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<title>09 January, 2022</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>Comprehensive analysis of disease pathology in immunocompetent and immunocompromised hamster models of SARS-CoV-2 infection</strong> -
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The pathogenesis of SARS-CoV-2 in the context of a specific immunological niche is not fully understood. Here, we used a golden Syrian hamster model to systematically evaluate the kinetics of host response to SARS-CoV-2 infection, following disease pathology, viral loads, antibody responses, and inflammatory cytokine expression in multiple organs. The kinetics of SARS-CoV-2 pathogenesis and genomewide lung transcriptome was also compared between immunocompetent and immunocompromised hamsters. We observed that the body weight loss was proportional to the SARS-CoV-2 infectious dose and lasted for a short time only in immunocompetent hamsters. Body weight loss was more prominent and prolonged in infected immunocompromised hamsters. While the kinetics of viral replication and peak live viral loads were not significantly different at low and high infectious doses (LD and HD), the HD-infected immunocompetent animals developed severe lung disease pathology. The immunocompetent animals cleared the live virus in all tested tissues by 12 days post-infection and generated a robust serum antibody response. In contrast, immunocompromised hamsters mounted an inadequate SARS-CoV-2 neutralizing antibody response, and the virus was detected in the pulmonary and multiple extrapulmonary organs until 16 days post-infection. These hamsters also had prolonged moderate inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the difference in disease presentation, distinct changes in the expression of inflammation and immune cell response pathways and network genes were seen in the lungs of infected immunocompetent and immunocompromised animals. This study highlights the interplay between the kinetics of viral replication and the dynamics of SARS-CoV-2 pathogenesis at organ-level niches and maps how COVID-19 symptoms vary in different immune contexts. Together, our data suggest that the histopathological manifestations caused by progressive SARS-CoV-2 infection may be a better predictor of COVID-19 severity than individual measures of viral load, antibody response, and cytokine storm at the systemic or local (lungs) levels in the immunocompetent and immunocompromised hosts.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.07.475406v1" target="_blank">Comprehensive analysis of disease pathology in immunocompetent and immunocompromised hamster models of SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19</strong> -
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Background: Long COVID or long-term complication after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe cases. We did this study to estimate the prevalence and identify the characteristics and predictors of Long COVID among our patients. Methodology: We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristic of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID. Results: We have analyzed 487 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47). Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) participants. Prevalence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n=72). The most common Long COVID symptom was fatigue (64.8%) followed by cough (32.4%). Statistically significant predictors of Long COVID were - Pre-existing medical conditions (Adjusted Odds ratio (aOR)=2.00, 95% CI: 1.16,3.44), having a more significant number of symptoms during acute phase of COVID-19 disease (aOR=11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR=2.32, 95% CI: 1.17,4.58), the severity of illness (aOR=5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR)=3.89, 95% CI: 2.49,6.08). Conclusion: A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.04.21268536v1" target="_blank">Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19</a>
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</div></li>
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<li><strong>VarLOCK - sequencing independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance</strong> -
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The COVID-19 pandemic continues to pose a threat to the general population. The ongoing vaccination programs provide protection to individuals and facilitate the opening of society and a return to normality. However, emergent and existing SARS-CoV-2 variants capable of evading the immune system endanger the efficacy of the vaccination strategy. To preserve the efficacy of SARS-CoV-2 vaccination globally, aggressive and effective surveillance for known and emerging SARS-CoV-2 Variants of Concern (VOC) is required. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. In this work, we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to allow rapid and sensitive discrimination of VOCs, that can be used at point of care and/or implemented in the pipelines of small or large testing facilities, and even determine proportion of VOCs in pooled population-level wastewater samples. This technology aims to complement the ongoing sequencing efforts to allow facile and, crucially, rapid identification of individuals infected with VOCs to help break infection chains. Here, we show the optimisation of our VarLOCK assays (Variant-specific SHERLOCK) for multiple specific mutations in the S gene of SARS-CoV-2 and validation with samples from the Cardiff University Testing Service. We also show the applicability of VarLOCK to national wastewater surveillance of SARS-CoV-2 variants. In addition, we show the rapid adaptability of the technique for new and emerging VOCs such as Omicron.
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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/10.1101/2022.01.06.21268555v1" target="_blank">VarLOCK - sequencing independent, rapid detection of SARS-CoV-2 variants of concern for point-of-care testing, qPCR pipelines and national wastewater surveillance</a>
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<li><strong>Comparison of infectious SARS-CoV-2 from the nasopharynx of vaccinated and unvaccinated individuals</strong> -
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The frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinated and 53 unvaccinated individuals, to assess the levels of infectious virus in vaccinated and unvaccinated individuals. Quantitative plaque assays showed no significant differences in the titers of virus between these cohorts. However, the proportion of nasopharyngeal samples with culturable virus was lower in the vaccinated patients relative to unvaccinated patients (21% vs. 40%). Finally, time-to-event analysis with Kaplan-Myer curves revealed that protection from culturable infectious virus waned significantly starting at 5 months after completing a 2-dose regimen of mRNA vaccines. These results have important implications in timing of booster dose to prevent onward transmission from breakthrough cases.
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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/10.1101/2021.12.28.21268460v2" target="_blank">Comparison of infectious SARS-CoV-2 from the nasopharynx of vaccinated and unvaccinated individuals</a>
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<li><strong>Prediction of Subsequent Need for Intensive Oxygen Supplementation in Galveston, Texas: A Retrospective Cohort Study and Multivariable Regression Model of Unvaccinated COVID-19 Patients</strong> -
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Objective The severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has caused a pandemic claiming more than 4 million lives worldwide. Overwhelming Coronavirus-Disease-2019 (COVID-19) respiratory failure placed tremendous demands on healthcare systems increasing the death toll. Cost-effective prognostic tools to characterize COVID-19 patients9 likely to progress to severe hypoxemic respiratory failure are still needed. Design We conducted a retrospective cohort study to develop a model utilizing demographic and clinical data collected in the first 12-hours admission to explore associations with severe hypoxemic respiratory failure in unvaccinated and hospitalized COVID-19 patients. Setting University based healthcare system including 6 hospitals located in the Galveston, Brazoria and Harris counties of Texas. Participants Adult patients diagnosed with COVID-19 and admitted to one of six hospitals between March 19th and June 31st, 2020. Primary outcome The primary outcome was defined as reaching a WHO ordinal scale between 6-9 at any time during admission, which corresponded to severe hypoxemic respiratory failure requiring high-flow oxygen supplementation or mechanical ventilation. Results We included 329 participants in the model cohort and 62 (18.8%) met the primary outcome. Our multivariable regression model found that lactate dehydrogenase (OR 3.38 (95% CI 2.04-5.59)), qSOFA score (OR: 2.24 (95% CI 1.22-4.12)), neutrophil to lymphocyte ratio (OR:1.08 (95% CI 1.02-1.14)), age (OR: 1.04 (95% CI 1.02-1.07)), BMI (OR: 1.08 (95% CI1.03-1.13)), oxygen saturation or admission SpO2 (OR: 0.91 (95% CI 0.83-0.99)), and admission date (OR: 0.99 (95% CI 0.98-0.99)). The final model showed an area under curve (AUC) of 0.85. The sensitivity analysis and point of influence analysis did not reveal inconsistencies. Conclusions Our study demonstrated that a combination of accessible demographic and clinical information provide a powerful predictive tool to identify subjects with CoVID-19 likely to progress to severe hypoxemic respiratory failure.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.05.21265970v2" target="_blank">Prediction of Subsequent Need for Intensive Oxygen Supplementation in Galveston, Texas: A Retrospective Cohort Study and Multivariable Regression Model of Unvaccinated COVID-19 Patients</a>
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<li><strong>Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)</strong> -
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Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020 and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. Results: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.29, 1.06-1.57, P-trend=0.01), body mass index (BMI) ≥25 vs <25 kg/m <sub>2</sub> (1.24, 1.11-1.39), Asian/Asian British vs White ethnicity (1.65, 1.10-2.49), and alcohol consumption ≥15 vs 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with decreased risk (0.80, 0.70-0.93, for ≥10 vs 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥30 vs <25 kg/m<sub>2</sub> (aGMR 1.10, 1.02-1.19), Asian/Asian British vs White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16), and number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.12, 1.02-1.23, P-trend=0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. Conclusions: Higher alcohol consumption and reduced light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.02.21265767v2" target="_blank">Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)</a>
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<li><strong>Temporary hold of mycophenolate boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients</strong> -
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Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept- treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.05.21268478v1" target="_blank">Temporary hold of mycophenolate boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients</a>
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<li><strong>Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial</strong> -
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Background: Neutralising antibody responses to SARS-CoV-2 vaccines have been reported to decline within 6 months of vaccination, particularly against Variants of Concern (VOC). We assessed the immunogenicity and safety of a booster dose of BBV152 administered 6 months after the second of a two-dose primary vaccination series. Methods: In an ongoing phase 2 trial (ClinicalTrials.gov: NCT04471519) the protocol was amended after six months to re-consent and randomise 184 previously vaccinated participants to receive a third dose of vaccine or placebo on Day 215. The primary outcome was to measure neutralising antibody titres by plaque-reduction neutralisation test (PRNT50) four weeks after the booster; safety as serious adverse events (SAE) was the key secondary outcome. Findings: Four weeks after a second BBV152 vaccination geometric mean titres (GMTs) of neutralising antibodies were 197.0 PRNT50 (95% CI: 155.6,249.4); this level declined to 23.9 PRNT50 (14.0,40.6) six months later, with a seroconversion rate of 75.4% (95% CI: 68.4,81.6). Four weeks after booster vaccination the GMT increased on Day 243 to 746.6 PRNT50 (514.9,1081) compared with 100.7 PRNT50 (43.6,232.6) in the placebo group. Corresponding seroconversion rates were 98.7% (92.8,99.9) and 79.8% (69.6,87.8). Increased titres in the placebo group were attributed to natural infection as the study was conducted during the second wave of COVID-19 in India. PRNT50 titres against the SARS-CoV-2 variants increased Alpha (32.6 fold), Beta (161.0 fold), Delta (264.7 fold), and Delta plus (174.2 fold) after the booster vaccination. We found that vaccine induces both memory B and T cells with a distinct AIM+ specific CD4+T central and effector memory phenotype, including CD8+ TEMRA phenotype. Reactogenicity after vaccine and placebo was minimal and comparable, and no SAEs were reported. Interpretation: Six months after a two dose BBV152 vaccination series cell mediated immunity and neutralising antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralising antibodies against homologous and heterologous SARS-CoV-2 variants increased 19 to 97 fold after a third vaccination. Booster BBV152 vaccination is safe and may be necessary to ensure persistent immunity to prevent breakthrough infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.05.22268777v1" target="_blank">Persistence of immunity and impact of a third (booster) dose of an inactivated SARS-CoV-2 vaccine, BBV152; a phase 2, double-blind, randomised controlled trial</a>
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<li><strong>The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Black Queen rule</strong> -
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The nature and dynamics of mutations associated with the emergence, spread and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (Marseille-4) for 10 months since its onset in July 2020. Here, we analysed and classified into subvariants and lineages 7,453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1+/-1.4 months, during which 4.1+/-2.6 mutations accumulated. Growth rate was 0.079+/-0.045, varying from 0.010 to 0.173. All the lineages exhibited a gamma distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in several mink lineages and in the alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.04.22268715v1" target="_blank">The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Black Queen rule</a>
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<li><strong>Innate and adaptive immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in elderly people</strong> -
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The immune factors associated with impaired SARS-CoV-2 vaccine response in the elderly are mostly unknown. We studied old and young people vaccinated with SARS-CoV-2 BNT162b2 mRNA before and after the first and second dose. Aging was associated with a lower anti-RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2 specific T cell response. The dramatic decrease in thymic function in the elderly, which fueled alteration in T cell homeostasis, and lower CD161+ T cell levels were associated with decreased T cell response two months after vaccination. Additionally, a deficient dendritic cell (DC) homing, activation and Toll like receptor (TLR)-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the elderly, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.07.22268806v1" target="_blank">Innate and adaptive immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in elderly people</a>
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<li><strong>Exploring the health impacts and inequalities of the new way of working: findings from a cross-sectional study.</strong> -
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Aim To explore the working Welsh adult population9s ability to work from home, their preferences for the future, and the self-reported health impacts of home-working. Subject and Method: A nationally-representative household survey was undertaken across Wales (Public Health Wales9 COVID-19, Employment and Health in Wales study), with cross-sectional data on home-working being collected between November 2020 and January 2021 from 615 employed working-aged adults in Wales (63.7% female, 32.7% aged 50-59). Respondents were asked about their ability to work from home, their perceptions of its impact on their health and their preferences for time spent home-working in future. Results Over 50% were able to work from home, and showed a preference towards home-working to some capacity, with over a third wishing to work from home at least half the time. However, those living in the most deprived areas, in atypical employment, with high wage precarity or with limiting pre-existing conditions were less likely to report being able to work from home. Of those that could work from home, over 40% reported that it worsened their mental well-being and loneliness, and for people in poorer health, home-working negatively impacted their diet, physical activity, smoking and alcohol use. People aged 30 to 39 and those who lived alone were more likely to report wanting to spend some time working in an office/base instead of at home. Conclusion The inequity in the ability to work from home reflects underlying inequalities in Wales, with those facing the greatest insecurity (e.g. those living in most deprived areas, those with more precarious work or financial circumstances) being less able to participate in home-working. Working from home offers greater flexibility, reduces the financial and time costs associated with commuting, and protects individuals from exposure to communicable diseases. However, working from home presents an enormous challenge to preserving the mental-wellbeing of the workforce, particularly for younger individuals and those with low mental well-being. Younger respondents and those in poorer health who could work from home were also more likely to engage in health-harming behaviours, and reduce their engagement in health-protective behaviours such as eating well and moving more. Reflecting on the future, providing pathways for accessing work from home arrangements, integrating hybrid models and preparing targeted health support for at risk groups may be best suited to the working population9s preferences and needs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.07.22268797v1" target="_blank">Exploring the health impacts and inequalities of the new way of working: findings from a cross-sectional study.</a>
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<li><strong>Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19</strong> -
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Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glyco-isoform distributions of 597 abundant serum glycopeptides and non-glycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR<0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated, between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glyco-isoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or of susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding, and, potentially, the clinical management of serious acute infectious conditions.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.07.21267956v1" target="_blank">Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19</a>
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</div></li>
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<li><strong>Consensus on COVID-19 vaccination in pediatric oncohematological patients, on behalf of infectious working group of Italian Association of Pediatric Hematology Oncology</strong> -
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<div>
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Vaccines represent the best tool to prevent the severity course and fatal consequences of pandemic by new Coronavirus 2019 infection (SARS CoV 2). Considering the limited data on vaccination of pediatric oncohematological patients, we develop a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS CoV 2 infection and disease (COVID 19) in the pediatric subject s; COVID 19 vaccines (type, schedule); which and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID 19; and other general prevention measures. Using the Delphi methodology fo r Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. AIEOP Centers showed an overall agreement on all the statements that were therefore approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID19, to permit the regular administration of chemotherapy or other treatmen ts, to perform control visits and hospital admissions, and to prevent treatment delays.
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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/10.1101/2022.01.06.22268792v1" target="_blank">Consensus on COVID-19 vaccination in pediatric oncohematological patients, on behalf of infectious working group of Italian Association of Pediatric Hematology Oncology</a>
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</div></li>
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<li><strong>Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants</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 The recently emerged SARS-CoV-2 omicron variant raised concerns around potential escape from vaccine- elicited immunity. Limited data are available on real-world vaccine effectiveness (VE) of mRNA-1273 against omicron. Here, we report VE of 2 or 3 mRNA-1273 doses against infection and hospitalization with omicron and delta, including among immunocompromised individuals. Methods This test negative study was conducted at Kaiser Permanente Southern California. Cases were individuals aged ≥18 years testing positive by RT-PCR with specimens collected between 12/6/2021 and 12/23/2021 with variant determined by spike gene status. Randomly sampled test negative controls were 5:1 matched to cases by age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression models were used to evaluate adjusted odds ratio (aOR) of vaccination with mRNA-1273 doses between cases and controls. VE(%) was calculated as (1-aOR)x100. Results 6657 test positive cases (44% delta, 56% omicron) were included. The 2-dose VE against omicron infection was 30.4% (95% CI, 5.0%-49.0%) at 14-90 days after vaccination and declined quickly thereafter. The 3-dose VE was 95.2% (93.4%-96.4%) against delta infection and 62.5% (56.2%-67.9%) against omicron infection. The 3-dose VE against omicron infection was low among immunocompromised individuals (11.5%; 0.0%-66.5%). None of the cases (delta or omicron) vaccinated with 3 doses were hospitalized compared to 53 delta and 2 omicron unvaccinated cases. Conclusions VE of 3 mRNA-1273 doses against infection with delta was high and durable, but VE against omicron infection was lower. VE against omicron infection was particularly low among immunocompromised individuals. No 3-dose recipients were hospitalized for COVID-19.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.07.22268919v1" target="_blank">Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants</a>
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</div></li>
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<li><strong>Statewide Impact of COVID-19 on Social Determinants of Health - A First Look: Findings from the Survey of the Health of Wisconsin</strong> -
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There is an urgent need to track the early and ongoing impact of the COVID-19 pandemic on population health from local to global scales. At the same time, there is an overall lack of U.S. state-specific surveillance data tracking social determinants of health (SDOH) and associations with population well-being, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic in populations. Statewide data can offer important insights into how SDOH shape the long-term effects of COVID-19 in the population since implementation of many policies and programs varied widely early on in the pandemic. In May of 2020, the Survey of the Health of Wisconsin (SHOW) program launched a statewide online/phone survey of early and ongoing impacts of COVID-19 on health and well-being across diverse communities and families. The goal of this study is to provide descriptive data including perceived COVID-19 risks, access to and results of COVID-19 antigen testing, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic on health and mental health in populations. Key findings include higher rates of testing and perceived past infection from COVID-19 among non-white respondents. Higher economic shifts and job changes in female vs male respondents. Families with children reported overall higher levels of stress, and stress from the pandemic. There were urban and rural differences in changes to access to care. Rural regions, which had a lower prevalence of infections early in the pandemic as compared to urban areas, also reported fewer delays or missed appointments due to COVID-19. Key findings show that SDOH are shaping impacts of health and well-being early on in the pandemic and future longitudinal follow-up will be important to shape policies and programs well into the future.
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</p>
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.18.21252017v2" target="_blank">Statewide Impact of COVID-19 on Social Determinants of Health - A First Look: Findings from the Survey of the Health of Wisconsin</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<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>Phase III Study of Novaferon in Non-hospitalized Adult Patients With Mild COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: Novaferon; Biological: Placebo<br/><b>Sponsors</b>: Genova Inc.; Tokyo Shinagawa 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>Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Human COVID-19 immunoglobulin (pH4) for intravenous injection; Drug: Placebo<br/><b>Sponsors</b>: Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd.; China National Biotec Group Company Limited; Beijing Tiantan Biological Products 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>A Telemedicine Brief Mindfulness Intervention in Post-COVID-19</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Other: Mindfulness<br/><b>Sponsors</b>: <br/>
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Fondazione Don Carlo Gnocchi Onlus; Catholic University of the Sacred Heart<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>Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo<br/><b>Sponsors</b>: Cinnagen; Vaxine Pty Ltd<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>Quality of Life and Lung Function on Post Covid-19 Patient</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise, Aerobic exercises<br/><b>Sponsor</b>: Qassim University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety, Tolerability, and Efficacy Study of IBI314 in Mild to Moderate Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: IBI314(low dose); Biological: IBI314(high dose); Biological: IBI314(medium dose); Other: Placebo<br/><b>Sponsor</b>: <br/>
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Innovent Biologics (Suzhou) 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>PTX-COVID19-B, an mRNA Humoral Vaccine, Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Demonstrate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B in Comparison to the Pfizer- BioNTech COVID-19 Vaccine.</strong> - <b>Condition</b>: Covid19 Vaccine<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Pfizer- BioNTech COVID-19 vaccine; Biological: Placebo<br/><b>Sponsor</b>: Providence Therapeutics Holdings 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>Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients.</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Drug: Raloxifene; Other: Placebo<br/><b>Sponsor</b>: Dompé Farmaceutici S.p.A<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>Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated<br/><b>Sponsor</b>: PT. Kimia Farma (Persero) Tbk<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>Spa Rehabilitation, Antioxidant and Bioenergetic Supportive Treatment of Patients With Post-Covid-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Dietary Supplement: ubiquinol (reduced coenzyme Q10); Other: mountain spa rehabilitation; Diagnostic Test: 2x14 ml of peripheral blood collected in a tube with anticoagulant<br/><b>Sponsors</b>: Comenius University; Sanatórium of Dr. Guhr, n.o.<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>Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial</strong> - <b>Conditions</b>: COVID-19; Long-COVID<br/><b>Interventions</b>: Other: symptom-focused rehabilitation; Other: usual care<br/><b>Sponsors</b>: Schön Klinik Berchtesgadener Land; Bavarian State Office for Health and Food Safety; Praxis im Zentrum Erlangen; Pneumologen Lichterfelde Berlin; Pneumopraxis Marburg; COVID ambulance Philipps-University Marburg; Pneumologie Elisenhof Munich; COVID ambulance Pneumology LMU Munich; COVID ambulance psychology LMU Munich; University Clinic Augsburg; COVID ambulance Schön Klinik Schönau<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Effect of Nicotinamide Mononucleotide (NMN) As an Adjuvant to Standard of Care (SOC) On Fatigue Associated With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Other: Nicotinamide Mononucleotide; Other: Nicotinamide Mononucleotide with L-Leucine; Other: Placebo<br/><b>Sponsor</b>: <br/>
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Vedic Lifesciences Pvt. 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>A Live Recombinant Newcastle Disease Virus-vectored COVID-19 Vaccine Phase 1 Study.</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Drug: Sodium Chloride; Biological: NDV- HXP-S IN low dose; Biological: NDV-HXP-S IM low dose; Biological: NDV-HXP-S IN high dose; Biological: NDV- HXP-S IM high dose<br/><b>Sponsor</b>: Sean Liu<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 Effectiveness of RPSG Intervention for Nurses During the COVID-19</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Interventions</b>: Behavioral: RPSG; Behavioral: AVMBM<br/><b>Sponsor</b>: National Taiwan University Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Reactogenicity, and Immunogenicity Study of Heterologous Booster Vaccination of a SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510)</strong> - <b>Condition</b>: COVID-19 (Healthy Volunteers)<br/><b>Interventions</b>: Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03; Other: Normal saline<br/><b>Sponsors</b>: Korea University Guro Hospital; Korean Center for Disease Control and Prevention<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<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>Anthranilamides with quinoline and β-carboline scaffolds: design, synthesis, and biological activity</strong> - In the present study, we report the design and synthesis of novel amide-type hybrid molecules based on anthranilic acid and quinoline or β-carboline heterocyclic scaffolds. Three types of biological screenings were performed: (i) in vitro antiproliferative screening against a panel of solid tumor and leukemia cell lines, (ii) antiviral screening against several RNA viruses, and (iii) anti-quorum sensing screening using gram-negative Chromobacterium violaceum as the reporter strain….</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 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1</strong> - A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients’ lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 NSP13 Inhibits Type I IFN Production by Degradation of TBK1 via p62-Dependent Selective Autophagy</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has seriously threatened global public health. Severe COVID-19 has been reported to be associated with an impaired IFN response. However, the mechanisms of how SARS-CoV-2 antagonizes the host IFN response are poorly understood. In this study, we report that SARS-CoV-2 helicase NSP13 inhibits type I IFN production by directly targeting TANK-binding kinase 1 (TBK1) for degradation….</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>Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells</strong> - Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (T(RM)) cells can mediate local immune protection against infections and cancer. Less beneficially, lung T(RM) cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. 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>Monoclonal antibodies and their target specificity against SARS-CoV-2 infections: Perspectives and challenges Short title: Monoclonal antibodies and SARS-CoV-2 infections</strong> - The world continues to be in the midst of a distressing pandemic of coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel virus with multiple antigenic systems. The virus enters via nasopharynx, oral and infects cells by the expression of the spike protein, and enters the lungs using the angiotensin-converting enzyme-2 receptor. The spectrum of specific immune responses to SARS-CoV-2 virus infection is increasingly…</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>Nucleic Acid-Based Vaccines Platform Against Covid-19 Pandemic</strong> - CONCLUSION: The fast global dissemination of the coronavirus has highlighted the urgent necessity to build an efficient vaccine to inhibit disease. Cooperative attempts throughout the world have paid to the fast and unprecedented production of vaccines. Much needs to be learned regarding SARSCoV-2 and vaccine development against it.</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>Discovery of compounds inhibiting SARS-COV-2 multi-targets</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic that has devastated the lives of millions. Researchers around the world are relentlessly working in hopes of finding a cure. Even though the virus shares similarities with reported SARS-CoV and MERS-CoV at the genomic and proteomic level, efforts to repurpose already known drugs against SARS-CoV-2 have resulted ineffective. In this succinct review, we discuss the different potential targets in SARS-CoV-2 at both…</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 need for a multi-level drug targeting strategy to curb the COVID-19 pandemic</strong> - Thousands of drugs, nutraceuticals and their combinations can be used to select candidate therapeutics for targeting SARS-CoV-2 and its symptoms in order to curb COVID-19. A comprehensive, multi-level strategy against COVID-19 should include drug targeting of biomolecules and biochemical pathways involved in the prevention and proliferation of the infection, and the fatal or serious symptoms following infection. Several drugs are routinely used in the treatment of different categories 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>GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia</strong> - Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that…</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 update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment</strong> - The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts 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>Antiviral activity of 5-aminolevulinic acid against variants of severe acute respiratory syndrome coronavirus 2</strong> - CONCLUSION: Our study suggests that 5-ALA with SFC warrants accelerated clinical evaluation as an antiviral drug candidate for treating patients infected with SARS-CoV-2 variants.</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>Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness</strong> - CONCLUSIONS: Our data indicate that R848 administration provides a useful model of ssRNA virus infection, which induces inflammation in the periphery and CNS, and virus infection-like illness. In turn, we show that nafamostat has a systemic anti-inflammatory effect in the presence of the TLR7/8 agonist. Therefore, the results indicate that nafamostat has anti-inflammatory actions, beyond its ability to inhibit TMPRSS2, that might potentiate its anti-viral actions in pathologies such as COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inflammasome activation in neutrophils of patients with severe COVID-19</strong> - Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) engages the inflammasome in monocytes and macrophages and leads to the cytokine storm in COVID-19. Neutrophils, the most abundant leukocytes, release neutrophil extracellular traps (NETs), which have been implicated in the pathogenesis of COVID-19. Our recent study shows that activation of the NLRP3 inflammasome is important for NET release in sterile inflammation. However, the role of neutrophil inflammasome formation…</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>Cangma Huadu granules, a new drug with great potential to treat coronavirus and influenza infections, exert its efficacy through anti-inflammatory and immune regulation</strong> - CONCLUSION: CMHD can significantly combats viral infections caused by HCoV-229E and H1N1, and the mechanism may be related to its multiple functions of anti-inflammatory, immunity regulating and inhibiting NF-κB signal transduction pathway.</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>Interferon Control of Human Coronavirus Infection and Viral Evasion: Mechanistic Insights and Implications for Antiviral Drug and Vaccine Development</strong> - Recognition of viral infections by various pattern recognition receptors (PRRs) activates an inflammatory cytokine response that inhibits viral replication and orchestrates the activation of adaptive immune responses to control the viral infection. The broadly active innate immune response puts a strong selective pressure on viruses and drives the selection of variants with increased capabilities to subvert the induction and function of antiviral cytokines. This revolutionary process dynamically…</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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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING</strong> - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346889253">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RNA 검출 방법</strong> - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR346026620">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS</strong> - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346889224">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hung Thanh Phan COVID-19 NEW SOLUTION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU344983394">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A METHOD TO REVEAL MOTIF PATTERNS OF COVID-19 USING MULTIPLE SEQUENCE ALIGNMENT</strong> - This present invention consists of different levels of computation and work in a pipeline manner i.e., input of one will be output of another and it is sequential process. Input data given in form of nucleotide sequence (DNA) of different COVID-19 patients (1). Using these nucleotide sequence perform mutation if possible and arrange them in a sequential order (2). Arrange number of nucleotide sequences of different patients in row wise and also compute number of characters in each row. (3). Compute frequency of occurrence of character in column wise and create a matrix having 4 rows and maximum sequence length will be the column size (4). Find the character like A, T, C, and G which one has maximum score and similarly find for each column to produce a final sequence (5). - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346039750">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REUSABILITY OF ANTIMICROBIAL MULTILAYER NANOFIBER MASK WITH HIGH PROTECTIVE</strong> - According to the present Invention, an antimicrobial multi-layer protective mask has a body section including at least first and second fabric layers having random fiber configuration; a middle layer including nanofiber membrane; and third and fourth fabric layers. There are two layers of fabric sandwiched between the nanofiber membrane and the third fabric layer. Fabric layers 1 through 4 each include a synergistic mixture of at least two metal oxide powders that exhibit synergistic antibacterial capabilities, such as the first metal’s mixed-oxidation state oxide and a second metal’s single-oxidation-state oxide. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346039053">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>METHODS OF TREATING SARS-COV-2 INFECTION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU344309338">link</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>一种具有广谱中和活性的新型冠状病毒重组蛋白及其制备方法</strong> - 本发明涉及一种具有广谱中和活性的新型冠状病毒重组蛋白及其制备方法，所述新型冠状病毒重组蛋白为CRM‑RBD重组蛋白，所述CRM‑RBD重组蛋白的氨基酸序列如SEQ ID NO：1所示，编码所述CRM‑RBD重组蛋白的核苷酸序列如SEQ ID</p></li>
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</ul>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">NO：2所示，利用所述核苷酸序列通过以下步骤制备得到重组纳米蛋白颗粒：构建得到大肠杆菌重组表达菌；培养大肠杆菌重组表达菌得到发酵液；获得包涵体粗提物；变性溶解得到包涵体变性蛋白；纯化得到纯化重组蛋白；复性得到复性后蛋白；对复性后蛋白进行分离纯化，得到重组纳米蛋白颗粒。本发明的新型冠状病毒重组蛋白对新冠病毒原型株、贝塔变异株、德尔塔变异株均具有中和保护效果。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN345743545">link</a></p>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>METHOD AND SYSTEM TO DETECT THE VITAL HEALTH PARAMETERS OF A PERSON</strong> - The present invention relates to detect the vital health parameters of a person through SPO2, a blood oxygen saturation sensor. The blood oxygen saturation sensor is arranged within a first shape body of a wearable glove; determining, a temperature through the temperature sensor, arranged within a second shape body of the wearable glove; determining, a pulse rate through a cardiac sensor, arranged within a third shape body of the wearable glove. Further, at a control unit, the detected blood oxygen level signal, temperature signal and pulse rate are received. The control unit is arranged on a palm shape body of the wearable glove to convert, segregate and transmit, the digital blood oxygen level signal, the digital temperature signal and the digital cardiac signal, on a cloud-based storage or a computing terminal. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN346033920">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>머신러닝 기반 수요예측을 이용한 피킹 로케이션 보충 서비스 제공 방법</strong> - 머신러닝 기반 수요예측을 이용한 피킹 로케이션 보충 서비스 제공 방법이 제공되며, 물류창고에 적재된 아이템의 카테고리, 부피 및 계절성을 포함하는 속성 데이터를 수집하는 단계, 적어도 하나의 인공지능 알고리즘을 이용하여 아이템의 1일 예상 출고량을 출력하는 단계, 물류창고 내 피킹 로케이션(Picking Location)의 부피를 아이템의 부피로 나누어 최대 재고수량을 산출하는 단계, 1일 예상 출고량의 제 1 배를 최소 출고수량으로 설정하고, 최대 재고수량의 제 2 배를 최소 재고수량으로 결정하는 단계, 피킹 로케이션 내 현재 재고수량을 추출하는 단계, 피킹 로케이션 내 현재 재고수량이 최소 출고수량 또는 최소 재고수량보다 작은지의 여부를 확인하는 단계 및 현재 재고수량이 최소 출고수량 또는 최소 재고수량보다 작은 경우, 보충수량을 계산하고 재고보충지시를 할당하는 단계를 포함한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR346015824">link</a></p></li>
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