Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Alveolar regeneration following viral infection is independent of tuft cells -
  Severe injuries following viral infection cause lung epithelial destruction with the presence of ectopic basal progenitor cells (EBCs), although the exact function of EBCs remains controversial. We and others previously showed the presence of ectopic tuft cells in the disrupted alveolar region following severe influenza infection. Here, we further revealed that the ectopic tuft cells are derived from EBCs. This process is amplified by Wnt signaling inhibition but suppressed by Notch inhibition. Further analysis revealed that p63-CreER labeled population de novo arising during regeneration includes alveolar epithelial cells when Tamoxifen was administrated after viral infection. The generation of the p63-CreER labeled alveolar cells is independent of tuft cells, demonstrating segregated differentiation paths of EBCs in lung repair. EBCs and ectopic tuft cells can also be found in the lung parenchyma post SARS-CoV-2 infection, suggesting a similar response to severe injuries in humans.
  🖺 Full Text HTML: Alveolar regeneration following viral infection is independent of tuft cells
• Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development -
  The SARS-CoV-2 non-structural protein 14 (NSP14) is a dual function enzyme containing an N-terminal exonuclease domain (ExoN) and C-terminal Guanine-N7-methyltransferase (N7-MTase) domain. Both enzymatic activities appear to be essential for the viral life cycle and thus may be targeted for anti-viral therapeutics. NSP14 forms a stable complex with the SARS-CoV-2 zinc binding protein NSP10, and this interaction greatly enhances the nuclease but not the methyltransferase activity. In this study, we have determined the crystal structure of SARS-CoV-2 NSP14 in the absence of NSP10 to 1.7 [A] resolution. Comparisons of this structure with the structure of NSP14/NSP10 complexes solved to date reveal significant conformational changes that occur within the NSP14 ExoN domain upon binding of NSP10, including significant movements and helix to coil transitions that facilitate the formation of the ExoN active site and provide an explanation of the stimulation of nuclease activity by NSP10. Conformational changes are also seen in the MTase active site within a SAM/SAH interacting loop that plays a key role in viral mRNA capping. We have also determined the structure of NSP14 in complex with cap analogue 7MeGpppG, offering new insights into MTase enzymatic activity. We have used our high resolution crystals to perform X-ray fragment screening of NSP14, revealing 72 hits bound to potential sites of inhibition of the ExoN and MTase domains. These structures serve as excellent starting point tools for structure guided development and optimization of NSP14 inhibitors that may be used to treat COVID-19 and potentially other future viral threats.
  🖺 Full Text HTML: Crystal structures and fragment screening of SARS-CoV-2 NSP14 reveal details of exoribonuclease activation and mRNA capping and provide starting points for antiviral drug development
• Heteologous saRNA-Prime, DNA Dual-Antigen-Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies -
  We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (SASA S) delivered by a nano- lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression. The N antigen is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment and increase MHC class I and II stimulation potential. The S sequence in the SASA S vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to increase cross-reactivity across variants. CD-1 mice received vaccination by homologous and heterologous prime > boost combinations. Humoral responses to S were the highest with any regimen including the SASA S vaccine, and IgG bound to wild type and Delta (B.1.617.2) variant S1 at similar levels. An AdS+N boost of an SASA S prime particularly enhanced both CD4+ and CD8+ T-cell responses to both wild type and Delta S peptides relative to all other vaccine regimens. Sera from mice receiving SASA S homologous or heterologous vaccination were found to be highly neutralizing of all pseudovirus strains tested: Wuhan, Beta, Delta, and Omicron strain. The findings here support the clinical testing of heterologous vaccination by an SASA S > AdS+N regimen to provide increased protection against emerging SARS-CoV-2 variants.
  🖺 Full Text HTML: Heteologous saRNA-Prime, DNA Dual- Antigen-Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies
• Mawazo Institute 2021 COVID-19 Follow-Up Survey Report -
  This report draws on a survey conducted in 2021 by the Mawazo Institute, a nonprofit research institute based in Nairobi, Kenya. The survey aimed to determine the lasting impact of the COVID-19 pandemic on Africa’s higher education and research sector in the year after lockdowns and restrictions first began, and thus to provide a more comprehensive follow up to an earlier Mawazo Institute survey conducted in 2020. Full findings, along with an interactive map displaying regional differences in key results, are available at https://mawazoinstitute.org/publications.
  🖺 Full Text HTML: Mawazo Institute 2021 COVID-19 Follow-Up Survey Report
• Innate immune response and distinct metabolomic signatures together drive and shape the SARS-CoV-2-specific T cell response during COVID-19 -
  The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell response during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-4, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients who got infected with ancestral virus. We observed the induction of anti-RBD and SARS-CoV-2 neutralizing antibodies together with antigen-specific T cell responses as early as 0-4 days post- infection. T cell responses were largely preserved against the delta and omicron variants as compared to the ancestral strain. We determined innate immune responses at an early (days 0-4 post-COVID-19 positivity) time point of active infection in response to TLR 3/7/8 mediated activation. Interestingly, the innate immune response exhibited by the elevated levels of IL-6, IL-1{beta}, and IL-23 correlated with a robust SARS-CoV-2-specific Th1 response at the later time point (14-16 days post covid positivity). To further understand the association of metabolic pathways induced upon active COVID-19 infection with innate and T cell response, metabolomic profiling was performed. As compared to healthy individuals, COVID-19 patients displayed a distinct metabolic signature with an enrichment of pyroglutamate, itaconate, and azelaic acid, which correlated with the SARS-CoV-2-induced innate and T cells response. Our observations reveal mechanisms and potential interventional approaches that may assist in COVID-19 therapeutics and vaccine adjuvant strategies.
  🖺 Full Text HTML: Innate immune response and distinct metabolomic signatures together drive and shape the SARS-CoV-2-specific T cell response during COVID-19
• Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19 -

  As a novel approach we will combine trajectories or longitudinal studies of gene expression with information on annual influenza epidemics. Seasonality of gene expression in immune cells from blood could be a consequence of within- host seasonal immunity interacting with the seasonal pandemics of influenza (flu) in temperate regions and, thus, with potential valuable analogy transfer to the proposed seasonal development of covid-19. Here we operationalized within- host immunity as genes with both a significant seasonal term and a significant flu term in the sine-cosine model. Information on gene expression was based on microarray using RNase buffered blood samples collected randomly from a population-based cohort of Norwegian middle-aged women in 2003-2006, The Norwegian Women and Cancer (NOWAC) study. The unique discovery (N=425) and replication (N=432) design were based on identical sampling and preprocessing. Data on proportion of sick leaves due to flu, and the flu intensities per week was obtained from the National Institute of Public Health, giving a semi-ecological analysis. The discovery analysis found 2942 (48.1%) significant genes in a generalized seasonal model over four years. For 1051 within-host genes both the seasonal and the flu term were significant. These genes followed closely the flu intensities. The trajectories showed slightly more genes with a maximum in early winter than in late summer. Moving the flu intensity forward in time indicated a better fit 3-4 weeks before the observed influenza. In the replication analyses, 369 genes (35.1% of 1051) were significant. Exclusion of genes with unknown functions and with more than a season in difference reduced the number of genes in the discovery dataset to 305, illustrating the variability in the measurements and the problem in assessing weak biological relationships. Thus, we found for the first time a clear seasonality in gene expression with marked responses to the annual seasonal influenza in a unique discovery - replication design. Hypothetically, this could support the within-host seasonal immunity concept.

  🖺 Full Text HTML: Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19
• Understanding a national increase in COVID-19 vaccination intention: a mixed methodological approach -
  Recently the Netherlands saw a substantial increase in pro-COVID-19 vaccination intention (48 to 75%). Using qualitative methods we identified vaccination beliefs and contextual factors informing this increase. Quantitative methods confirm that intentions were a function of beliefs: people with stronger intention to vaccinate were motivated most by protecting others and reopening society, those reluctant were mostly concerned by (unknown long-term) side effects. We demonstrate that belief shifts track intentional shifts, and offer insights for improving pro-vaccination campaigns.
  🖺 Full Text HTML: Understanding a national increase in COVID-19 vaccination intention: a mixed methodological approach
• Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia -

  Purpose: We quantified changes in dispensing of common medicines proposed for 9re-purposing9 due to their perceived benefits as therapeutic or preventive treatments for COVID-19 in Australia, a country with relatively low COVID-19 incidence in 2020. Methods: We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidised medicines proposed for re- purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) and compared characteristics of initiators in 2020 and 2019. Results: In March 2020, we observed a 99% (95%CI 96%-103%) increase in hydroxychloroquine dispensing (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in April through November 2020. Conclusions: Most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users. However, we observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns, indicating that a small proportion may be COVID-19 related. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.

  🖺 Full Text HTML: Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia
• Is virtual care the new normal? Evidence supporting Covid-19’s durable transformation on healthcare delivery -

  Objective: Despite the surge of telemedicine use during the early stages of the coronavirus-19 (COVID-19) pandemic, research has not evaluated the extent to which the growth of telemedicine has been sustained during recurring pandemic waves. This study provides data on the long-term durability of video-based telemedicine visits and their impact on urgent and non-urgent healthcare delivery from one large health system in New York City. Materials and Methods: Electronic health record (EHR) data of patients between January 1st, 2020 and November 30th, 2021 were used to conduct the analyses and longitudinal comparisons of telemedicine or in-person visit volumes. Patient diagnosis data were used to differentiate COVID-19 suspected visits from non-COVID-19 ones while comparing the visit types. Results: While COVID-19 prompted an increase in telemedicine visits and a simultaneous decline in in-person clinic visits, telemedicine use has stabilized since then for both COVID-19 and non-COVID suspected visits. For COVID-19 suspected visits, utilization of virtual urgent care facilities is higher than the trend. The data further suggests that virtual healthcare delivery supplements, rather than replaces, in-person care. Discussion: The COVID-19 pandemic has transformed the use of telemedicine as a means of healthcare delivery, and the data presented here suggests that this is an enduring transformation. Conclusion: Telemedicine use increased with the surge of infection cases during the pandemic, but evidence suggests that it will persist after the pandemic, especially for younger patients, for both urgent and non- urgent care. These findings have implications for the healthcare delivery system, insurers and policymakers.

• Real world performance of inactivated SARS-CoV-2 vaccine (CoronaVac) against infection, hospitalization and death due to COVID-19 in adult population in Indonesia -

  Background: Inactivated SARS-CoV-2 vaccine has been included in the national COVID-19 vaccination program in Indonesia since January 2021. The study aims to assess the impacts of inactivated COVID-19 vaccine on infection, hospitalization, and death among adult population aged ≥18 years in Bali, Indonesia. Methods: Test-negative, case control study was conducted by linking SARS-CoV-2 laboratory records, vaccination, and health administrative data for the period of January 13 to June 30, 2021. Case-subjects were defined as individuals who had a positive RT-PCR test for SARS-CoV-2 during the period; they were matched with controls (tested negative) (1:1) based on age, sex, district of residence, and week of testing. We estimated the odds of vaccination in PCR confirmed, hospitalization and death due to COVID-19, accounting for the presence of comorbidities and prior infection. Vaccine effectiveness was estimated as (1-odds ratio) x 100%. Results: Total 109,050 RT-PCR test results were retrieved during the January 13 to June 30, 2021. Of these, 14,168 subjects were eligible for inclusion in the study. Total 5518 matched case-control pairs were analyzed. Adjusted vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection was 14.5% (95% confidence interval -11 to 34.2) at 0-13 days after the first dose; 66.7% (95% CI: 58.1- 73.5) at ≥14 days after the second dose. The adjusted effectiveness against hospitalization and COVID-19-associated death was 71.1% (95% CI: 62.9-77.6) and 87.4% (95% CI: 65.1-95.4%) at ≥14 days after receiving the second dose, respectively. Conclusions: Two- dose of inactivated CoronaVac vaccine showed high effectiveness against laboratory confirmed COVID-19 infection, hospitalization, and death associated with COVID-19 among adults aged ≥18 years.

  🖺 Full Text HTML: Real world performance of inactivated SARS-CoV-2 vaccine (CoronaVac) against infection, hospitalization and death due to COVID-19 in adult population in Indonesia
• Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping -

  Accurate tracing of epidemic spread over space enables effective control measures. We examined three metrics of infection and disease in a pediatric cohort (N=3,000) over two chikungunya and one Zika epidemic, and in a household cohort (N=1,793) over one COVID-19 epidemic in Managua, Nicaragua. We compared spatial incidence rates (cases/total population), infection risks (infections/total population), and disease risks (cases/infected population). We used generalized additive and mixed-effects models, Kulldorf9s spatial scan statistic, and intracluster correlation coefficients. Across different analyses and all epidemics, incidence rates considerably underestimated infection and disease risks, producing large and spatially non-uniform biases distinct from biases due to incomplete case ascertainment. Infection and disease risks exhibited distinct spatial patterns, and incidence clusters inconsistently identified areas of either risk. While incidence rates are commonly used to infer infection and disease risk in a population, we find that this can induce substantial biases and adversely impact policies to control epidemics.

  🖺 Full Text HTML: Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping
• Increased receptor affinity and reduced recognition by specific antibodies contribute to immune escape of SARS-CoV-2 variant Omicron -
  In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by characterization of this variant, and wildtype Wuhan and Delta variant (B.1.617.2). Convalescent sera as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna- mRNA-1273(R) or Pfizer-BNT162b2(R)) were used for comparison in this study. Our data demonstrate that both the Delta as well as Omicron variants exhibit higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not Delta variant escaped antibody recognition, most likely because only Omicron exhibit the mutation at position E484 associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape.
  🖺 Full Text HTML: Increased receptor affinity and reduced recognition by specific antibodies contribute to immune escape of SARS-CoV-2 variant Omicron
• Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial -

  The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP- CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

  🖺 Full Text HTML: Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial
• Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study -

  Background: SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods: Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings: Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid- March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions: Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.

  🖺 Full Text HTML: Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study
• Dissecting the Role of the Human Microbiome in COVID-19 via Metagenome-assembled Genomes -
  Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome- assembled genomes (MAGs) from a total of 514 nasopharyngeal and fecal samples of patients with COVID-19 and controls. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5,403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that, thanks to the high taxonomic resolution of nrMAGs, the gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression. The genomic content of nrMAGs presented here has the potential to inform microbiome-based therapeutic developments for COVID-19 progression and post-COVID conditions.
  🖺 Full Text HTML: Dissecting the Role of the Human Microbiome in COVID-19 via Metagenome-assembled Genomes

From Clinical Trials

• Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Bronchipret
  Sponsors:   Dr. Frank Behrens;   Bionorica SE
  Recruiting

• EPIC-Peds: Study of Oral PF-07321332 (Nirmatrelvir)/Ritonavir in Nonhospitalized COVID-19 Pediatric Patients at Risk for Severe Disease - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir;   Drug: ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• Evaluating Public Health Interventions to Improve COVID-19 Testing Among Underserved Populations - Condition:   COVID-19
  Intervention:   Behavioral: Public Health Intervention Package
  Sponsors:   Kathleen Fairfield;   MaineHealth
  Not yet recruiting

• COVID-19 Serologic Strategies for Skilled Nursing Facilities - Condition:   COVID-19
  Intervention:   Other: Cohorting
  Sponsors:   NYU Langone Health;   Brown University;   National Institute on Aging (NIA)
  Recruiting

• Safety, Tolerability and Immunogenicity of Recombinant COVID-19 Vaccine Betuvax-CoV-2 - Condition:   COVID-19
  Interventions:   Biological: Betuvax-CoV-2;   Drug: Placebo
  Sponsors:   Human Stem Cell Institute, Russia;   Betuvax LLC;   CEG BIO LLC
  Active, not recruiting

• Evaluation of Full Versus Fractional Dose of COVID-19 Vaccine Given as a Booster for the Prevention of COVID 19 in Adults in Mongolia- Mongolia, Indonesia, Australia Coronavirus (MIACoV). - Condition:   COVID-19
  Interventions:   Biological: Tozinameran - Standard Dose;   Biological: Tozinameran - Fractional Dose
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   PATH;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19 - Condition:   COVID-19
  Interventions:   Biological: COVID-19 convalescent and vaccinated plasma;   Other: Current standard of care
  Sponsors:   Centre Hospitalier Universitaire de Besancon;   Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen;   NHS Blood and Transplant
  Not yet recruiting

• Efficacy of TCM Capsules Lian Hua Qing Wen Jiao Nang in Mild COVID-19 Patients - Condition:   COVID-19
  Interventions:   Other: TCM intervention;   Other: Placebo intervention
  Sponsor:   Singapore Chung Hwa Medical Institution
  Not yet recruiting

• **Safety and Immune Response of Adjuvanted SARS-CoV-2 (COVID-19) Beta Variant RBD Recombinant Protein (DoCo-Pro-RBD-1

• MF59®) and mRNA (MIPSCo-mRNA-RBD-1) Vaccines in Healthy Adults** - Condition:   SARS-CoV-2
  Interventions:   Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59);   Biological: SARS-CoV-2 beta variant RBD mRNA vaccine;   Other: Normal Saline
  Sponsors:   University of Melbourne;   Southern Star Research
  Not yet recruiting

• Immuno-bridging and Broadening Study of a Whole, Inactivated COVID-19 Vaccine BBV152 in Healthy Adults - Condition:   COVID-19
  Intervention:   Biological: BBV152
  Sponsor:   Ocugen
  Active, not recruiting

• Self-Management Interventions for Long-COVID - Condition:   COVID-19
  Interventions:   Behavioral: Education and Strategies Intervention;   Behavioral: Mindfulness Skills Intervention
  Sponsors:   Toronto Rehabilitation Institute;   Canadian Institutes of Health Research (CIHR);   University Health Network, Toronto
  Recruiting

• COVID-19 Hyper Coagulability Care by LLLT - Condition:   COVID-19 Pneumonia
  Interventions:   Radiation: Low level laser Therapy;   Other: Circulatory exercises
  Sponsor:   Cairo University
  Recruiting

• The BOOSTED (Booster Options Or Switching Tested for Effectiveness and Downsides Study) Trial (COVID-19) - Conditions:   COVID-19;   Vaccine Reaction;   COVID-19 Pandemic
  Interventions:  
  Behavioral: Moderna Booster Vaccine;   Behavioral: Pfizer Booster Vaccine
  Sponsor:  
  University of California, San Francisco
  Enrolling by invitation

• An Open-label, Randomized, Parallel-arm Study Investigating the Efficacy and Safety of Intravenous Administration of Pamrevlumab Versus Standard of Care in Patients With COVID-19 - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Pneumonia;   Covid19
  Intervention:  
  Drug: Pamrevlumab
  Sponsor:   Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  Completed

• Safety, Reactogenicity, and Immunogenicity Trial of CV2CoV mRNA Vaccine Against SARS-CoV-2 in Seropositive Adult Participants - Condition:   SARS-CoV-2
  Interventions:   Biological: CV2CoV (2 µg);   Biological: CV2CoV (4 µg);   Biological: CV2CoV (8 µg);   Biological: CV2CoV (12 µg);   Biological: CV2CoV (16 µg);   Biological: CV2CoV (20 µg)
  Sponsors:   GlaxoSmithKline;   CureVac AG
  Not yet recruiting

From PubMed

• Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening - Experiments with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited by the need for biosafety level 3 (BSL3) conditions. A SARS-CoV-2 replicon system rather than an in vitro infection system is suitable for antiviral screening since it can be handled under BSL2 conditions and does not produce infectious particles. However, the reported replicon systems are cumbersome because of the need for transient transfection in each assay. In this study, we constructed a bacterial…

• Combined Computational NMR and Molecular Docking Scrutiny of Potential Natural SARS-CoV-2 M(pro) Inhibitors - In continuation of the search for potential drugs that inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this work, a combined approach based on the modeling of NMR chemical shifts and molecular docking is suggested to identify the possible suppressors of the main protease of this virus among a number of natural products of diverse nature. Primarily, with the aid of an artificial neural network, the problem of the reliable determination of the stereochemical structure…

• Anthropometric Parameters, Physical Activity, Physical Fitness, and Executive Functions among Primary School Children - Physical activity during childhood and adolescence favors brain development and cognitive functioning, particularly the executive functions. This study aimed to assess potential associations between anthropometric parameters, physical activity, physical fitness, and executive functions among elementary school children returning to school after the COVID-19 lockdown in Chile. School-age male and female participants (n = 90; age, 10-12 years) participated in the study. To determine the association…

• Agathis robusta Bark Essential Oil Effectiveness against COVID-19: Chemical Composition, In Silico and In Vitro Approaches - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the causative agent of Coronavirus Disease 2019 (COVID-19), has seriously threatened global health. Alongside the approved vaccines, the discovery of prospective anti-COVID-19 drugs has been progressively targeted. Essential oils (EOs) provide a rich source of compounds with valuable antiviral activities that may contribute as effective agents against COVID-19. In this study, the EO of Agathus robusta bark was investigated for its…

• Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors - The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual…

• Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity - The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain…

• Secondary Structure of Influenza A Virus Genomic Segment 8 RNA Folded in a Cellular Environment - Influenza A virus (IAV) is a member of the single-stranded RNA (ssRNA) family of viruses. The most recent global pandemic caused by the SARS-CoV-2 virus has shown the major threat that RNA viruses can pose to humanity. In comparison, influenza has an even higher pandemic potential as a result of its high rate of mutations within its relatively short (<13 kbp) genome, as well as its capability to undergo genetic reassortment. In light of this threat, and the fact that RNA structure is…

• Molecular Mechanisms of Alveolar Epithelial Stem Cell Senescence and Senescence-Associated Differentiation Disorders in Pulmonary Fibrosis - Pulmonary senescence is accelerated by unresolved DNA damage response, underpinning susceptibility to pulmonary fibrosis. Recently it was reported that the SARS-Cov-2 viral infection induces acute pulmonary epithelial senescence followed by fibrosis, although the mechanism remains unclear. Here, we examine roles of alveolar epithelial stem cell senescence and senescence-associated differentiation disorders in pulmonary fibrosis, exploring the mechanisms mediating and preventing pulmonary…

• Screening of Natural Products Inhibitors of SARS-CoV-2 Entry - The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities….

• Virtual Screening of Natural Chemical Databases to Search for Potential ACE2 Inhibitors - The angiotensin-converting enzyme II (ACE2) is a multifunctional protein in both health and disease conditions, which serves as a counterregulatory component of RAS function in a cardioprotective role. ACE2 modulation may also have relevance to ovarian cancer, diabetes, acute lung injury, fibrotic diseases, etc. Furthermore, since the outbreak of the coronavirus disease in 2019 (COVID-19), ACE2 has been recognized as the host receptor of severe acute respiratory syndrome coronavirus 2…

• Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease - A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2’,4’-trihydroxy-6,7,5’-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of…

• Potential “Therapeutic” Effects of Tocotrienol-Rich Fraction (TRF) and Carotene “Against” Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB Signaling Pathways - CONCLUSION: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.

• Development of Eco-Friendly Nanomembranes of Aloe vera/PVA/ZnO for Potential Applications in Medical Devices - Due to the current COVID-19 pandemic, there is a crucial need for the development of antimicrobial and antiviral personal protective equipment such as facemasks and gowns. Therefore, in this research we fabricated electrospun nanofibers composite with polyvinyl alcohol, aloe vera, and zinc oxide nanoparticles for end application in medical devices. Electrospun nanofibers were made with varying concentrations of aloe vera (1%, 2%, 3%, 4%) having a constant concentration of ZnO (0.5%) with varying…

• Novel Antiviral and Antibacterial Durable Polyester Fabrics Printed with Selenium Nanoparticles (SeNPs) - The COVID-19 pandemic has clearly shown the importance of developing advanced protective equipment, and new antiviral fabrics for the protection and prevention of life-threatening viral diseases are needed. In this study, selenium nanoparticles (SeNPs) were combined with polyester fabrics using printing technique to obtain multifunctional properties, including combined antiviral and antibacterial activities as well as coloring. The properties of the printed polyester fabrics with SeNPs were…

• In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication - (1) Background: Humic substances are well-known human nutritional supplement materials and they play an important performance-enhancing role as animal feed additives. For decades, ingredients of humic substances have been proven to carry potent antiviral effects against different viruses. (2) Methods: Here, the antiviral activity of a humic substance containing ascorbic acid, Se^(-) and Zn^(2+) ions intended as a nutritional supplement material was investigated against SARS-CoV-2 virus B1.1.7…

From Patent Search

• 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

• 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

• 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

• A CENTRAL TRANSACTION AUTHENTIC SYSTEM FOR OTP VERIFICATION - The present invention relates to a central transaction authentic system (100) for OTP verification. The system (100) comprises one or more user display units (102), one or more financial units (104), an account deposit unit (106), an OTP authentication unit (108) and a service server unit (110). The central transaction authentic system (100) for OTP verification work as Anti-money laundering measure. The system (100) also helpful for minimizing rate of cybercrime. The central transaction authentic system (100) for OTP verification that can neutralize digital financial fraud. The present invention provides a central transaction authentic system (100) for OTP verification that can monitor and analyze every transaction and customer interaction across its customer base for suspicious and potentially criminal activity. - link

• FORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAP - ABSTRACTFORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAPThe present invention provides formulations for herbal medicated transparent soaps and method of preparation of the same. Transparent soaps are prepared by saponification of mixture of non-edible oils to get the desired consistency and cleaning action. Nonvolatile alcohols and other transparency promoters are used to get good transparency and binding properties. Herbal extracts of different herbs are added to get medicated properties. - link

• SOCIAL NAVIGATION SYSTEM FOR MOBILE ROBOTS IN THE EMERGENCY DEPARTMENT TECHNOLOGY - The emergency department (ED) is a safety-critical environment in which healthcare workers (HCWs) are overburdened, overworked, and have limited resources, especially during the COVID-19 pandemic. One way to address this problem is to explore the use of robots that can support clinical teams, e.g., to deliver materials or restock supplies. However, due to EDs being overcrowded, and the cognitive overload HCWs experience, robots need to understand various levels of patient acuity so they avoid disrupting care delivery. In this invention, we introduce the Safety-Critical Deep Q-Network (SafeDQN) system, a new acuity-aware navigation system for mobile robots. SafeDQN is based on two insights about care in EDs: high-acuity patients tend to have more HCWs in attendance and those HCWs tend to move more quickly. We compared SafeDQN to three classic navigation methods, and show that it generates the safest, quickest path for mobile robots when navigating in a simulated ED environment. We hope this work encourages future exploration of social robots that work in safety-critical, human-centered environments, and ultimately help to improve patient outcomes and save lives. Figure 1. - link

• A MACHINE LEARNING BASED SYSTEM FOR DETECTING OMICRON VARIANT FROM A GENOME SEQUENCE AND METHOD THEREOF - The present invention discloses a machine learning based system for detecting omicron variant from a genome sequence and method thereof. The system includes, but not limited to, a processing unit having a memory unit and a machine learning interface embedded on it for validating a variant-induced changes in the one or more condition-specific cell variables are combined to output a single numerical variant score for each of the one or more variants, the variant score computed by one of outputting the score for a fixed condition; summing the variant-induced changes across conditions; computing the maximum of the absolute variant-induced changes across conditions. - link

• A SYSTEM BASED ON DEEP LEARNING FOR ANALYZING DELAYED ENHANCEMENT MAGNETIC RESONANCE IMAGING TO IDENTIFY COVID 19 AND METHOD THEREOF - The present invention discloses a system based on deep learning for analyzing delayed enhancement magnetic resonance imaging to identify COVID 19 and method thereof. The method and system include, but not limited to, a processing unit adapted to process the data based on deep learning data modelling in the magnetic resonance imaging associated with the digital image scanning system for diagnosis COVID 19 with the spatial resolution that each frame is deposited is 256 * 256, and being creating that level and vertical resolution respectively are 256 pixels (pixel), the read/write address that the read/write address of each image element, which is controlled by processing unit and forms circuit and finishes; And the data that will be stored in memory are input to a real-time microcontroller, it is characterized in that: analyze and compare by the Multi-source Information Fusion analytical system by using the real-time microcontroller to deliver the D/A changer then, digital signal is become analogue signal output. - link