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<title>01 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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<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>Personalized Expanded Kelleni’s Immunomodulatory COVID-19 Protocol Safely Used to Manage Severe COVID-22: A Case-Report.</strong> -
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<div>
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Version 5 represents my keynote presentation today at the 35th World Congress on Pharmacology on August 01, 2022, Rome, Italy. The earlier versions represent my trials to send it to journals wishing for a peer-review. Background: SARS CoV-2 is continuing to evolve, and multiple new variants have been previously reported. The current hepatitis of unknown origin described in the pediatric population could be a presentation of a novel pathogen/variant; SARS CoV-3 to be investigated that might cause unusual presentations in vulnerable groups as pediatric, geriatric and immunocompromised patients, and I call this potential new syndrome; COVID-22. Case presentation: A female in her late seventh decade with a history of chronic hepatitis B viral infection and moderately reduced kidney function suffered a syndrome of severe headache, acute epigastric abdominal pain, nausea, vomiting, confusion, and insomnia that could have been attributed to pancreatitis. However, oxygen saturation, CT chest and laboratory investigations showed evidence of severe COVID-19 while she suffered silent hypoxia and didn’t complain of cough, sore throat, or fever. She was safely and effectively managed using personalized expanded Kelleni’s protocol. Conclusion: The possibility of a novel SARS CoV-2 variant has not been excluded and it could include an immune-evasive variant that might selectively affect certain high-risk groups. I call for routine oxygen saturation screening by pulse oximeter for all high-risk patients currently seeking medical advice for any reason and I suggest if the current criteria to diagnose pediatric hepatitis of unknown origin is modified to include patients with ALT or AST level lower than the currently adopted 500 IU/L, the iceberg would be better revealed.
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🖺 Full Text HTML: <a href="https://osf.io/ysfr2/" target="_blank">Personalized Expanded Kelleni’s Immunomodulatory COVID-19 Protocol Safely Used to Manage Severe COVID-22: A Case-Report.</a>
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<li><strong>Unguided online treatment of disturbed grief, posttraumatic stress, and depression in adults bereaved during the COVID-19 pandemic: a randomized controlled trial</strong> -
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<div>
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Objective: This randomized controlled trial is the first study examining short-term effects of an unguided online grief-specific cognitive behavioral therapy (CBT) (compared to waitlist controls) in reducing early persistent complex bereavement disorder (PCBD), posttraumatic stress disorder (PTSD), and depression symptoms in adults bereaved during the COVID-19 pandemic. Method: Sixty-five Dutch adults, bereaved at least three months earlier during the COVID-19 pandemic, with clinically relevant early PCBD, PTSD, and/or depression symptoms, were randomly allocated to an immediate treatment (n = 32) or waitlist condition (n = 33). Telephone interviews were conducted to assess PCBD, PTSD, and depression symptoms (measured with the Traumatic Grief Inventory-Clinician Administered, PTSD Checklist for DSM-5, and Patient Health Questionnaire-9, respectively) at baseline, post-treatment, and post-waiting period. Participants received an eight-week unguided online grief-specific CBT including exposure, cognitive restructuring, and behavioral activation assignments. Analyses of covariance were performed. Results: Intention-to-treat analyses indicated that people in the intervention condition showed significantly lower PCBD (d = 0.90), PTSD (d = 0.71), and depression (d = 0.57) symptom-levels post-treatment relative to waitlist controls post-waiting period, while taking baseline symptom-levels and the use of professional psychological co-intervention into account. Completers analyses yielded similar results for PCBD and PTSD, but no significant between-group effect was found for depression. Conclusions: The online CBT proved to be an effective intervention, reducing PCBD, PTSD, and depression symptoms. Pending replication of these findings, online interventions may be more widely implemented in clinical practice to improve treatment options for emotionally distressed recently bereaved people.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/8xb5h/" target="_blank">Unguided online treatment of disturbed grief, posttraumatic stress, and depression in adults bereaved during the COVID-19 pandemic: a randomized controlled trial</a>
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</div></li>
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<li><strong>Profiling post-COVID syndrome across different variants of SARS-CoV-2</strong> -
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Background: Self-reported symptom studies rapidly increased our understanding of SARS-CoV-2 during the pandemic and enabled the monitoring of long-term effects of COVID-19 outside the hospital setting. It is now evident that post-COVID syndrome presents with heterogeneous profiles, which need characterisation to enable personalised care among the most affected survivors. This study describes post-COVID profiles, and how they relate to different viral variants and vaccination status. Methods: In this prospective longitudinal cohort study, we analysed data from 336,652 subjects, with regular health reports through the Covid Symptom Study (CSS) smartphone application. These subjects had reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2. 9,323 individuals subsequently developed Long-COVID, defined as symptoms lasting longer than 28 days. 1,459 had post-COVID syndrome, defined as more than 12 weeks of symptoms. Clustering analysis of the time-series data was performed to identify distinct symptom profiles for post-COVID patients, across variants of SARS-CoV-2 and vaccination status at the time of infection. Clusters were then characterised based on symptom prevalence, duration, demography, and prior conditions (comorbidities). Using an independent testing sample with additional data (n=140), we investigated the impact of post-COVID symptom clusters on the lives of affected individuals. Findings: We identified distinct profiles of symptoms for post-COVID syndrome within and across variants: four endotypes were identified for infections due to the wild-type variant; seven for the alpha variant; and five for delta. Across all variants, a cardiorespiratory cluster of symptoms was identified. A second cluster related to central neurological, and a third to cases with the most severe and debilitating multi-organ symptoms. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. The three main clusters were confirmed in an independent testing sample, and their functional impact was assessed. Interpretation: Unsupervised analysis identified different post-COVID profiles, characterised by differing symptom combinations, durations, and functional outcomes. Phenotypes were at least partially concordant with individuals reported experiences. Our classification may be useful to understand distinct mechanisms of the post-COVID syndrome, as well as subgroups of individuals at risk of prolonged debilitation. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimers Society, and ZOE Limited, UK.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278159v1" target="_blank">Profiling post-COVID syndrome across different variants of SARS-CoV-2</a>
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<li><strong>Higher Perceived Stress during the COVID-19 pandemic increased Menstrual Dysregulation and Menopause Symptoms</strong> -
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Purpose The increased stress the globe has experienced with the COVID-19 pandemic has affected mental health, disproportionately affecting women. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated. Methods Residents in British Columbia, Canada, were surveyed online as part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE). A subgroup (n=4171) who were assigned female sex at birth (age 25-69) and were surveyed within the first 6-12 months of the pandemic (August 2020-February 2021), prior to the widespread rollout of vaccines, were retrospectively asked if they noticed changes in their menstrual or menopausal symptoms, as well as completing validated measures of stress, depression, and anxiety. Results We found that 27.8% reported menstrual cycle disturbances and 6.7% reported increased menopause symptoms. Those who scored higher on perceived stress, depression, and anxiety scales were more likely to have reproductive cycle disturbances. Free text responses revealed that reasons for disturbances were perceived to be related to the pandemic. Conclusions The COVID-19 pandemic has highlighted the need to research womens health issues, such as menstruation. Our data indicates that in the first year of the pandemic, almost a third of the menstruating population reported disturbances in their cycle, which is approximately two times higher than in non-pandemic situations and four times higher than any reported changes in menopausal symptoms across that first year of the pandemic.
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</div>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.30.22278213v1" target="_blank">Higher Perceived Stress during the COVID-19 pandemic increased Menstrual Dysregulation and Menopause Symptoms</a>
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<li><strong>Sociodemographic factors affecting not receiving COVID-19 vaccine in Japan among people who originally intended to vaccinate: a prospective cohort study</strong> -
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Background Vaccine hesitancy is a major issue for acquiring herd immunity. However, some individuals may go unvaccinated owing to inhibitory factors other than vaccine hesitancy. If there is even a small number of such people, support is needed for equitable vaccine distribution and acquiring herd immunity. We investigated sociodemographic factors that affected not undergoing COVID-19 vaccination in Japan among individuals who initially had strong intention to vaccinate. Methods We conducted this prospective cohort study on workers aged 20-65 years from December 2020 (baseline), to December 2021 using a self-administered questionnaire survey. There were 27,036 participants at baseline and 18,560 at follow-up. We included 6,955 participants who answered yes to this question at baseline: “Would you like to receive a COVID-19 vaccine as soon as it becomes available?” We applied multilevel logistic regression analyses to examine the association between sociodemographic factors and being unvaccinated at follow-up. Results In all, 289 participants (4.2%) went unvaccinated. The odds ratios (ORs) for being unvaccinated were significantly higher for participants aged 30-39 and 40-49 than those aged 60-65 years. Being divorced, widowed, or single, having low income, and having COVID-19 infection experience also had higher ORs. Conclusions We found that some participants who initially had strong intention to vaccinate may have gone unvaccinated owing to vaccine side effects and the financial impact of absenteeism due to side effects. It is necessary to provide information repeatedly about the need for vaccination as well as social support to ensure that those who intend to vaccinate are able to do so.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.29.22277984v1" target="_blank">Sociodemographic factors affecting not receiving COVID-19 vaccine in Japan among people who originally intended to vaccinate: a prospective cohort study</a>
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<li><strong>Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study</strong> -
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Objective To examine infants in Scotland aged 0-27 days with confirmed SARS-CoV-2 infection; the risk of neonatal infection by factors including maternal infection status and gestation at birth; and the need for hospital admission among infected neonates. Design Population-based cohort study. Setting and population All live births in Scotland, 1 March 2020 to 31 January 2022. Results There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100,000 live births (141/92,009). Among infants born to women with confirmed infection around the time of birth, the infection rate was 1,811 per 100,000 live births (15/828). Nearly two-thirds (92/141, 65.2%) of babies with confirmed neonatal infection had an associated admission to neonatal or (more commonly) paediatric care. Of those admitted to hospital, 6/92 (6.5%) infants were admitted to neonatal or paediatric intensive care, however none of these six had COVID-19 recorded as the main diagnosis underlying their admission. There were no neonatal deaths among babies with confirmed infection. Implications and relevance Confirmed neonatal SARS-CoV-2 infection is uncommon. Secular trends in the neonatal infection rate broadly follow those seen in the general population, albeit at a lower level. Maternal infection at birth increases the risk of neonatal infection, but most babies with neonatal infection are born to women without confirmed infection. A high proportion of neonates with confirmed infection are admitted to hospital, with resulting implications for the baby, family, and services, although their outcomes are generally good.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278152v1" target="_blank">Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study</a>
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<li><strong>Institutional trust in times of Corona</strong> -
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During the corona pandemic, governments of all countries appealed strongly to the trust of their populations by implementing drastic social and economic measures to prevent the spread of the virus. This study seeks to understand mechanisms that influence the level of institutional trust at the time of the corona pandemic. We are specifically interested in how three explanatory factors (socioeconomic status, experienced economic insecurity and dissatisfaction with the implemented corona policies) can, in mutual association, explain differences in institutional trust. This study is based on data from a large-scale panel survey on the social impact of COVID-19, carried out by Kieskompas research agency (N=22,696). Using a serial mediation analysis, we show that SES has both a direct and indirect effect on the level of institutional trust. People with higher SES experience less economic insecurity and have less dissatisfaction with the corona policies and, partly as a result of this, stronger institutional trust. It is also true that economic insecurity increases dissatisfaction with the corona policies and, partly as a result of this, weakens the level of trust.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278140v1" target="_blank">Institutional trust in times of Corona</a>
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<li><strong>EARLY WARNING INDICATORS AT FACILITIES IN THE SOUTHERN HIGHLANDS REGION OF TANZANIA: LESSONS FOR HIV DRUG RESISTANCE SURVEILLANCE</strong> -
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Background The World Health Organization early warning indicators (EWIs) permit surveillance of factors associated with the emergence of HIV drug resistance (HIVDR). We examined cross- and within-region performance on HIVDR EWIs for selected HIV care and treatment clinics (CTCs) in five regions of southern Tanzania. Methods In 2016, we retrospectively collected EWI data from 50 CTCs for the January to December 2013 period. EWIs included the following: on time ART pick-up, retention on ART, ARV stockouts, and pharmacy prescribing and dispensing practices. Data for pediatric and adult people living with HIV were abstracted from source files, and frequencies and proportions were calculated for each EWI overall, as well as stratified by region, facility, and age group. Results Across and within all regions, on average, on-time pick-up of pills (63.0%), retention on ART (76.0%), and pharmacy stockouts (69.0%) were consistently poor for the pediatric population. Similarly, on-time pill pick up (66.0%), retention on ART (72.0%) and pharmacy stockouts (53.0%) for adults were also poor. By contrast, performance on pharmacy prescribing and dispensing practices were as desired for both pediatric and adult populations with few facility-level exceptions. Conclusion In this study, regions and facilities in the southern highlands of Tanzania reported widespread presence of HIVDR risk factors, including sub-optimal timeliness of pill pickup, retention on ART, and drug stockouts. Routine EWI monitoring provides a check on quality of service delivery, as well as affordable, large-scale surveillance for HIVDR risk factors. EWI monitoring remains relevant particularly in the context of new ART drug roll-out such as dolutegravir, during the COVID-19 pandemic when resultant HIV service disruptions require careful monitoring, and for virologic suppression as countries move closer to epidemic control.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278164v1" target="_blank">EARLY WARNING INDICATORS AT FACILITIES IN THE SOUTHERN HIGHLANDS REGION OF TANZANIA: LESSONS FOR HIV DRUG RESISTANCE SURVEILLANCE</a>
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<li><strong>The Efficacy of Facemasks in the Prevention of COVID-19: A Systematic Review</strong> -
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Facemasks have become a symbol of disease prevention in the context of COVID-19; yet, there still exists a paucity of collected scientific evidence surrounding their epidemiological efficacy in the prevention of SARS-CoV-2 transmission. This systematic review sought to analyze the efficacy of facemasks, regardless of type, on the prevention of SARS-CoV-2 transmission in both healthcare and community settings. The initial review yielded 1732 studies, which were reviewed by three study team members. Sixty-one full text studies were found to meet entry criteria, and 13 studies yielded data that was used in the final analysis. In all, 243 subjects were infected with COVID-19, of whom 97 had been wearing masks and 146 had not. The probability of getting COVID-19 for mask wearers was 7% (97/1463, p=0.002), for non-mask wearers, probability was 52% (158/303, p=0.94). The Relative Risk of getting COVID-19 for mask wearers was 0.13 (95% CI: 0.10-0.16). Based on these results, we determined that across healthcare and community settings, those who wore masks were less likely to contact COVID-19. Future investigations are warranted as more information becomes available.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278153v1" target="_blank">The Efficacy of Facemasks in the Prevention of COVID-19: A Systematic Review</a>
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<li><strong>Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Tyrol, Austria: Updated analysis involving 22,607 blood donors covering the period October 2021 to April 2022</strong> -
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Background: Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. Methods: We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Results: Median age of participants was 45.3 years (IQR: 30.9-55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8-86.0%) to 95.8% (94.9-96.4%) and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271-296) to 1437 (1360-1518) BAU/mL. The percentages of participants in categories with undetectable levels, and detectable levels at <500, 500-<1000, 1000-<2000, 2000-<3000, and ≥3,000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2-19.9; p-value < 0.001). Conclusion: Anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278141v1" target="_blank">Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Tyrol, Austria: Updated analysis involving 22,607 blood donors covering the period October 2021 to April 2022</a>
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<li><strong>The Effect of the COVID-19 Pandemic on Mental Health in Low and Middle Income Countries</strong> -
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We track the effects of the COVID-19 pandemic on mental health in eight Low and Middle Income Countries (LMICs) in Asia, Africa, and South America utilizing repeated surveys of 21,162 individuals. Many respondents were interviewed over multiple rounds pre- and post-pandemic, allowing us to control for time trends and within-year seasonal variation in mental health. We demonstrate how mental health fluctuates with agricultural crop cycles, deteriorating during pre-harvest “lean” periods. Ignoring this seasonal variation leads to unreliable inferences about the effects of the pandemic. Controlling for seasonality, we document a large, significant, negative impact of the pandemic on mental health, especially during the early months of lockdown. In a random effects aggregation across samples, depression symptoms increased by around 0.3 standard deviations in the four months following the onset of the pandemic. The pandemic could leave a lasting legacy of depression. Absent policy interventions, this could have adverse long-term consequences, particularly in settings with limited mental health support services, which is characteristic of many LMICs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.29.22278182v1" target="_blank">The Effect of the COVID-19 Pandemic on Mental Health in Low and Middle Income Countries</a>
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<li><strong>SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021</strong> -
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We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that ~15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.29.22278190v1" target="_blank">SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021</a>
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<li><strong>Priority age targets for COVID-19 vaccination in Ethiopia under limited vaccine supply</strong> -
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Background The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. An illustrative example is what occurred in Ethiopia, where nine months after the launch of the national vaccination program in March 2021, only 3% of the population received two doses of COVID-19 vaccine. In the meantime, a new wave of cases caused by the emergence of Delta variant of SARS-CoV-2 was observed between July and November 2021. Methods We used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different socio-demographic settings. Results We found that, during the first year of the pandemic, 46.1-58.7% of SARS-CoV-2 infections and 24.9-48% of critical cases occurred in SWSZ were likely associated with infectors under 30 years of age. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase to 66.7-70.6%. However, our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively to the number of available doses. Vaccination of all individuals aged 50 years or older would have averted 40 (95%CI: 18-60), 90 (95%CI: 61-111), and 62 (95%CI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged 30 years or more would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered. Conclusions Despite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278142v1" target="_blank">Priority age targets for COVID-19 vaccination in Ethiopia under limited vaccine supply</a>
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<li><strong>Failure to balance social contact matrices can bias models of infectious disease transmission</strong> -
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Spread of transmissible diseases is dependent on contact patterns in a population (i.e. who contacts whom). Therefore, many epidemic models incorporate contact patterns within a population through contact matrices. Social contact survey data are commonly used to generate contact matrices; however, the resulting matrices are often imbalanced, such that the total number of contacts reported by group A with group B do not match those reported by group B with group A. While the importance of balancing contact matrices has been acknowledged, how these imbalances affect modelled projections (e.g., peak infection incidence, impact of public health measures) has yet to be quantified. Here, we explored how imbalanced contact matrices from age-stratified populations (<15, 15+) may bias transmission dynamics of infectious diseases. First, we compared the basic reproduction number of an infectious disease when using imbalanced versus balanced contact matrices from 177 demographic settings. Then, we constructed a susceptible exposed infected recovered transmission model of SARS-CoV-2 and compared the influence of imbalanced matrices on infection dynamics in three demographic settings. Finally, we compared the impact of age-specific vaccination strategies when modelled with imbalanced versus balanced matrices. Models with imbalanced matrices consistently underestimated the basic reproduction number, had delayed timing of peak infection incidence, and underestimated the magnitude of peak infection incidence. Imbalanced matrices also influenced cumulative infections observed per age group, and the projected impact of age-specific vaccination strategies. For example, when vaccine was prioritized to individuals <15 in a context where individuals 15+ underestimated their contacts with <15, imbalanced models underestimated cumulative infections averted among 15+ by 24.4%. We conclude stratified transmission models that do not consider reciprocity of contacts can generate biased projections of epidemic trajectory and impact of targeted public health interventions. Therefore, modellers should ensure and report on balancing of their contact matrices for stratified transmission models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.28.22278155v1" target="_blank">Failure to balance social contact matrices can bias models of infectious disease transmission</a>
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<li><strong>Two years after lockdown: longitudinal trajectories of sleep disturbances and mental health over the COVID-19 pandemic and the effects of age, gender, and chronotype.</strong> -
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Since the first lockdown of Spring 2020, the COVID-19 contagion waves pervasively disrupted the sleep and mental health of the worldwide population. Notwithstanding the largest vaccination campaign in human history, the pandemic has continued to impact the everyday life of the general population for two years now. The present study provides the first evidence of the longitudinal trajectories of sleep disturbances and mental health throughout the pandemic in Italy, also describing the differential time course of age groups, genders, and chronotypes. A total of 1062 Italians participated in a three-time points longitudinal study covering two critical stages of the emergency [the first lockdown (April 2020) and the second lockdown (December 2020)] and providing a long-term overview two years after the pandemic outbreak (April 2022). We administered validated questionnaires to evaluate sleep quality/habits, insomnia, depression, stress, and anxiety symptoms. Analyses showed a gradual improvement in sleep disturbances, depression, and anxiety. Conversely, sleep duration progressively decreased, particularly in evening-type and younger people. Participants reported substantial earlier bedtime and get-up time. Stress levels increased during December 2020 and then stabilised. This effect was stronger in the population groups apparently more resilient during the first lockdown (older people, men, and morning-types). Our results describe a promising scenario two years after the pandemic onset. However, the improvements were relatively small, the perceived stress increased, and the re-establishment of pre-existing social/working dynamics led to general sleep curtailment. Further long-term monitoring is required to claim the end of the COVID-19 emergency on Italians9 sleep and mental health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.29.22278180v1" target="_blank">Two years after lockdown: longitudinal trajectories of sleep disturbances and mental health over the COVID-19 pandemic and the effects of age, gender, and chronotype.</a>
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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>Puerto Rico COVID-19 Vaccine Uptake Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Educational intervention<br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br/><b>Sponsors</b>: BioNTech SE; 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>Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Dietary Supplement: SmartProbio C; Dietary Supplement: Placebo<br/><b>Sponsors</b>: Medi Pharma Vision; Veterinary Research Institute; Brno 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>Beta-glucans for Hospitalised Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MC 3x3; Drug: Placebo<br/><b>Sponsors</b>: Concentra Educacion e Investigación Biomédica; Wohlstand Pharmaceutical<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth; Biological: Clover SCB-2019<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; University of Oxford<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 and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated; Biological: mRNA COVID-19 vaccine (Moderna); Biological: Viral Vector COVID-19 vaccine (AstraZeneca)<br/><b>Sponsor</b>: WestVac Biopharma 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>Effect of Pulmonary Rehabilitation Program on Post Hospitalization Severe COVID- 19 Patients</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Combination Product: respiratory exercises - incentive spirometer - walking<br/><b>Sponsor</b>: Fayoum 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>Physiotherapy in Post COVID-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Cognitive behavioral principles-based treatment program; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Rehabilitation for People With Post COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Multidimensional intervention; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/<br/><b>Sponsor</b>: Medical University of Lublin<br/><b>Suspended</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 Clinical Trial of Immuno-bridging Between Different Manufacture Scales of Recombinant COVID-19 Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Pneumonia<br/><b>Intervention</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma 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 CHW Intervention to Identify and Decrease Barriers to COVID 19 Testing & Vaccination</strong> - <b>Conditions</b>: Vaccine Hesitancy; COVID-19 Testing; Community Health Workers<br/><b>Intervention</b>: Behavioral: Community Health Worker led curriculum<br/><b>Sponsors</b>: Charles Drew University of Medicine and Science; Los Angeles County Department of Public Health; National Library of Medicine (NLM)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate Safety and Immunogenicity of COVID-19 Vaccine in Children 6 Months to < 12 Years</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Biological/Vaccine: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Initial Vaccination Period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Open Label Crossover Vaccination period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Booster Vaccination); Other: Placebo<br/><b>Sponsor</b>: Novavax<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 Phase II/III Study of PIKA Recombinant SARS-CoV-2 Vaccine as a Booster Dose.</strong> - <b>Condition</b>: Covid-19 Vaccine<br/><b>Intervention</b>: Biological: PIKA COVID-19 vaccine<br/><b>Sponsor</b>: Yisheng Biopharma (Singapore) Pte. Ltd.<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>Human TMPRSS2 non-catalytic ectodomain and SARS-CoV-2 S2’ subunit interaction mediated SARS-CoV-2 endocytosis: a model proposal with virtual screening for potential drug molecules to inhibit this interaction</strong> - This study proposes a novel model for integration of SARS-CoV-2 into host cell via endocytosis as a possible alternative to the prevailing direct fusion model. It is known that the SARS-CoV-2 spike protein undergoes proteolytic cleavage at S1-S2 cleavage site and the cleaved S2 domain is primed by the activated serine protease domain (SPD) of humanTMPRSS2 to become S2’. The activated SPD of TMPRSS2 is formed after it is cleaved by autocatalysis from the membrane bound non-catalytic ectodomain…</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>Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial</strong> - CONCLUSIONS: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.</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>Unveiling the “Template-Dependent” Inhibition on the Viral Transcription of SARS-CoV-2</strong> - Remdesivir is one nucleotide analogue prodrug capable to terminate RNA synthesis in SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) by two distinct mechanisms. Although the “delayed chain termination” mechanism has been extensively investigated, the “template-dependent” inhibitory mechanism remains elusive. In this study, we have demonstrated that remdesivir embedded in the template strand seldom directly disrupted the complementary NTP incorporation at the active site. Instead, the translocation…</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>Tackling medical misinformation in allergy and immunology practice</strong> - SummaryWhen Dictionary.com named “misinformation” the word of the year, it stated that “The rampant spread of misinformation poses new challenges for navigating life …”. That was in 2018, two years before the global COVID-19 pandemic fundamentally changed the manner in which misinformation inhibited public health efforts unlike any other time in human history. Our patients are continually seeking information pertaining to their health. When we see them for new patient consultations or follow up…</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>Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties</strong> - Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was performed using in silico analyses. Molecular modelling was performed to assess their enzyme inhibitory potential on the main protease SARS-CoV-2 M^(Pro), 3-chymotrypsin-like protease SARS-CoV-2…</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>Access to Health Care for Migrants Along the Mexico-United States Border: Applying a Framework to Assess Barriers to Care in Mexico</strong> - CONCLUSIONS: While Mexico’s health regulations are inclusive of migrants, in practice there are major barriers to access public health services, which might inhibit migrants from seeking those services. In order to comply with its commitment to guarantee the right to health of all persons, the Mexican health authorities should address the implementation gap between an inclusive policy, and the barriers to access that still remain.</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>DNA aptamers inhibit SARS-CoV-2 spike-protein binding to hACE2 by an RBD- independent or dependent approach</strong> - Objective: Nobody knows when the COVID-19 pandemic will end or when and where the next coronavirus will outbreak. Therefore, it is still necessary to develop SARS-CoV-2 inhibitors for different variants or even the new coronavirus. Since SARS-CoV-2 uses its surface spike-protein to recognize hACE2, mediating its entry into cells, ligands that can specifically recognize the spike-protein have the potential to prevent infection. Methods: We have recently discovered DNA aptamers against 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>Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone</strong> - Stress in poultry can lead to changes in body metabolism and immunity, which can increase susceptibility to infectious diseases. However, knowledge regarding chicken responses to viral infection under stress is limited. Dexamethasone (Dex) is a synthetic glucocorticoid similar to that secreted by animals under stress conditions, and has been widely used to induce stress in chickens. Herein, we established a stress model in 7-day-old chickens injected with Dex to elucidate the effects of stress…</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>Repurposing Metformin for Vascular Disease</strong> - Metformin has seen use as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS) metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have…</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>Theaflavin 3-gallate inhibits the main protease (M<sup>pro</sup>) of SARS-CoV-2 and reduces its count in vitro</strong> - The main protease (M^(pro)) of SARS-CoV-2 has been recognized as an attractive drug target because of its central role in viral replication. Our previous preliminary molecular docking studies showed that theaflavin 3-gallate (a natural bioactive molecule derived from theaflavin and found in high abundance in black tea) exhibited better docking scores than repurposed drugs (Atazanavir, Darunavir, Lopinavir). In this study, conventional and steered MD-simulations analyses revealed stronger…</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>Behavioral activation / inhibition systems and lifestyle as predictors of mental disorders in adolescent athletes during Covid19 pandemic</strong> - CONCLUSIONS: Analyzing the data, it can thus be concluded that whilst behavioral inhibition and activation systems seem to work together to significantly predict mental disorders, lifestyle cannot.</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 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model</strong> - SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding…</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>Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A Review</strong> - This review explores the role of transmembrane neuropilin-1 (NRP-1) in pregnancy, preeclampsia (PE), human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Since these conditions are assessed independently; this review attempts to predict their comorbid clinical manifestations. Dysregulation of NRP-1 contributes to the pathogenesis of PE by (a) impairing vascular endothelial growth factor (VEGF) signaling for adequate spiral…</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>Current evidence on the use of anakinra in COVID-19</strong> - Despite the progressing knowledge in COVID-19 management, remdesivir is the only agent that got approval to inhibit viral replication. However, there are limited data about effective immunomodulatory agents to prevent cytokine release in COVID-19. Cytokine release syndrome in COVID-19 resembles secondary hemophagocytic lymphohistiocytosis, in which interleukin-1 (IL-1) plays a key role. Anakinra is the first recombinant IL-1 receptor antagonist studied for off-label use in COVID-19 treatment….</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>FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling</strong> - FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated in both epithelial and natural killer (NK) cells. The histone acetyltransferase TIP60 contributes to the acetylation of SUPT16H middle domain…</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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