The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants which have led to substantial changes in the epidemiology of the virus. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant was first detected in late November 2021 and exhibited a high degree of immune evasion, leading to increased infection rates in many countries. However, estimates of the magnitude of the Omicron wave have relied mainly on routine testing data, which are prone to several biases. Here we infer the dynamics of the Omicron wave in England using PCR testing and genomic sequencing obtained by the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys testing random samples of the population of England. We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections in England during February-March 2022 as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct genomic variants, intermittent epidemics of similar magnitude as the Omicron wave may become the 9new normal9.
Thick, viscous respiratory secretions are a major pathogenic feature of COVID19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID19 patients. We find the percent solids and protein content are greatly elevated in COVID19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) are major components of respiratory secretions in COVID19 and are likewise abundant in cadaveric lung tissues from these patients. COVID19 secretions exhibit heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observe increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor stimulated gene 6 (TSG6) staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicate that increases in HA and DNA in COVID19 respiratory secretion samples correlate with enhanced inflammatory burden and suggest that DNA and HA may be viable therapeutic targets in COVID19 infection.
Background Respiratory viruses, including SARS-CoV-2, can infect the eyes or pass into the nose via the nasolacrimal duct. The importance of transmission via the eyes is unknown but might plausibly be reduced in those who wear glasses. Previous studies have mainly focussed on protective eyewear in healthcare settings. Methods Participants from the Virus Watch prospective community cohort study in England and Wales responded to a questionnaire on the use of glasses and contact lenses. This included frequency of use, purpose, and likelihood of wearing a mask with glasses. Infection was confirmed through data linkage with Second Generation Surveillance System (Pillar 1 and Pillar 2), weekly questionnaires to self-report positive polymerase chain reaction or lateral flow results, and, for a subgroup, monthly capillary blood testing for antibodies (nucleocapsid and spike). A multivariable logistic regression model, controlling for age, sex, income and occupation, was used to identify odds of infection depending on the frequency and purpose of using glasses or contact lenses. Findings 19,166 Virus Watch participants responded to the questionnaire, with 13,681 (71.3%, CI 70.7-72.0) reporting they wore glasses. A multivariable logistic regression model showed a 15% lower odds of infection for those who reported using glasses always for general use (OR 0.85, 95% 0.77-0.95, p = 0.002) compared to those who never wore glasses. The protective effect was reduced in those who said that wearing glasses interfered with mask wearing. No protective effect was seen for contact lens wearers. Interpretation People who wear glasses have a moderate reduction in risk of COVID-19 infection highlighting the importance of the eye as a route of infection. Eye protection may make a valuable contribution to the reduction of transmission in community and healthcare settings.
Purpose: To assess the trustworthiness and impact of preprint trial reports during the COVID-19 pandemic. Data sources: WHO COVID-19 database and the L-OVE COVID-19 platform by the Epistemonikos Foundation (up to August 3rd, 2021) Design: We compare the characteristics of COVID-19 trials with and without preprints, estimate time to publication of COVID-19 preprint reports, describe discrepancies in key methods and results between preprint and published trial reports, report the number of retracted preprints and publications, and assess whether including versus excluding preprint reports affects meta-analytic estimates and the certainty of evidence. For the effects of eight therapies on mortality and mechanical ventilation, we performed meta-analyses including preprints and excluding preprints at 1 month, 3 months, and 6 months after the first trial addressing the therapy became available either as a preprint or publication (120 meta-analyses in total). Results: We included 356 trials, 101 of which are only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. Half of all preprints remain unpublished at six months and a third at one year. There were few important differences in key methods and results between trial preprints and their subsequent published reports. We identified four retracted trials, three of which were published in peer-reviewed journals. With two exceptions (2/60; 3.3%), point estimates were consistent between meta-analyses including versus excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. There were nine comparisons (9/60; 15%) for which the rating of the certainty of evidence differed when preprints were included versus excluded, for four of these comparisons the certainty of evidence including preprints was higher and for five of these comparisons the certainty of evidence including preprints was lower. Limitations: The generalizability of our results is limited to COVID-19. Preprints that are subsequently published in journals may be the most rigorous and may not represent all trial preprints. Conclusion: We found no compelling evidence that preprints provide less trustworthy results than published papers. We show that preprints remain the only source of findings of many trials for several months, for a length of time that is unacceptable in a health emergency. We show that including preprints may affect the results of meta-analyses and the certainty of evidence. We encourage evidence users to consider data from preprints in contexts in which decisions are being made rapidly and evidence is being produced faster than can be peer-reviewed.
While there is compelling evidence of the effectiveness of COVID-19 vaccines, increasing attention has also been paid to the fact that, like all vaccines, they are not 100% effective. Therefore, some fully vaccinated people have developed cases of COVID-19, and some of these individuals have died as a result. The purpose of this study was to estimate the number of fully vaccinated (or “breakthrough”) deaths from COVID-19 in the United States. Data was compiled from state COVID-19 dashboards and various other sources for as many states as possible. As of March 27, 2022 based on data from 46 U.S. states and the District of Columbia, an estimated minimum of 57,617 breakthrough COVID-19 deaths had occurred in the United States. Furthermore, based on this incomplete data, a total of 12.8% of all COVID-19 deaths in the included regions and time periods were among fully vaccinated individuals (whether boosted or not). Extrapolating this data to the entire United States implies that the minimum total number of such deaths as of March 27, 2022 was 79,917. Data from a MMWR article, if similarly extrapolated to the entire country, implies a significantly larger number of breakthrough deaths throughout the United States: 99,152.
Especially during global pandemics but also in the context of epidemic waves, the capacity for diagnostic qRT- PCRs rapidly becomes a limiting factor. Furthermore, excessive testing incurs high costs and can result in an overstrained work force in diagnostics departments. Obviously, people aim to shorten their isolation periods, hospitals need to discharge convalescent people, and re-employ staff members after infection. The aim of the study was to optimize retesting regimens for test-to-release from isolation and return-to-work applications. For this purpose, we investigated the association between Ct values at the first diagnosis of SARS-CoV-2 infection and the period until test negativity was reached, or at least until the Ct value exceeded 30, which is considered to indicate the transition to a non-infectious state. We included results from the testing of respiratory material samples for the detection of SARS- CoV-2 RNA, tested from 01 March 2020 to 31 January 2022. Lower initial Ct values were associated with longer periods of SARS-CoV-2 RNA positivity. Starting with Ct values of <20, 20-25, 25-30, 30-35, and >35, it took median intervals of 20 (interval: 14-25), 16 (interval: 10-21), 12 (interval: 7-16), 7 (interval: 5-14), and 5 (interval: 2-7) days, respectively, until the person tested negative. Accordingly, a Ct threshold of 30 was surpassed after 13 (interval: 8-19), 9 (interval: 6-14), 7 (interval: 6-11), 6 (interval: 4-10), and 3 (interval: 1-6) days, respectively, in individuals with aforementioned start Ct values. Furthermore, the time to negativity was longer for adults versus children, wild-type SARS-CoV-2 variant versus other variants of concern, and in patients who were treated in the intensive care units. Based on these data, we propose an adjusted retesting strategy according to the initial Ct value in order to optimize available PCR resources.
Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS- CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 6 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 91 Veterans and 33 healthcare workers; neutralizing titers were correlated to clinical variables with multivariate regression. In 36 participants, post-booster effect was measured. Results: After completion of the primary vaccine series, neutralizing antibody IC-50 titers were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (52.5-fold increase). Age >65 years (β=-0.94, p=0.001) and malignancy (β=-0.88, p=0.002) significantly reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p=0.004); (β=-0.66, p=0.014)], diabetes mellitus [(β=-0.57, p=0.032); (β=-0.44, p=0.028)], and systemic steroid use [(β=-0.066, p=0.032); (β=-0.55, p=0.037)]. Interestingly, the booster neutralizing antibody titer response was unaffected by clinical factors. Conclusion: Multiple clinical factors impacted the strength and duration of post-vaccination serum neutralizing antibodies in this adult population. Response to the booster dose was universally robust, however. This suggests that the antibody response to the booster dose benefits from a sustained and effective anti-Spike memory immune response.
The COVID-19 pandemic triggered declines in life expectancy at birth around the world. The United States of America (USA) was hit particularly hard among high income countries. Early data from the USA showed that these losses varied greatly by race/ethnicity in 2020, with Hispanic and Black Americans suffering much larger losses in life expectancy compared to white people. We add to this research by examining trends in lifespan inequality, average years of life lost, and the contribution of specific causes of death and ages to race/ethnic life expectancy disparities in the USA from 2010 to 2020. We find that life expectancy in 2020 fell more for Hispanic and Black males (4.5 years and 3.6 years, respectively) compared to white males (1.5 years). These drops nearly eliminated the previous life expectancy advantage for the Hispanic compared to white population, while dramatically increasing the already large gap in life expectancy between Black and white people. While the drops in life expectancy for the Hispanic population were largely attributable to official COVID-19 deaths, Black Americans additionally saw increases in cardiovascular disease and 9deaths of despair9 over this period. In 2020, lifespan inequality increased slightly for Hispanic and white populations, but decreased for Black people, reflecting the younger age pattern of COVID-19 deaths for Hispanic people. Overall, the mortality burden of the COVID-19 pandemic hit race/ethnic minorities particularly hard in the USA, underscoring the importance of the social determinants of health during a public health crisis.
Background Long Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid. Methods 534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. A significant change over time was reported by comparison with 92 healthy controls. Results The technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 [19%] had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months. Conclusion Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.
Objective The study aimed to establish the performance of the SARS-CoV-2 Rapid Antibody Test (IgG and IgM) and the Elecsys® Anti-SARS-CoV-2 S assay in vaccinated individuals. Methods A panel of serum samples from Boca Biolistics was utilized to assess antibodies following vaccination, consisting of samples drawn prior to vaccination, after the first dose, or at least 14 days after the second dose of Moderna mRNA-1273 or Pfizer-BioNTech BNT162b2 COVID-19 vaccines. Agreement between the two methods was measured and stratified by test evaluator and assay lot. Results Agreement between the SARS-CoV-2 Rapid Antibody Test (IgG) and Elecsys Anti-SARS-CoV-2 S assay qualitative measurements at the different assessment points for both mRNA-1273 and BNT162b2 ranged between 97.06% (95% confidence interval [CI] 84.67, 99.93) to 100% (95% CI 82.35, 100). Agreement of the SARS-CoV-2 Rapid Antibody Test (IgG) with the Elecsys Anti- SARS-CoV-2 S assay was not highly influenced by either lot or evaluator. There was a medium-to-strong correlation between the semi-quantitative SARS-CoV-2 Rapid Antibody Test (IgG) result and quantitative Elecsys Anti-SARS-CoV-2 S assay in samples taken after both doses of the vaccines, with higher intensity bands being associated with higher total anti-S antibody titer (mRNA-1273, p=0.0019; BNT162b2, p<0.0001). Conclusion Semi-quantitative SARS-CoV-2 Rapid Antibody Test (IgG) and quantitative Elecsys Anti-SARS-CoV-2 S assay correlated well, suggesting that the SARS-CoV-2 Rapid Antibody Test (IgG) is helpful in understanding the immune response post-vaccination. The current data support the use of the SARS-CoV-2 Rapid Antibody Test (IgG) in the vaccinated population.
Public health departments such as CDC and California Department of Public Health (CA-DPH) advise HEPA-purifiers to limit transmission of SARS-CoV-2 in classrooms and community spaces. CA-DPH recommends 4-6 air exchanges per hour often necessitating multiple HEPA-purifiers per room, unaffordable in under-resourced community settings. Pressure to seek cheap, rapid air filtration resulted in proliferation of lower-cost, Do-It-Yourself (DIY) air purifiers whose performance is not well characterized compared to HEPA-purifiers. Primary metrics are clean air delivery rate (CADR), noise generated (dBA), and affordability ($$). CADR measurement often requires hard-to-replicate laboratory experiments with generated aerosols. In this study, we use simplified, low-cost measurement tools of ambient aerosols enabling scalable evaluation of aerosol filtration efficiencies (0.3 to 10 microns), estimated CADR, and noise generation to compare a dozen HEPA-purifiers and DIY purifier designs. DIY purifiers consist of one or two box fans coupled to single MERV 13-16 filters (1“-5” thick) or quad filters in a cube. Accounting for reduced filtration efficiency (%) of MERV 13-16 filters (versus HEPA) at the most penetrating particle size of 0.3 microns, estimated CADR of DIY purifiers using 2" (67%), 4" (66%), and 5" (85%) filters at lowest fan speed was 293 cfm ($35), 322 cfm ($58), and 405 cfm ($120) comparable to best-in-class, low-noise generating HEPA-purifier running at maximum speed with at 282 cfm ($549). Quad filter designs, popularly known as Corsi-Rosenthal box, achieved gains in estimated CADR less than 80% over single filter designs, less than the 100% gain by adding a second DIY purifier. Replacing one of the four filters with a second fan resulted in gains of 125%-150% in estimated CADR. DIY alternatives using single filters compare favorably to HEPA- purifiers in estimated CADR, noise generated at five to ten times lower cost, enabling cheap, rapid aerosol removal around the world.
Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still desperately needed. Recently, two antiviral drugs have shown to be effective in reducing hospitalizations in clinical trials. In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries, corresponding to four current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium, with 1.5, 38, 57 and 74% of their populations vaccinated. For each location, we varied antiviral coverage and antiviral effect in reducing viral load (25, 50, 75 or 100% reduction). Irrespective of location, widespread antiviral treatment of symptomatic infections (≥50% coverage) is expected to prevent the majority of COVID-19 deaths. Furthermore, even treating 20% of adult symptomatic infections, is expected to reduce mortality by a third in all countries, irrespective of the assumed treatment efficacy in reducing viral load. Our results suggest that early antiviral treatment is needed to mitigate transmission, with early treatment (within two days of symptoms) preventing 50% more infections compared to late treatment (started on days 3 to 5 after developing symptoms). Our results highlight the synergistic effect of vaccination and antiviral treatment: as vaccination rate increased, antiviral treatment had a bigger impact on overall transmission. These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly control SASRS-CoV-2 transmission and reduce COVID-19 hospitalizations and deaths.
Background: There are calls for research into the mental health consequences of living through the COVID-19 pandemic. Australia9s initial, effective suppression of COVID-19 offers insights into these indirect impacts in the relative absence of the disease. We aimed to describe the mental health experiences of Australian caregivers and children over 12 months, reporting differences related to demographic, socioeconomic and lockdown characteristics. Methods: Data were from Australia9s only nationally representative, repeated cross-sectional survey of caregivers with children (0-17 years). N=2020 caregivers participated in June 2020, N=1434 in September 2020, and N=2508 in July 2021. Caregivers reported their mental health (poor versus not, Kessler-6), and perceived impacts of the pandemic on theirs and their children9s mental health (negative versus none/positive). Data were weighted to approximate population distributions of caregiver age, gender, sole-caregiving, number and ages of children, state/territory and neighbourhood-level disadvantage. Results: Perceived impacts on mental health were more frequently negative for female (versus male) caregivers and older (versus younger) children. Poor caregiver mental health (K6) was more common for families experiencing socioeconomic adversity (especially financial), while perceived impacts were more frequently negative for more socially advantaged groups. Caregivers who experienced the least total lockdown reported similar K6 over time. Otherwise, poor mental health and perceived negative impacts increased over time with increasing total length of lockdown. Conclusion: Despite Australia9s low infection rates, the negative mental health experiences of the COVID-19 pandemic are real and concerning. Addressing poor mental health must be central to ongoing pandemic recovery efforts for families and children.
A Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) and Inactivated COVID-19 Vaccine (Vero Cell) - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-09); Biological: Inactivated COVID-19 vaccine (Vero cells)
Sponsors:
National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19 - Condition: COVID-19
Intervention: Dietary Supplement: Rhea® Health Tone
Sponsor: Indonesia University
Completed
Aerobic Exercise in People With Post-COVID-19 - Condition: COVID-19
Interventions: Other: Conventional rehabilitation; Other: Aerobic exercise
Sponsor: Istituti Clinici Scientifici Maugeri SpA
Recruiting
A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: CoronaVac; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: other approved COVID-19 vaccines
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01C; Biological: SCTV01E; Biological: mRNA vaccine manufactured by Pfizer or Moderna; Biological: Sinopharm inactivated COVID-19 vaccine
Sponsor: Sinocelltech Ltd.
Not yet recruiting
COVID-19 Treatment Cascade Optimization Study - Condition: COVID-19
Interventions: Behavioral: Navigation Services; Behavioral: Brief Counseling; Behavioral: Critical Dialogue; Behavioral: Referral and Digital Brochure
Sponsors: University of Illinois at Urbana-Champaign; National Institute of Allergy and Infectious Diseases (NIAID); Comprehensive Behavioral Health Center; North Jersey Community Research Initiative; University of Michigan
Not yet recruiting
Phase 1/2 Study to Evaluate the Efficacy and Safety of Inhaled IBIO123 in Participants With Mild to Moderate COVID-19 Illness - Condition: COVID-19
Interventions: Biological: IBIO123; Other: Placebo
Sponsor: Immune Biosolutions Inc
Recruiting
Compass Course: COVID-19 - Condition: COVID-19
Intervention: Behavioral: Compass Course
Sponsor:
Allina Health System
Recruiting
Improving COVID-19 Vaccine Uptake Among Black and Latino Youth - Condition: COVID-19
Interventions: Behavioral: Culturally-Tailored COVID-19 Vaccine Uptake Intervention; Behavioral: Standard Care
Sponsors: Nemours Children’s Health System; National Institute of General Medical Sciences (NIGMS); University of Delaware; ChristianaCare
Recruiting
Phase 1&2 Study to Evaluate the Safety & Efficacy of Inhaled IBIO123 in Severe COVID-19 Illness - Condition: COVID-19
Interventions: Biological: IBIO123; Other: Placebo
Sponsor: Immune Biosolutions Inc
Recruiting
Clinical Evaluation of Rapid RNA Test for Covid-19 - Condition: COVID-19
Intervention: Diagnostic Test: rapid RT-LAMP test to detect SARS-COV-2 RNA
Sponsors: University of Southampton; West Hertfordshire Hospitals NHS Trust; University of Oxford
Completed
Clinical Evaluation of Rapid Antibody Test for Covid-19 - Condition: COVID-19
Intervention: Diagnostic Test: Livzon Rapid Antibody Test for COVID-19
Sponsors: University of Southampton; West Hertfordshire Hospitals NHS Trust
Completed
ApTOLL for the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: ApTOLL; Other: Saline
Sponsors:
Macarena Hernández Jiménez; Centro para el Desarrollo Tecnológico Industrial
Recruiting
Platform Trial to Compare Homologous Boost of Authorized COVID-19 Vaccines and Heterologous Boost With UB-612 Vaccine - Condition: COVID-19 Vaccines
Interventions: Biological: UB-612; Biological: BNT162b2 vaccine; Biological: ChAdOx1-S vaccine; Biological: Sinopharm BIBP
Sponsors: Vaxxinity, Inc.; Syneos Health
Recruiting
A Study to Evaluate the Efficacy and Safety of Ivermectin in COVID-19 Prevention - Condition: COVID-19
Interventions: Drug: Ivermectin Tablets; Drug: Matching placebo tablets
Sponsor: MedinCell S.A
Recruiting
Invalidation of dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) as SARS-CoV-2 main protease inhibitors and the discovery of PGG as a papain-like protease inhibitor - The COVID-19 pandemic spurred a broad interest in antiviral drug discovery. The SARS-CoV-2 main protease (M ^(pro) ) and papain-like protease (PL ^(pro) ) are attractive antiviral drug targets given their vital roles in viral replication and modulation of host immune response. Structurally disparate compounds were reported as M ^(pro) and PL ^(pro) inhibitors from either drug repurposing or rational design. Two polyphenols dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) were recently reported as…
Anti-SARS-CoV-2 IgG and Neutralizing Antibody Levels in Patients with Past COVID-19 Infection: A Longitudinal Study - CONCLUSION: SARS-CoV-2 quantitative IgG antibody titers are significantly reduced at long-term follow-up (>6 months). Due to the limited information on seroconversion, comprehensive studies should be conducted for long-term follow-up of the immune response against SARS-CoV-2.
Impact of COVID-19 lockdown on the atmospheric boundary layer and instability process over Indian region - The abrupt reduction in the human activities during the first lockdown of the COVID-19 pandemic created unprecedented changes in the background atmospheric conditions. Several studies reported the anthropogenic and air quality changes observed during the lockdown. However, no attempts are made to investigate the lockdown effects on the Atmospheric Boundary Layer (ABL) and background instability processes. In this study, we assess the lockdown impacts on the ABL altitude and instability…
Directed Evolution-Driven Increase of Structural Plasticity Is a Prerequisite for Binding the Complement Lectin Pathway Blocking MASP-Inhibitor Peptides - MASP-1 and MASP-2 are key activator proteases of the complement lectin pathway. The first specific mannose-binding lectin-associated serine protease (MASP) inhibitors had been developed from the 14-amino-acid sunflower trypsin inhibitor (SFTI) peptide by phage display, yielding SFTI-based MASP inhibitors, SFMIs. Here, we present the crystal structure of the MASP-1/SFMI1 complex that we analyzed in comparison to other existing MASP-1/2 structures. Rigidified backbone structure has long been…
A Cell-Free Assay for Rapid Screening of Inhibitors of hACE2-Receptor-SARS-CoV-2-Spike Binding - We present a cell-free assay for rapid screening of candidate inhibitors of protein binding, focusing on inhibition of the interaction between the SARS-CoV-2 Spike receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2). The assay has two components: fluorescent polystyrene particles covalently coated with RBD, termed virion- particles (v-particles), and fluorescently labeled hACE2 (hACE2F) that binds the v-particles. When incubated with an inhibitor, v-particle-hACE2F…
Dichlorophenylpyridine-Based Molecules Inhibit Furin through an Induced-Fit Mechanism - Inhibitors of the proprotein convertase furin might serve as broad-spectrum antiviral therapeutics. High cellular potency and antiviral activity against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported for (3,5-dichlorophenyl)pyridine-derived furin inhibitors. Here we characterized the binding mechanism of this inhibitor class using structural, biophysical, and biochemical methods. We established a MALDI-TOF-MS-based furin activity assay, determined IC(50) values, and…
Antifungal Activity of Fibrate-Based Compounds and Substituted Pyrroles That Inhibit the Enzyme 3-Hydroxy-methyl- glutaryl-CoA Reductase of Candida glabrata (CgHMGR), Thus Decreasing Yeast Viability and Ergosterol Synthesis - Due to the emergence of multidrug-resistant strains of yeasts belonging to the Candida genus, there is an urgent need to discover antifungal agents directed at alternative molecular targets. The aim of the current study was to evaluate the capacity of three different series of synthetic compounds to inhibit the Candida glabrata enzyme denominated 3-hydroxy- methyl-glutaryl-CoA reductase and thus affect ergosterol synthesis and yeast viability. Compounds 1c (α-asarone-related) and 5b (with a…
Large thrombus in transit in a COVID-19 patient - The course of COVID-19 patients may be complicated by thromboembolic events. We report on a 48-year-old female COVID-19 patient who underwent surgical removal of a large intracardiac thrombus. As per our centre protocol, critically ill COVID-19 patients are anticoagulated by the direct thrombin inhibitor Argatroban with close monitoring of anti-IIa activity. An intra-atrial thrombus formation fixed in a patent foramen ovale but also large mobile portions in both atria was diagnosed 4 days after…
A Spike Protein-Based Subunit SARS-CoV-2 Vaccine for Pets: Safety, Immunogenicity, and Protective Efficacy in Juvenile Cats - Whereas, multiple vaccine types have been developed to curb the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) among humans, there are very few vaccines being developed for animals including pets. To combat the threat of human-to-animal, animal-to-animal, and animal-to-human transmission and the generation of new virus variants, we developed a subunit SARS-CoV-2 vaccine which is based on the recombinant spike protein extracellular domain expressed in insect cells and then…
Host Cell Glycocalyx Remodeling Reveals SARS-CoV-2 Spike Protein Glycomic Binding Sites - Glycans on the host cell membrane and viral proteins play critical roles in pathogenesis. Highly glycosylated epithelial cells represent the primary boundary separating embedded host tissues from pathogens within the respiratory and intestinal tracts. SARS-CoV-2, the causative agent for the COVID-19 pandemic, reaches into the respiratory tract. We found purified human milk oligosaccharides (HMOs) inhibited the viral binding on cells. Spike (S) protein receptor binding domain (RBD) binding to…
Multiple SARS-CoV-2 Variants Exhibit Variable Target Cell Infectivity and Ability to Evade Antibody Neutralization - The continuous emergence of SARS-coronavirus 2 (SARS-CoV-2) variants, especially the variants of concern (VOC), exacerbated the impact of the coronavirus disease 2019 (COVID-19) pandemic. As the key of viral entry into host cells, the spike (S) protein is the major target of therapeutic monoclonal antibodies (mAbs) and polyclonal antibodies elicited by infection or vaccination. However, the mutations of S protein in variants may change the infectivity and antigenicity of SARS-CoV-2, leading to…
Interdisciplinarity for social justice enterprise: intersecting education, industry and community arts perspectives - The role of interdisciplinarity in achieving authentic and transformative learning outcomes is both contested and complex. At the same time, traditional disciplinary ways of being, doing and knowing have been further tested by the impact of COVID-19 on students, schools and communities. In Tasmania, already experiencing amongst the lowest levels of educational attainment in Australia, the educational implications of COVID-19 have been polarising. Preliminary reports have employed…
Biological Activities of Some Natural Compounds and Their Cytotoxicity Studies against Breast and Prostate Cancer Cell Lines and Anti-COVID19 Studies - In this study, we investigated the inhibition effects of matairesinol, pregnanolone, hamamelitannin, secoisolariciresinol, and secoisolariciresinol diglicoside compounds on HMG-CoA reductase and urease enzymes. We have obtained results for the HMG-CoA reductase enzyme at the millimolar level, and for the urease enzyme at the micromolar level. Molecular docking calculations were made for their biological activities were compared. In docking calculations, proteins of experimentally used enzymes,…
Isotyping and quantitation of the humoral immune response to SARS-CoV-2 - Understanding the immune response to SARS-CoV-2 is important for development of effective diagnostics and vaccines. We report here a broad antibody response to SARS-CoV-2 spike protein receptor binding domain (RBD) in 100 convalescent patient plasma samples. Antibody isotypes IgA, IgM, and IgG exhibited significantly higher anti-RBD titers when compared to SARS-CoV-2 negative controls. IgG subtyping indicated IgG1 and IgG3 to be most abundant. Greater than 90 % of SARS- CoV-2 positive plasma…
Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro - This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA- dependent RNA polymerase) and 3CL…
MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link
CBD Covid 19 Protection - - link
沼泽红假单胞菌5-氨基乙酰丙酸合成酶突变体及应用 - 本发明公开了沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体及应用，所述沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体的氨基酸序列如SEQ ID NO.1所示。本发明的沼泽红假单胞菌5‑氨基乙酰丙酸合成酶突变体不仅相较于未突变的5‑氨基乙酰丙酸合成酶提高了酶活性，而且还提高了解调较高浓度血红素反馈抑制的能力，这使得本发明的宿主细胞生产5‑ALA的能力得到显著提升，约提升了40%。 - link
荚膜红细菌5-氨基乙酰丙酸合成酶突变体及应用 - 本发明提供了一种荚膜红细菌5‑氨基乙酰丙酸合成酶突变体及应用，荚膜红细菌5‑氨基乙酰丙酸合成酶突变体的氨基酸序列如SEQ ID NO.1所示。本发明的荚膜红细菌5‑氨基乙酰丙酸合成酶突变体与野生型的荚膜红细菌5‑氨基乙酰丙酸合成酶相比，在宿主细胞中对5‑氨基乙酰丙酸产量提升约22%；在20μM血红素存在下，突变型5‑氨基乙酰丙酸合成酶C201A能够保持较高的相对酶活。 - link
METHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGES - ABSTRACTMETHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGESThe present invention provides a new approach is proposed that includes fuzzy-based approach and similarity function for filtering the mixed noise. In a peer group, the similarity function was adaptive to edge information and local noise level, which was utilized for detecting the similarity among pixels. In addition, a new filtering method Modified Trilateral Filter (MTF) with Improved Generalized Fuzzy Peer Group (IGFPG) is proposed to remove mixed impulse and Adaptive White Gaussian Noise from Color Images. The modified trilateral filter includes Kikuchi algorithm and loopy belief propagation to solve the inference issues on the basis of passing local message. In this research work, the images were collected from KODAK dataset and a few real time multimedia images like Lena were also used for testing the effectiveness of the proposed methodology. - link
一种病毒核酸提取无醇裂解液、试剂盒及提取方法 - 本发明公开了一种病毒核酸提取无醇裂解液、试剂盒及提取方法。本发明病毒核酸提取无醇裂解液由胍盐、无机盐、表面活性剂和缓冲液组成；所述胍盐为异硫氰酸胍和盐酸胍中的任一种或两种；所述无机盐为氯化钠和氯化钾中的任一种或两种；所述表面活性剂为聚乙二醇和吐温20；所述缓冲液的pH值为7.5~8.5。本发明可有效避免传统核酸提取裂解液中醇类挥发或刺激性气味对人体造成伤害；配制方法简单，无有毒化学试剂，安全无污染，既可手工操作提取，也可用于自动化平台；与有醇裂解液相比，病毒核酸检测的灵敏度相当，准确度一致，线性范围相当。 - link
用于预防SARS-CoV-2奥密克戎株的腺病毒载体疫苗 - 本发明涉及用于预防SARS‑CoV‑2奥密克戎株的腺病毒载体疫苗。本发明采用密码子偏好性进行优化得到新的S基因序列，其能高效在人源细胞内高效表达，免疫机体后可高效表达S抗原，产生针对奥密克戎株SARS‑CoV‑2的中和抗体，可以有效保护机体免受奥密克戎株的侵染。 - link
表达SARS-CoV-2奥密克戎突变株病毒抗原肽的核酸序列及其应用 - 本发明提供表达SARS‑CoV‑2奥密克戎突变株病毒抗原肽的核酸序列及其应用。奥密克戎株原始的S基因序列蛋白不能有效在细胞内高效表达；本发明采用密码子偏好性进行优化得到新的S基因序，使其能高效在人源细胞内高效表达，产生相应的多肽，诱导产生相应的免疫保护反应，为SARS‑CoV‑2奥密克戎株的疫苗的研发提供基础。 - link
A STUDY ON MENTAL HEALTH, STRESS AND ANXIETY AMONG COLLEGE STUDENTS DURING COVID-19 - SARS-Cov-2 virus causes an infectious disease coronavirus(COVID-19).The Students life is made harder by COVID-19.The human reaction that happens normally to everyone through physical or emotional tension is stress. Feeling of angry, nervous and frustration caused through any thought or events leads to stress. As college closures and cancelled events, students are missing out on some of the biggest moments of their young lives as well as everyday moments like chatting with friend, participating in class and cultural programme. For students facing life changes due to the outbreak are feeling anxious, isolated and disappointed which lead them to feel all alone. We like to take the help of expert adolescent psychologist to find out the techniques to practice self-care and look after their mental health. We would like to find out whether techniques used reduce the anxiety and stress among Engineering Students. - link
A METHOD FOR THE TREATMENT OF COVID-19 INFECTIONS WITH PALMITOYLETHANOLAMIDE - - link