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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for critical COVID-19</strong> -
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Background: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequalae. Methods: In this prospective single-center study, we performed CPET in 60 patients, 12 months after a critical COVID-19 infection that required intensive care unit (ICU) treatment. Lung function at rest and chest computed tomography (CT) scan were also performed. Results: Twelve months after severe COVID-19 pneumonia, the majority of the patients had a peak O2 uptake (VO2) considered within normal limits. However, length of ICU stay remained an independent predictor of VO2. Surprisingly, more than half of the patients with a normal peak predicted VO2 showed ventilatory inefficiency during exercise (high VE/VCO2 ratio and high VE/VCO2 slope) with increased physiological dead space (VD/Vt) and low end-tidal CO2 partial pressure (PETCO2) values. This impairment was even more pronounced in patients with persistent dyspnea. Notably, peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay. Conclusions: Even if reduced exercise capacity was rare 12 months after critical COVID-19, more than half of the patients with normal exercise capacity showed ventilatory inefficiency.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22279779v1" target="_blank">Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for critical COVID-19</a>
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<li><strong>A Cross-Sectional Study of Quantitative CT Measurements Associated with the Diffusion Capacity of the Lung in Recovered COVID-19 Patients with Clear Chest CTs</strong> -
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Impairment of the diffusion capacity of the lung for carbon monoxide (DLco) is commonly reported in convalescent and recovered COVID-19 patients, although the cause is not fully understood especially in patients with no radiological sequelae. In a group of 47 patients at 7 - 51 weeks post infection with either none or minimal scarring or atelectasis on chest CT scans (total &lt; 0.1% of lung volume), dispersions in DLco-adj % and total lung capacity (TLC) % of predicted were observed, with median(quartiles) of 87(78, 99)% and 84(78, 92)%, respectively. Thirteen(27.1%) patients had DLco-adj% &lt; 80%. Although the DLco-adj% did not significantly correlate with the severity of the illness in the acute phase, time since the onset of symptoms, the volume of residual lesions on CT, age or sex, DLco-adj/alveolar volume (Kco-adj) % predicted was correlated with the measurements of small blood vessel volume fraction (diameter &lt;= 5mm) and parenchyma density on CT. Multivariate analysis revealed that these two CT metrics significantly contributed to the variance in DLco-adj% independent of TLC%. Comparing to between-subject variability of DLco-adj in healthy individuals, patients in this cohort with DLco-adj% &lt; 80% were likely abnormal with a degree of disease not visually detectable on CT. However, it is not clear whether the associated variance of parenchyma density and small-vessel volume fraction were a consequence of the COVID-19 disease or a pre-existing background variance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.13.22279543v1" target="_blank">A Cross-Sectional Study of Quantitative CT Measurements Associated with the Diffusion Capacity of the Lung in Recovered COVID-19 Patients with Clear Chest CTs</a>
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<li><strong>What is the effectiveness of financial support schemes for individuals requested to self-isolate following a positive Covid test or positive contact: A rapid review</strong> -
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Testing for COVID-19 has been deployed globally as a tool to interrupt transmission through isolating positive contacts from the broader population. Financial support systems have been deployed to increase the isolation compliance, there is uncertainty as to the effectiveness of these measures. Three reviews were identified, as well as four primary studies that were published after the review search dates. Six studies showed that financial support for isolation was associated with a higher compliance to isolate. Two epidemiological modelling studies found that increased levels of social isolation were associated with a reduction in COVID-19 transmission. The findings from a DCE demonstrated a positive relationship with longer isolation duration and higher financial requirements. An economic model showed that support programmes have the potential to be a cost-effective intervention. A retrospective observational study offered evidence supporting the viability of delivering medically assisted isolation hotels for people unable to isolate at home. Further to the COVID-19 literature, two household surveys found that financial support and improved social restriction information was associated with compliance with H1N1 isolation Policy and practice implications: There is limited evidence to suggest that financial support for isolation can increase compliance, lower social engagement, and reduce infection levels. There is insufficient evidence to inform the optimal scale of financial support required There was no evidence related to effectiveness of financial support for disadvantaged populations who are required to isolate or any insight to the impact of financial support on equality The overall certainty in the evidence is relatively low. Most studies relied on participant reported data on preference or behaviour, and where observational data were used there were issues with data quality and unobserved cofounders.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.15.22279969v1" target="_blank">What is the effectiveness of financial support schemes for individuals requested to self-isolate following a positive Covid test or positive contact: A rapid review</a>
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<li><strong>O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Contribute to the Mutational Trajectory in Variants of Concern</strong> -
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The emergence of a polybasic cleavage motif for the protease furin in the SARS-CoV-2 spike protein has been established as a major factor for enhanced viral transmission in humans. The peptide region N-terminal to that motif is extensively mutated in major variants of concern including alpha, delta and omicron. Besides furin, spike proteins from these variants appear to rely on other proteases for maturation including TMPRSS2 that may share the same cleavage motif. Glycans found near the cleavage motif have raised questions about proteolytic processing and the consequences of variant-borne mutations. Here, with a suite of chemical tools, we establish O-linked glycosylation as a major determinant of SARS-CoV-2 spike cleavage by the host proteases furin and TMPRSS2 and a likely driving force for the emergence of common mutations in variants such as omicron, delta and alpha. We provide direct evidence that the glycosyltransferase GalNAc-T1 primes glycosylation at Thr678 in the living cell. A novel strategy for rapid bioorthogonal modification of Thr678-containing glycopeptides reveals that introduction of a negative charge completely abrogates furin activity. In a panel of synthetic glycopeptides containing elaborated O-glycans, we find that sialic acid moieties reduce furin cleavage rate by up to 65%. Similarly, O-glycosylation had a general negative impact on spike cleavage by TMPRSS2, with core 1 (Gal{beta}1-3GalNAc-) O-glycan-containing glycopeptides having the largest effect. With a chemistry-centered approach, we thus firmly establish O-glycosylation as a major determinant of spike maturation. We propose that a disruption of O-GalNAc glycosylation is a substantial driving force for the evolution of variants of concern.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.15.508093v1" target="_blank">O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Contribute to the Mutational Trajectory in Variants of Concern</a>
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<li><strong>A hybrid structure determination approach to investigate the druggability of the nucleocapsid protein of SARS-CoV-2</strong> -
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The ongoing pandemic caused by SARS-CoV-2 has called for concerted efforts to generate new insights into the biology of betacoronaviruses to inform drug screening and development. Here, we establish a workflow to determine the RNA recognition and druggability of the nucleocapsid N-protein of SARS-CoV-2, a highly abundant protein crucial for the viral life cycle. We use a synergistic method that combines NMR spectroscopy and protein-RNA cross-linking coupled to mass spectrometry to quickly determine the RNA binding of two RNA recognition domains of the N-protein. Finally, we explore the druggability of these domains by performing an NMR fragment screening. This workflow identified small molecule chemotypes that bind to RNA binding interfaces and that have promising properties for further drug development.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.15.507991v1" target="_blank">A hybrid structure determination approach to investigate the druggability of the nucleocapsid protein of SARS-CoV-2</a>
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<li><strong>Fast bioluminescent nucleic acid detection using one-pot isothermal amplification and dCas9-based split luciferase complementation</strong> -
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Nucleic acid detection methods based on isothermal amplification techniques show great potential for point-of-care diagnostic applications. However, most current methods rely on fluorescent or lateral flow assay readout, requiring external excitation or post-amplification reaction transfer. Here, we developed a bioluminescent nucleic acid sensor (LUNAS) platform in which target dsDNA is sequence-specifically detected by a pair of dCas9-based probes mediating split NanoLuc luciferase complementation. Whereas LUNAS itself features a detection limit of ~1 pM for dsDNA targets, the LUNAS platform is easily integrated with recombinase polymerase amplification (RPA), providing attomolar sensitivity in a single-pot assay. We designed a one-pot RT-RPA-LUNAS assay for detecting SARS-CoV-2 RNA without the need for RNA isolation and demonstrated the diagnostic performance for COVID-19 patient nasopharyngeal swab samples using a digital camera to record the ratiometric signal. Detection of SARS-CoV-2 from samples with viral RNA loads of ~200 cp/microL was achieved within ~20 minutes, showing that RPA-LUNAS is attractive for point-of-care diagnostic applications.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.507659v1" target="_blank">Fast bioluminescent nucleic acid detection using one-pot isothermal amplification and dCas9-based split luciferase complementation</a>
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<li><strong>Cognitive status and rehabilitation outcomes of patients in acute rehabilitation post Covid-19</strong> -
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Objective: This study aims to 1) characterize cognitive functioning in patients admitted for inpatient rehabilitation due to Covid-19 diagnosis and 2) examine how cognitive status at admission is associated with rehabilitation outcomes. Design: Retrospective chart review. Setting: An inpatient rehabilitation center located in Chicago, Illinois. Participants: 80 participants in acute rehabilitation due to Covid-19 disease/ Intervention: Not applicable. Main Outcome Measures: Cognitive functioning as measured by the Montreal Cognitive Assessment (MoCA) and rehabilitation outcomes as measured by Functional Index Measure (FIM) and Section GG items for self-care and mobility (GG-SC and GG-M respectively). Results: On average, our sample presented with mild cognitive impairment as assessed by the (MoCA). The most significant deficits were demonstrated in executive function, attention, language, and delayed free recall measures. Higher levels of overall cognitive function were associated with higher cognitive measures of rehabilitation outcomes. Weaker associations were observed with outcome measures of self-care and motor functioning. Conclusion: Cognitive impairments are common in patients in acute rehabilitation due to Covid-19 and cognitive performance may help predict rehabilitation outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.10.22279806v1" target="_blank">Cognitive status and rehabilitation outcomes of patients in acute rehabilitation post Covid-19</a>
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<li><strong>Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types</strong> -
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The relationship between N-antigen concentration and viral load within a specimen and across different specimens is essential for interpretation of rapid diagnostic tests (RDT) clinical performance in different use cases. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one on saliva. Antigen concentration correlated with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs in nasal samples. Given lower antigen concentrations in saliva, tests using saliva is expected to require improved analytical sensitivity to achieve clinical sensitivity similar to testing of nasal samples.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22279810v1" target="_blank">Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types</a>
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<li><strong>COVID-19 induced birth sex ratio changes in England and Wales</strong> -
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Background The sex ratio at birth (male live births divided by total live births) may be a sentinel health indicator. Stressful events reduce this ratio 3-5 months later by increasing male fetal loss. This ratio can also change 9 months after major population events that are linked to an increase or decrease in the frequency of sexual intercourse at the population level, with the ratio either rising or falling respectively after the event. We postulated that stress caused by the COVID-19 pandemic may have affected the ratio in England and Wales. Methods Publicly available, monthly live birth data for England and Wales was obtained from the Office for National Statistics up to December 2020. The sex ratio at birth for 2020 (global COVID-19 onset) was predicted using data from 2012-2019. Observed and predicted values were compared. Results Three months after COVID-19 was declared pandemic (March 2020), there was a significant fall in the sex ratio at birth to 0.5100 in June 2020 which was below the 95% prediction interval of 0.5102-0.5179. Nine months after the pandemic declaration, (December 2020), there was a significant rise to 0.5171 (95% prediction interval 0.5085-0.5162). However, December 2020 had the lowest number of live births of any month from 2012 to 2020. Conclusions Given that June 2020 falls within the crucial window when population stressors are known to affect the sex ratio at birth, these findings imply that the start of the COVID-19 pandemic caused population stress with notable effects on those who were already pregnant by causing a disproportionate loss of male fetuses. The finding of a higher sex ratio at birth in December 2020, i.e., 9 months after COVID-19 was declared a pandemic, suggests that lockdown restrictions initially spurred more sexual activity in a subset of the population in March 2020.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.09.22279763v1" target="_blank">COVID-19 induced birth sex ratio changes in England and Wales</a>
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<li><strong>Detecting changes in population trends in infection surveillance using community SARS-CoV-2 prevalence as an exemplar</strong> -
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Background: Monitoring infection trends is vital to informing public health strategy. Detecting and quantifying changes in growth rates can inform policymakers9 rationale for implementing or continuing interventions aimed at reducing impact. Substantial changes in SARS-CoV-2 prevalence with emergence of variants provides opportunity to investigate different methods to do this. Methods: We included PCR results from all participants in the UK9s COVID-19 Infection Survey between 1 August 2020-30 June 2022. Change-points for growth rates were identified using iterative sequential regression (ISR) and second derivatives of generalised additive models (GAMs). Consistency between methods and timeliness of detection were compared. Findings: Of 8,799,079 visits, 147,278 (1.7%) were PCR-positive. Over the time period, change-points associated with emergence of major variants were estimated to occur a median 4 days earlier (IQR 0-8) in GAMs versus ISR, with only 2/48 change-points identified by only one method. Estimating recent change-points using successive data periods, four change-points (4/96) identified by GAMs were not found when adding later data or by ISR; 77% (74/96) of change-points identified by successive GAMs were identified by ISR. Change-points were detected 3-5 weeks after they occurred in both methods but could be detected earlier within specific subgroups. Interpretation: Change-points in growth rates of SARS-CoV-2 can be detected in near real-time using ISR and second derivatives of GAMs. To increase certainty about changes in epidemic trajectories both methods could be run in parallel. Running either method in near real-time on different infection surveillance data streams could provide timely warnings of changing underlying epidemiology. Funding: UK Health Security Agency, Department of Health and Social Care (UK), Welsh Government, Department of Health (on behalf of the Northern Ireland Government), Scottish Government, National Institute for Health Research.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.14.22279931v1" target="_blank">Detecting changes in population trends in infection surveillance using community SARS-CoV-2 prevalence as an exemplar</a>
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<li><strong>Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates</strong> -
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Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.13.22279890v1" target="_blank">Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates</a>
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<li><strong>Real-world Use of Nirmatrelvir-Ritonavir in COVID-19 Outpatients During the Emergence of Omicron Variants BA.2/BA2.12.1</strong> -
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Background: Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with in vitro activity against SARS-CoV-2, has been shown to reduce risk of progression to severe COVID-19 among high-risk individuals during the Delta-variant phase. We sought to determine the effectiveness of NMV-r against Omicron lineage variants BA.2/BA2.12.1, and assess for evidence of a clinical rebound effect. Methods: We conducted a retrospective observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from March 26th, 2022 to June 23rd, 2022, using records from a statewide health system linked to vaccine and mortality data. Propensity score matching was performed on NMV-r treated outpatients with outpatients not treated with antiviral therapy. The primary outcome was 28-day all-cause hospitalization; secondary outcomes were COVID-19-related hospitalization, 28-day all-cause mortality, and 28-day ED visits. Logistic regression was used to determine NMV-r treatment effectiveness; subgroup analyses were performed to assess for heterogeneity in treatment effect. Results: Of 14,953 SARS-CoV-2 infected outpatients, 3,614 NMV-r treated patients were matched to 4,835 untreated outpatients. NMV-r was associated with significantly lower odds of 28-day all-cause hospitalization as compared to no antiviral treatment [31 (0.9%) vs. 64 (1.3%), adjusted odds ratio (aOR): 0.48 (95% CI 0.31-0.75)]. NMV-r was also associated with lower odds of COVID-19 related hospitalization [aOR (95% CI): 0.42 (0.25-0.68)] and 28-day all-cause mortality [aOR (95% CI): 0.05 (0.00-0.38)]. Using ED visits within 28 days as a surrogate for rebound symptoms, we observed no clinically evident rebound effect with NMV-r treatment [140 (3.9%) vs 205 (4.2%), aOR: 0.81 (95% CI 0.65-1.02), p = 0.075]. Conclusion: Real-world evidence during an Omicron BA.2/BA2.12.1 predominant period demonstrated an association of NMV-r treatment with reduced 28-day hospitalization and all-cause mortality, and without an increase in rebound symptoms as assessed by ED visits within 28 days after treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22279866v1" target="_blank">Real-world Use of Nirmatrelvir-Ritonavir in COVID-19 Outpatients During the Emergence of Omicron Variants BA.2/BA2.12.1</a>
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<li><strong>Angiotensin 1-7 in severe COVID-19 patients: a phase 1 clinical trial</strong> -
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Background: The coronavirus-related disease (COVID-19) is mainly characterized by a respiratory involvement, with few available therapeutics for critically cases. The renin-angiotensin system (RAS) has a relevant role in the pathogenesis of COVID-19, as the virus enter host9s cells via the angiotensin-converting enzyme 2 (ACE2) and RAS disequilibrium promote inflammation and fibrosis. Exogenous angiotensin-(1-7) might modulate RAS in COVID-19 patients; however, no data on its safety are available in this setting. Methods: This investigator-initiated, open label, phase I clinical trial was conducted to test the safety of intravenous administration of Angiotensin-(1-7) in severe COVID-19 patients admitted in two intensive care units (ICU) in Belo Horizonte, Brazil. In addition to standard of care, intravenous administration of Angiotensin-(1-7) was started at 5 mcg/Kg<em>day and increased to 10 mcg/Kg</em>day after 24 hours and continued for a maximum of 7 days or until ICU discharge. The rate of serious adverse events (SAEs) served as the primary outcome of the study. Results: Between August and December 2020, 28 patients were included (mean age of 55.8 + or -12.0 years). All but one patient underwent dose escalation after 24 hours and 8 (28.5%) received the treatment until day 7. No significant differences in mean blood pressure and heart rate were observed before and after the initiation of the drug. During the period of intervention, 5/28 (17.8%) patients required vasopressors, 4 at low dose norepinephrine (i.e. &lt;0.05 mcg/kg<em>min), while one patient required higher doses because of septic shock. One patient presented with sinus bradycardia, which was considered possibly related to the study drug and resolved after discontinuation. Six patients (21.4%) died before ICU discharge. Conclusions: Intravenous infusion of Angiotensin-(1-7) up to 10 mcg/Kg</em>day was safe in severe COVID-19 patients and could represent a potential therapeutic strategy in this setting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.15.22279897v1" target="_blank">Angiotensin 1-7 in severe COVID-19 patients: a phase 1 clinical trial</a>
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<li><strong>Humoral and Cellular Immunogenicity and Safety of 3 Doses of CoronaVac and BNT162b2 in Young Children and Adolescents with Kidney Diseases</strong> -
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Background: Patients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged &lt;5 years, 0.1ml BNT162b2 to those aged 5-11 years, and 0.3ml BNT162b2 to those aged 11-18 years. Results: Antibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; p&lt;0.0001). However, T cell response against Omicron BA.1 was preserved, which likely confer protection against severe COVID-19. Hybrid immunity was observed after vaccination in infected patients, as evidenced by higher Omicron BA.1 neutralization response among infected patients receiving 2 doses than those uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusions: Our findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.14.22279916v1" target="_blank">Humoral and Cellular Immunogenicity and Safety of 3 Doses of CoronaVac and BNT162b2 in Young Children and Adolescents with Kidney Diseases</a>
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<li><strong>The impact of COVID-19 on population cancer screening programs in Australia: modelled evaluations for breast, bowel and cervical cancer</strong> -
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<b>Background</b>&lt;br /&gt;Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel and cervical cancer screening programs on cancer outcomes and cancer services.&lt;br /&gt;&lt;br /&gt;<b>Methods</b>&lt;br /&gt;We used the <i>Policy1</i> modelling platforms to estimate outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9 and 12 months. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts.&lt;br /&gt;&lt;br /&gt;<b>Results</b>&lt;br /&gt;We estimated that a 12-month screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020-2021) and colorectal cancer (up to 12·1% reduction over 2020-21), and increase cervical cancer diagnoses (up to 3·6% over 2020-2022), with upstaging expected for these cancer types.&lt;br /&gt;&lt;br /&gt;<b>Conclusions</b>&lt;br /&gt;Findings illustrate that maintaining screening participation is critical to sustaining a reduced cancer burden. We provide program-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programs, and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.11.22279831v1" target="_blank">The impact of COVID-19 on population cancer screening programs in Australia: modelled evaluations for breast, bowel and cervical cancer</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>Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: Olfactory training with essential oils;   Other: Olfactory training with fragrance-free oils<br/><b>Sponsor</b>:   Ditte Gertz Mogensen<br/><b>Recruiting</b></p></li>
<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 Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Interventions</b>:   Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg;   Biological: BNT162b4 5 µg;   Biological: BNT162b4 10 µg;   Biological: BNT162b4 15 µg<br/><b>Sponsors</b>:   BioNTech SE;   Pfizer<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trial of 2nd Booster Dose of COVID-19 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Invitation to get a 2nd booster dose of COVID-19 vaccine<br/><b>Sponsor</b>:   Norwegian Institute of Public Health<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Text-Messaging (TM);   Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>:   University of Utah;   Utah Department of Health;   Association for Utah Community Health;   National Institutes of Health (NIH);   National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Text-Messaging (TM);   Behavioral: Conversational Agent (CA);   Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>:   University of Utah;   Utah Department of Health;   Association for Utah Community Health;   National Institutes of Health (NIH);   National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AD17002 + Formulation buffer;   Biological: Placebo<br/><b>Sponsors</b>:   Advagene Biopharma Co. Ltd.;   Gadjah Mada University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Community-based Health Education based on core intervention package;   Behavioral: Health Information Sharing Group<br/><b>Sponsors</b>:   The Hong Kong Polytechnic University;   Food and Health Bureau, Hong Kong<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia</strong> - <b>Conditions</b>:   Olfactory Disorder;   COVID-19<br/><b>Intervention</b>:   Drug: Simvastatin<br/><b>Sponsors</b>:   Washington University School of Medicine;   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID)</strong> - <b>Condition</b>:   Post COVID-19 Condition<br/><b>Intervention</b>:   Behavioral: Personalized multidisciplinary day-hospital intervention<br/><b>Sponsor</b>:   Assistance Publique - Hôpitaux de Paris<br/><b>Not yet recruiting</b></p></li>
<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 Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: standard-of-care plus Paxlovid;   Drug: standard-of-care<br/><b>Sponsor</b>:   Ruijin Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: PTX-COVID19-B;   Biological: Comirnaty®<br/><b>Sponsor</b>:   Everest Medicines (Singapore) Pte. Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: PTX-COVID19-B;   Biological: Vaxzevria®<br/><b>Sponsor</b>:   Everest Medicines (Singapore) Pte. Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cardiopulmonary Rehabilitation in Post-acute COVID-19 Syndrome</strong> - <b>Condition</b>:   Post Acute COVID-19 Syndrome<br/><b>Interventions</b>:   Other: Cardiopulmonary rehabilitation;   Other: Health education<br/><b>Sponsor</b>:   Taipei Medical University Shuang Ho Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Active Intervention Group<br/><b>Sponsor</b>:   Pennington Biomedical Research Center<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19</strong> - <b>Conditions</b>:   Long COVID;   COVID-19<br/><b>Intervention</b>:   Behavioral: Cardiac Rehabilitation<br/><b>Sponsor</b>:   University of California, San Francisco<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern</strong> - Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2^(+)-TMPRSS2 cells, with IC(50) values ranging from 0.32 to 1.22 µM….</p></li>
<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 and the potential of Janus family kinase (JAK) pathway inhibition: A novel treatment strategy</strong> - Recent evidence proposed that the severity of the coronavirus disease 2019 (COVID-19) in patients is a consequence of cytokine storm, characterized by increased IL-1β, IL-6, IL-18, TNF-α, and IFN-γ. Hence, managing the cytokine storm by drugs has been suggested for the treatment of patients with severe COVID-19. Several of the proinflammatory cytokines involved in the pathogenesis of COVID-19 infection recruit a distinct intracellular signaling pathway mediated by JAKs. Consequently, JAK…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In vitro</em> Screening of Herbal Medicinal Products for Their Supportive Curing Potential in the Context of SARS-CoV-2</strong> - COVID-19 herbal medicinal products may have the potential for symptom relief in nonsevere or moderate disease cases. In this in vitro study we screened the five herbal medicinal products Sinupret extract (SINx), Bronchipret thyme-ivy (BRO-TE), Bronchipret thyme-primula (BRO TP), Imupret (IMU), and Tonsipret (TOP) with regard to their potential to (i) interfere with the binding of the human angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 spike S1 protein, (ii) modulate the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode</strong> - The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Complement C5a inhibition: a new form of COVID-19 treatment for mechanically ventilated patients?</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity</strong> - The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. The main protease (M^(pro)) is an promising target for anti-SARS-CoV-2 drug design. Here, we report the discovery of potent non-covalent non-peptide M^(pro) inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified the non-covalent hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Severe refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab</strong> - A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic properties and molecular docking study of some phenolic compounds as anti-human lung cancer potential: A biochemical approach</strong> - Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> studies of M<sup>pro</sup> and PL<sup>pro</sup> from SARS-CoV-2 and a new class of cephalosporin drugs containing 1,2,4-thiadiazole</strong> - The SARS-CoV-2 proteases M^(pro) and PL^(pro) are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics: ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement</strong> - By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial</strong> - BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture</strong> - Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQs mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring experiences with telehealth-delivered allied healthcare services for people with permanent and significant disabilities funded through a national insurance scheme: a qualitative study examining challenges and suggestions to improve services</strong> - CONCLUSIONS: Some people with permanent and significant disabilities who accessed allied healthcare via telehealth during the pandemic experienced challenges, particularly children. These unique barriers to telehealth need customised solutions so that people with disabilities are not left behind when telehealth services become more mainstream. Increasing experience with telehealth, setting expectations before consultations, supplying resources for therapy and assessing the suitability of clients…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Disinfection effect of hexadecyl pyridinium chloride on SARS-CoV-2 in vitro</strong> - The novel coronavirus (COVID-19 or 2019-nCoV) is a respiratory virus that can exist in the mouth and saliva of patients and spreads through aerosol dispersion. Therefore, stomatological hospitals and departments have become high-infection-risk environments. Accordingly, oral disinfectants that can effectively inactivate the virus have become a highly active area of research. Hexadecyl pyridinium chloride, povidone-iodine, and other common oral disinfectants are the natural primary choices for…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host</strong> - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the viruss inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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