Background: To strategically develop preventive and therapeutic measures against coronavirus disease 2019 and its causative virus, SARS-CoV-2, it is critical to fully characterize immune response and sustained immune activation following viral infection and vaccination. However, the mechanisms controlling intrapersonal variation in antibody titers against SARS-CoV-2 antigens remain unclear. To gain further insights into how we can optimize therapeutic and preventive care, we performed a robust molecular and cellular investigation of immune responses in infected, recovered, and vaccinated individuals. Methods: We evaluated the expression of 29 cytokines and assessed their correlation with neutralizing potency. We further investigated memory B-cell response in patients infected with the original SARS-CoV-2 strain or other variants of concern, and in vaccinated individuals. Results: Correlation analyses showed that the relationship between neutralizing activity and cytokine expression differed according to disease severity and viral strain. Furthermore, long-term longitudinal analyses revealed that post-vaccination neutralizing potential was more strongly associated with various cytokine expression levels in recovered patients than in naive individuals. Notably, we found a similar distribution of virus-specific antibody gene families in triple-vaccinated individuals and a patient with COVID-19 pneumonia for one year. Conclusion: Our results showed that distinct immune responses occur depending on the viral strain suggesting that therapeutic options should be selected on a case-by-case basis. Furthermore, longitudinal analyses revealed biomarker candidates that correlated with repeated vaccination that may be applicable to therapies regulating specific immune responses and novel monoclonal antibodies.
Rapid antigen tests play an important role in the monitoring and mitigation of the COVID-19 pandemic, as it provides an easy, fast and efficient diagnosis with minimum infrastructure requirements. However, as new variants of concern continue to emerge, mutations in the virus genome may impair the recognition of the mutated antigen by the tests. Therefore, it is essential to re-assess the test9s sensitivity as the virus mutation profile undergoes significant changes. Here, we prospectively accessed the performance of the DPP SARS-CoV-2 Antigen test in the context of an omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing center in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct RT-qPCR methods was employed as reference and 13 samples with discordant PCR results were excluded. The assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5%, specificity of 99.2% and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct<31 = 93.7%; Ct>31 = 47.4%). Furthermore, we were able to confirm that the positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n=40) and multiplex RT-qPCR (n=17). Altogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for the Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in a setting with high disease prevalence and limited PCR testing capability.
The current COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has become a major public health concern. The ability to identify the presence of virus in infected hosts with sufficient speed and sensitivity is critical to control the epidemic timely. Here, we use self-assembly of arrayed gold nanoparticles (AuNPs) on the coronavirus which we call the plasmo-virus particle, to achieve a rapid, sensitive, sample preparation-free assay enabling direct detection of SARS-CoV-2 in a point-of-care (POC) setting. The AuNPs of the plasmo-virus particle serve as plasmonic nanoprobes that specifically bind to the spike protein (S-protein) sites on the surface of SARS-CoV-2. Optical interactions between the self-assembled plasmonic nanoprobes generate multiple modes of highly enhanced plasmonic coupling. Measuring changes of the multimode plasmonic coupling-induced extinction peaks allows for quantifying SARS-CoV-2 at low titers with a limit of detection (LOD) of 1.4 x 10^1 pfu/mL. Using a miniaturized standalone biochip reading device, we further demonstrate the nano assembly assay for smartphone-operated SARS-CoV-2 detection for viral transport medium (VTM) samples within 10 min without any sample purification steps. We anticipate that the high sensitivity and speed of the POC detection performance of this biosensor technology could be broadly accepted for timely personalized diagnostics of infectious agents under low-resource settings.
Objective: Assess the impact of allocation concealment and blinding on the results of trials addressing COVID-19 therapeutics. Data sources: World Health Organization (WHO) COVID-19 database and the Living Overview of the Evidence (L-OVE) COVID-19 platform by the Epistemonikos Foundation (up to February 4th 2022) Methods: We included trials that compared drug treatments, antiviral antibodies and cellular therapies with placebo or standard care. For the five most commonly reported outcomes, if sufficient data were available, we performed random-effects meta-regression comparing the results of trials with and without allocation concealment and trials in which both healthcare providers and patients were blinded with trials in which healthcare providers and/or patients were aware of the intervention. A ratio of odds ratios (ROR) > 1 or a difference in mean difference (DMD) > 0 indicates that trials without allocation concealment or open-label trials produced larger effects than trials with allocation concealment or blinded trials. Results: As of February 4th 2022, we have identified 488 trials addressing COVID-19 drug treatments and antiviral antibodies and cellular therapies. Of these, 436 trials reported on one or more of our outcomes of interest and were included in our analyses. We found that trials without allocation concealment probably overestimate mortality (ROR 1.14 [95% CI 0.92 to 1.41]), need for mechanical ventilation (ROR 1.26 [95% CI 0.97 to 1.64]), admission to hospital (ROR 1.93 [95% CI 0.83 to 4.48]), duration of hospitalization (DMD 1.94 [95% CI 0.86 to 3.02]), and duration of mechanical ventilation (DMD 2.64 [95% CI -0.90 to 6.18]), but results were imprecise. We did not find compelling evidence that double-blind and open-label trials produce consistently different results for mortality (ROR 1.00 [95% CI 0.87 to 1.15]), need for mechanical ventilation (ROR 1.03 [95% CI 0.84 to 1.26]), and duration of hospitalization (DMD 0.47 days [95% CI -0.38 to 1.32]). We found that open-label trials may overestimate the beneficial effects of interventions for hospitalizations (ROR 1.87 [95% CI 0.95 to 3.67] and duration of mechanical ventilation (DMD 1.02 days [95% CI -1.30 to 3.35]), but results were imprecise. Conclusion: We found compelling evidence that, compared to trials with allocation concealment, trials without allocation concealment may overestimate the beneficial effects of treatments. We did not find evidence that trials without blinding addressing COVID-19 interventions produce consistently different results from trials with blinding. Our results suggest that consideration of blinding status may not be sufficient to judge risk of bias due to imbalances in co-interventions. Evidence users may consider evidence of differences in co-interventions between trial arms when judging the trustworthiness of open-label trials. We suggest, however, evidence users to remain skeptical of trials without allocation concealment.
Background: Uptake of COVID-19 vaccination remains suboptimal in the United States and other settings. Though early reports indicated that a strong majority of people were interested in receiving the COVID-19 vaccine, the association between vaccine intention and uptake is not yet fully understood. Methods: During 24 February-5 December 2021, we enrolled California residents receiving molecular tests for SARS-CoV-2 infection who had not yet received any COVID-19 vaccine doses. Unvaccinated participants provided information on their intentions to receive COVID-19 vaccination in a telephone-administered survey. We matched study participants with a state-wide immunization registry and fit a Cox proportional hazards model comparing time to vaccination among those unvaccinated at study enrollment by vaccination intention (willing, unsure, or unwilling). Findings: Among 864 participants who were unvaccinated at the time of interview, 272 (31%) had documentation of receipt of COVID-19 vaccination later; including 194/423 (45.9%) who had initially reported being willing to receive vaccination, 41/185 (22.2%) who reported being unsure about vaccination, and 37/278 (13.3%) who reported unwillingness to receive vaccination. Adjusted hazard ratios (aHRs) for registry-confirmed COVID-19 vaccination were 0.49 (95% confidence interval: 0.32-0.76) and 0.21 (0.12-0.36) for participants expressing uncertainty and unwillingness to receive vaccination, respectively, as compared with participants who reported being willing to receive vaccination. Time to vaccination was shorter among participants from higher-income households (aHR 3.30 [2.02-5.39]) and who reported co-morbidities or immunocompromising conditions (aHR 1.54 [1.01-2.36]); time to vaccination was longer among participants who tested positive for SARS-CoV-2 infection (aHR 0.60 [0.43-0.84]). Sensitivity of self-reported COVID-19 vaccination status was 82% (80-85%) overall, and 98% (97-99%) among those referencing vaccination records; specificity was 87% (86-89%). Interpretation: Reported willingness to receive COVID-19 vaccination was an imperfect predictor of real-world vaccine receipt. Improving messaging about the importance of COVID-19 vaccination, regardless of previous SARS-CoV-2 infection status, may improve vaccine uptake among populations who express hesitancy to initiate vaccination.
Background: The COVID-19 pandemic that emerged in Wuhan, China at the end of 2019, spread rapidly around the world with almost 600 million cases and 6.3 million deaths today. The most affected were health workers with at least three times the risk of contracting the disease than the general community. Most studies on seroprevalence in health workers focus on hospital care establishments and what happens in Primary Health Care (PHC) has not been investigated with the same intensity. Objectives: to determine the prevalence and know the variation of antibody titers for SARS-CoV-2 in serial samples of primary healthcare personnel from the commune of La Pintana. Method: an analytical observational study with a cross-sectional and a longitudinal component, carried out from November 2020 to June 2021. The first component consisted of an IgG antibody seroprevalence study performed at baseline (time 0) in volunteer of a universe of 900 workers. The longitudinal component considered the monitoring of IgG antibodies in those who presented a positive result at baseline and the analysis of neutralizing antibodies in a random sub-sample of 50% of them. Additionally, sociodemographic and clinical information was collected via a questionnaire. Univariate, bivariate, and longitudinal analyses were performed to evaluate differences in antibodies. The study was approved by the Universidad del Desarrollo9s Scientific Ethics Committee. Results: 463 primary healthcare workers participated, mostly women and with a median of 38 years; doctors and nurses represented 9.5% each and 14.7% had a history of COVID-19. The seroprevalence at baseline was 22.3% and was associated with younger age, being a doctor and having been in close contact of a case. IgG titers increased with the vaccine, but decreased over time. At the 6-month follow-up, 76% had neutralizing antibodies. Those belonging to indigenous peoples had higher IgG levels and higher rates of neutralizing antibodies. Conclusion: Healthcare workers were highly affected by COVID-19, and the medical profession and younger age were factors associated with increased risk. Antibodies decrease over time, highlighting the importance of follow-up studies, as well as the importance of vaccination boosters in healthcare workers, especially those in PHC.
Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-19 convalescent plasma (CCP) therapy. In this systematic review we performed a metanalysis of 6 controlled studies (including 2 randomized controlled trials; totaling 368 treated patients and 1119 control), an individual patient data analysis of 125 case reports/series (totaling 265 patients), and a descriptive analysis of 13 uncontrolled large case series without individual patient data available (totaling 358 patients). The metanalysis showed a risk ratio for mortality of 0.61 in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients. On the basis of this evidence, we encourage initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.
Background: Paxlovid is authorized for the treatment of COVID-19 and must be used within the first 5 days of symptom onset. This limited window for initiating treatment makes rapid access critical. Federal Test-to-Treat programs provide tests, prescriptions, and medication in one visit3. Objective: The objective of this study was to map the location of and identify disparities in access to Test-to-Treat programs in the United States (U.S.). Methods: We obtained location data for public providers of Paxlovid and Test-to-Treat programs in the contiguous U.S. and examined their spatial distribution at the zip code tabulation area level. We defined zip codes as underserved if there was no Test-to-Treat program located within the zip code or within 20 miles of its boundaries. Results: More than 52,000,000 people, representing 16% of the continental U.S. population, do not have access to a Test-to-Treat program in their zip code or within 20 miles. The majority of zip codes representing metropolitan areas have a Test-to-Treat program within 20 miles (77%). In contrast, only 30% of small towns and 23% of rural areas have nearby access. Zip codes with a high proportion of Hispanic and Black residents were likely to have access to nearby Test-to-Treat programs (72%, 70%). In contrast, zip codes with a high proportion of Native American residents were likely to be underserved (70%). About half of high-poverty zip codes do not have access to a Test-to-Treat program within 20 miles. Discussion: Disparities in outcomes related to COVID-19 have been apparent since the beginning of the pandemic and continue to grow. While the multi-dimensional measure of social vulnerability was used to expand the federal Test-to-Treat program, some populations remain without access.
The birth-death exposed-infectious (BDEI) model describes the transmission of pathogens featuring an incubation period (when the host is already infected but not yet infectious), for example Ebola and SARS-CoV-2. In a phylodynamics framework, it serves to infer such epidemiological parameters as the basic reproduction number R0, the incubation period and the infectious time from a phylogenetic tree (a genealogy of pathogen sequences). With constantly growing sequencing data, the BDEI model should be extremely useful for unravelling information on pathogen epidemics. However, existing implementations of this model in a phylodynamic framework have not yet caught up with the sequencing speed. While the accuracy of estimations should increase with data set size, existing BDEI implementations are limited to medium data sets of up to 500 samples, for both computing time and numerical instability reasons. We improve accuracy and drastically reduce computing time for the BDEI model by rewriting its differential equations in a highly parallelizable way, and by using a combination of numerical analysis methods for their efficient resolution. Our implementation takes one minute on a phylogenetic tree of 10 000 samples. We compare our parameter estimator to the existing implementations on simulated data. Results show that we are not only much faster (50 000 times), but also more accurate. An application of our method to the 2014 Ebola epidemic in Sierra-Leone is also convincing, with very fast calculation and precise estimates. Our BDEI estimator should become an important tool for routine epidemiological surveillance. It is available at github.com/evolbioinfo/BDEI.
Objectives To quantify the morbidity impact of long COVID in Australia during the 2021-2022 Omicron wave in comparison to acute COVID-19 morbidity and mortality, and to other causes of morbidity and mortality in Australia. Design Burden of disease study using inputs from previously published population-based case-control, cross-sectional, or cohort studies. Setting Australia Participants People with symptomatic COVID-19 infection from 10/12/21 to 09/04/22. Main outcomes measured Years lived with disability (YLDs) from acute COVID-19 and long COVID measured as the product of the prevalence, duration and severity of each long COVID symptom determined from existing literature, summed across all long COVID symptoms and applied to the population of COVID-19 surviving cases in Australia during the 2021-2022 Omicron wave. Additionally, acute COVID YLDs and years of life lost from COVID deaths were estimated to generate total COVID-19 disability-adjusted life years (DALYs). Results During the Omicron wave in Australia, 5,300 (95% uncertainty interval [UI] 2,200-8,400) YLDs were attributable to long COVID, accounting for 74% of the overall YLDs from COVID-19 infections in this period. The overall DALYs due to COVID-19 in this four-month period were 51,000 (95% UI 21,000-80,900), comprising 2.4% of total DALYs. This is comparable to the health loss caused by dementia and drug use disorders. Conclusion Long COVID requires consideration in pandemic policy planning given it is responsible for the majority of the total morbidity loss from COVID-19, even during an Omicron wave in a highly vaccinated population. Further research into the symptom profile and duration of long COVID following Omicron infection, and more robust severity measurement, will allow for more accurate estimation of long COVID morbidity.
Symptomatic COVID-19 appears to be associated with suicidal ideation but longitudinal evidence is still scarce. SARS-CoV2-induced neurological damages might underline this association, but findings are inconsistent. We therefore investigated the association between COVID-19 disease and subsequent suicidal ideation in the general population, using both self-reported symptoms and serology as well as inverse probability weighting to draw as near as possible to the direct association. Using data from the nationwide French EpiCov cohort, COVID-19 disease was assessed through 1) COVID-19 illness (self-reported symptoms of sudden loss of taste/smell or fever alongside cough, shortness of breath or chest oppression, between February and November 2020), and 2) SARS-CoV2 infection (Spike protein ELISA test screening in dried-blood-spot samples). Suicidal ideation was self-reported between December 2020 and July 2021. Inverse probability weighting with propensity scores was used as an adjustment strategy, leading to balanced sociodemographic and health-related factors between the exposed and non-exposed groups of both COVID-19 disease measures. Then, modified Poisson regression models were used to investigate the association of COVID-19 illness and SARS-CoV2 infection with subsequent suicidal ideation. Among 52,050 participants from the EpiCov cohort, 1.68% [1.54%-1.82%] reported suicidal ideation in the first half of 2021, 9.57% [9.24%-9.90%] had a SARS-CoV2 infection in 2020 and 13.23% [12.86%-13.61%] reported COVID-19 symptoms in 2020. COVID-19 illness in 2020 was associated with higher risks of subsequent suicidal ideation in the first half of 2021 (Relative Riskipw [CI95%]= 1.43 [1.20-1.69]) while SARS-CoV2 infection in 2020 was not (RRipw = 0.88 [0.69-1.12]). If COVID-19 illness was associated with subsequent suicidal ideation, the exact role of SARS-CoV2 infection with respect to suicide risk has yet to be clarified. Psychological support should be offered to persons recovering from symptomatic COVID-19 in order to minimize suicidal ideation risk. Moreover, if such psychological support is to be implemented, serology status alone does not seem a relevant criterion to define persons who suffered from COVID-19 to prioritize.
Background: Monkeypox virus re-surged in May 2022 as a new potential global health threat with outbreaks bursting in multiple countries across different continents. This study was conducted during the first month of the WHO announcement to assess the healthcare workers (HCWs) within Saudi Arabia, exploring their perception, worries, and vaccine acceptance for Monkeypox in-line with the resolving COVID-19 pandemic. Methods: A national cross-sectional survey was conducted between May 27 and June 10, 2022, in Saudi Arabia. Data were collected on the sociodemographic and job-related characteristics, COVID-19 infection status, HCWs9 worry levels of Monkeypox compared to COVID-19 and its sources, their perceptions, awareness, and HCWs9 Monkeypox vaccination advocacy. Results: Among the 1130 HCWs who completed survey, 41.6% already developed COVID-19. Still, 56.5% were more worried from COVID-19 compared to Monkeypox, while the rest were more worried of Monkeypox disease. The main reason for their worry among 68.8% of the participants was development of another worldwide pandemic post COVID-19, followed by their worry of acquiring the infection themselves or their families (49.6%). Most HCWs (60%) rated their self-awareness of Monkeypox disease as moderate to high. Males and those who previously developed COVID-19 were significantly less likely to worry about Monkeypox. The worry about Monkeypox developing into a pandemic and the perception of Monkeypox being a severe disease correlated significantly positively with the odds of high worry from the disease. Regarding participants9 advocacy for HCWs9 vaccination against Monkeypox disease, those who developed COVID-19 previously and those who supported application of tighter infection control measures compared to the current ones to combat the disease were significantly predicted to agree for vaccination. 74.2% of the surveyed HCWs perceived that they need to read more about the Monkeypox disease after the survey. Conclusion: During the first month of the WHO9s Monkeypox international alert, about half of HCWs in this study were more worried about Monkeypox disease as compared to COVID-19, and its possible progression into another pandemic. In addition, the majority were in favor of applying tighter infection prevention measures to combat the disease. The current study highlights areas needed for healthcare administrative about the HCWs9 perceptions and readiness for Monkeypox especially in the event of any occurrence of local or international pandemic.
Background Identifying optimal COVID-19 policies is challenging. For Victoria, Australia (6.6 million people), we ranked 44 policy packages (two levels of stringency of public health and social measures [PHSMs]; providing respirators during infection surges; 11 vaccination schedules of current and next-generation vaccines) in the context of 64 future SARS-CoV-2 variants (combinations of transmissibility, virulence, immune escape, and incursion date). Methods We used an agent-based model to estimate morbidity, mortality, and costs over 18 months from 1 April 2022 for each scenario. Policies were ranked on cost-effectiveness (health system only and health system plus GDP perspectives), deaths and days exceeding hospital occupancy thresholds. Findings The median number of infections across the 44 policies was 6.2 million (range 5.4 to 7.1 million). Higher stringency PHSMs ranked better from a health system perspective, but not a health system plus GDP perspective. The provision of respirators to replace surgical/cloth masks had minimal impact. Vaccinating all ages was superior to nil further vaccination and targeted vaccination of individuals aged ≥60 years. Averaging over 64 future SARS-CoV-2 variant scenarios the optimal policy was a multivalent vaccine for all age groups with higher stringency PHSMs and no respirator provision. For the SARS-CoV-2 variant scenario approximating recent BA.4/5, Omicron-targeted vaccines were more likely optimal even with a three-month delay compared to boosting with current-generation vaccines. Interpretation Modelling that accommodates future scenarios with uncertainty, and that can be rapidly updated as new data arises, can provide a framework for pandemic decision making.
Puerto Rico COVID-19 Vaccine Uptake Study - Condition: COVID-19
Intervention: Other: Educational intervention
Sponsors: University of Puerto Rico; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
A Study to Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1)
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection - Condition: COVID-19
Interventions: Dietary Supplement: SmartProbio C; Dietary Supplement: Placebo
Sponsors: Medi Pharma Vision; Veterinary Research Institute; Brno University Hospital
Completed
An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens - Condition: COVID-19
Interventions: Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth; Biological: Clover SCB-2019
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; University of Oxford
Not yet recruiting
Effect of Pulmonary Rehabilitation Program on Post Hospitalization Severe COVID- 19 Patients - Condition: Post COVID-19 Condition
Intervention: Combination Product: respiratory exercises - incentive spirometer - walking
Sponsor: Fayoum University Hospital
Completed
Physiotherapy in Post COVID-19 Syndrome Patients - Condition: Post-COVID-19 Syndrome
Interventions: Other: Cognitive behavioral principles-based treatment program; Other: Control intervention
Sponsor: Universidad de Granada
Recruiting
Rehabilitation for People With Post COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Other: Multidimensional intervention; Other: Control intervention
Sponsor: Universidad de Granada
Recruiting
rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray
Sponsor: Sichuan Huiyang Life Science and Technology Corporation
Recruiting
A CHW Intervention to Identify and Decrease Barriers to COVID 19 Testing & Vaccination - Conditions: Vaccine Hesitancy; COVID-19 Testing; Community Health Workers
Intervention: Behavioral: Community Health Worker led curriculum
Sponsors: Charles Drew University of Medicine and Science; Los Angeles County Department of Public Health; National Library of Medicine (NLM)
Recruiting
Study to Evaluate Safety and Immunogenicity of COVID-19 Vaccine in Children 6 Months to < 12 Years - Condition: COVID-19
Interventions: Biological: Biological/Vaccine: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Initial Vaccination Period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Open Label Crossover Vaccination period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Booster Vaccination); Other: Placebo
Sponsor: Novavax
Recruiting
Lollipop COVID-19 Testing Study - Conditions: COVID-19; SARS CoV 2 Infection; COVID-19 Pandemic
Intervention: Diagnostic Test: Lollipop Swab
Sponsor: University of Wisconsin, Madison
Not yet recruiting
SWITCH ON: Analysing the Immunogenicity of Additional Booster Vaccinations in HCW - Condition: Covid-19 Vaccination
Interventions: Drug: Direct boost mRNA; Drug: Direct boost adeno; Drug: Post-poned boost mRNA; Drug: Post-poned boost adeno
Sponsors: Erasmus Medical Center; ZonMw (Funding organisation, The Hague, The Netherlands); LUMC, University Hospital (Leiden, The Netherlands); UMCG, University Hospital (Groningen, The Netherlands); AUMC, University Hospital (Amsterdam, The Netherlands)
Not yet recruiting
Immunogenicity and Safety of BBIBP-Cov Coadministered With PPV23 and IIV4 in Hemodialysis Population - Conditions: Hemolysis; COVID-19
Interventions: Biological: coadministration; Biological: COVID-19 vaccine; Biological: IIV4+PPV23
Sponsors: China National Biotec Group Company Limited; Hunan Provincial Center for Disease Control and Prevention; Sichuan Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Xiangya Hospital of Central South University; Beijing Institute of Biological Products Co Ltd.; Chengdu Institute of Biological Products Co.,Ltd.; Shanghai Institute Of Biological Products
Not yet recruiting
Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old - Condition: SARS-CoV-2
Interventions: Biological: CV0501 (3 μg); Biological: CV0501 (6 μg); Biological: CV0501 (12 μg); Biological: CV0501 (25 μg); Biological: CV0501 (50 μg); Biological: CV0501 (75 μg); Biological: CV0501 (100 μg); Biological: CV0501 (150 μg); Biological: CV0501 (200 μg)
Sponsor: GlaxoSmithKline
Not yet recruiting
The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test - Conditions: Anxiety; Fear
Interventions: Behavioral: The Kaleidescope; Behavioral: The visual illusion cards
Sponsor: Ondokuz Mayıs University
Completed
Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective - SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although, extrapulmonary manifestations of Covid-19 like neurological, cardiovascular, and gastrointestinal have been confirmed. Exaggerated immune response and release of a high…
Peptidic defective interfering gene nanoparticles against Omicron, Delta SARS-CoV-2 variants and influenza A virus in vivo - Defective interfering genes (DIGs) are short viral genomes and interfere with wild-type viral replication. Here, we demonstrate that the new designed SARS-CoV-2 DIG (CD3600) can significantly inhibit the replication of SARS-CoV-2 including Alpha, Delta, Kappa and Omicron variants in human HK-2 cells and influenza DIG (PAD4) can significantly inhibit influenza virus replication in human A549 cells. One dose of influenza DIGs prophylactically protects 90% mice from lethal challenge of A(H1N1)pdm09…
Coronaviruses exploit a host cysteine-aspartic protease for replication - Highly pathogenic coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)^(1,2), Middle East respiratory syndrome coronavirus (MERS-CoV)³, and SARS-CoV-1⁴ vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture^(5-7) and in patient tissues^(8-10), suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that a cysteine-aspartic protease of the…
Mast cells promote viral entry of SARS-CoV-2 via formation of chymase/spike protein complex - The pulmonary pathological findings associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result from the release of multiple proinflammatory cytokines, which causes the subsequential damage of the lungs. The current study was undertaken to investigate the responses of mast cells to viral inoculation and their contribution to host defenses from the point of view of viral entry. Pseudovirions, in which the spike glycoprotein of SARS-CoV-2 was incorporated, triggered…
Fatty Acid Synthase inhibitor TVB-3166 prevents S-acylation of the Spike protein of human coronaviruses - The Spike protein of SARS-CoV-2 and other coronaviruses mediates host cell entry and is S-acylated on multiple phylogenetically conserved cysteine residues. Multiple protein acyltransferase enzymes have been reported to post-translationally modify Spike proteins; however, strategies to exploit this modification are currently lacking. Using resin-assisted capture mass spectrometry, we demonstrate here the Spike protein is S-acylated in SARS-CoV-2-infected human and monkey cells. We further show…
Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity - SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2-infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of…
Exploration of Novel Lichen Compounds as Inhibitors of SARS-CoV-2 Mpro: Ligand-Based Design, Molecular Dynamics, and ADMET Analyses - In the year 2019-2020, the whole world witnessed the spread of a disease called COVID-19 caused by SARS-CoV-2. A number of effective drugs and vaccine has been formulated to combat this outbreak. For the development of anti-COVID-19 drugs, the main protease (Mpro) is considered a key target as it has rare mutations and plays a crucial role in the replication of the SARS CoV-2. In this study, a library of selected lichen compounds was prepared and used for virtual screening against SARS-CoV-2…
PEDOT:PSS in Solution Form Exhibits Strong Potential in Inhibiting SARS-CoV-2 Infection of the Host Cells by Targeting Viruses and Also the Host Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with over 5 million fatalities. Vaccines against this virus have been globally administered; however, SARS-CoV-2 variants with spike protein mutations are continuously identified with strong capability to escape vaccine-elicited protection. Due to the high mutation rate and transmission ability, the development of a broad-spectrum SARS-CoV-2 inhibitor is highly in demand. In this study, the effect of…
Rational design of AAVrh10-vectored ACE2 functional domain to broadly block the cell entry of SARS-CoV-2 variants - The frequently emerging SARS-CoV-2 variants have weakened the effectiveness of existing COVID-19 vaccines and neutralizing antibody therapy. Nevertheless, the infections of SARS-CoV-2 variants still depend on angiotensin-converting enzyme 2 (ACE2) receptor-mediated cell entry, and thus the soluble human ACE2 (shACE2) is a potential decoy for broadly blocking SARS-CoV-2 variants. In this study, we firstly generated the recombinant AAVrh10-vectored shACE2 constructs, a kind of adeno-associated…
The protective effect of xanthenone against LPS-induced COVID-19 acute respiratory distress syndrome (ARDS) by modulating the ACE2/Ang-1-7 signaling pathway - OBJECTIVE: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disease that has a high rate of morbidity and mortality. It’s an acute diffusive lung injury caused by the release of pro-inflammatory cytokines into the lungs. Specific microRNAs have been identified to play a crucial role in the renin-angiotensin system signaling pathways the main pathophysiological pathway responsible for ARDS. Since the ARDS life-threatening complication associated with COVID-19 is an ongoing…
Effects of natural RNA modifications on the activity of SARS-CoV-2 RNA-dependent RNA polymerase - RNA-dependent RNA polymerase (RdRp) plays the key role in replication of RNA viruses, including SARS-CoV-2. Processive RNA synthesis by RdRp is crucial for successful genome replication and expression, especially in the case of very long coronaviral genomes. Here, we analyzed the activity of SARS-CoV-2 RdRp (the nsp12-nsp7-nsp8 complex) on synthetic primer-templates of various structures, including substrates with mismatched primers or template RNA modifications. It has been shown that RdRp…
Porcine Deltacoronavirus Infection Cleaves HDAC2 to Attenuate Its Antiviral Activity - Protein acetylation plays an important role during virus infection. Thus, it is not surprising that viruses always evolve elaborate mechanisms to regulate the functions of histone deacetylases (HDACs), the essential transcriptional and epigenetic regulators for deacetylation. Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes severe diarrhea in suckling piglets and has the potential to infect humans. In this study, we found that PDCoV infection inhibited cellular…
“Intention to receive COVID-19 vaccine among healthcare workers: a comparison between two surveys” - CONCLUSIONS: Present study showed an undesirable rate of intention to receive COVID-19 vaccine among healthcare workers, especially decreasing over the time, emphasize the need of interventions to promote healthcare workers’ intention to receive the vaccine and reduce the spread of COVID-19 disease.
APOE interacts with ACE2 inhibiting SARS-CoV-2 cellular entry and inflammation in COVID-19 patients - Apolipoprotein E (APOE) plays a pivotal role in lipid including cholesterol metabolism. The APOE ε4 (APOE4) allele is a major genetic risk factor for Alzheimer’s and cardiovascular diseases. Although APOE has recently been associated with increased susceptibility to infections of several viruses, whether and how APOE and its isoforms affect SARS-CoV-2 infection remains unclear. Here, we show that serum concentrations of APOE correlate inversely with levels of cytokine/chemokine in 73 COVID-19…
Bovine coronavirus nucleocapsid suppresses IFN-β production by inhibiting RIG-I-like receptors pathway in host cells - The present study aimed to explore if bovine coronavirus nucleocapsid (BCoV N) impacts IFN-β production in the host cells and to reveal further molecular mechanism of BCoV pathogenesis. Human embryonic kidney (HEK) 293 T cells were transiently transfected with pMyc-BCoV-N recombinant plasmids, then infected with the vesicular stomatitis virus (VSV). Expression levels of beta interferon (IFN-β) mRNA were detected using RT-qPCR. The results showed that BCoV N gene was 1347 bp that was consistent…