While the first infection by an emerging disease is often unknown, information on early cases can be used to date it, which is of great interest to trace the disease9s origin and understand early infection dynamics. In the context of the COVID-19 pandemic, previous studies have estimated the date of emergence (e.g., first human SARS-CoV-2 infection in Wuhan, emergence of the Alpha variant in the UK) using mainly genomic data. Another dating attempt only relied on case data, estimating a date of emergence using a non-Markovian stochastic model and considering the first case detection. Here, we extend this stochastic approach to use available data of the whole early case dynamics. Our model provides estimates of the delay from the first infection to the Nth reported case. We first validate our model using data concerning the spread of the Alpha SARS-CoV-2 variant in the UK. Our results suggest that the first Alpha infection occurred on (median) August 21 (95% interquantile range across retained simulations, IqR: July 23-September 5), 2020. Next, we apply our model to data on the early reported cases of COVID-19. We used data on the date of symptom onset up to mid-January, 2020. We date the first SARS-CoV-2 infection in Wuhan at (median) November 28 (95%IqR: November 2-December 9), 2019. Our results fall within ranges previously estimated by studies relying on genomic data. Our population dynamics-based modelling framework is generic and flexible, and thus can be applied to estimate the starting time of outbreaks, in contexts other than COVID-19, as long as some key parameters (such as transmission and detection rates) are known.
The Covid-19 pandemic resulted in significant challenges to the provision of face-to-face clinics in geriatric perioperative care (G-POC). There are no studies evaluating the use of telemedicine in this population. A pilot study at North Bristol NHS Trust demonstrated that delivery of GPOC clinics via video consultation was feasible, but did not record outcome measures to demonstrate effectiveness and was not compared to face to face clinic. This study aims to provide proof of concept examining the outcomes of virtual G-POC consultations, compared to a face-to-face clinic, using standardised perioperative outcomes. It will test the feasibility of the intervention with a view to developing a randomised controlled trial.
Objective: To analyze the treatment outcomes for COVID-19 during the early stages of the pandemic at the Mexican Institute of Social Security. Material and Methods: In this retrospective observational study, we investigated 130,216 patients with COVID-19 treated in two Mexican states during 2020. A competing risk analysis was performed using death and recovery as possible outcomes, followed by a cox-regression and Kaplan-Meier analysis. Additionally, machine learning models were built to predict the outcomes at fixed times. Results: Higher prevalence of obesity, diabetes, and heart disease comorbidities were found, which is consistent with Mexico′s epidemiological profile. Mortality occurred around 15-20 days from the start of symptoms. Patients undertaking cephalosporin in combination with neuraminidase inhibitors (NAIs) had the worst survival rates, while patients undertaking adamantane, fluoroquinolone, or penicillin had the best survival rates. Conclusions: Our findings recommend against using specific treatment combinations, and should help improve the country′s clinical guidelines. Keywords: Coronavirus Infections, Anti-Bacterial Agents, Antiviral Agents, Pragmatic Clinical Trials as Topic, Machine Learning, Mexico
Background Following widespread exposure to Omicron variants, COVID-19 has transitioned to endemic cir- culation. Populations now have diverse infection and vaccination histories, resulting in heterogeneous immune landscapes. Careful consideration of vaccination is required through the post-Omicron phase of COVID-19 management to minimise disease burden. We assess the impact and cost-effectiveness of targeted COVID-19 vaccination strategies to support global vaccination recommendations. Methods We integrated immunological, transmission, clinical and cost-effectiveness models, and simulated populations with different characteristics and immune landscapes. We calculated the expected number of infections, hospitalisations and deaths for different vaccine scenarios. Costs (from a healthcare perspective) were estimated for exemplar country income level groupings in the Western Pacific Region. Results are reported as incremental costs and disability-adjusted life years averted compared to no additional vaccination. Parameter and stochastic uncertainty were captured through scenario and sensitivity analysis. Findings Across different population demographics and income levels, we consistently found that annual elder-targeted boosting strategies are most likely to be cost-effective or cost-saving, while paediatric programs are unlikely to be cost-effective. Results remained consistent while accounting for uncertain- ties in the epidemiological and economic models. Half-yearly boosting may only be cost-effective in higher income settings with older population demographics and higher cost-effectiveness thresholds. Interpretation These results demonstrate the value of continued booster vaccinations to protect against severe COVID-19 disease outcomes across high and middle-income settings and show that the biggest health gains relative to vaccine costs are achieved by targeting older age-groups. Funding Funded by the World Health Organization.
Background: The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for pathogen surveillance systems to augment both early warning and outbreak monitoring/control efforts. Wastewater samples provide a rapid and accurate source of environmental surveillance data to complement direct patient sampling. Due to its global presence and critical missions, the US military is a leader in global pandemic preparedness efforts. Clinical testing for COVID-19 on US Air Force (USAF) bases (AFBs) was effective, but costly with respect to direct costs and indirect costs of lost time. To remain operating at peak capacity such bases sought a more passive surveillance option and piloted wastewater surveillance (WWS) at 17 AFBs to demonstrate feasibility, safety, and utility from May 2021 to January 2022. Objective: Here we model the costs of a wastewater program for pathogens of pandemic potential within the specific context of US military installations using assumptions based on the results of the USAF and Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) pilot program. The objective was to determine the cost of deploying WWS to all AFBs, relative to clinical swab testing surveillance regimes. Methods: A simple WWS cost projection model was built based on subject matter expert input and actual costs incurred during a WWS pilot program at USAF AFBs. Several SARS-CoV-2 circulation scenarios were considered and costs of both WWS and clinical swab testing were projected. Break even analysis was conducted to determine how reduction in swab testing could open up space to enable WWS to occur in complement. Results: Our model confirms that wastewater surveillance is complimentary and highly cost-effective when compared to existing alternative forms of biosurveillance. We find that the cost of WWS was between $10.5 - $18.5 million less expensive annually in direct costs as compared to clinical swab testing surveillance. When indirect cost of lost work is incorporated, including assumed lost work required to go obtain a clinical swab test, we estimate that over two thirds of clinical swab testing could be maintained with no additional costs upon implementation of WWS. Conclusions: Our results support adoption of wastewater surveillance across US military installations as part of a more comprehensive and early warning system that will enable adaptive monitoring during disease outbreaks.
A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial - Conditions: Long COVID-19 Syndrome; Chronic Fatigue Syndrome
Interventions: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet
Sponsors: Cardresearch
Recruiting
Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel - Conditions: COVID-19; Influenza A; Influenza B
Interventions: Diagnostic Test: Panbio™
Sponsors: Abbott Rapid Dx
Not yet recruiting
Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities - Conditions: COVID-19; Vaccine
Interventions: Behavioral: REDES; Behavioral: Control
Sponsors: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University
Recruiting
Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes - Conditions: Normobaric Hypoxia; Hypoventilation; Normoxia
Interventions: Other: Repeated sprint
Sponsors: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Not yet recruiting
The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray - Conditions: SARS-CoV-2; Prevention
Interventions: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient
Sponsors: The Second Affiliated Hospital of Chongqing Medical University
Recruiting
Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening - Conditions: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance
Interventions: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot
Sponsors: Tulane University; National Heart, Lung, and Blood Institute (NHLBI)
Recruiting
Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use - Conditions: COVID-19; Influenza A; Influenza Type B
Interventions: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel
Sponsors: Abbott Rapid Dx
Recruiting
Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19 - Conditions: Post-COVID-19 Syndrome
Interventions: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation without maintenance program
Sponsors: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design)
Not yet recruiting
Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention - Conditions: Child Mental Health
Interventions: Behavioral: Child Mental Health Literacy Program
Sponsors: Universidad de Valparaiso
Recruiting
Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression - Conditions: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19
Interventions: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging
Sponsors: City University of New York, School of Public Health; University of North Carolina, Chapel Hill
Not yet recruiting
Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting - Conditions: Post COVID-19 Condition (PCC)
Interventions: Device: RDX-19
Sponsors: KNOWBio Inc.; NAMSA
Recruiting
A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine - Conditions: SARS-CoV-2 Infection
Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.
Recruiting
CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study - Conditions: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia
Interventions: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate
Sponsors: I.M. Sechenov First Moscow State Medical University
Recruiting
Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease - Conditions: COVID-19 Pneumonia; Virus Diseases; COVID-19
Interventions: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment
Sponsors: AVB Biotechnology
Recruiting
A Phase 1 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine - Conditions: SARS-CoV-2 Infection
Interventions: Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 10 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 60 μg
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital
Recruiting
Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV-2 Infection - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in high morbidity and mortality rates worldwide. Although the epidemic has been controlled in many areas and numerous patients have been successfully treated, the risk of reinfection persists due to the low neutralizing antibody titers and weak immune response. To provide long-term immune protection for infected patients, novel bispecific CB6/dendritic cell (DC)-specific…
Molecular Design of Novel Inhibitor by TargetingIL-6Rα using Combined Pharmacophore and Experimentally Verified Plant Products with Scaffold-Hopping Techniques: A Dual Therapeutic Strategy for COVID-19 and Cancer - The IL-6/IL-6R/gp130 complex serves as a significant indicator of cytokine release syndrome in COVID-19 and chronic inflammation, increasing the risk of cancer. Therefore, we identified IL-6Rα as a potential target to block gp130 interaction. Notably, there has been no reception of approval for an orally available drug to serve this purpose, to date. In this study, we targeted IL-6Rα to inhibit IL-6Rα/gp130 interaction. The selection of the lead candidate L821 involved the amalgamation of three…
The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity - Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection….
Structure-based virtual screening, ADMET analysis, and molecular dynamics simulation of Moroccan natural compounds as candidates for the SARS-CoV-2 inhibitors - The lack of treatments and vaccines effective against SARS-CoV-2 has forced us to explore natural compounds that could potentially inhibit this virus. Additionally, Morocco is renowned for its rich plant diversity and traditional medicinal uses, which inspires us to leverage our cultural heritage and the abundance of natural resources in our country for therapeutic purposes. In this study, an extensive investigation was conducted to gather a collection of phytoconstituents extracted from…
The double-edged sword of the hippocampus-ventromedial prefrontal cortex resting-state connectivity in stress susceptibility and resilience: A prospective study - The hippocampus has long been considered a pivotal region implicated in both stress susceptibility and resilience. A wealth of evidence from animal and human studies underscores the significance of hippocampal functional connectivity with the ventromedial prefrontal cortex (vmPFC) in these stress-related processes. However, there remains a scarcity of research that explores and contrasts the roles of hippocampus-vmPFC connectivity in stress susceptibility and resilience when facing a real-life…
Influenza A virus replication has a stronger dependency on Raf/MEK/ERK signaling pathway activity than SARS-CoV-2 - The recent COVID-19 pandemic again highlighted the urgent need for broad-spectrum antivirals, both for therapeutic use in acute viral infection and for pandemic preparedness in general. The targeting of host cell factors hijacked by viruses during their replication cycle presents one possible strategy for development of broad-spectrum antivirals. By inhibiting the Raf/MEK/ERK signaling pathway, a central kinase cascade of eukaryotic cells, which is being exploited by numerous viruses of…
Coffee as a dietary strategy to prevent SARS-CoV-2 infection - CONCLUSIONS: This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era.
Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8+ T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine - CONCLUSION: TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.
Intranasal G5-BGG/pDNA vaccine elicits protective systemic and mucosal immunity against SARS-CoV-2 by transfecting mucosal dendritic cells - Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines that provide both disease protection and transmission inhibition. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA…
Colloidal aggregation confounds cell-based Covid-19 antiviral screens - Colloidal aggregation is one of the largest contributors to false-positives in early drug discovery and chemical biology. Much work has focused on its impact on pure-protein screens; here we consider aggregations role in cell-based infectivity assays in Covid-19 drug repurposing. We began by investigating the potential aggregation of 41 drug candidates reported as SARs-CoV-2 entry inhibitors. Of these, 17 formed colloidal-particles by dynamic light scattering and exhibited detergent-dependent…
Application of Luteolin in Neoplasms and Nonneoplastic Diseases - Researchers are amazed at the multitude of biological effects of 3’,4’,5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and pro-oxidant, as well as antimicrobial, anti-inflammatory, and cancer-preventive, properties. The anticancer properties of luteolin constitute a mosaic of pathways due to which this flavonoid influences cancer cells. Not only is it able to induce apoptosis and inhibit cancer cell proliferation, but it also suppresses angiogenesis…
HSP90AB1 Is a Host Factor Required for Transmissible Gastroenteritis Virus Infection - Transmissible gastroenteritis virus (TGEV) is an important swine enteric coronavirus causing viral diarrhea in pigs of all ages. Currently, the development of antiviral agents targeting host proteins to combat viral infection has received great attention. The heat shock protein 90 (HSP90) is a critical host factor and has important regulatory effects on the infection of various viruses. However, its roles in porcine coronavirus infection remain unclear. In this study, the effect of HSP90 on TGEV…
Therapeutic Effect and Safety Evaluation of Naringin on Klebsiella pneumoniae in Mice - Critically ill patients with Corona Virus Disease 2019 (COVID-19) often develop secondary bacterial infections that pose a significant threat to patient life safety, making the development of drugs to prevent bacterial infections in the lungs critical to clinical care. Naringin (NAR) is one of the significant natural flavonoids rich in Pummelo Peel (Hua Ju Hong), with anti-inflammatory, antimicrobial, and antioxidant activities, and is commonly used in treating respiratory tract infectious…
Interaction of Methylene Blue with Severe Acute Respiratory Syndrome Coronavirus 2 Envelope Revealed by Molecular Modeling - Methylene blue has multiple antiviral properties against Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2). The ability of methylene blue to inhibit different stages of the virus life cycle, both in light-independent and photodynamic processes, is used in clinical practice. At the same time, the molecular aspects of the interactions of methylene blue with molecular components of coronaviruses are not fully understood. Here, we use Brownian dynamics to identify methylene blue…
Genetic Predisposition to Elevated Levels of Circulating ADAM17 Is Associated with the Risk of Severe COVID-19 - High levels of ADAM17 activity have emerged as an important mediator in severe COVID-19. This study aims to characterize eventual causal relationships between ADAM17 and COVID-19. Using Mendelian randomization analyses, we examined the causal effects of circulating ADAM17 on COVID-19 outcomes using summary statistics from large, genome-wide association studies of ADAM17 (up to 35,559 individuals) from the Icelandic Cancer Project and deCODE genetics, as well as critically ill COVID-19 patients…