians, those practicing in community health centers, and in the South had higher odds of reporting reduced colposcopies. Qualitative interviews highlighted pandemic-related care disruptions and lack of tracking systems to identify overdue screenings.
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</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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<b>Conclusions</b>: Reductions in cervical cancer screening and colposcopy among nearly half of clinicians more than one year into the pandemic raise concerns that inadequate screening and follow-up will lead to future increases in preventable cancers.
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</p>
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<b>Funding</b>: This study was funded by the American Cancer Society, who had no role in the study’s design, conduct, or reporting.
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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/10.1101/2023.01.11.23284437v1" target="_blank">A cross sectional survey examining the association of clinician characteristics with perceived changes in cervical cancer screening and colposcopy practice during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Prior SARS-CoV-2 Infection and COVID-19 Vaccine Effectiveness against Outpatient Illness during Widespread Circulation of SARS-CoV-2 Omicron Variant, US Flu VE Network</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). Methods: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Results: 455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%, 99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%, 76%) against Omicron; VE against Delta could not be estimated. Conclusions: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.10.23284397v1" target="_blank">Prior SARS-CoV-2 Infection and COVID-19 Vaccine Effectiveness against Outpatient Illness during Widespread Circulation of SARS-CoV-2 Omicron Variant, US Flu VE Network</a>
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</div></li>
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<li><strong>Using early detection data to estimate the date of emergence of an epidemic outbreak</strong> -
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While the first infection by an emerging disease is often unknown, information on early cases can be used to date it, which is of great interest to trace the disease9s origin and understand early infection dynamics. In the context of the COVID-19 pandemic, previous studies have estimated the date of emergence (e.g., first human SARS-CoV-2 infection in Wuhan, emergence of the Alpha variant in the UK) using mainly genomic data. Another dating attempt only relied on case data, estimating a date of emergence using a non-Markovian stochastic model and considering the first case detection. Here, we extend this stochastic approach to use available data of the whole early case dynamics. Our model provides estimates of the delay from the first infection to the N<sup>th</sup> reported case. We first validate our model using data concerning the spread of the Alpha SARS-CoV-2 variant in the UK. Our results suggest that the first Alpha infection occurred on (median) August 20 (95% interquantile range across retained simulations, IqR: July 20-September 4), 2020. Next, we apply our model to data on the early reported cases of COVID-19. We used data on the date of symptom onset up to mid-January, 2020. We date the first SARS-CoV-2 infection in Wuhan at (median) November 26 (95%IqR: October 31-December 7), 2019. Our results fall within ranges previously estimated by studies relying on genomic data. Our population dynamics-based modelling framework is generic and flexible, and thus can be applied to estimate the starting time of outbreaks, in contexts other than COVID-19, as long as some key parameters (such as transmission and detection rates) are known.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.09.23284284v1" target="_blank">Using early detection data to estimate the date of emergence of an epidemic outbreak</a>
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</div></li>
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<li><strong>Did COVID-19 or COVID-19 vaccines influence the patterns of Dengue in 2021: An exploratory analysis of two observational studies from North India</strong> -
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Background Dengue which is endemic in India and has been occurring for decades apparently witnessed a rise in disease burden in 2021 in specific regions of the nation. We aim to explore less studied risk factors of Dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era. Methods This was an exploratory analysis involving participants from two prior observational studies conducted during the period of Feb 2021-April 2022 in a tertiary hospital in North India. Healthcare workers constituted the majority of study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: CovidNoVaccine (CNV), VaccineNoCOVID (VNC), CovidAfterVaccine (CAV), VaccineAfterCOVID (VAC) and NoVaccineNoCovid (NVNC) groups. The occurrence of lab-confirmed Dengue and severe forms of Dengue were the main outcomes of interest. We tried to predict determinants of Dengue occurrence and severity with a particular focus on COVID-19 history and vaccination status. Results A total of 1520 vaccinated individuals and 181 unvaccinated individuals were included. Of these 1701 participants, symptomatic Dengue occurred in 133 (7.8%) and was of 9severe9 category in 42 (31.6%). Individuals with a history of COVID-19 in 2020 had 2 times higher odds of developing symptomatic Dengue. The VAC group had 3.6, 2- and 1.9 times higher odds of developing Dengue than the NVNC, VNC, and CAV groups. The severity of dengue was not affected by COVID-19 or COVID-19 vaccination. Conclusions COVID-19 may enhance the risk of developing symptomatic dengue. Future research dealing with long COVID should explore the propensity of COVID-19 victims towards symptomatic forms of other viral illnesses. Individuals receiving the COVID-19 vaccine after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-mediated enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals. Further large-scale, multicentric, robust studies with a better enrolment of unvaccinated people will help understand the interplay of factors involved in COVID-19 and Dengue.
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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/10.1101/2023.01.09.23284366v1" target="_blank">Did COVID-19 or COVID-19 vaccines influence the patterns of Dengue in 2021: An exploratory analysis of two observational studies from North India</a>
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</div></li>
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<li><strong>Country Learning on Maintaining Quality Essential Health Services (EHS) during COVID-19 in Timor-Leste: A mixed methods qualitative analysis</strong> -
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Objective: This research study examines the enabling factors, strengths, and challenges experienced by the Timor-Leste health system as it sought to maintain quality essential health services (EHS) during the COVID-19 pandemic. Design: A mixed methods qualitative analysis Setting: National, municipal, facility levels in Baucau, Dili and Ermera Municipalities in TLS Participants Key informant interviews (n=40) and focus group discussions (n=6) working to maintain quality EHS in TLS. Results: A reduction in people accessing general health services was observed in 2020, reportedly due to fears of contracting COVID-19 in healthcare settings, limited resources (eg. human resources, personal protective equipment, clinical facilities, etc) and closure of health services. However, improvements in maternal child health services simultaneously improved in the areas of skilled birth attendants, prenatal coverage, and vitamin A distribution, for example. Five themes emerged as enabling factors for maintaining quality EHS including 1) high level strategy for maintaining quality EHS, 2) implementation of quality activities across the three levels of the health system, 3) measurement for quality and factors affecting service utilization 4) the positive impact of quality improvement leadership in health facilities during COVID-19, and 5) learning from each other for maintaining quality EHS now and for the future. Other countries may benefit from the challenges, strengths and enablers found on planning for quality. Conclusion: The maintenance of quality essential health services (EHS) is critical to mitigate adverse health effects from the COVID-19 pandemic. When quality health services are delivered prior to and maintained during public health emergencies, they build trust within the health system and promote healthcare seeking behavior. Planning for quality as part of emergency preparedness can facilitate a high standard of care by ensuring health services continue to provide a safe environment, reduce harm, improve clinical care, and engage patients, facilities, and communities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.11.23284424v1" target="_blank">Country Learning on Maintaining Quality Essential Health Services (EHS) during COVID-19 in Timor-Leste: A mixed methods qualitative analysis</a>
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</div></li>
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<li><strong>Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia</strong> -
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We report on an analysis of Australian COVID-19 case data to estimate the impact of TTIQ systems on SARS-CoV-2 transmission in 2020-21. We estimate that in a low prevalence period in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. In a higher prevalence period in the state of Victoria (hundreds of cases per day), TTIQ contributed to a 42% reduction in transmission. Our results also suggest that case-initiated contact tracing can support timely quarantine in times of system stress. Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy through 2020 and 2021.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.10.23284209v1" target="_blank">Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia</a>
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<li><strong>The impacts of COVID-19 and its policy response on access and utilization of maternal and child health services in Tanzania: a mixed methods study</strong> -
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The SARS-Cov-2 virus (COVID-19) has had a global social and economic impact. Despite the growing evidence, its effects on access and delivery of maternal and child health services in low-income countries are still unclear. This cross-sectional case study was conducted in Mjini Magharibi, Chake Chake, and Ilala districts in Tanzania to help fill this gap. The study combined qualitative and quantitative data collection methods, providing an account of the evolution of the pandemic and the associated control measures in Tanzania. We drew from 34 in-depth interviews, 60 semi-structured interviews, and 14 focus group discussions with key informants, patients, and health providers, and complemented the findings with a review of pandemic reports and health facility records. We followed the Standards for Reporting Qualitative Research to provide an account of the findings. Our account of the pandemic shows that there was a non-linear policy response in Tanzania, with diverse control measures adopted at various stages of the epidemic. There was a perception that COVID-19 services were prioritized during the epidemic at the expense of regular ones. There were reports of reorganisation of health facilities, reallocation of staff, rescheduled antenatal and postnatal clinics, and reduced time for health education and child monitoring. Scarcity of essential commodities was reported, such as vaccines, equipment, and medical supplies. Such perceptions were in part supported by the routine utilization evidence in the three districts, showing a lower uptake of antenatal, postnatal, family planning, and immunization services, as well as fewer institutional deliveries. Our findings suggest that, despite the erratic policy response in Tanzania, fear caused by the pandemic and the diversion of resources to control COVID-19 may have contributed most to lower the utilization of mother and child services. For future emergencies, it will be crucial to ensure the policy response does not weaken the population’s demand for services.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.11.23284423v1" target="_blank">The impacts of COVID-19 and its policy response on access and utilization of maternal and child health services in Tanzania: a mixed methods study</a>
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<li><strong>Validation of a MALDI-TOF MS method for SARS-CoV-2 detection on the Bruker Biotyper and nasopharyngeal swabs. A Brazil - UK collaborative study.</strong> -
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We had developed a MALDI-TOF mass spectrometry method for detection of SARS-CoV-2 virus in saliva-gargle samples using Shimadzu MALDI-TOF mass spectrometers in the UK. This was validated in the USA to CLIA-LDT standards for asymptomatic infection detection remotely via sharing protocols, shipping key reagents, video conference and data exchange. In Brazil, more so than in the UK and USA, there is a need to develop non-PCR dependent rapid affordable SARS-CoV-2 infection screening tests, which also identify variant SARS-CoV-2 and other virus infections. Travel restrictions necessitated remote collaboration with validation on the available Clinical MALDI-TOF - the Bruker Biotyper (microflex LT/SH) - and on nasopharyngeal swab samples, as salivary gargle samples were not available. The Bruker Biotyper was shown to be almost log10^3 more sensitive at detection of high molecular weight spike proteins. A protocol for saline swab soaks out was developed and duplicate swab samples collected in Brazil were analysed by MALDI-TOF MS. The swab collected sample spectra varied from that of gargle-saliva in three additional mass peaks in the mass region expected for IgG heavy chains and human serum albumin. A subset of clinical samples with additional high mass, probably Spike-related proteins, were also found. Spectral data comparisons and analysis, subjected to machine learning algorithms in order to resolve RT-qPCR positive from RT-qPCR negative swab samples, showed a 78% agreement with RT-qPCR scoring for SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.09.23284367v1" target="_blank">Validation of a MALDI-TOF MS method for SARS-CoV-2 detection on the Bruker Biotyper and nasopharyngeal swabs. A Brazil - UK collaborative study.</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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<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 and Safety of Jaktinib in Patients With COVID-19 Pneumoia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Jaktinib; Drug: Placebo<br/><b>Sponsor</b>: First Affiliated Hospital of Zhejiang University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<br/><b>Enrolling by invitation</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>Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Traditional Chinese Medicine Formulation; Other: Placebo Treatment<br/><b>Sponsor</b>: First Affiliated Hospital Xi’an Jiaotong University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 dose 1; Drug: SHEN26 dose 2; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SA58 Nasal Spray; Drug: Placebo<br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd.; Beijing Ditan 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>Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: CoronaVac/CoronaVac; Biological: CoronaVac/BNT162b2<br/><b>Sponsor</b>: Institut Pasteur de Tunis<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 on the Safety and Efficacy of Meplazumab for Injection in Adults With Mild and Moderate COVID-19 Infections</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Positive Emotions With Long COVID-19</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Microdosing of mindfulness<br/><b>Sponsor</b>: University of California, Davis<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>An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: Prevention of COVID-19 Caused by SARS-CoV-2<br/><b>Intervention</b>: Biological: randomized, double-blinded, placebo-controlled<br/><b>Sponsor</b>: Yu Qin<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 the Anti-COVID-19 Antibody SA55 for Injection in Patients With Hematological Malignancies Who Are Persistently Positive for COVID-19</strong> - <b>Conditions</b>: Hematological Malignancy; COVID-19<br/><b>Intervention</b>: Biological: Anti-COVID-19 Antibody SA55 for Injection<br/><b>Sponsor</b>: Beijing Boren 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>A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia</strong> - <b>Conditions</b>: Chronic Lymphocytic Leukemia; COVID-19 Infection<br/><b>Interventions</b>: Procedure: Biospecimen Collection; Biological: mRNA COVID-19 Vaccine; Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1<br/><b>Sponsors</b>: City of Hope Medical Center; National Cancer Institute (NCI)<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular mechanisms in chloroquine-exposed muscle cells elucidated by combined proteomic and microscopic studies</strong> - CONCLUSION: We demonstrated that CQ exposure (secondarily) impacts biological processes beyond lysosomal function and linked a variety of proteins with known roles in the manifestation of other neuromuscular diseases.</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>Predicting the systemic exposure and lung concentration of nafamostat using physiologically-based pharmacokinetic modeling</strong> - Nafamostat has been actively studied for its neuroprotective activity and effect on various indications, such as coronavirus disease 2019 (COVID-19). Nafamostat has low water solubility at a specific pH and is rapidly metabolized in the blood. Therefore, it is administered only intravenously, and its distribution is not well known. The main purposes of this study are to predict and evaluate the pharmacokinetic (PK) profiles of nafamostat in a virtual healthy population under various dosing…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome</strong> - Dexamethasone (DEX) is a potent synthetic glucocorticoid used for the treatment of variety of inflammatory and immune-mediated disorders. The RECOVERY clinical trial revealed benefits of DEX therapy in COVID-19 patients. Severe SARS-CoV-2 infection leads to an excessive inflammatory reaction commonly known as a cytokine release syndrome that is associated with activation of the toll like receptor 4 (TLR4) signaling pathway. The possible mechanism of action of DEX in the treatment of COVID-19 is…</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>P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions</strong> - BACKGROUND: Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.</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>4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine</strong> - RNA structure plays an important role in regulating cellular function and there is a significant emerging interest in targeting RNA for drug discovery. Here we report the identification of 4-aminoquinolines as modulators of RNA structure and function. Aminoquinolines have a broad range of pharmacological activities, but their specific mechanism of action is often not fully understood. Using electrophoretic mobility shift assays and enzymatic probing we identified 4-aminoquinolines that bind the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sleep as a protective factor of children’s executive functions: A study during COVID-19 confinement</strong> - Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children’s sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental…</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 Y-Shaped, S-O-N-O-S-Bridged Cross-Link between Three Residues C22, C44, and K61 Is Frequently Observed in the SARS-CoV-2 Main Protease</strong> - As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (M^(Pro)) for pathogenesis and replication. During crystallographic analyses of M^(Pro) crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged post-translational cross-link that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel covalent modification, this cross-link serves potentially as a redox switch to regulate the catalytic activity of M^(Pro), 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>Environmentally persistent free radicals enhance SARS-CoV-2 replication in respiratory epithelium</strong> - Epidemiological evidence links lower air quality with increased incidence and severity of COVID-19; however, mechanistic data have yet to be published. We hypothesized air pollution-induced oxidative stress in the nasal epithelium increased viral replication and inflammation. Nasal epithelial cells (NECs), collected from healthy adults, were grown into a fully differentiated epithelium. NECs were infected with the ancestral strain of SARS-CoV-2. An oxidant combustion by-product found in air…</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 computational study on the molecular mechanisms of panduratin A as a potential inhibitor on SARS-CoV-2 protein targets</strong> - Panduratin A from Boesebergia rotunda was recently reported as a potent anti-SARS-CoV-2 compound. However, the molecular mechanisms underlying the inhibition by Panduratin A and its target remained unclear. Molecular docking calculations were performed between panduratin A and five important proteins, i.e., main protease (Mpro), papain-like protease (PLpro), receptor binding domain (RBD) of spike proteins, RNA-dependent-RNA-polymerase (RdRp), and 2’-O-methyltransferase (MTase). The estimated…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-inflammatory and antiviral activities of flavone <em>C</em>-glycosides of <em>Lophatherum gracile</em> for COVID-19</strong> - Lophatherum gracile (L. gracile) has long been used as a functional food and herbal medicine. Previous studies have demonstrated that extracts of L. gracile attenuate inflammatory response and inhibit SARS-CoV-2 replication; however, the underlying active constituents have yet to be identified. This study investigated the bioactive components of L. gracile. Flavone C-glycosides of L. gracile were found to dominate both anti-inflammatory and antiviral effects. A simple chromatography-based method…</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>Hypercapnia alters stromal-derived Wnt production limiting β-catenin signaling and proliferation in alveolar type 2 cells</strong> - Persistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with ARDS secondary to SARS-CoV-2 pneumonia, low tidal volumes to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here, using a mouse model 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>A simple in-host model for COVID-19 with treatments: model prediction and calibration</strong> - In this paper, we provide a simple ODEs model with a generic nonlinear incidence rate function and incorporate two treatments, blocking the virus binding and inhibiting the virus replication to investigate the impact of calibration on model predictions for the SARS-CoV-2 infection dynamics. We derive conditions of the infection eradication for the long-term dynamics using the basic reproduction number, and complement the characterization of the dynamics at short-time using the resilience 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 nanomolar affinity of C-phycocyanin from virtual screening of microalgal bioactive as potential ACE2 inhibitor for COVID-19 therapy</strong> - The global pandemic of COVID-19 caused by SARS-CoV-2 has caused more than 400 million infections with more than 5.7 million deaths worldwide, and the number of validated therapies from natural products for treating coronavirus infections needs to be increased. Therefore, the virtual screening of bioactive compounds from natural products based on computational methods could be an interesting strategy. Among many sources of bioactive natural products, compounds from marine organisms, particularly…</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>Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents</strong> - CONCLUSION: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIME^(R) for the delivery of siRNAs in both cell lines.</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>Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage</strong> - CONCLUSIONS: These results suggest that PP stimulation may contribute to inflammation pathogenesis via the p38 phosphorylation-mediated NF-κB pathway as a result of mitochondrial damage.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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