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194 lines
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<title>18 August, 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>Genetic diversity and spread dynamics of SARS-CoV-2 variants present in African populations</strong> -
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The dynamics of COVID-19 disease have been extensively researched in many settings around the world, but little is known about these patterns in Africa. 6139 complete nucleotide genomes from 51 African nations were obtained and analyzed from the National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Influenza Data (GISAID) databases to examine genetic diversity and spread dynamics of SARS-CoV-2 lineages circulating in Africa. We investigated their diversity using several clade and lineage nomenclature systems, and used maximum parsimony inference methods to recreate their evolutionary divergence and history. According to this study, only 193 of the 2050 Pango lineages discovered worldwide circulated in Africa after two years of the COVID-19 pandemic outbreak, with five different lineages dominating at various points during the outbreak. We identified South Africa, Kenya, and Nigeria as key sources of viral transmissions between Sub-Saharan African nations because they had the most SARS-CoV-2 genomes sampled and sequenced. These results shed light on the evolutionary dynamics of the circulating viral strains in Africa. Genomic surveillance is one of the important techniques in the pandemic preparedness toolbox and to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa, genomic surveillance activities across the continent must be expanded. The effectiveness of molecular surveillance as a method for tracking pandemics strongly depends on continuous and reliable sampling, speedy virus genome sequencing, and prompt reporting and we have to improve in all these aspects in Africa. Additionally, the pandemic breakout revealed that current land-border regulations aimed at limiting virus’s international transmission are ineffective and a lot needs to be done to implement and improve our African land-borders as far as epidemiology is concerned in order to contain such outbreaks in the future.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.17.504290v1" target="_blank">Genetic diversity and spread dynamics of SARS-CoV-2 variants present in African populations</a>
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</div></li>
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<li><strong>Natural variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics</strong> -
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The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity, whether arisen naturally or through vaccination. Understanding the structure of the viral spike assists in determining the impact of mutations on the antigenic surface. One class of mutation impacts glycosylation attachment sites, which have the capacity to influence the antigenic structure beyond the immediate site of attachment. Here, we compare the glycosylation of a recombinant viral spike mimetic of the P.1 (Gamma) strain, which exhibits two additional N-linked glycan sites compared to the equivalent mimetic of the Wuhan strain. We determine the site-specific glycosylation of these variants and investigate the impact of these glycans by molecular dynamics. The N188 site is shown to exhibit very limited glycan maturation, consistent with limited enzyme accessibility. Structural modeling and molecular dynamics reveal that N188 is located within a cavity by the receptor binding domain, which influences the dynamics of these attachment domains. These observations suggest a mechanism whereby mutations affecting viral glycosylation sites have a structural impact across the antigenic surface.
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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/10.1101/2022.08.17.504157v1" target="_blank">Natural variations within the glycan shield of SARS-CoV-2 impact viral spike dynamics</a>
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<li><strong>Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds</strong> -
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Multivalent antigen display is a well-established design principle to enhance humoral immunity elicited by subunit vaccines. Protein-based virus-like particles (VLPs) are an important vaccine platform that implements this principle but also contain thymus-dependent off-target epitopes, thereby generating neutralizing and defocused antibody responses against the scaffold itself. Here, we present DNA origami as an alternative platform to display the receptor binding domain (RBD) of SARS-CoV-2. DNA-based scaffolds provide nanoscale control over antigen organization and, as thymus-independent antigens, are expected to induce only extrafollicular B-cell responses. Our icosahedral DNA-based VLPs elicited valency-dependent BCR signaling in two reporter B-cell lines, with corresponding increases in RBD-specific antibody responses following sequential immunization in mice. Mouse sera also neutralized the Wuhan strain of SARS-CoV-2 - but did not contain boosted, DNA-specific antibodies. Thus, multivalent display using DNA origami can enhance immunogenicity of protein antigens without generating scaffold-directed immunological memory and may prove useful for rational vaccine design.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.16.504128v1" target="_blank">Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds</a>
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<li><strong>Antigen Specific T Cells in People with Obesity at Five Months Following ChAdOx1 COVID-19 Vaccination</strong> -
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Background/Objectives: People with obesity (PWO) face an increased risk of severe outcomes from COVID19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID19 adenovirus vector vaccination. Subjects/Methods: We investigated SARSCoV2 specific T cell responses in 50 subjects, five months following a two dose primary course of ChAdOx1 nCoV19 (AZD1222) vaccination. We further divided our cohort into PWO (n=30) and matched controls (n=20). T cell (CD4+, CD8+) cytokine responses (IFNg, TNFa) to SARSCoV2 spike peptide pools were determined using multicolour flow cytometry. Results: Circulating T cells specific for SARSCoV2 were readily detected across our cohort, with robust responses to spike peptide stimulation across both T cell lines. PWO and controls had comparable levels of both CD4+ and CD8+ SARSCoV2 spike specific T cells. Polyfunctional T cells associated with enhanced protection against viral infection were detected at similar frequencies in both PWO and controls. Conclusions: These data indicate that PWO who have completed a primary course of ChAdOx1 COVID19 vaccination have robust, durable, and functional antigen specific T cell immunity that is comparable to that seen in people without obesity.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278821v1" target="_blank">Antigen Specific T Cells in People with Obesity at Five Months Following ChAdOx1 COVID-19 Vaccination</a>
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</div></li>
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<li><strong>Comparative Analysis of Reported Deaths Cases Associated with the New Coronavirus COVID-19 Pandemic in the South Caucasus Countries (Armenia, Azerbaijan, Georgia) from March 2020 to May 2022</strong> -
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The results of a statistical analysis of daily, total by days of the week and monthly data on officially reported deaths cases from the new coronavirus COVID-19 in the countries of the South Caucasus (Armenia, Azerbaijan, Georgia) from March 12, 2020 to May 31, 2022 are presented. All data are normalized per 1 million populations (mortality rate, hereinafter, this normalization is assumed everywhere). In particular, the following results were obtained. The daily mortality rate in Armenia averaged 3.591 (range: 0-23.622), in Azerbaijan - 1.184 (range: 0-10.969), in Georgia - 5.596 (range: 0-23.189). The total monthly mortality rate in Armenia averaged 107.9 (variability range: 1.01-415.4), in Azerbaijan - 35.6 (variability range: 0.39-122.9), in Georgia - 168.1 (variability range: 0-547.4). A direct linear correlation was observed between the indicated countries in cases of daily and total monthly mortality. An analysis of the intraweek course of mortality showed that in Armenia, on weekdays, the average daily mortality is 4.319, and on weekends - 3.477 (an increase compared to weekends by about 24%); in Azerbaijan, on weekdays and weekends, the average daily mortality is 1.368 and 1.421, respectively (the difference is insignificant); in Georgia on weekdays, the average daily mortality is 7.558, and on weekends - 6.855 (an increase of about 10% compared to weekends).
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.14.22278754v1" target="_blank">Comparative Analysis of Reported Deaths Cases Associated with the New Coronavirus COVID-19 Pandemic in the South Caucasus Countries (Armenia, Azerbaijan, Georgia) from March 2020 to May 2022</a>
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<li><strong>Impact of the COVID-19 pandemic on the socioeconomic inequality of health behavior among Japanese adolescents: a two-year-repeated cross-sectional survey</strong> -
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Background: Although disparities in socioeconomic status in health behaviors have been highlighted globally, they are not well understood in Japanese adolescents. The purpose of this study was to clarify the changes in socioeconomic disparities in adolescents9 fundamental health behaviors, such as physical activity, screen time (ST), sleep, breakfast intake, and bowel movement before and during COVID-19. Methods: This was a repeated cross-sectional study which used data from the 2019 and 2021 National Sports-Life Survey of Children and Young in Japan. Data of 766 and 725 participants in 2019 and 2021, respectively, were analyzed. Favorable health behaviors were defined as daily moderate-to-vigorous physical activity (MVPA) of at least 60 minutes, ST of less than 2 hours, sleep of 8 to 10 hours, daily breakfast intake, and bowel movement frequency of at least once in every 3 days. We calculated the slope index of inequality (SII) and relative index of inequality (RII) in each health behavior for equivalent household income levels for assessing absolute and relative economic inequalities. Results: Compliance with MVPA and ST recommendation significantly declined from 20.1% and 23.0% in 2019 to 11.7% and 14.9% in 2021, respectively. The SII and RII increased in MVPA for income levels, but decreased in daily breakfast in 2019 to 2021. Although the widening and narrowing of the disparity was inconclusive for ST, it exacerbated for the higher income groups. Conclusions: Our study revealed widening of economic disparities in the achievement of recommended MVPA and narrowing of it in breakfast intake among adolescents before and during COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.11.22278499v1" target="_blank">Impact of the COVID-19 pandemic on the socioeconomic inequality of health behavior among Japanese adolescents: a two-year-repeated cross-sectional survey</a>
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<li><strong>Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program</strong> -
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Background: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). Objective: To identify risk factors associated with PASC/long-COVID. Design: Retrospective case-control study. Setting: 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). Patients: 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system. Measurements: Risk factors included demographics, comorbidities, and treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC. Results: Among 8,325 individuals with PASC, the majority were >50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30+ days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls. Conclusions: This national study identified important risk factors for PASC such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.15.22278603v1" target="_blank">Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program</a>
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<li><strong>Long-term changes in human mobility responses to COVID-19-related information in Japan</strong> -
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This study investigates how human mobility has changed in the long-term in response to the COVID-19-related information in Japan. We use publicly available data from Google on human mobility in retail & recreation and residential spent time. These variables can be explained using daily data on the number of infected cases, whether the state of the emergency is declared or not, and the cumulated number of the vaccinated person. In the regression analysis, we use the 9interactive effects model9 to control complicated unobservable factors that vary across time and cross-sectional dimensions. Our regression results find that people feared an unknown virus in the 1st wave, but the habituation trend for human mobility is noticed for the repeated similar infection information. However, from a different kind of information about the spread of new variants, people9s habituation comes to a halt to some extent. Further, the spatial interaction of infection information is observed. We also show that people reacted appropriately to infection information even without a state of emergency declaration. Also, vaccination promotion encourages people to go out with security. When implementing policies to control human mobility, it is essential to consider the timing, and the degree of information penetration, carefully.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.15.22278703v1" target="_blank">Long-term changes in human mobility responses to COVID-19-related information in Japan</a>
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<li><strong>The impact of the Covid-19 pandemic on Italian population-based cancer screening activities and test coverage: results from national cross-sectional repeated surveys</strong> -
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<b>Background</b><br />In Italy, population-based screening programs for breast, cervical and colorectal cancers are mandatory, and Regions are in charge of their delivery. From March to May 2020, a severe lockdown was imposed due to the Covid-19 pandemic by the Italian Ministry of Health, with the suspension of screening programs. This paper describes the impact of the pandemic on Italian screening activities and test coverage in 2020.<br /><br /><b>Methods</b><br />The regional number of subjects invited and of screening tests performed in 2020 were compared with those in 2019. Invitation and examination coverage were also calculated. PASSI surveillance system, through telephone interviews, investigated the population screening test coverage, before and during the pandemic, accordingly to educational attainment, perceived economic difficulties and citizenship.<br /><br /><b>Results</b><br />A reduction of subjects invited and tests performed, with differences among periods and geographic macro areas, was observed in 2020 vs. 2019. The reduction in examination coverage was larger than that in invitation coverage for all screening campaigns. From the second half of 2020, the trend for test coverage showed a decrease in all the macro areas for all the screening campaigns. Compared with the pre-pandemic period, there was a greater difference according to level of education in the odds of having had a test last year vs. never having been screened or not being up to date with screening tests. In addition, foreigners had less access to screening than Italians did.<br /><br /><b>Conclusions</b><br />The lockdown and the ongoing Covid-19 emergency caused an important delay in screening activities. This increased the pre-existing individual and geographical inequalities in access. The opportunistic screening did not mitigate the pandemic impact.<br /><br />
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<b>Funding</b>
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This study was partially supported by Italian Ministry of Health – Ricerca Corrente Annual Program 2023.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.15.22278787v1" target="_blank">The impact of the Covid-19 pandemic on Italian population-based cancer screening activities and test coverage: results from national cross-sectional repeated surveys</a>
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<li><strong>Rapid waning of protection induced by prior BA.1/BA.2 infection against BA.5 infection</strong> -
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SARS-CoV-2 omicron subvariants BA.1 and BA.2 became dominant in many countries in early 2022. These subvariants are now being displaced by BA.4 and BA.5. While natural infection with BA.1/BA.2 provides some protection against BA.4/BA.5 infection, the duration of this protection remains unknown. We used the national Portuguese COVID-19 registry to investigate the waning of protective immunity conferred by prior BA.1/BA.2 infection towards BA.5. We divided the individuals infected during the period of BA.1/BA.2 dominance (>90% of sample isolates) in successive 15-day intervals and determined the risk of subsequent infection with BA.5 over a fixed period. Compared with uninfected people, one previous infection conferred substantial protection against BA.5 re-infection at 3 months (RR=0.12; 95% CI: 0.11-0.12). However, although still significant, the protection was reduced by two-fold at 5 months post-infection (RR=0.24; 0.23-0.24). These results should be interpreted in the context of vaccine breakthrough infections, as the vaccination coverage in the individuals included in the analyses is >98% since the end of 2021. This waning of protection following BA.1/BA.2 infection highlights the need to assess the stability and durability of immune protection induced with the adapted vaccines (based on BA.1) over time.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.16.22278820v1" target="_blank">Rapid waning of protection induced by prior BA.1/BA.2 infection against BA.5 infection</a>
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<li><strong>What level of air filtration (ACH) is equivalent to an N95 respirator?</strong> -
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N95 respirators reduce risk of catching COVID-19 from an infected person both at near-field (e.g. < 6 feet) and far-field (e.g. > 6 feet). Air filtration is usually not effective at near-field, but emulating the far-field equivalent of N95 requires 95% reduction of particles (20x) from airborne particulate sources. A wide range of air change per hour (ACH) recommendations for air filtration exist ranging from 2 to 12 ACH (CDC, CDPH, etc.). Instead of inert airborne contaminant (e.g. salt water) which can be disruptive in occupied rooms, we describe a simpler procedure using an optical particle counter to track the decay of ambient aerosols (0.3 μm diameter) and measure ACH from exponential decay coefficients in a room and a whole house. Surface deposition in an unventilated room without ventilation or filtration was measured to be 0.6 ACH using ambient aerosols. ACH was also measured to be 3 to 17 using low-noise generating HEPA purifiers ($299-$999, reported CADR 114 to 1360 cfm) and Do-It-Yourself (DIY) air purifiers ($55-$160, 1“-5”, MERV 13-16, 1-filter and 4-filter Corsi-Rosenthal boxes). Using ACH and volume of room/house, estimated CADR per dollar varied 4x from below 80 cfm / $100 for tested HEPA purifiers at their highest speed (for maximum CADR) up to above 350 cfm / $100 run with tested DIY air purifiers running on their lowest speed (for reduced noise generation). Differences in CADR were observed in room versus house, and purifiers with higher airspeed had higher than expected CADR, possibly reflecting better mixing. Using 0.6 ACH as baseline for unventilated rooms, at least 12 ACH is required for far-field protection equivalent to N95 respirators (95%), and this ACH can be achieved using either HEPA or DIY air filtration in a room or building and verified with ambient aerosols.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278555v4" target="_blank">What level of air filtration (ACH) is equivalent to an N95 respirator?</a>
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<li><strong>Brain imaging and neuropsychological assessment of individuals recovered from mild COVID-19</strong> -
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As SARS-CoV-2 infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection in comparison with matched controls. Following a case-control design, 223 non-vaccinated individuals with a positive polymerase chain reaction test (PCR) for SARS-CoV-2 obtained between 1 March and 31 December 2020 received magnetic resonance imaging (MRI) and neuropsychological assessments within the framework of the Hamburg City Health Study (median 9.7 months after testing). Two hundred twenty-three healthy controls, examined prior to the SARS-CoV-2 pandemic, were drawn from the main study and matched for age, sex, education and cardiovascular risk factors. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. The present analysis included 223 individuals recovered from mainly mild to moderate SARS-CoV-2 infections (100 female/123 male, age [years], mean +- SD, 55.54 +- 7.07) and 223 matched healthy controls (93 female/130 male, 55.74 +- 6.60). Among all 11 MR imaging markers tested, significant differences between groups were found in global measures of mean diffusivity and extracellular free-water which were both elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 +- 0.018 vs. 0.142 +- 0.017, P<.001; mean diffusivity [10-3 mm2/s]: 0.747 +- 0.021 vs. 0.740 +- 0.020, P<.001). Classification accuracy for detecting post-SARS-CoV-2 individuals based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content may last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.08.22277420v2" target="_blank">Brain imaging and neuropsychological assessment of individuals recovered from mild COVID-19</a>
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<li><strong>LIMITED EVIDENCE FOR NEUROPSYCHOLOGICAL DYSFUNCTION IN PATIENTS INITIALLY AFFECTED BY SEVERE COVID-19</strong> -
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in coronavirus disease 2019 (COVID-19), has caused a pandemic. There is now considerable evidence that neuropsychological functions could be affected. We further tested this hypothesis on a sample of post COVID-19 patients, who, initially, had been severely affected. METHODS: We tested 22 post COVID-19 patients who, after the intensive care unit, were submitted to our rehabilitation unit to be treated for severe post COVID-19 sequelae. All patients were assessed with a comprehensive neuropsychological battery including measures assessing perceptual, attentive, mnestic, linguistic, and executive functions, and overall cognitive status. The patients were also administered rehabilitation measures including scales for investigating aerobic capacity/endurance deficits, dyspnea, and fatigue. RESULTS: Our findings revealed that evidence of neuropsychological disorders on post COVID-19 patients was very limited. Furthermore, COVID-19 severity and other relevant variables were not correlated with patients’ scores on the neuropsychological tests. CONCLUSIONS: We suggest that the relation between COVID-19 and neuropsychological disorders is unclear. New studies and metanalyses are highly required to shed light on this highly complex issue.
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🖺 Full Text HTML: <a href="https://osf.io/hcnsd/" target="_blank">LIMITED EVIDENCE FOR NEUROPSYCHOLOGICAL DYSFUNCTION IN PATIENTS INITIALLY AFFECTED BY SEVERE COVID-19</a>
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<li><strong>Transcriptomic and epigenetic assessment of ageing male skin identifies disruption of Ca2+ homeostasis; exacerbated by smoking and UV exposure</strong> -
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Skin ageing has been widely associated with the formation and presence of increasing quantities of senescent cells, the presence of which are thought to reduce cell renewal. This study aimed to identify key factors influencing fibroblast and skin aging in European males using RNA-seq data. Key differences in study designs included known sources of biological differences (sex, age, ethnicity), experimental differences, and environmental factors known to accelerate skin ageing (smoking, UV exposure) as well as study specific batch effects which complicated the analysis. To overcome these complications samples were stratified by these factors and differential expression assessed using Salmon and CuffDiff. Functional enrichment and consistency across studies, stratification’s and tools identified age related alterations in the transcriptomes of fibroblasts and skin. Functional enrichment of results identified alterations in protein targeting to membranes and the ER, and altered calcium homeostasis in aged fibroblasts. Extension to skin controlled for differences in fibroblast culturing methods confirming transient age related alterations in intracellular calcium homeostasis. In middle aged males (40-65) increased keratinisation, skin, epithelial and epidermal development was seen in conjunction with alterations to ER Calcium uptake, leading to the identification of related processes including; an unfolded protein response, altered metabolism, increased MMP expression, and altered Calcium handling, which were further exacerbated by UV-exposure. Interestingly the genes and processes subsequently decreased in old males (> 65), which exhibited signs of increased senescence. Extension to Illumina 450k array data from ageing skin uncovered evidence of epigenetic regulation; genes and isoforms with overlapping differentially methylated CpGs were differentially expressed. Smoking led to additional enrichment of genes relating to tissue development, cell adhesion, vasculature development, peptide cross-linking, calcium homeostasis, cancer and senescence. The results consistently identified alterations in ER and golgi Calcium uptake, which disrupt intracellular and extracellular calcium gradients that regulate metabolic and differentiation signalling in skin and fibroblasts, leading to age related declines skin structure and function. Interestingly many diseases and infections with overlapping molecular consequences, (ER Calcium stress, reduced protein targeting to membranes) including COVID-19 are identified by the analysis, suggesting that COVID-19 infection compounds pre-existing cellular stresses in aged males, which could help explain higher COVID-19 mortality rates in aged males, as well as highlighting potential ways to reduce them.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.16.504102v1" target="_blank">Transcriptomic and epigenetic assessment of ageing male skin identifies disruption of Ca2+ homeostasis; exacerbated by smoking and UV exposure</a>
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<li><strong>Intrahost SARS-CoV-2 k-mer identification method (iSKIM) for rapid detection of mutations of concern reveals emergence of global mutation patterns</strong> -
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Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM (intrahost SARS-CoV-2 k-mer identification method) to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.16.504117v1" target="_blank">Intrahost SARS-CoV-2 k-mer identification method (iSKIM) for rapid detection of mutations of concern reveals emergence of global mutation patterns</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>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07321332 (nirmatrelvir)/ritonavir<br/><b>Sponsor</b>: Pfizer<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>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo 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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<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>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>: University Vila Velha<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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University 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>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., 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>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International 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>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>: COVID-19; Vaccine Uptake<br/><b>Intervention</b>: Behavioral: Tough Talks COVID<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19; AMS-H-03; Hydrogen-oxygen Gas<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment<br/><b>Sponsor</b>: Shanghai Zhongshan 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>Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019</strong> - <b>Condition</b>: Coronavirus Disease 2019<br/><b>Interventions</b>: Drug: Huashi Baidu granule; Drug: compound pholcodine oral solution<br/><b>Sponsor</b>: Shanghai Children’s Medical Center<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>Evaluation of Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: ZR202-CoV; Biological: ZR202a-CoV; Biological: Comirnaty®<br/><b>Sponsor</b>: Shanghai Zerun Biotechnology Co.,Ltd<br/><b>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antimicrobial peptides: Defending the mucosal epithelial barrier</strong> - The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence 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>SEMgsa: topology-based pathway enrichment analysis with structural equation models</strong> - CONCLUSIONS: SEMgsa is a novel yet powerful method for identifying enrichment with regard to gene expression data. It takes into account topological information and exploits pathway perturbation statistics to reveal biological information. SEMgsa is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph .</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 spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2)…</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>Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum</strong> - The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee’s serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE(490), exhibited ultrabright fluorescence due to the rigidity…</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>Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents</strong> - Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung, but notably in the LDLN, where the extent 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>Complement C3 inhibition in severe COVID-19 using compstatin AMY-101</strong> - Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated…</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>Adding Insult to Injury - Does COVID-19 Promote ARDS by Inhibiting Surfactant?</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lysine-Targeted Reversible Covalent Ligand Discovery for Proteins via Phage Display</strong> - Binding via reversible covalent bond formation presents a novel and powerful mechanism to enhance the potency of synthetic inhibitors for therapeutically important proteins. Work on this front has yielded the anticancer drug bortezomib as well as the antisickling drug voxelotor. However, the rational design of reversible covalent inhibitors remains difficult even when noncovalent inhibitors are available as a scaffold. Herein, we report chemically modified phage libraries, both linear 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>SOCS1 Haploinsufficiency Presenting as Severe Enthesitis, Bone Marrow Hypocellularity, and Refractory Thrombocytopenia in a Pediatric Patient with Subsequent Response to JAK Inhibition</strong> - Haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1) is a recently discovered autoinflammatory disorder with significant rheumatologic, immunologic, and hematologic manifestations. Here we report a case of SOCS1 haploinsufficiency in a 5-year-old child with profound arthralgias and immune-mediated thrombocytopenia unmasked by SARS-CoV-2 infection. Her clinical manifestations were accompanied by excessive B cell activity, eosinophilia, and elevated IgE levels. Uniquely, this is 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>Furin cleavage is required for swine acute diarrhea syndrome coronavirus spike protein-mediated cell-cell fusion</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) was reported in China in 2017 and is a causative agent of porcine enteric disease. Recent studies indicate that cells from various hosts are susceptible to SADS-CoV, suggesting the zoonotic potential of this virus. However, little is known about the mechanisms through which this virus enters cells. In this study, we investigated the role of furin in SADS-CoV spike (S)-mediated cell-cell fusion and entry. We found that the SADS-CoV S protein…</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>Molecular interactions of Zyesami with the SARS-CoV-2 nsp10/nsp16 protein complex</strong> - Background SARS-CoV-2 emerged in late 2019, causes COVID-19. Patients treated with Zyesami were found to be 3-fold decrease in respiratory failure and improvement in clinical outcome. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins that essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that required nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis….</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>Lower serum alpha 1 antitrypsin levels in patients with severe COVID-19 compared with patients hospitalized due to non-COVID-19 pneumonia</strong> - CONCLUSION: Patients admitted due to severe COVID-19 had lower A1AT levels in comparison to patients admitted due to non-COVID pneumonia. This observation may suggest an association between mildly diminished A1AT and higher risk of SARS-CoV-2 infection with severe COVID-19 disease.</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>Interaction of panduratin A and derivatives with the SARS-CoV-2 main protease (m<sup>pro</sup>): a molecular docking study</strong> - Panduratin A (Pa-A) is a prenylated cyclohexenyl chalcone isolated from the rhizomes of the medicinal and culinary plant Boesenbergia rotunda (L.) Mansf., commonly called fingerroots. Both an ethanolic plant extract and Pa-A have shown a marked antiviral activity against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the COVID-19 pandemic disease. Pa-A functions as a protease inhibitor inhibiting infection of human cells by the virus. We have modeled 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>Prognostic Value of Serial Measurement of Serum Des-Arg(6)-Bradykinin Levels in Severe COVID-19 Patients</strong> - CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.</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>Restriction of SARS-CoV-2 replication in the human placenta</strong> - Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this…</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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