Accurately estimating relative transmission rates of SARS-CoV-2 Variant of Concern and Variant of Interest viruses remains a scientific and public health priority. Recent studies have used the sample proportions of different variants from sequence data to describe variant frequency dynamics and relative transmission rates, but frequencies alone cannot capture the rich epidemiological behavior of SARS-CoV-2. Here, we extend methods for inferring the effective reproduction number of an epidemic using confirmed case data to jointly estimate variant-specific effective reproduction numbers and frequencies of co-circulating variants using case data and genetic sequences across states in the US from January to October 2021. Our method can be used to infer structured relationships between effective reproduction numbers across time series which may be amendable to various analyses including other features related to the effective reproductive number such as non-pharmaceutical interventions or build up of population immunity. We use this model to estimate the effective reproduction number of SARS-CoV-2 Variants of Concern and Variants of Interest in the United States and estimate consistent growth advantages of particular variants across different locations.
Background: Vaccine mandates and vaccine passports (VMVP) for SARS-CoV-2 are thought to be a path out of the pandemic by increasing vaccination through coercion and excluding unvaccinated people from different settings because they are viewed as being at significant risk of transmitting SARS-CoV-2. While variants and waning efficacy are relevant, SARS-CoV-2 vaccines reduce the risk of infection, transmission, and severe illness/hospitalization in adults. Thus, higher vaccination levels are beneficial by reducing healthcare system pressures and societal fear. However, the benefits of excluding unvaccinated people are unknown. Methods: A method to evaluate the benefits of excluding unvaccinated people to reduce transmissions is described, called the number needed to exclude (NNE). The NNE is analogous to the number needed to treat (NNT=1/ARR), except the absolute risk reduction (ARR) is the baseline transmission risk in the population for a setting (e.g., healthcare). The rationale for the NNE is that exclusion removes all unvaccinated people from a setting, such that the ARR is the baseline transmission risk for that type of setting, which depends on the secondary attack rate (SAR) typically observed in that type of setting and the baseline infection risk in the population. The NNE is the number of unvaccinated people who need to be excluded from a setting to prevent one transmission event from unvaccinated people in that type of setting. The NNE accounts for the transmissibility of the currently dominant Delta (B.1.617.2) variant to estimate the minimum NNE in six types of settings: households, social gatherings, casual close contacts, work/study places, healthcare, and travel/transportation. The NNE can account for future potentially dominant variants (e.g., Omicron, B.1.1.529). To assist societies and policymakers in their decision-making about VMVP, the NNEs were calculated using the current (mid- to-end November 2021) baseline infection risk in many countries. Findings: The NNEs suggest that at least 1,000 unvaccinated people likely need to be excluded to prevent one SARS-CoV-2 transmission event in most types of settings for many jurisdictions, notably Australia, California, Canada, China, France, Israel, and others. The NNEs of almost every jurisdiction examined are well within the range of the NNTs of acetylsalicylic acid (ASA) in primary prevention of cardiovascular disease (CVD) (≥ 250 to 333). This is important since ASA is not recommended for primary prevention of CVD because the harms outweigh the benefits. Similarly, the harms of exclusion may outweigh the benefits. These findings depend on the accuracy of the model assumptions and the baseline infection risk estimates. Conclusions: Vaccines are beneficial, but the high NNEs suggest that excluding unvaccinated people has negligible benefits for reducing transmissions in many jurisdictions across the globe. This is because unvaccinated people are likely not at significant risk — in absolute terms — of transmitting SARS-CoV-2 to others in most types of settings since current baseline transmission risks are negligible. Consideration of the harms of exclusion is urgently needed, including staffing shortages from losing unvaccinated healthcare workers, unemployment/unemployability, financial hardship for unvaccinated people, and the creation of a class of citizens who are not allowed to fully participate in many areas of society.
Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in- hospital mortality. Unbiased proteomics using longitudinally collected biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using longitudinal measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 upregulated and 40 downregulated proteins associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. Using longitudinal clinical and proteomic data, our results suggest that while both acute and long-term COVID- associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.
It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic coronavirus infections from 2011-2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Respiratory samples were collected from participants that met testing criteria and blood samples were collected annually. Respiratory samples were tested for each of the endemic coronaviruses from 2011-2016 and for SARS- CoV-2 from 2020-2021 via rt-PCR. 2021 blood samples were tested for SARS-CoV-2 antibodies and a subset of 2011-2016 blood samples from four-years-old participants were tested for endemic coronavirus antibodies. By April 2021, 854 (49%) active participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic coronavirus infections from 2011-2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic coronavirus infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.
Abstract Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The ability of antibody-based therapies, including convalescent plasma, to affect established disease remains to be elucidated. Only few monoclonal therapies and only when used at a very early stage of infection have shown efficacy. Here, we conducted a proof-of-principle study of convalescent plasma therapy in a phase I trial in 30 COVID-19 patients including immunocompromised individuals hospitalized early after onset of symptoms. A comprehensive longitudinal monitoring of the virologic, serologic, and disease status of recipients in conjunction with detailed post-hoc seroprofiling of transfused convalescent plasma, allowed deciphering of parameters on which plasma therapy efficacy depends. Plasma therapy was safe and had a significant effect on viral clearance depending on neutralizing and spike SARS-CoV-2 antibody levels in the supplied convalescent plasma. Endogenous immunity had strong effects on virus control. Lack of endogenous neutralizing activity at baseline was associated with a higher risk of systemic viremia. The onset of endogenous neutralization had a noticeable effect on viral clearance but, importantly, even after adjusting for their endogenous neutralization status recipients benefitted from therapy with high neutralizing antibody containing plasma. In summary, our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia in the early stages of infection and provide directions for improved efficacy evaluation of current and future SARS-CoV-2 therapies beyond antibody-based interventions. Incorporating an assessment of the endogenous immune response and its dynamic interplay with viral production is critical for determining therapeutic effects.
Mucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.
The aim of this study was to identify the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n=583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021.Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS- CoV-2 infection even amongst children.
Importance: Understanding how SARS-CoV-2 seroprevalence varies regionally across California is critical to the public health response to the pandemic. Objective: To estimate how many Californians have antibodies against SARS-CoV-2 from prior infection or vaccination. Design: Wave 1 of CalScope: a repeated cross-sectional serosurvey of adults and children enrolled between April 20, 2021 and June 16, 2021. Setting: A population-based random sample of households in seven counties in California (Alameda, El Dorado, Kern, Los Angeles, Monterey, San Diego, and Shasta) were invited to complete an at-home SARS-CoV-2 antibody test and survey instrument. Participants: Invitations were sent to 200,000 randomly selected households in the seven counties. From each household, 1 adult (18 years and older) and 1 child (aged 6 months to 17 years) could enroll in the study. There were no exclusion criteria. Main Outcome(s) and Measures: All specimens were tested for antibodies against the nucleocapsid and spike proteins of SARS-CoV-2. The primary outcome was serostatus category, which was determined based on antibody test results and self-reported vaccination status: seronegative, antibodies from infection only, antibodies from infection and vaccination, and antibodies from vaccination alone. We used inverse probability of selection weights and iterative proportional fitting to account for non-response. Results: 11,161 households enrolled in wave 1 of CalScope, with 7,483 adults and 1,375 children completing antibody testing. As of June 2021, 27% (95%CI [23%, 31%]) of adults and 30% (95%CI [24%, 36%]) of children had evidence of prior SARS-CoV-2 infection; 33% (95%CI [28%, 37%]) of adults and 57% (95%CI [48%, 66%]) of children were seronegative. Serostatus varied regionally. Californians 65 years or older were most likely to have antibodies from vaccine alone (59%; 95%CI [48%, 69%]) and children between 5-11 years old were most likely to have antibodies from prior infection alone (36%; 95%CI [21%, 52%]). Conclusions and Relevance: As of June 2021, a third of adults in California and most children under 18 remained seronegative. Seroprevalence varied regionally and by demographic group, suggesting that some regions or populations might remain more vulnerable to subsequent surges than others.
Albeit the efficacy of COVID-19 vaccines in immunocompromised patients is undermined, it is still found beneficial. Patients with cancer have a much lower COVID- 19 vaccination rate globally, and the vaccination coverage in breast cancer patients in China remains elusive. A total of 23029 patients with benign breast diseases and breast cancers were included in the study, and the vaccination rates of patients with benign breast tumors and other benign breast diseases, nonmetastatic and metastatic breast cancer were 44.0%, 54.7%, 19.2% and 9.6%, respectively. Breast cancer in situ patients had a similar vaccination rate with patients with benign breast tumors (45.9% vs 44.0%) while those with invasive breast cancer had much lower vaccination rates. The overall vaccination rate remains meager in breast cancer patients, and gap was found in patients with lower clinical stage. Hence vaccination should be further promoted among patients with benign breast diseases and breast cancer.
The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease. While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.
Due to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS- CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern.
Abstract Objectives This study aims to estimate the prevalence and longevity of detectable SARS-CoV-2 antibodies as well as T and B memory cells during infection with SARS-CoV-2 and after recovery. In addition, prevalence of COVID-19 reinfection, and the preventive efficacy of previous infection with SARS-CoV-2 were investigated. Methods and analyses A synthesis of existing research was conducted. The Cochrane Library for COVID-19 resources, the China Academic Journals Full Text Database, PubMed, and Scopus as well as preprint servers were searched for studies conducted between 1 January 2020 to 1 April 2021. We included studies with the relevant outcomes of interest. All included studies were assessed for methodological quality and pooled estimates of relevant outcomes were obtained in a meta-analysis using a bias adjusted synthesis method. Proportions were synthesized with the Freeman-Tukey double arcsine transformation and binary outcomes using the odds ratio (OR). Heterogeneity between included studies was assessed using the I2 and Cochrans Q statistics and publication bias was assessed using Doi plots. Results Fifty-four studies, from 18 countries, with around 12 000 000 individuals, followed up to 8 months after recovery were included. At 6-8 months after recovery, the prevalence of SARS-CoV-2 specific immunological memory remained high; IgG 90.4% (95%CI 72.2 to 99.9, I2=89.0%, 5 studies), CD4+ 91.7% (95%CI 78.2 to 97.1, one study), and memory B cells 80.6% (95%CI 65.0 to 90.2, one study) and the pooled prevalence of reinfection was 0.2% (95%CI 0.0 to 0.7, I2 = 98.8, 9 studies). Individuals previously infected with SARS-CoV-2 had an 81% reduction in odds of a reinfection (OR 0.19, 95% CI 0.1 to 0.3, I2 = 90.5%, 5 studies). Conclusion Around 90% of people previously infected with SARS-CoV-2 had evidence of immunological memory to SARS-CoV-2, which was sustained for at least 6-8 months after recovery, and had a low risk of reinfection.
Background Non-random selection into analytic subsamples could introduce selection bias in observational studies of SARS-CoV-2 infection and COVID-19 severity (e.g. including only those have had a COVID-19 PCR test). We explored the potential presence and impact of selection in such studies using data from self-report questionnaires and national registries. Methods Using pre-pandemic data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (mean age=27.6 (standard deviation [SD]=0.5); 49% female) and UK Biobank (UKB) (mean age=56 (SD=8.1); 55% female) with data on SARS-CoV-2 infection and death-with-COVID-19 (UKB only), we investigated predictors of selection into COVID-19 analytic subsamples. We then conducted empirical analyses and simulations to explore the potential presence, direction, and magnitude of bias due to selection when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19. Results In both ALSPAC and UKB a broad range of characteristics related to selection, sometimes in opposite directions. For example, more educated participants were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB. We found bias in many simulated scenarios. For example, in one scenario based on UKB, we observed an expected odds ratio of 2.56 compared to a simulated true odds ratio of 3, per standard deviation higher BMI. Conclusion Analyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depends on the outcome definition, the true effect of the risk factor, and the assumed selection mechanism.
Genes with moderate to low expression heritability may explain a large proportion of complex trait heritability, but these genes are insufficiently captured in transcriptome-wide association studies (TWAS) partly due to the relatively small available reference datasets for developing expression genetic prediction models to capture the moderate to low genetically regulated components of gene expression. Here, we introduce a new method, Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction model accuracy and the power of TWAS by using a large expression quantitative trait loci (eQTL) summary-level dataset. We applied SUMMIT to the eQTL summary-level data provided by the eQTLGen consortium, which involve 31,684 blood samples from 37 cohorts. Through simulation studies and analyses of GWAS summary statistics for 24 complex traits, we show that SUMMIT substantially improves the accuracy of expression prediction in blood, successfully builds expression prediction models for genes with low expression heritability, and achieves higher statistical power than several benchmark methods. In the end, we conducted a case study of COVID-19 severity with SUMMIT and identified 11 likely causal genes associated with COVID-19 severity.
Australian Phase 2/3b Study to Assess Effectiveness of a Protein-based Covid-19 Vaccine (Spikogen) - Condition: COVID-19
Intervention: Biological: Spikogen/Covax-19
Sponsors:
Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute; Cinnagen
Not yet recruiting
COVID-19 Administration of Single-Dose Subcutaneous Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition: COVID-19
Intervention: Drug: casirivimab+imdevimab
Sponsor:
Regeneron Pharmaceuticals
Recruiting
GlowTest COVID-19 Antigen Home Test Kit QRI Use Study - Condition: Covid 19
Intervention: Diagnostic Test: GlowTest COVID-19 Antigen Home Test
Sponsors: Arion Bio; CSSi Life Sciences
Not yet recruiting
Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC] - Condition: COVID-19
Interventions: Biological: Homologous mRNA booster vaccine; Biological: Heterologous mRNA booster vaccine; Biological: Non-mRNA booster vaccine A; Biological: Non- mRNA booster vaccine B; Biological: Non-mRNA booster vaccine C
Sponsors: Tan Tock Seng Hospital; A*Star; Duke-NUS Graduate Medical School; KK Women’s and Children’s Hospital
Recruiting
Study of GRT-R910 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Boost Vaccine in Healthy Volunteers - Condition: COVID-19
Interventions: Biological: GRT-R910 booster 113 days after prime; Biological: GRT-R910 booster 28 days after prime
Sponsor: Gritstone Oncology, Inc.
Recruiting
Safety and Immunogenicity of COVID-19 Vaccine, Inactivated in Healthy Population Aged From 3 to 11 Years - Condition: COVID-19
Intervention: Biological: COVID-19 Vaccine,Inactivated
Sponsor: Sinovac Biotech Co., Ltd
Not yet recruiting
Study of Immunogenicity Equivalence of a Homologous Third Dose of Covid-19 (Recombinante) Vaccine - Condition: COVID-19
Intervention: Biological: Covid -19 (recombinante) vaccine
Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
Recruiting
Study to Evaluate the Safety and Efficacy of a Monoclonal Antibody Cocktail for the Prevention of COVID-19 - Condition: COVID-19
Interventions: Drug: ADM03820; Other: Placebo
Sponsors:
Ology Bioservices; Enabling Biotechnologies (EB)
Not yet recruiting
Communities Fighting COVID-19! - Condition: Covid19
Interventions: Other: COVID-19 Testing Home-based (Aim 1); Other: COVID-19 Testing Mobile (Aim 1); Other: COVID-19 Testing Mobile Approach 1 (Aim 2); Other: COVID-19 Testing Mobile Approach 2 (Aim 2)
Sponsors: San Diego State University; National Cancer Institute (NCI)
Recruiting
Usefulness of DORNASE in COVID-19 on HFNO - Condition: COVID-19 Pneumonia
Intervention: Procedure: inhalations
Sponsor:
University Medical Centre Ljubljana
Not yet recruiting
Communities Fighting COVID Return to School - Condition: COVID-19
Interventions: Behavioral: At-home COVID-19 testing; Behavioral: Family- based model; Behavioral: Onsite COVID-19 testing
Sponsors: San Diego State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting
Phase Ⅱ and Ⅲ Trial of a SARS-CoV-2 Vaccine LYB001 - Condition: COVID-19
Interventions: Biological: LYB001; Biological: Placebo
Sponsor: Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
The Effect of Micellized Food Supplements on Health-related Quality of Life in Patients With Post-acute COVID-19 Syndrome. - Condition: Post-acute COVID-19 Syndrome
Intervention: Dietary Supplement: Curcumin/Boswellia Serrata/Ascorbic acid mixture
Sponsor: PhysioMetrics
Not yet recruiting
Safety and Immunogenicity of Recombinant Protein RBD Fusion Dimer Vaccine Against the Virus That Cause COVID-19, Known as Severe Acute Respiratoy Syndrome Coronavirus 2 (SARS-CoV-2) - Conditions: COVID-19; SARS-CoV-2 Acute Respiratory Disease
Interventions:
Biological: COVID-19 Vaccine HIPRA; Biological: Cominarty (Pfizer-BioNtech)
Sponsors:
Hipra Scientific, S.L.U; Laboratorios Hipra, S.A.; National Institute of Hygiene and Epidemiology, Vietnam
Recruiting
Virus-inspired hollow mesoporous gadolinium-bismuth nanotheranostics for magnetic resonance imaging-guided synergistic photodynamic-radiotherapy - The anti-tumor efficacy of single photodynamic therapy (PDT) and radiotherapy (RT) has been greatly affected by inadequate tumor uptake of photo/radiation sensitizers, limited laser penetration depth, and radiation sickness caused by high doses of X-rays. Here, we report a biomimetic coronavirus-inspired hollow mesoporous gadolinium/bismuth nanocarrier loaded with a new NIR photosensitizer HB (referred to as HB@VHMBi-Gd) for magnetic resonance imaging (MRI)-guided synergistic photodynamic-RT….
Author Correction: Amantadine inhibits known and novel ion channels encoded by SARS-CoV-2 in vitro - No abstract
The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting - Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral, structural and replicative enzymes that are encoded in an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshift elements and thereby impact virulence. This prompted us to comprehensively dissect the…
Plant lectins as prospective antiviral biomolecules in the search for COVID-19 eradication strategies - Lectins or clusters of carbohydrate-binding proteins of non-immune origin are distributed chiefly in the Plantae. Lectins have potent anti-infectivity properties for several RNA viruses including SARS-CoV-2. The primary purpose of this review is to review the ability of lectins mediated potential biotherapeutic and bioprophylactic strategy against coronavirus causing COVID-19. Lectins have binding affinity to the glycans of SARS-COV-2 Spike glycoprotein that has N-glycosylation sites. Apart from…
A rapid real-time polymerase chain reaction-based live virus microneutralization assay for detection of neutralizing antibodies against SARS-CoV-2 in blood/serum - CONCLUSION: We describe a rapid RT-PCR-based SARS-CoV-2 microneutralization assay for the detection of neutralizing antibodies. This can effectively be used to test the antiviral activity of serum antibodies for the investigation of both disease-driven and vaccine-induced responses.
Unexplained arterial thrombosis: approach to diagnosis and treatment - Arterial thrombotic events in younger patients without a readily apparent etiology present significant diagnostic and management challenges. We present a structured approach to diagnosis with consideration of common causes, including atherosclerosis and embolism, as well as uncommon causes, including medications and substances, vascular and anatomic abnormalities, systemic disorders, and thrombophilias. We highlight areas of management that have evolved within the past 5 years, including the use…
Is pregnancy a risk factor for in-hospital mortality in reproductive-aged women with SARS-CoV-2 infection? A nationwide retrospective observational cohort study - CONCLUSIONS: With the adjustment for intervention that was shown to be an independent factor associated with mortality, pregnancy appeared to have a favorable effect on SARS-CoV-2 infection. Given the immunosuppressed state of pregnancy, this finding is in line with the hypothetical protective role of a weaker immune response that inhibits the production of proinflammatory cytokine. With the adjustment for intervention, pregnancy was found associated with more favorable outcome of COVID-19, in…
A Report on Multi-Target Anti-Inflammatory Properties of Phytoconstituents from Monochoria hastata (Family: Pontederiaceae) - This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (** p < 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter- connected. Therefore, multiple…
Computational Simulation of HIV Protease Inhibitors to the Main Protease (Mpro) of SARS-CoV-2: Implications for COVID-19 Drugs Design - SARS-CoV-2 is highly homologous to SARS-CoV. To date, the main protease (Mpro) of SARS-CoV-2 is regarded as an important drug target for the treatment of Coronavirus Disease 2019 (COVID-19). Some experiments confirmed that several HIV protease inhibitors present the inhibitory effects on the replication of SARS-CoV-2 by inhibiting Mpro. However, the mechanism of action has still not been studied very clearly. In this work, the interaction mechanism of four HIV protease inhibitors Darunavir…
Involvement of the ACE2/Ang-(1-7)/MasR Axis in Pulmonary Fibrosis: Implications for COVID-19 - Pulmonary fibrosis is a chronic, fibrotic lung disease affecting 3 million people worldwide. The ACE2/Ang-(1-7)/MasR axis is of interest in pulmonary fibrosis due to evidence of its anti-fibrotic action. Current scientific evidence supports that inhibition of ACE2 causes enhanced fibrosis. ACE2 is also the primary receptor that facilitates the entry of SARS-CoV-2, the virus responsible for the current COVID-19 pandemic. COVID-19 is associated with a myriad of symptoms ranging from asymptomatic…
Development of a PROTAC-Based Targeting Strategy Provides a Mechanistically Unique Mode of Anti-Cytomegalovirus Activity - Human cytomegalovirus (HCMV) is a major pathogenic herpesvirus that is prevalent worldwide and it is associated with a variety of clinical symptoms. Current antiviral therapy options do not fully satisfy the medical needs; thus, improved drug classes and drug-targeting strategies are required. In particular, host-directed antivirals, including pharmaceutical kinase inhibitors, might help improve the drug qualities. Here, we focused on utilizing PROteolysis TArgeting Chimeras (PROTACs), i.e.,…
Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment - Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In…
The Impact of COVID-19 Pandemic on Management and Outcome in Patients with Heart Failure - CONCLUSIONS: Mortality rates in HF patients infected with COVID-19 were high. The COVID-19 pandemic resulted in the reduced usage of health services but without increased overall mortality.
Prevalence and Outcomes Associated with Hyperuricemia in Hospitalized Patients with COVID-19 - CONCLUSION: In patients admitted to the hospital for COVID-19, higher serum UA levels were independently associated with AKI, MAKE, and in-hospital mortality in a dose-dependent manner. In addition, hyperuricemia was associated with higher procalcitonin and troponin I levels.
Discovery of 9,10-dihydrophenanthrene derivatives as SARS-CoV-2 3CL(pro) inhibitors for treating COVID-19 - The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CL^(pro)) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2…
METHODS OF TREATING SARS-COV-2 INFECTION - - link
REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link
P2P 네트워크를 이용한 내장된 화상회의 시스템 - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - link
A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link
A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link
靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗 - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - link
跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途 - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - link
PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - link
Use of Diminazene Aceturate, Xanthenone, ACE 2 activators or analogs for the Treatment and therapeutic use of COVID-19 on human patients. - - link
ACTIVE RIDER SAFETY SYSTEM FOR TWO WHEELERS - The present invention relates to an active rider safety system for two wheelers comprising, a protective case equipped by a user for riding, where the case is integrated with multiple piezoelectric sensor that determines fastening of the case by user, a processing unit linked to the sensor, where the unit detects absence of case upon fetching data from the sensor below a threshold value and thereby terminates operation of ignition by stopping a coupled motor operated via a radio frequency module, an alcohol detection sensor that detects presence of alcohol and send data to processing unit, a temperature sensor that measures temperature of the user, an accelerometer sensor that activates upon ignition us tuned on to determine presence of a crash and a navigation module that via communication module sends location of user to pre saved users and concerned authorities. - link