Background: Secondary infection (SI) diagnosis in COVID-19 is challenging, due to overlapping clinical presentations, practical limitations in obtaining samples from the lower respiratory tract (LRT), and low sensitivity of microbiologic cultures. Research Question: Can metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) help diagnose SIs complicating COVID-19? Study Design and Methods: We enrolled 42 inpatients with COVID-19 classified as microbiologically-confirmed SI (Micro-SI, n=8), clinically-diagnosed SI (Clinical-SI, n=13, i.e. empiric antimicrobials), or no clinical suspicion for SI (No-Suspected-SI, n=21) at time of enrollment. From baseline and follow-up plasma samples (days 5 and 10 post-enrollment), we quantified mcfDNA for all detected microbes by mcfDNA sequencing and measured nine host-response biomarkers. From LRT samples among intubated subjects, we quantified bacterial burden with 16S rRNA gene quantitative PCR. Results: We performed mcfDNA-Seq in 82 plasma samples. Sequencing was successful in 60/82 (73.2%) samples, which had significantly lower levels of human cfDNA than failed samples (p<0.0001). McfDNA detection was significantly higher in Micro-SI (15/16 [94%]) compared to Clinical-SI samples (8/14 [57%], p=0.03), and unexpectedly common in No-Suspected-SI samples (25/30 [83%]), similar to detection rate in Micro-SI. We detected culture-concordant mcfDNA species in 13/16 Micro-SI samples (81%) and mcfDNA levels tracked with SI outcome (resolution or persistence) under antibiotic therapy. McfDNA levels correlated significantly with LRT bacterial burden (r=0.74, p=0.02) as well as plasma biomarkers of host response (white blood cell count, IL-6, IL-8, and SPD, all p<0.05). Baseline mcfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p=0.03). Interpretation: High circulating levels of mcfDNA in a substantial proportion of patients with COVID-19 without clinical suspicion for SI suggest that SIs may often remain undiagnosed. McfDNA-Seq, when clinically available, can offer a non-invasive diagnostic tool for pathogen identification, with prognostic value on host inflammatory response and clinical outcomes.
Background: The pandemic of COVID-19 raised the urgent need of safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 mcg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48290 subjects were included (24144 and 21146 in the placebo and Abdala groups, respectively). The product was well tolerated. No severe adverse events with demonstrated cause-effect relationship attributable to vaccine were reported. The incidence of adverse reactions in the placebo and Abdala vaccine arms were 446/24144 (1.9%) and 615/24146 (2.5%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 hours. The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). In the case of mild/moderate disease the vaccine efficacy was 91.96% (84.69-95.78) and 94.46% (58.52-99.28) for the severe forms (serious/critical disease). There were five critical patients (of which four died), all in the placebo group, indicating that Abdala vaccine efficacy for both conditions was of 100%. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.
LEAF-4L6715 is a liposomal formulation encapsulating transcrocetin (TC) developed to enhance the diffusion of oxygen in the body. Here, we report the final results of the phase I/II clinical trial (NCT04378920; EUDRACT2020-001393-30) initiated to identify an optimal regimen and to assess the activity of TC in the context of acute respiratory distress syndrome (ARDS). More specifically, LEAF-4L6715 was developed to treat patients with ARDS due to severe SARS-CoV-2 infection who have a ratio of partial arterial pressure to inspired fraction of oxygen (PaO2/FiO2 ratio) <200 treated with artificial ventilation support in an intensive care unit. A total of 37 patients were treated (across 6 dosing cohorts) with LEAF-4L6715 given as an intravenous infusion for over 90 minutes. The dose of LEAF-4L6715 was increased until the transaminase levels were elevated and 4 grade 3 events occurred among 8 patients. The recommended dosage was determined to be a fixed concentration of 300 mg administered every 12 hours. An improvement in the PaO2/FiO2 ratio and SOFA score was observed. The overall 28-day survival rate of 81%. This study identified the recommended dose for LEAF-4L6715 and the dose-limiting toxicity and showed an overall favorable risk/benefit profile. These preliminary findings are promising for the activity of LEAF-4L6715 but will require confirmation in a randomized phase III trial.
Abstract Purpose: Incentivized peer referral (IPR) has been shown to be an effective method of recruitment for men who have sex with men but has not been studied extensively in men who have sex with women (MSW), particularly among Black MSW. We aimed to determine if IPR was more effective than uncompensated peer referral for recruiting young Black men into a community STI screening study. Methods: We used data from the Check It study, a chlamydia (Ct) screening and treatment program for young Black men ages 15-26 in New Orleans, LA. Enrollment was compared before and after IPR was implemented using Multiple Series Analysis (MTSA). IPR was introduced to increase recruitment that had been severely diminished because of the COVID-19 shutdown. Results: Of 1527 men enrolled, 1399 (91.6%) were enrolled pre-IPR and 128 (8.4%) were enrolled post-IPR. The percentage of men referred by a friend or peer was higher in the post-IPR period than in the pre-IPR period (45.7% vs. 19.7%, p<0.001). Post-pandemic, we observed a statistically significant increase of 2.007 more recruitments (p=0.044, 95% CI (0.0515, 3.964)) at the start of the post-IPR era, compared to the pre-IPR era. Overall, we also observed a trending increase in recruitments in the IPR era relative to the pre-IPR era (0.0174 recruitments/week, p=0.285, 95% CI (-0.0146, 0.0493)) with less recruitment decay in the post-IPR compared to pre-IPR. Conclusions: IPR may be an effective means of engaging young Black men in community based STI research and prevention programs, particularly when clinic access is limited.
ABSTRACT Vaccination elicits a complex combination of immune responses. Immune memory formation is observed not only in the antibody responses of B-cells, but also in the T-cell response. Moreover, some live attenuated vaccines such as measles-containing vaccines can induces heterologous protection, likely through induction of memory characteristics in the innate immune response. Little is known about the immunological interaction that may occur when different vaccines are administered soon after one another, especially in relation to the novel COVID-19 vaccines. The aim of this study was to compare the innate and adaptive immune responses between persons randomized to receive either a MMR or a placebo (0.9% NaCl) injection prior to their SARS-CoV-2 mRNA vaccination. We compared: i) the cytokine and chemokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10, IL-17, IL-22, interferon [IFN]-α and IFN-γ) after in-vitro stimulation of peripheral blood mononuclear cells (PBMCs) with heterologous stimuli (severe acute respiratory syndrome coronavirus [SARS-CoV]-2, measles mumps and rubella [MMR] vaccine, Toll-like receptor [TLR]-3 ligand, TLR-7/8 ligand, or TLR-4 ligand), and ii) the SARS-CoV-2 neutralizing antibody responses. Ninety-five participants in the CROWN CORONATION trial (NCT04333732; a randomized control trial comparing MMR to placebo for prevention of COVID-19) agreed to an additional single blood sample collection for this immunological study. Samples were collected around 196 (SD 22) days after administration of MMR or placebo, and around 105 (SD 27) days after their second SARS-CoV-2 mRNA vaccine injection. Twenty-four percent of participants were older than fifty and sixty-seven percent were female. The median TNF-α response to stimulation with MMR was 8315.3 pg/mL in the MMR group and 4340.5 pg/mL in the placebo group; adjusted median difference (95% CI) 3012.5 (-4734.1; -323.5); p=0.017. No other significant differences were noted in the cytokine and chemokine responses between treatment groups. The SARS-CoV-2 neutralization assay geometric mean (SD) IC50 in the MMR group was 507.6 (2.6) and in the placebo group was 515.7 (2.2); ratio of geometric means (95% CI) 1.0 (0.7; 1.5). Pre-exposure to MMR vaccine was generally not associated with changes in cytokine and chemokine responses of stimulated PBMCs at 105 (27) days after SARS-CoV-2 mRNA vaccination. MMR vaccination led only to an increase of TNF-α production in response to an additional ex-vivo stimulation with the MMR vaccine. The SARS-CoV-2 neutralization IC50 values did not differ between MMR and placebo groups. Further studies using a repeated measures design would be better suited to explore or rule-out any short-lived vaccine response and vaccine-vaccine immunological interaction.
Background: Evaluating the performance of SARS-CoV-2 serological assays and clearly articulating the utility of selected antigen, isotypes and thresholds is crucial to understanding the prevalence of infection within selected communities. Methods: This cross-sectional study, implemented in 2020, screened PCR-confirmed COVID-19 patients (n=86), banked pre-pandemic and negative donors (n=96), health care workers and family members (n=552), and university employees (n=327) for anti-SARS-CoV-2 receptor-binding domain (RBD), trimeric spike protein (S), and nucleocapsid protein (N) IgG and IgA antibodies with a laboratory developed Enzyme-Linked Immunosorbent Assay (ELISA) and tested how antigen, isotype and threshold choices affected the seroprevalence. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen/isotype combination; and (iii) the maximal Youden index. Results: We found vastly different seroprevalence estimates depending on selected antigens, isotypes and the applied threshold method, ranging from 0.0% to 85.4%. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%. Conclusions: This study revealed the importance of evaluating serosurvey tools for antigen, isotype, and threshold-specific sensitivity and specificity, in order to interpret qualitative serosurvey outcomes reliably and consistently across studies.
The primary objective of this study was to identify a universal wastewater biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology (WBE). A total of 2,624 wastewater samples (41 weeks) were collected weekly during May 2021- April 2022 from 64 wastewater facilities across Missouri, U.S. Three wastewater biomarkers, caffeine and its metabolite, paraxanthine, and pepper mild mottle virus (PMMoV), were compared for the population normalization effectiveness for wastewater SARS-CoV-2 surveillance. Paraxanthine had the lowest temporal variation and strongest relationship between population compared to caffeine and PMMoV. This result was confirmed by data from ten different Wisconsin WWTPs with gradients in population sizes, indicating paraxanthine is a promising biomarker of the real-time population across a large geographical region. The estimated real-time population was directly compared against the population patterns with human movement mobility data. Of the three biomarkers, population normalization by paraxanthine significantly strengthened the relationship between wastewater SARS-CoV-2 viral load and COVID-19 incidence rate the most (40 out of 61 sewersheds). Caffeine could be a promising population biomarker for regions where no significant exogenous caffeine sources (e.g., discharges from food industries) exist. In contrast, PMMoV showed the highest variability over time, and therefore reduced the strength of the relationship between sewage SARS-CoV-2 viral load and the COVID-19 incidence rate, as compared to wastewater data without population normalization and the population normalized by either recent Census population or the population estimated based on the number of residential connections and average household size for that municipality from the Census. Overall, the findings of this long-term surveillance study concluded that the paraxanthine has the best performance as a biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology.
Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods Plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralising titres against all variants. Of 180 with complete data, 160 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.
Background : Birth dissatisfaction may increase the risk for postpartum depression and requests for an elective cesarean for the next birth. The outbreak of COVID-19 pandemic has had a considerable impact on the healthcare systems and their users in many aspects. We investigated predictors of birth satisfaction in a sample of Iranian postpartum women during the COVID-19 epidemics’ fifth wave. Methods : This cross-sectional study was conducted on 601 postpartum women admitted to postpartum wards of Mobini maternity hospital using a convenience sampling method between 2 Aug and 18 September 2021. We collected data on socio-demographic, obstetric, labor and birth, and psychological variables. We used the general linear model and multiple linear regression analyses to determine predictors of birth satisfaction. Results : The mean birth satisfaction score was 28.6±7.3. The percentages of mothers who gave birth by elective and emergency cesarean were 19.5% and 10.8%, respectively. Overall predictors of birth satisfaction were emergency cesarean [-7.463(-9.310, -5.616), instrumental birth [-3.571(-6.907, -0.235)], episiotomy [-2.227 ( -3.591, -0.862)], Entonox analgesia [-1.548(-2.726, -0.371)], Well-being score < 50 [-1.812(-3.146, -0.478)], fear of COVID -19 [-1.216(-2.288,, -0.144)], low satisfaction with pregnancy -2.539(-3.952, -1.127) and low satisfaction with spouse’s support [-2.419(-4.598, -0.240)]. Conclusions : During the pandemic, fear of COVID -19, low level of well-being, low satisfaction with pregnancy and low satisfaction with spouse’s support as well as women9s experience of emergency cesarean, instrumental birth, episiotomy, and Entonox analgesia, are exerting negative influences on birth satisfaction. To improve birth satisfaction and thus maternal mental health interventions to lower fear of contracting COVID -19 and reduce rates of episiotomy, emergency cesarean, and instrumental birth are recommended.
Background Limited data are available on effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines in real-world use - especially against Omicron variants in SARS-CoV-2 infection-naive population. During an outbreak in Shanghai9 s SARS-CoV-2 infection-naive population, we evaluated vaccine effectiveness (VE) against Omicron infection, severe or critical COVID-19, and COVID-19-related death. Methods A matched case-control study was conducted among people aged ≥3 years between 2 December 2021 through 13 May 2022. Cases were SARS-CoV-2 infected individuals, individuals with severe/critical COVID-19, or COVID-19-related deaths. Controls were selected from consecutively test negative individuals at the same time as cases were diagnosed and were exact-matched on year-of-age, gender, birthplace, illness onset date, and residency district in ratios of 1:1 with infected individuals and 4:1 with severe/critical COVID-19 and COVID-19-related deaths. Results Our study included 612597 documented SARS-CoV-2 infections, among which 1485 progressed to severe or critical illness and 568 died. Inactivated vaccine was 16.3% (95% CI: 15.4%-17.2%) effective against infection, 88.6% (95% CI: 85.8%-90.9%) effective against severe/critical COVIID-19 and 91.7% (95% CI: 86.9%-94.7%) against COVID-19 death. Ad5-vectored vaccine was 13.2% (95% CI: 10.9%-15.5%) effective against infection and 77.9% (95% CI: 15.6%-94.2%) effective against severe/critical COVIID-19. Booster vaccination with inactivated vaccines enhanced protection against severe COVID-19 (92.7%, 95% CI: 90.1%-94.6%) and COVID-19 death (95.9%, 95% CI: 91.4%-98.1%). Inactivated VE against infection began to wane 12 weeks after the last dose but two- and three-dose sustained high protection levels (>80%) against severe/critical illness and death. Conclusions Our real-world study found high and durable two- and three-dose inactivated VE against Omicron-associated severe/critical illness and death across all age groups, but lower effectiveness against Omicron infection. High direct protection from severe/fatal Omicron COVID-19 provided by inactivated vaccines, and a consequent potential reduction in health-care utilization, reinforces the critical importance of full-series vaccination and timely booster dose administration for all eligible individuals.
Background: We chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022. Methods: Anonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections. Results: Sero-prevalence was ≤1% by the 3rd snapshot in September 2020 and <5% by January 2021 (4th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), ~80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained <15% through September/October 2021, increasing through subsequent Omicron waves to ~40% by March 2022 (7th) and ~60% by July/August 2022 (8th). By August 2022, at least 70-80% of children ≤19 years, 60-70% of adults 20-59 years, but ~40% of adults ≥60 years had been infected. Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots. Interpretation: By August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely-dependent on vaccine-induced protection alone, and should be prioritized for additional doses.
The COVID-19 pandemic has become one of the global health challenges in the current context. In Nepal, the first confirmed case was reported on 23 January 2020, and since then it has resulted in several negative impacts including economic disruption and deterioration of physical and mental health. In such a pandemic, it is indispensable to understand the knowledge and behavioral patterns of the general population regarding COVID-19. Therefore, our study aimed to assess the knowledge, attitude and practice on COVID-19, among the general population and its relationship with socio-demographic conditions. The questionnaire survey was conducted to collect data from eight districts of Nepal which included Kathmandu, Bhaktapur, Lalitpur, Morang, Sunsari, Rupandehi, Chitwan, and Kaski. Descriptive statistics, parametric and non-parametric statistical tests, and a logistic regression model were used for analysis. The study showed that 93.3% of respondents had knowledge of overall preventive practice whereas only 32% had knowledge of overall symptoms of COVID-19. Regarding attitude, only 14.3% believed that they will get rid of COVID-19 soon. The preventive practice was reduced after lockdown compared to that during lockdown. The respondents with white-collar occupations, high-income, and unmarried were good at KAP. Similarly, highly educated and those residing in urban areas had good knowledge and practice. The study findings will help in the development of targeted programs to improve the knowledge, attitude, practice of the general population on COVID-19, which is of paramount importance to deal with the existing pandemic and also such possible future waves of the pandemic.
Given the shortage of global COVID-19 vaccines, a critical public concern is whether the strategy of allocation exerts a heterogeneous effect on settings that have imbalanced accessibility. Exacerbated by the mutational characteristics of the pathogen, traits of immunity protection of vaccines, and diversification of human behaviors, the pathway to the full eradication of the COVID-19 pandemic is becoming increasingly complicated and indeterminate. Population-wide evaluation of public interventions remains crucial to evaluate the performance of epidemiology policies. This study employs a mathematical compartmental model combined with the observational data of the United States to examine the potential effect of vaccine allocation on the trajectory of COVID-19 transmission and the elicited equity implications. The outcomes imply that allocation strategies substantially impact the cumulative equilibrium size of a pandemic controlling for confounding factors. Under a framework of a two-dose primary vaccination strategy aiming to curb the total infections for high-accessibility settings (HAS) and low-accessibility settings(LAS), the traits of vaccination, pathogen, and human effort integrally affect the equilibrium of the COVID-19 pandemic in the medium perspective (i.e., up to 5 years). Vaccine allocation increases the healthcare and cost burden for HAS temporarily, in contrast, it reduces the risk of COVID-19 transmission for the LAS. The effects are consistent across a variety of profiles. By enhancing the administration rates of primary doses (i.e., mainly through dose 1 and dose 2), the magnitude of the COVID-19 pandemic decreases contingent on confounding factors. To minimize the magnitude of infection, it is of importance to dynamically monitor the immunity protection of vaccines, the dynamics of virus transmission, and the gap in the human effort.
Devising effective mass testing strategies to control and suppress COVID-19 pandemic waves make up a complex sociotechnical challenge. It requires a trade-off between performing detection technologies in terms of specificity and sensitivity, and the availability and cost of individual tests per technology. Overcoming this trade-off requires first predicting the level of risk of exposure across the population available. Then selecting testing strategies that match resources to maximize positive case detection and optimize the number of tests and their total cost during sustained mass testing campaigns. In this article, we derive the behavior of four different mass testing strategies, grounded in guidelines and public health policies issued by the Costa Rican public healthcare system. We assume a (privacy-preserving) pre-classifier applied to patient data, Capable of partitioning suspected individuals into low-risk and high-risk groups. We consider the impact of three testing technologies, RT-qPCR, antigen-based testing and saliva-based testing (RT-LAMP). When available, we introduced a category of essential workers. Numerical simulation results confirm that strategies using only RT-qPCR tests cannot achieve sufficient stock capacity to provide efficient detection regardless of prevalence, sensitivity, or specificity. Strategies that harness the power of both pooling and RT-LAMP either maximize stock capacity or detection, efficiency, or both. Our work reveals that investing both in data quality and classification accuracy can improve the odds of achieving pandemic control and mitigation. Future work will concentrate, based on our findings, on constructing representative synthetic data through agent-based modeling and studying the properties of specific pre-classifiers under various scenarios.
Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition: COVID-19
Interventions: Biological: SARS-CoV-2 subunit protein recombinant vaccine; Biological: Active Comparator
Sponsors: PT Bio Farma; Universitas Padjadjaran; Udayana University
Recruiting
A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E-1 on D0; Biological: SCTV01E-1 on D28; Biological: SCTV01E-1 on D150; Biological: SCTV01E on D0; Biological: SCTV01E on D28; Biological: SCTV01E on D150; Biological: SCTV01E-1 on D120; Biological: SCTV01E on D120
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients - Condition: COVID-19 Pneumonia
Intervention: Diagnostic Test: the LIT test
Sponsors: Gazi University; Oxford MediStress
Completed
Efficacy and Safety of ES16001 in Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: ES16001 40 mg; Drug: ES16001 80 mg; Drug: ES16001 160 mg; Drug: Placebo
Sponsor: Genencell Co. Ltd.
Recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: 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)
Not yet recruiting
SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study - Condition: COVID-19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)
Sponsors: 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)
Not yet recruiting
Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID) - Condition: Post COVID-19 Condition
Intervention: Behavioral: Personalized multidisciplinary day-hospital intervention
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study - Condition: COVID-19 Pneumonia
Interventions: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care
Sponsor: Ruijin Hospital
Recruiting
Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older - Condition: SARS-CoV-2 Infection
Interventions: Biological: PTX-COVID19-B; Biological: Comirnaty®
Sponsor: Everest Medicines (Singapore) Pte. Ltd.
Not yet recruiting
Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older - Condition: SARS-CoV-2 Infection
Interventions: Biological: PTX-COVID19-B; Biological: Vaxzevria®
Sponsor: Everest Medicines (Singapore) Pte. Ltd.
Not yet recruiting
CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19 - Conditions: Long COVID; COVID-19
Intervention: Behavioral: Cardiac Rehabilitation
Sponsor: University of California, San Francisco
Not yet recruiting
The Impact of a Web-based Psychoeducation Programme With a Motivational AI Chatbot on Covid-19 Vaccine Hesitancy - Conditions: Vaccine Hesitancy; COVID-19
Interventions: Behavioral: AI-driven Vaccine Communicator; Behavioral: Self-learning of COVID-19 vaccine knowledge
Sponsor: The Hong Kong Polytechnic University
Not yet recruiting
Motivation, Syringe Exchange, and COVID-19 - Condition: COVID-19 Pandemic
Intervention: Behavioral: Connect2Test
Sponsors: University of Oregon; National Institute on Drug Abuse (NIDA)
Recruiting
Rehabilitation Therapy for Post COVID 19 Chronic Fatigue Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Other: intensive combined rehabilitation therapy
Sponsor: Cairo University
Not yet recruiting
HRQOL of Life After ECMO Due to COVID-19. - Conditions: ARDS; COVID-19 Pneumonia; Extracorporeal Membrane Oxygenation
Intervention: Other: Phone Interview
Sponsor: Medical University of Vienna
Recruiting
Highly efficient antifogging/antimicrobial dual-functional chitosan based coating for optical devices - The coating is frequently adopted to modify the product surface without influencing the essential features of the pristine products. Recently, significant demand has existed for efficient anti-fogging/anti-microbial surfaces in various applications to inhibit microbial growth with high transparency in high-humidity environments, especially in pandemics such as COVID-19. The current study used dual-functional chitosan (Ch) polysaccharide coating with highly hydrophilic properties to be…
SARS-CoV-2-encoded Inhibitors of Human LINE-1 Retrotransposition - The ongoing pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2) is causing a devastating impact on public health worldwide. However, details concerning the profound impact of SARS-CoV-2 on host cells remain elusive. Here, we investigated the effects of SARS-CoV-2-encoded viral proteins on the intracellular activity of long interspersed element 1 (L1) retrotransposons using well-established reporter systems. Several non-structural or accessory proteins (Nsps) of SARS-CoV-2 (i.e.,…
Identification of hACE2-interacting sites in SARS-CoV-2 Spike Receptor Binding Domain for Antiviral Drugs Screening - The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (RBD) and found that peptide 391-465 aa is the major hACE2-interacting sites in SARS-CoV-2 Spike RBD. We then identified essential amino acid residues…
Correlation of alpha-1 antitrypsin levels and exosome associated neutrophil elastase endothelial injury in subjects with SARS-CoV2 infection - CONCLUSIONS: Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.
Deciphering the binding mechanism of inhibitors of the SARS-CoV-2 main protease through multiple replica accelerated molecular dynamics simulations and free energy landscapes - The pneumonia outbreak caused by the SARS-CoV-2 virus poses a serious threat to human health and the world economy. The development of safe and highly effective antiviral drugs is of great significance for the treatment of COVID-19. The main protease (M^(pro)) of SARS-CoV-2 is a key enzyme for viral replication and transcription and has no homolog in humans. Therefore, the M^(pro) is an ideal target for the design of drugs against COVID-19. Insights into the inhibitor-M^(pro) binding mechanism…
Impact of Stress and Decision Fatigue on Parenting Practices Related to Food and Physical Activity During COVID-19 - CONCLUSIONS: In the face of a major public health crisis, adaptive parental responses may emerge, but perceived stress may inhibit such behavior change. Perceived stress and decision fatigue may represent important explanatory factors in parental health promoting behaviors during times of uncertainty and change.
BDA-410 inhibits SARS-CoV-2 main protease activity and viral replication in mammalian cells - No abstract
The SARS-CoV-2 envelope protein disrupts barrier function in an in vitro human blood-brain barrier model - Patients with coronavirus disease 2019 (COVID-19) have been frequently reported to exhibit neurological manifestations and disruption of the blood-brain barrier (BBB). Among the risk factors for BBB breakdown, the loss of endothelial cells and pericytes has caused widespread concern. Recent studies have revealed that severe acute respiratory syndrome coronavirus 2 envelope (S2E) protein caused cell death. We tested the hypothesis that the S2E protein alone could induce BBB dysfunction. The S2E…
Differential effect of SARS-CoV-2 infection on stress granule formation in Vero and Calu-3 cells - Stress granule formation is induced by numerous environmental stressors, including sodium arsenite treatment and viral infection. Accordingly, stress granules can inhibit viral propagation and function as part of the antiviral host response to numerous viral infections. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antagonizes stress granule formation, in part, via interaction between SARS-CoV-2 nucleocapsid (N) protein and Ras-GTPase-activating SH3-domain-binding protein 1…
Dexamethasone, but Not Vitamin D or A, Dampens the Inflammatory Neutrophil Response to Protect At-risk COVID-19 Patients - Dexamethasone (DEX) was the first drug shown to save lives of critically ill coronavirus disease 2019 (COVID-19) patients suffering from respiratory distress. A hyperactivated state of neutrophils was found in COVID-19 patients compared to non-COVID pneumonia cases. Given the beneficial effects of DEX in COVID-19 patients, we investigated the effects of DEX and of other immunomodulatory drugs vitamin D3 (VD3) and retinoic acid (RA) on neutrophil function. DEX, but not VD3 or RA, significantly…
Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin - In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), that is responsible for proteolytic priming of the SARS-CoV-2 spike protein, appears as a rational therapeutic target. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Previously,…
New Chemicals Suppressing SARS-CoV-2 Replication in Cell Culture - Candidates to being inhibitors of the main protease (Mpro) of SARS-CoV-2 were selected from the database of Voronezh State University using molecular modeling. The database contained approximately 19,000 compounds represented by more than 41,000 ligand conformers. These ligands were docked into Mpro using the SOL docking program. For one thousand ligands with best values of the SOL score, the protein-ligand binding enthalpy was calculated by the PM7 quantum-chemical method with the COSMO solvent…
Dual Inhibition of HIV-1 and Cathepsin L Proteases by Sarcandra glabra - The COVID-19 pandemic continues to impose a huge threat on human health due to rapid viral mutations. Thus, it is imperative to develop more potent antivirals with both prophylactic and treatment functions. In this study, we screened for potential antiviral compounds from Sarcandra glabra (SG) against Cathepsin L and HIV-1 proteases. A FRET assay was applied to investigate the inhibitory effects and UPLC-HRMS was employed to identify and quantify the bioactive components. Furthermore, molecular…
Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2 - The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic and has inflicted enormous damage on the lives of the people and economy of many countries worldwide. However, therapeutic agents against SARS-CoV-2 remain unclear. SARS-CoV-2 has a spike protein (S protein), and cleavage of the S protein is essential for viral entry. Nattokinase is produced by Bacillus subtilis var. natto and is beneficial to human health….
Impact of Clarified Apple Juices with Different Processing Methods on Gut Microbiota and Metabolomics of Rats - The consumption of processed foods has increased compared to that of fresh foods in recent years, especially due to the coronavirus disease 2019 pandemic. Here, we evaluated the health effects of clarified apple juices (CAJs, devoid of pectin and additives) processed to different degrees, including not-from-concentrate (NFC) and from-concentrate (FC) CAJs. A 56-day experiment including a juice-switch after 28 days was designed. An integrated analysis of 16S rRNA sequencing and untargeted…