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203 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>06 May, 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>A lay perspective on prioritization for intensive care in pandemic times: Vaccination status matters</strong> -
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During a pandemic, demand for intensive care often exceeds availability. Experts agree that allocation should maximize benefits and must not be based on whether patients could have taken preventive measures. However, intensive care units (ICUs) are often overburdened by individuals with severe COVID-19 who have chosen not to be vaccinated to prevent the disease. This article reports an experiment that investigated the German public’s prioritization preferences during the fourth wave of the coronavirus pandemic (N = 1,014). In a series of scenarios, participants were asked to decide on ICU admission for patients who differed in terms of health condition, expected treatment benefits, and vaccination status. The results reveal an ingroup bias, as vaccinated individuals preferred to allocate more resources to the vaccinated than to the unvaccinated. Participants also favored admitting a heart attack patient rather than a COVID-19 patient with the same likelihood of benefiting from ICU admission, indicating a preference for maintaining regular ICU services rather than treating those with severe COVID-19. Finally, participants were more likely to admit a patient to intensive care when this meant withholding rather than withdrawing care from another patient. The results indicate that lay prioritizations violate established allocation principles, presaging potential conflicts between those in need of intensive care and those who provide and allocate it. It is therefore recommended that allocation principles should be explained to enhance public understanding. Additionally, vaccination rates should be increased to relieve ICUs and reduce the need for such triage decisions.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/aj782/" target="_blank">A lay perspective on prioritization for intensive care in pandemic times: Vaccination status matters</a>
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<li><strong>Net-shaped DNA nanostructure designed for rapid/sensitive detection and potential inhibition of SARS-CoV-2 virus</strong> -
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We present a net-shaped DNA nanostructure (called “DNA Net” herein) design strategy for selective recognition and high-affinity capture of the intact SARS-CoV-2 virions through spatial pattern-matching and multivalent interactions between the aptamers (targeting wild type spike-RBD) positioned on the DNA Net and the trimeric spike glycoproteins displayed on the viral outer surface. Carrying a designer nanoswitch, the DNA Net-aptamers releases fluorescent signal upon virus binding that is easily read by a hand-held fluorimeter for a rapid (in 10 mins), simple (mix-and-read), sensitive (PCR equivalent), room temperature compatible, and inexpensive (~ $1.26/test) COVID-19 test assay. The DNA Net-aptamers also impede authentic wild-type SARS-CoV-2 infection in cell culture with a near 1,000-fold enhancement of the monomeric aptamer. Furthermore, our DNA Net design principle and strategy can be customized to tackle other life- threatening and economically influential viruses like influenza and HIV, whose surfaces carry class-I viral envelope glycoproteins like the SARS-CoV-2 spikes in trimeric forms.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.04.490692v1" target="_blank">Net-shaped DNA nanostructure designed for rapid/sensitive detection and potential inhibition of SARS-CoV-2 virus</a>
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<li><strong>The spread and burden of the COVID-19 pandemic in sub-Saharan Africa: comparison between predictions and actual data and lessons learned.</strong> -
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Introduction Sub-Saharan Africa (SSA) was predicted to be severely affected by the coronavirus disease 2019 (COVID-19) pandemic, but the actual data seem to have contradicted these forecasts. This study attempted to verify this observation by comparing predictions against actual data on the spread and burden of the COVID-19 pandemic in SSA. Methods Focused on the period from March 1 st to September 30 th , 2020, we compared (1) the predicted interval dates when each SSA country would report 1 000 and 10 000 COVID-19 cases, to the actual dates when these numbers were attained, as well as (2) the daily number of predicted versus actual COVID-19 cases. Further, we calculated the case fatality ratio of the COVID-19 infection in SSA, and the correlation coefficient between the weekly average number of confirmed COVID-19 cases reported by each country and the weekly average stringency index of its anti-COVID-19 policy measures. Results 84.61% (33) and 100% (39) of the 39 SSA countries for which predictions were made did not reach a total of 1 000 and 10 000 confirmed COVID-19 cases at the predicted interval dates. The daily number of confirmed COVID-19 cases was lower than the one projected for all SSA countries. The case fatality ratio of the COVID-19 infection in SSA was 3.42%. Among the 44 SSA countries for which the correlation could be estimated, it was negative for 17 (38.6%) of them. Conclusions The natural characteristics of SSA and the public health measures implemented might partly explain that the actual data were lower than the predictions on the COVID-19 pandemic in SSA, but the low case ascertainment and the numerous asymptomatic cases did significantly influence this observation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.04.22274692v1" target="_blank">The spread and burden of the COVID-19 pandemic in sub-Saharan Africa: comparison between predictions and actual data and lessons learned.</a>
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<li><strong>Optimal thromboprophylaxis strategies in non-critically ill patients with COVID-19 pneumonia. The PROTHROMCOVID Randomized Controlled Trial.</strong> -
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Background : Hospitalized patients with COVID-19 are at increased risk for thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. Objective: To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. Design, setting, and participants : Randomized controlled, multicenter trial (PROTHROMCOVID) enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Interventions: Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) doses of tinzaparin during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. Measurements: The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Results : Of the 311 subjects randomized, 300 were included in the analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]. The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (P= 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Conclusions: In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to increase benefit regarding the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Trial Registration ClinicalTrials.gov Identifier (NCT04730856). Funding: This independent research initiative was supported by Leo-Pharma; Tinzaparin was provided by Leo Pharma.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274594v1" target="_blank">Optimal thromboprophylaxis strategies in non-critically ill patients with COVID-19 pneumonia. The PROTHROMCOVID Randomized Controlled Trial.</a>
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<li><strong>Have infection control and prevention measures resulted in any adverse outcomes for care home and domiciliary care residents and staff?</strong> -
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Background / Aim of Rapid Review Care for older and vulnerable people must sustain core infection prevention and control (IPC) practices and remain vigilant for COVID-19 transmission to prevent virus spread and protect residents and healthcare professionals from severe infections, hospitalisations and death. However, these measures could potentially lead to adverse outcomes such as decreased mental wellbeing in patients and staff. A recent publication by Public Health England examines the effectiveness of IPC practices for reducing COVID-19 transmission in care homes (Duval et al., 2021). We explore evidence relating to adverse outcomes from IPC practices to help inform policy recommendations and identify gaps within the literature where further research can be prioritised. Key Findings Extent of the evidence base 15 studies were identified: 14 primary studies and one rapid review Recency of the evidence base Of the primary studies, six were published in 2020 and eight were published in 2021 The rapid review was published in 2021. Summary of findings This rapid review focuses on adverse outcomes resulting from increased IPC measures put in place during the COVID-19 pandemic. Whilst there is some evidence to show that there may be a link between IPC measures and adverse outcomes, causation cannot be assumed. During the COVID-19 restrictions, the cognition, mental wellbeing and behaviour of residents in care homes were negatively affected Increased IPC procedures during the COVID-19 pandemic increased stress and burden among care staff because of increased workload and dilemmas between adhering well to IPC procedures and providing the best care for the care recipients COVID-19 IPC procedures were not well developed at the beginning of the COVID-19 pandemic, but evidence from 2021 suggests that good adherence to IPC measures can enable visitations by family members and medical professionals into care homes Only one study investigating domiciliary care was found. Therefore, it is difficult to make conclusions related specifically to this care setting No published studies have reported on the costs or cost-effectiveness of IPC measures or have explored the cost implications of adverse outcomes associated with IPC measures Best quality evidence Only one study was deemed as high quality based on the quality appraisal checklist ranking. This was a mixed methods study design (Tulloch et al., 2021). Policy Implications Since March 2020, there have been many changes to government guidelines relating to procedures to keep the population safe from COVID-19 harm. Policies vary according to country, even within the UK. Important issues such as care home visitation policies have changed in such a way that care home staff have felt it difficult to keep up with the changes, which in itself increased the burden on those staff. The following implications were identified from this work: IPC policies should be clear, concise and tailored to care homes and domiciliary care settings Increased attention to workforce planning is needed to ensure adequate staffing and to reduce individual burden Restrictions (e.g. visitation) for care home residents needs to be balanced by additional psychological support Further research with robust methods in this area is urgently needed especially in the domiciliary care setting Strength of Evidence One limitation is the lack of high-quality evidence from the included studies. Confidence in the strength of evidence about adverse outcomes of COVID-19 IPC procedures was rated as low overall. Whilst the majority of studies achieved a moderate score based on the quality appraisal tools used, due to the nature of the methods used, the overall quality of evidence is low.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.04.22274657v1" target="_blank">Have infection control and prevention measures resulted in any adverse outcomes for care home and domiciliary care residents and staff?</a>
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<li><strong>Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2</strong> -
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Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS- CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilised pre- pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterised samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274395v1" target="_blank">Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2</a>
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<li><strong>Correlation of Suspected COVID-19 Symptoms with COVID-19 Positivity in Children</strong> -
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Background: Early in the pandemic, COVID-19 was found to infect adults at higher rates than children, leaving limited data on disease presentation in children. Further understanding of the epidemiology of COVID-19 symptoms among children is needed. Our aim was to explore how symptoms vary between children testing positive for COVID-19 infection versus children testing negative. Methods: Data analysis of symptom prevalence among pediatric patients presenting to emergency departments (ED) in the Johns Hopkins Health System (JHHS) with concern for COVID-19 who subsequently received COVID-19 testing. Inclusion criteria included patients 0-17 years-of-age, ED evaluation between March 15th, 2020 - May 11th, 2020, and those who were ordered for COVID-19 testing. Chart review was performed to document symptoms using ED provider notes. Comparisons were made using chi-squared t-tests and Student’s t-tests. Results: Fever (62.6%) and cough (47.9%) were the most prevalent symptoms among children with suspected COVID-19 infection. Compared to children with a negative COVID-19 test, children who tested positive had higher prevalence of myalgia (21.7% vs 6.0%) and loss of taste/smell (15.2% vs 0.9%). Over half of the children who tested positive for COVID-19 had public insurance (52.2%) and 58.7% of the positive tests occurred among children with Hispanic ethnicity. Conclusions: Myalgia and loss of taste/smell were found to be significantly more prevalent among COVID-19 positive children compared to children testing negative. Additionally, children with public insurance and those with Hispanic ethnicity were more likely to test positive, emphasizing the importance of social factors in the screening and decision-making process.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274641v1" target="_blank">Correlation of Suspected COVID-19 Symptoms with COVID-19 Positivity in Children</a>
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<li><strong>SARS-CoV-2 neutralizing antibodies in Chile after a vaccination campaign with five different schemes</strong> -
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Using levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines technologies and heterologous boosters. In 120 randomly selected seropositive individuals from a population-based study, we conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274622v1" target="_blank">SARS-CoV-2 neutralizing antibodies in Chile after a vaccination campaign with five different schemes</a>
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<li><strong>Antibody responses to AZD1222 vaccination in West Africa</strong> -
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Background: There are no data on vaccine elicited neutralising antibody responses for the most widely used vaccine, AZD1222, in African populations following scale up. Here, we measured i. baseline SARS-CoV-2 seroprevalence and levels of protective antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies to nucleocapsid (N), coupled with virus neutralisation approaches and ii. neutralizing antibody responses to VOC prior to vaccination (January 2021) and after two-doses of AZD1222 vaccine administered between June and July 2021 in Lagos, Nigeria, during a period when the Delta variant was also circulating. Methods: Health workers at multiple sites in Lagos were recruited to the study. For binding antibody measurement, IgG antibodies against SARS-COV-2 Wuhan-1 receptor-binding domain (RBD), trimeric spike protein (S), nucleocapsid protein (N) and Omicron S1 were measured using the Luminex-based SARS-CoV-2-IgG assay by flow cytometry. For plasma neutralising antibody measurement, SARS-CoV-2 lentiviral pseudovirus (PV) were prepared by transfecting 293T cells with Wuhan-614G wild type (WT), B.1.617.2 (Delta) and BA.1 (Omicron) plasmids in conjunction with HIV-1 expression vectors and luciferase encoding genome flanked by LTRs. We performed serial plasma dilutions from each time point and mixed plasma with PV before infecting HeLa-ACE2 cell lines, reading out luminescence and calculating ID50 (dilution of sera required to inhibit 50% of PV infection). Results: Our study population who received at least one dose of vaccine comprised 140 participants with a median age of 40 (interquartile range: 33, 48). 62/140 (44%) participants were anti-N IgG positive prior to administration of first vaccine dose. 49 had plasma samples available at baseline prior to vaccination and at two follow-up timepoints post vaccination for neutralization assays. Half of the participants, 25/49 (51%) were IgG anti-N positive at baseline. Of the 24 individuals anti-N Ab negative at baseline, 12/24 had ID50 above the cut-off of 20. In these individuals, binding antibodies to S were also detectable, and neutralisation correlated with IgG anti-S. Overall, neutralizing Ab titres to WT 1 month after second dose were 2579 and at 3 months post second-dose were 1695. As expected, lower levels of neutralization were observed against the Delta GMT 549 and Omicron variants 269 at 1 month. Positive anti-N IgG Ab status at baseline was associated with significantly higher titres of neutralizing antibodies following vaccination across all tested VOC. Those with anti-N Abs present at baseline did not experience waning of responses between months 1 and 3 post second dose. When data were analysed for negative anti-N IgG status at any timepoint, there was a significant decline in neutralization and binding antibodies between 1 month and 3 months post second-dose. The GMT in these individuals for Delta and Omicron was approximately 100, nearly a log lower in comparison to WT. We tested anti-N IgG in subjects who were anti-N IgG negative at baseline (n=78) and became positive between 1- and 3-months post second dose and found 7/49 (14%) with de-novo infection, with one additional participant demonstrating both reinfection and breakthrough infection to yield a total breakthrough rate of 8/49 (16%). Neutralising and binding Ab titres 1 month post vaccine, prior to breakthrough, did not appear to be associated with breakthrough infection. Neutralizing titres were higher at the last time point in individuals who had experienced vaccine breakthrough infection (with no evidence of infection prior to vaccine), indicating a boosting effect of infection in addition to vaccine. We noted that the increase in titres against Delta PV observed in breakthrough was significantly greater than the increase for WT and Omicron PVs, coincident with in the Delta wave of infection during the sampling period. Conclusions: AZD1222 is immunogenic in this real world west African cohort with significant background seroprevalence and incidence of breakt
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.04.22274668v1" target="_blank">Antibody responses to AZD1222 vaccination in West Africa</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Change in stroke presentations during COVID-19 pandemic in South-Western Sydney.</strong> -
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Background: Australia managed relatively well during the global COVID-19 pandemic owing to our swift mandated public health response. During the NSW lockdown restrictions, we noted a decrease in acute stroke presentations at our institution, similar to what was subsequently reported worldwide. Aims: We aimed to test our hypothesis that (i) the true numbers of ischaemic strokes did not change, however patients were presenting later and (ii) the proportion of TIAs decreased. Methods: We conducted a retrospective audit of all stroke and TIA presentations in 2020 and compared these with data from 2019. We collected information about stroke subtype, severity, time from stroke/TIA onset to presentation and acute reperfusion therapies. Results: Between January-February and April-March 2020, there was a 15% drop in acute stroke presentations (128 vs. 109). In the same period “stroke mimic” presentations dropped by 22%. The proportion of patients attending the emergency department within 4.5hrs was only 36% compared with 48% over the similar period in</p></div></li>
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<li>Conclusions: Although the raw numbers of ischemic stroke presentations remained stable during NSW Covid lockdown, the proportion of patients presenting within time window for acute reperfusion therapies fell. The number of TIAs similarly fell suggesting COVID-19 discouraged patients from presenting to hospital which placed them at higher risk of disabling stroke. The opportunity cost of lockdown restrictions on stroke outcome should be considered in future policy directives.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.02.22274456v1" target="_blank">Change in stroke presentations during COVID-19 pandemic in South-Western Sydney.</a>
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<li><strong>Incorporating crowdsourced perceptions of human behavior into computational forecasts of US national incident cases of COVID-19</strong> -
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Computational forecasts of COVID-19 targets may benefit from temporal signals associated with human behavior. Non- pharmaceutical interventions (NPI) have been shown to reduce the spread of an infectious agent, but accurate information about how the general public interprets and acts upon guidelines developed by public health officials is difficult to collect. For 36 weeks from September, 2020 to April, 2021, we asked two crowds twenty one questions about their perceptions of their communities adherence to NPI and public health guidelines and collected 10,120 responses. Crowdsourced NPI signals were mapped to a mean perception of adherence—or MEPA—and included in computational forecasts. Several MEPA signals linearly correlated with one through four week ahead incident cases of COVID-19 at the US national level. Including questions related to masking, testing, and limiting large gatherings increased out of sample predictive performance for 1-3 week ahead probabilistic forecasts of incident cases of COVID-19 when compared to a model that was trained on only past incident cases. In addition, we found that MEPA signals could be clustered which suggests a more focused survey may have sufficed and provided similar performance. Crowdsourced perceptions of non-pharmaceutical adherence may be an important signal to improve forecasts of the trajectory of an infectious agent and increase public health situational awareness.
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🖺 Full Text HTML: <a href="https://osf.io/7vrmy/" target="_blank">Incorporating crowdsourced perceptions of human behavior into computational forecasts of US national incident cases of COVID-19</a>
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<li><strong>Asymptomatic SARS-CoV-2 infection by age: A systematic review and meta-analysis</strong> -
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Abstract: Objectives: This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons by year of age. Methods: We searched PubMed, Embase, medRxiv and Google Scholar on 10 September 2020 and 1 March 2021. We included studies conducted during January to October 2020, prior to routine vaccination against COVID-19. Since we expected the relationship between the asymptomatic proportion and age to be non- linear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age. Results: A total of 38 studies were included in the meta-analysis. In total, 6556 out of 14850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14850, 95%CI 43.3%-45.0%). The asymptomatic proportion peaked in adolescents (36.2%, 95%CI 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95%CI 3.4%-12.7%). Conclusions: Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.05.22274697v1" target="_blank">Asymptomatic SARS-CoV-2 infection by age: A systematic review and meta-analysis</a>
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<li><strong>Which innovations can improve timeliness of investigations and address the backlog in endoscopy for patients with potential symptoms of upper and lower Gastrointestinal (GI) cancers? Rapid Review</strong> -
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Background / Aim of Rapid Review Many patients were not able to access routine diagnostic care through 2020/21 because of extraordinary pressures on the NHS due to COVID-19 and the UK national lockdowns. For some patients this can have serious short and long-term consequences to their health and life expectancy. The NHS has limited resources and is looking for new ways to meet many demands and patient needs. This Rapid Review Report aims to answer the question: Which innovations can be used to accelerate the patients journey through the endoscopic cancer diagnosis pathway?. The report highlights evidence of innovations and new ways to improve the timeliness of access to endoscopy and to address the backlog of unmet need for patients who have waited a long time for such tests and investigations by selecting those at highest for prioritisation. It does not evaluate in terms of effectiveness on clinical outcomes. Key Findings Extent of the evidence base Nine papers were included in the rapid review in total. Two reviews were identified. One review examined the novel colon capsule endoscopy (CCE) procedure and the second review summarised the effects of COVID-19 on colorectal cancer (CRC) screening, the potential long-term? outcomes, and ways to adapt CRC screening during the COVID-19 pandemic. ▪ Seven primary studies assessed innovations for the diagnosis of Gastrointestinal (GI) cancers. Five of these studies examined faecal immunochemical testing (FIT) for prioritising patients for further testing. Two studies reported pathways/innovations to triage patients e.g. from primary care. These methods of triage used interventions such as Cytosponge for oesophageal symptoms. Recency of the evidence base Of the primary studies, one was published in 2020 and six were published in 2021. Of the reviews, one was published in 2020 and one in 2021. Evidence of effectiveness The five studies investigating FIT found that it could help prioritise patients for further testing and improve targeting of high-risk patients. One review proposed CCE may offer a useful solution for investigating colorectal patients to reduce the need for some endoscopies following the pandemic. One review found a shift from current CRC screening and surveillance practices towards an individualized approach based on risk factors, could result in the allocation of resources to people with higher risks and prevent inappropriate use of healthcare resources for those with lower risks. Best quality evidence All studies were quality appraised using the relevant JBI checklist. Five studies were of low to moderate quality. Policy Implications Increased use of faecal immunochemical testing (FIT) could reduce the endoscopy backlog and save NHS resources if those with low FIT scores can be excluded from further testing. Policy in Wales supports prioritisation of potential gastrointestinal cancer patients for endoscopy using FIT test scores (NHS Wales 2021) although local implementation currently varies, so it is not yet fully utilised. The FIT test gives results which could be utilised by healthcare professionals to prioritise those who are most in need of urgent diagnosis. The viability of this method to prioritise those in greatest need of being referred for diagnosis through endoscopy is proven (though safety-netting is still required), and the FIT test is part of the diagnostic pathway already in Wales. It will be important to ensure all areas of Wales have equal access to the use of FIT testing for this purpose, and that clinical guidelines are harmonised and adhered to throughout Wales. Innovations to reduce backlog and speed up time to diagnosis should be explored including: o Triage in primary care settings such as GP surgeries using innovations such as the cytosponge for oesophageal symptoms (e.g. reflux). o Direct referral from primary care settings to specialist investigation, without the need for prior additional referrals in secondary care. Strength of Evidence The evidence presented in this review is recent, however with small samples (di Pietro et al., 20
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.04.22274653v1" target="_blank">Which innovations can improve timeliness of investigations and address the backlog in endoscopy for patients with potential symptoms of upper and lower Gastrointestinal (GI) cancers? Rapid Review</a>
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<li><strong>Longitudinal analyses of depression and anxiety highlight greater prevalence during COVID-19 lockdowns in the Dutch general population and a continuing increase in suicidal ideation in young adults</strong> -
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Objective: The pandemic of the coronavirus disease 2019 (COVID-19) has led to an increased burden on mental health. This study therefore investigated the development of major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidal ideation in the Netherlands during the first fifteen months of the pandemic and three nation-wide lockdowns. Methods: Participants of the Lifelines Cohort Study -a Dutch population-based sample- reported current symptoms of MDD and GAD, including suicidal ideation, according to DSM-IV criteria using a digital structured questionnaire. Between March 2020 and June 2021, 36,106 participants (aged 18-96) filled out a total of 629,811 questionnaires across 23 time points. Trajectories over time were estimated using generalized additive models and analyzed in relation to age, sex, and lifetime history of MDD/GAD to identify groups at risk. Results: We found non- linear trajectories for MDD and GAD with a higher number of symptoms and prevalence rates during periods of lockdown. The point prevalence of MDD and GAD peaked during the third hard lockdown at 2.88% (95% CI: 2.71%-3.06%) and 2.92% (95% CI: 2.76%-3.08%), respectively, in March 2021. Women, younger adults, and participants with a history of MDD/GAD reported significantly more symptoms. For suicidal ideation, we found a linear increase over time in younger participants which continued even after the lockdowns ended. For example, 4.63% (95% CI: 3.09%-6.96%) of 20-year-old participants reported suicidal ideation at our last measured time point in June 2021, which represents a 4.14x increase since the start of the pandemic. Conclusions: Our study showed greater prevalence of MDD and GAD during COVID-19 lockdowns suggesting that the pandemic and government enacted restrictions impacted mental health in the population. We furthermore found a continuing increase in suicidal ideation in young adults. This warrants for alertness in clinical practice and prioritization of mental health in public health policy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.02.22273554v1" target="_blank">Longitudinal analyses of depression and anxiety highlight greater prevalence during COVID-19 lockdowns in the Dutch general population and a continuing increase in suicidal ideation in young adults</a>
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<li><strong>Biological age is increased by stress and restored upon recovery</strong> -
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Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. By applying advanced epigenetic aging clocks, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment of animals. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. Elevation of biological age by stress may be a quantifiable and actionable target for future interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.04.490686v1" target="_blank">Biological age is increased by stress and restored upon recovery</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>Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2<br/><b>Sponsors</b>: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<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 COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology 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, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology 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 Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology 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>The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Chinese herbal medicine<br/><b>Sponsor</b>: <br/>
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Hong Kong Baptist University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-based Exercise Program in Patients With the Post-COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Home- based physical training<br/><b>Sponsor</b>: University of Sao Paulo<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>Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<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>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<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>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, LLC<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>High Frequency Percussive Ventilation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Acute Respiratory Failure<br/><b>Intervention</b>: <br/>
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Device: High frequency Percussive ventilation<br/><b>Sponsor</b>: University Magna Graecia<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>Knowledge Mobilization Activities to Support Decision-Making by Youth, Parents and Adults: Study Protocol</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Plain Language Recommendation (PLR); Other: Standard Language Version (SLV)<br/><b>Sponsors</b>: McMaster University; Western University; The Hospital for Sick Children; University of Alberta<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>Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings</strong> - <b>Conditions</b>: Covid19; Diabetes Mellitus<br/><b>Intervention</b>: Device: continuous glucose monitoring<br/><b>Sponsor</b>: Tanureet K Arora<br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac</strong> - CONCLUSION: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.</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>Treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT)</strong> - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel prothrombotic disorder characterized by thrombosis, thrombocytopenia, and disseminated intravascular coagulation identified in hundreds of recipients of ChAdOx1 nCoV-19 (Oxford/AstraZeneca), an adenovirus vector coronavirus disease 2019 (COVID-19) vaccine. VITT resembles heparin-induced thrombocytopenia (HIT) in that patients have platelet-activating anti-platelet factor 4 antibodies; however, whereas heparin typically enhances…</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>Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection</strong> - The ability to treat severe viral infections is limited by our understanding of the mechanisms behind virus-induced immunopathology. While the role of type I interferons (IFNs) in early control of viral replication is clear, less is known about how IFNs can regulate the development of immunopathology and affect disease outcomes. Here, we report that absence of type I IFN receptor (IFNAR) is associated with extensive immunopathology following mucosal viral infection. This pathology occurred…</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>25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 M<sup>pro</sup> and RdRp-: an insight from molecular docking and dynamics simulation approaches</strong> - The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M^(pro)) of the virus mediate viral…</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>Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an <em>in silico</em> perspective</strong> - During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as 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>Potential Inhibitors of SARS-CoV-2 from <em>Neocarya macrophylla</em> (Sabine) Prance ex F. White: Chemoinformatic and Molecular Modeling Studies for Three Key Targets</strong> - CONCLUSION: The findings of this study have shown that N. macrophylla contains potential leads for SARS-CoV-2 inhibition and thus, should be studied further for development as therapeutic agents against COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IL-25 blockade augments antiviral immunity during respiratory virus infection</strong> - IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal…</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>Megakaryocytes in pulmonary diseases</strong> - Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are…</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>Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study</strong> - CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of 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>Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach</strong> - Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS-CoV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as “variant of concern” due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous…</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>Development of an At-home Metal Corrosion Laboratory Experiment for STEM Outreach in Biomaterials During the Covid-19 Pandemic</strong> - Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building integrated, adaptive and responsive healthcare systems - lessons from paramedicine in Ontario, Canada</strong> - CONCLUSIONS: The findings of this study add to the discourse on governing health systems towards being more integrated, adaptive and responsive to population needs. Governance strategies include: supporting networks of local organizational relationships; considering the role of a functionally flexible health workforce; promoting a shared vision and framework for collaboration; and enabling distributed, local control and experimentation.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants</strong> - As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension…</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>Computational study on the affinity of potential drugs to SARS-CoV-2 main protease</strong> - Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using Molecular and Quantum Mechanics as well as Molecular Docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the Docking…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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