The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of inter-individual variability. We identified six distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate and clearance rate, by clustering data from 810 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection, as well as an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during omicron infection, following vaccination, and following re-infection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.
Objectives Identify workplace risk factors for SARS-Cov-2 infection, using data collected by a United Kingdom electricity-generating company. Methods Using a test-negative design case-control study we estimated the odds ratios (OR) of infection by job category, site, test reason, sex, vaccination status, vulnerability, site outage, and site COVID-19 weekly risk rating, adjusting for age, test date and test type. Results From an original 80,077 COVID-19 tests, there were 70,646 included in the final analysis. Most exclusions were due to being visitor tests (5,030) or tests after an individual first tested positive (2,968). Women were less likely to test positive than men (OR=0.71; 95% confidence interval=0.58-0.86). Test reason was strongly associated with positivity and although not a cause of infection itself, due to differing test regimes by area it was a strong confounder for other variables. Compared to routine tests, tests due to symptoms were highest risk (94.99; 78.29-115.24), followed by close contacts (16.73; 13.80-20.29) and looser work contacts 2.66 (1.99-3.56). After adjustment, we found little difference in risk by job category, but some differences by site with three sites showing substantially lower risks, and one site showing higher risks in the final model. Conclusions Infection risk was not associated with job category. Vulnerable individuals were at slightly lower risk, tests during outages were higher risk, vaccination showed no evidence of an effect on testing positive, and site COVID-19 risk rating did not show an ordered trend in positivity rates.
Deep learning models have proven the potential to aid professionals with medical image analysis, including many image classification tasks. However, the scarcity of data in medical imaging poses a significant challenge, as the limited availability of diverse and comprehensive datasets hinders the development and evaluation of accurate and robust imaging algorithms and models. Few-shot learning approaches have emerged as a potential solution to address this issue. In this research, we propose to deploy the Generalized Metric Learning Model for Few-Shot X-ray Image Classification. The model comprises a feature extractor to embed images into a lower-dimensional space and a distance-based classifier for label assignment based on the relative distance of these embeddings. We extensively evaluate the model using various pre-trained convolutional neural networks (CNNs) and vision transformers (ViTs) as feature extractors. We also assess the performance of the commonly used distance-based classifiers in several few-shot settings. Finally, we analyze the potential to adapt the feature encoders to the medical domain with both supervised and self-supervised frameworks. Our model achieves 0.689 AUROC in 2-way 5-shot COVID-19 recognition task when combined with REMEDIS (Robust and Efficient Medical Imaging with Self-supervision) domain-adapted model as feature extractor, and 0.802 AUROC in 2-way 5-shot tuberculosis recognition task with domain-adapted DenseNet-121 model. Moreover, the simplicity and flexibility of our approach allows for easy improvement in the feature, either by incorporating other few-shot methods or new, powerful architectures into the pipeline.
The role of perceived experts (i.e., medical professionals and biomedical scientists) as potential anti-vaccine influencers has not been characterized systematically. We describe the prevalence and importance of anti-vaccine perceived experts by constructing a coengagement network based on a Twitter data set containing over 4.2 million posts from April 2021. The coengagement network primarily broke into two large communities that differed in their stance toward COVID-19 vaccines, and misinformation was predominantly shared by the anti-vaccine community. Perceived experts had a sizable presence within the anti-vaccine community and shared academic sources at higher rates compared to others in that community. Perceived experts occupied important network positions as central anti-vaccine nodes and bridges between the anti- and pro-vaccine communities. Perceived experts received significantly more engagements than other individuals within the anti- and pro-vaccine communities and there was no significant difference in the influence boost for perceived experts between the two communities. Interventions designed to reduce the impact of perceived experts in spreading anti-vaccine misinformation may be warranted.
Background Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig9s disease, is a rare neurological disease and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management be multidisciplinary clinics. Patients and Methods This prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. All evaluable patients were analysed in a modified intention-to-treat analysis. EudraCT number. 2018-000668-28 Findings Between 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection. Interpretation Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS.
Abstract Background: Elective percutaneous coronary intervention (PCI) historically required hospitalization post procedure. Same day discharge (SDD) has emerged as a safe and cost efficient option, although the impact of the coronavirus disease of 2019 (COVID-19) pandemic on rates of SDD and associated care episode costs remains uncertain. Methods: A national sample of consecutive patients undergoing elective PCI at 42 hospitals (Ascension, St.Louis, MO) between May 2019 to April 2021 were identified using internal registry data and administrative claims data. Rates of SDD before and after the COVID-19 pandemic (March 2020) were compared using multivariable logistic regression adjusted for patient and procedural characteristics. Additionally, an interrupted time series model was used to determine the effect of the pandemic and policy on SDD rates before and after pandemic declaration. Lastly, we estimated total costs per PCI episode in pre and post pandemic periods. Results: In total, 12,740 interventions were performed within 42 Ascension facilities that met study eligibility criteria (5955 PCI prior to the pandemic and 6785 after). Demographic data were similar between both populations although higher rates of dyslipidemia, prior myocardial infarction, and heart failure history were noted in the post pandemic group. Pandemic declaration was associated with a higher likelihood of SDD (OR 2.09, CI 1.93-2.25, p < 0.001). From pre-pandemic to post-pandemic, mean SDD rose from 34% to 45% (p< 0.001) with an accelerated monthly SDD adoption rate after the pandemic (0.1% per month vs 1.0% per month, p=0.02). Total costs per episode were $679.52 (95% CI $476.12 ? $882.92, p < 0.001) higher in the post-pandemic period, driven by increased material costs. SDD was associated with a $2137.05 (95% CI $1925.03 - $2349.07, p < 0.001) reduction in costs relative to non-SDD episodes throughout the study period. Conclusion: Among a large national risk-adjusted sample of consecutive patients, the COVID-19 pandemic accelerated adoption of SDD. As a care strategy, SDD was associated with reduced episode costs during elective PCI in the post-pandemic period .
Abstract Objective: This study aimed to investigate the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies among individuals aged 18 years and older Design: Prospective cohort study. Settings: Population-based study was conducted within the Arizona State University (ASU) community. Participants: The study recruited 1,397 adult participants that volunteered over a period of three days (March 1-March 3 of 2022). Primary outcome measures: Seroprevalence was conducted in the community to assess the presence of SARS-CoV-2-specific antibodies resulting from previous exposure to SARS-CoV-2 and/or vaccination. Results: The seroprevalence of anti-receptor binding domain (RBD) antibodies was found to be 96.3% using a semi-quantitative chemiluminescent immunoassay and 98% using an electrochemiluminescent immunoassay. For anti-nucleocapsid (NC) antibodies, the seroprevalence was 39.1% by an ELISA assay and 41.4% by an electrochemiluminescent immunoassay. Individuals that experienced breakthrough infections exhibited the highest levels of anti-RBD antibodies. Additionally, saliva samples showed promise as a potential diagnostic biofluid for measuring antibody levels, as they exhibited a strong correlation with the data obtained from serum samples. Conclusion: Accurate estimation of population-based serosurveillance for SARS-CoV-2 will monitor the trend of infection in the community and delineate the geographical spread of the infection. Cumulative incidence of SARS-CoV-2 infection during and after outbreaks is crucial for informing the development of effective risk mitigation protocols within the community. Protocols may include measures such as encouraging booster shots, extending mask mandates, or transitioning to online classes. Serosurveys repeated at regular intervals can also guide containment measures in communities and prompt respond to future outbreaks. Strengths and limitations of this study: * We simultaneously investigated active infection and seroprevalence for the university population. * Our study was strengthened by having the participants self-report data independently validated with diagnostic tests. * Saliva samples could be a potential diagnostic biofluid for measuring antibody levels. * Our study was performed within the university setting therefore it only reflects the COVID-19 situation within that community. * The number of breakthrough infections and the longitudinal samples were small, thus requiring confirmation.
Abstract: Context: Globally, there is still widespread of violence against women and girls. Timor-Leste reports high prevalence of GBV with 30% women have experienced intimate partner (IPV) or non-partner sexual violence. Several studies reported about the increase of domestic violence gender-based violence (D-GBV) against girls and women worldwide during the COVID-19 pandemic. Aims: To understand whether women living with these two diseases experienced D- GBV during the lockdowns in Timor-Leste. Methods and Material: The study was a qualitative phenomenology design, utilizing purposive sampling technic. Was conducted in eight municipalities from early October 2022 to end of February 2023. It considered eight independent variables to identified the occurrence of D-GBV. Subject 42 in-depth interviews: 19 HIV, 23 TB participants, and 3 FGDs. Data analysis with NVIVO version 12.1. Results: The D- GBV were widely reported from all municipalities. Psychological, socio-economic, verbal, and physical violence were mostly reported. The COVID-19 pandemic exacerbated D- GBV, and impeded participants to apply coping mechanisms in dealing with the violence. Stigma and discrimination were prevalent. The main causes of the violence were economic factors, jealousy, denial, cultural issues, and failure to perform household work. The participants reported using various coping mechanisms to deal with D- GBV: seeking external support or avoidance and staying, facing the perpetrator at home. Conclusions: The triple vulnerabilities (weaknesses of system to combat D-GBV, stigma, discrimination against female TB and HIV patients. It is recommended to train clinician working on D-GBV subject.
THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL - Condition: COVID-19
Intervention: Dietary Supplement: Neomune
Sponsors: Universitas Sriwijaya; M. Djamil General Hospital
Completed
Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: COVID-19
Intervention: Drug: Obeldesivir
Sponsor: Gilead Sciences
Not yet recruiting
KAND567 Versus Placebo in Subjects Hospitalized With COVID-19 - Condition: Covid19
Interventions: Drug: KAND567; Drug: Microcrystalline cellulose
Sponsor: Kancera AB
Terminated
Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome - Conditions: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome
Intervention: Behavioral: Aerobic Exercise Training
Sponsors: University of Witten/Herdecke; Verein und Institut für Rehabilitationsforschung Norderney
Completed
A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection - Condition: COVID-19
Interventions: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo
Sponsor: University of Chicago
Active, not recruiting
Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong - Conditions: Digital Health Literacy; COVID-19
Intervention: Behavioral: Digital health literacy intervention
Sponsor: The Hong Kong Polytechnic University
Not yet recruiting
COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy
Intervention: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
Sponsors: Duke University; American Society of Hematology
Not yet recruiting
Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions: Mental Health; COVID-19; Misinformation
Interventions: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging
Sponsors: Harvard Medical School (HMS and HSDM); Partners in Health
Active, not recruiting
Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh - Condition: Pulmonary Pathology
Intervention: Behavioral: Pulmonary Rehabilitation
Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Active, not recruiting
A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Biological: BNT162b2 (Omi XBB.1.5)
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19. - Condition: Nervous System Diseases
Interventions: Drug: Tianeptine; Drug: Placebo
Sponsors: Military Institute od Medicine National Research Institute; ABM Industries
Recruiting
Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition - Condition: Cognitive Behavioral Therapy
Intervention: Behavioral: cognitive behavioral therapy
Sponsor: Tri-Service General Hospital
Not yet recruiting
The Effectiveness of Natural Resources for Reducing Stress - Conditions: Distress, Emotional; COVID-19
Interventions: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure
Sponsors: Klaipėda University; Research Council of Lithuania
Active, not recruiting
Study of LAU-7b for the Treatment of Long COVID in Adults - Condition: Long COVID
Interventions: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles
Sponsor: Laurent Pharmaceuticals Inc.
Not yet recruiting
Complementary and Integrative Medicine as an Online Intervention in Patients With Post-covid Syndrome After COVID-19 - Condition: Post-COVID Syndrome
Interventions: Behavioral: Complementary and Integrative Medicine online intervention, routine care and book; Behavioral: Routine care and book
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
Pathophysiology and clinical management of coronavirus disease (COVID-19): a mini-review - An unprecedented global pandemic caused by a novel coronavirus named SARS-CoV-2 has created a severe healthcare threat and become one of the biggest challenges to human health and the global economy. As of July 2023, over 767 million confirmed cases of COVID-19 have been diagnosed, including more than 6.95 million deaths. The S protein of this novel coronavirus binds to the ACE2 receptor to enter the host cells with the help of another transmembrane protease TMPRSS2. Infected subjects that can…
Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial - BACKGROUND: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows:…
Development of ELISA-Based Assay for Detection of SARS-CoV-2 Neutralizing Antibody - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs). The gold standard test for the detection of NAbs is the viral plaque reduction and neutralization test; however, various other methods…
The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 - The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins…
The hope and hype of ellagic acid and urolithins as ligands of SARS-CoV-2 Nsp5 and inhibitors of viral replication - Non-structural protein 5 (Nsp5) is a cysteine protease that plays a key role in SARS-CoV-2 replication, suppressing host protein synthesis and promoting immune evasion. The investigation of natural products as a potential strategy for Nsp5 inhibition is gaining attention as a means of developing antiviral agents. In this work, we have investigated the physicochemical properties and structure-activity relationships of ellagic acid and its gut metabolites, urolithins A-D, as ligands of Nsp5….
Customizably designed multibodies neutralize SARS-CoV-2 in a variant-insensitive manner - The COVID-19 pandemic evolves constantly, requiring adaptable solutions to combat emerging SARS-CoV-2 variants. To address this, we created a pentameric scaffold based on a mammalian protein, which can be customized with up to 10 protein binding modules. This molecular scaffold spans roughly 20 nm and can simultaneously neutralize SARS-CoV-2 Spike proteins from one or multiple viral particles. Using only two different modules targeting the Spike’s RBD domain, this construct outcompetes human…
Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific - Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although Chloroquine failed to suppress viral replication in Calu-3 cells and patients. In contrast, Fluoxetine represses viral replication in human precision-cut lung slices (PCLS) and Calu-3 cells. Thus, it is unlikely that these compounds have similar mechanisms of action. Here, we analysed a subset of these compounds in the viral replication…
Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals - Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an…
Azvudine and mortality in patients with coronavirus disease 2019: A retrospective cohort study - CONCLUSION: Our results reveal that in patients with COVID-19, FNC administration was associated with a significantly reduced 28-day mortality.
Hexamethylene Amiloride Binds the SARS-CoV-2 Envelope Protein at the Protein-Lipid Interface - The SARS-CoV-2 envelope (E) protein forms a five-helix bundle in lipid bilayers whose cation-conducting activity is associated with the inflammatory response and respiratory distress symptoms of COVID-19. E channel activity is inhibited by the drug 5-(N,N-hexamethylene) amiloride (HMA). However, the binding site of HMA in E has not been determined. Here we use solid-state NMR to measure distances between HMA and the E transmembrane domain (ETM) in lipid bilayers. ^(13) C, ^(15) N-labeled HMA is…
Effectiveness of Bivalent Omicron-Containing Booster Vaccines against SARS-CoV-2 Omicron Variant among Individuals with and without Prior SARS-CoV-2 Infection - In this study, we evaluated the effectiveness of the bivalent mRNA COVID-19 vaccines against the Omicron variant in individuals with or without prior SARS-CoV-2 infection history. We assessed the SARS-CoV-2-specific neutralizing antibody in serum samples by surrogate virus neutralizing assay (sVNT) and determined the serum’s neutralizing capacity against the Omicron BA.5 by a plaque reduction neutralizing test (PRNT50). The results of the sVNT assay demonstrate a higher percentage of inhibition…
Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters - The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat…
Interchangeability of the Assays Used to Assess the Activity of Anti-SARS-CoV-2 Monoclonal Antibodies - The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of therapeutic anti-SARS-CoV-2 mAbs typically include binding or cell-based neutralization assays. We assessed the inhibitory activity of five anti-SARS-CoV-2 mAbs using ELISA, surface plasmon…
Phenothiazines Inhibit SARS-CoV-2 Entry through Targeting Spike Protein - Novel coronavirus disease 2019 (COVID-19), a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and continues to threaten humanity due to the persistent emergence of new variants. Therefore, developing more effective and broad-spectrum therapeutic and prophylactic drugs against infection by SARS-CoV-2 and its variants, as well as future emerging CoVs, is urgently needed. In this study, we screened several…
Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity - Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding…