Covid-19 Sentry

Contents

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

From Preprints

• Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1 -
  FDA-approved and Emergency Use Authorized (EUA) vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease, however, information on their long-term efficacy and protective breadth against SARS-CoV-2 Variants of Concern (VOCs) is currently scarce. Here we describe the durability and broad- spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HTTM in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], B.1.617 [Delta]) for at least 3 months after the final boost. Protective efficacy and post-exposure immunity were evaluated using a heterologous P.1 challenge nearly 3 months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Post-challenge IgG concentrations were restored to peak immunity levels and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (non-vaccinated but challenged) macaques suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide long-lasting and protective immunity against circulating VOCs.
  🖺 Full Text HTML: Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1
• A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease -

  Billions of doses of COVID-19 vaccines have been administered around the world, dramatically reducing SARS-CoV-2 incidence in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines as of August 2021. We included efficacy data from Phase 3 clinical trials for 13 vaccines within the WHO Emergency Use Listing evaluation process and real-world effectiveness for 5 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include effects against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for both partial and complete vaccination, and against SARS-CoV-2 variants of concern. In addition, we review the epidemiological principles behind the design and interpretation of vaccine effects, and explain important sources of heterogeneity between studies.

  🖺 Full Text HTML: A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease
• COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis -

  Background Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. Methods Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates vs. D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data was analyzed using correlation and linear regression. Results One population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 – 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3. Conclusions The two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

  🖺 Full Text HTML: COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis
• LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein -
  The interactions between severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to COVID-19. The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary ACE2 receptor. We performed two independent cell-based systematic screens to determine whether there are additional proteins by which the spike protein of SARS-CoV-2 can interact with human cells. We discovered that in addition to ACE2, expression of LRRC15 also causes spike protein binding. This interaction is distinct from other known spike attachment mechanisms such as heparan sulfates or lectin receptors. Measurements of orthologous coronavirus spike proteins implied the interaction was restricted to SARS-CoV-2, suggesting LRRC15 represents a novel class of spike binding interaction. We localized the interaction to the C-terminus of the S1 domain, and showed that LRRC15 shares recognition of the ACE2 receptor binding domain. From analyzing proteomics and single-cell transcriptomics, we identify LRRC15 expression as being common in human lung vasculature cells and fibroblasts. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19.
  🖺 Full Text HTML: LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein
• Legal hunting for conservation of highly threatened species: The case of African rhinos -
  Legal hunting of highly threatened species – and especially the recreational practice of ‘trophy hunting’ – is controversial with selected ethical objections being increasingly voiced. Less attention has been paid to how hunting (even of threatened species) can be useful as a conservation tool, and likely outcomes if this was stopped. As case studies, we examine the regulated legal hunting in South Africa and Namibia of two African rhino species. Counter- intuitively, removing a small number of specific males can enhance population demography and genetic diversity, encourage range expansion, and generate meaningful socio-economic benefits to help fund effective conservation (facilitated by appropriate local institutional arrangements). Legal hunting of these species has been sustainable, as very small proportions of the populations of both species are hunted each year, and numbers of both today are higher in these countries than when controlled recreational hunting began. Terminating this management option and funding source could have negative consequences at a time when rhinos are being increasingly viewed as liabilities and COVID-19 has significantly impacted revenue generation for wildlife areas. Provided that there is appropriate governance and management, conservation of certain highly threatened species can be supported by cautiously selective and limited legal hunting.
  🖺 Full Text HTML: Legal hunting for conservation of highly threatened species: The case of African rhinos
• LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19 -
  Although numerous promising therapeutic targets for human diseases have been discovered, most have not been successfully translated into clinical practice. A bottleneck in the application of basic research findings to patients is the enormous cost, time, and effort required for high-throughput screening of potential drugs for given therapeutic targets. Recent advances in 3D docking simulations have not solved this problem, given that 3D protein structures with sufficient resolution are not always available and that they are computationally expensive to obtain. Here we have developed LIGHTHOUSE, a graph-based deep learning approach for discovery of the hidden principles underlying the association of small-molecule compounds with target proteins, and we present its validation by identifying potential therapeutic compounds for various human diseases. Without any 3D structural information for proteins or chemicals, LIGHTHOUSE estimates protein-compound scores that incorporate known evolutionary relations and available experimental data. It identified novel therapeutics for cancer, lifestyle-related disease, and bacterial infection. Moreover, LIGHTHOUSE predicted ethoxzolamide as a therapeutic for coronavirus disease 2019 (COVID-19), and this agent was indeed effective against alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are rampant worldwide. Given that ethoxzolamide is already approved for several diseases, it could be rapidly deployed for the treatment of patients with COVID-19. We envision that LIGHTHOUSE will bring about a paradigm shift in translational medicine, providing a bridge from bench side to bedside.
  🖺 Full Text HTML: LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19
• Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and thrombosis -
  SARS-CoV-2 is a worldwide health concern, and new treatment strategies are needed 1. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4), and its mouse homologue, caspase-11 (CASP11), are upregulated in SARS-CoV-2 infections, and that CASP4 expression correlates with severity of SARS-CoV-2 infection in humans. SARS-CoV-2-infected Casp11-/- mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) and gasdermin-D knock out (Gsdmd-/-) mice. GSDMD is a downstream effector of CASP11 and CASP1. Notably, viral titers were similar in the three genotypes. Global transcriptomics of SARS-CoV-2-infected WT, Casp11-/- and Gsdmd-/- lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11-/- mice. We confirmed that protein levels of inflammatory mediators IL-1{beta}, IL6, and CXCL1, and neutrophil functions, were reduced in Casp11-/- lungs. Additionally, Casp11-/- lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11, promotes detrimental SARS-CoV-2-associated inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.
  🖺 Full Text HTML: Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and thrombosis
• Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta- variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.
  🖺 Full Text HTML: Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD
• Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis -
  Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)/ coronavirus disease 2019 (COVID-19) infection is the leading cause of respiratory tract infection associated mortality worldwide. The aim of the current investigation was to identify the differentially expressed genes (DEGs) and enriched pathways in COVID-19 infection and its associated complications by bioinformatics analysis, and to provide potential targets for diagnosis and treatment. Valid next- generation sequencing (NGS) data of 93 COVID 19 samples and 100 non COVID 19 samples (GSE156063) were obtained from the Gene Expression Omnibus database. Gene ontology (GO) and REACTOME pathway enrichment analysis was conducted to identify the biological role of DEGs. In addition, a protein-protein interaction network, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network and receiver operating characteristic curve (ROC) analysis were used to identify the key genes. A total of 738 DEGs were identified, including 415 up regulated genes and 323 down regulated genes. Most of the DEGs were significantly enriched in immune system process, cell communication, immune system and signaling by NTRK1 (TRKA). Through PPI, modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network analysis, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were selected as hub genes, which were expressed in COVID-19 samples relative to those in non COVID-19 samples, respectively. Among them, ESR1, UBD, FYN, STAT1, ISG15, EGR1, ARRB2, UBE2D1, PRKDC and FOS were suggested to be diagonstic factors for COVID-19. The findings from this bioinformatics analysis study identified molecular mechanisms and the key hub genes that might contribute to COVID-19 infection and its associated complications.
  🖺 Full Text HTML: Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis
• The impact of heating, ventilation, and air conditioning design features on the transmission of viruses, including the 2019 novel coronavirus: a systematic review of filtration -

  Historically, viruses have demonstrated airborne transmission. Emerging evidence suggests the novel coronavirus (SARS-CoV-2) that causes COVID-19 may also spread by airborne transmission. This is more likely in indoor environments, particularly with poor ventilation. In the context of potential airborne transmission, a vital mitigation strategy for the built environment is heating, ventilation, and air conditioning (HVAC) systems. HVAC features could modify virus transmission potential. A systematic review following international standards was conducted to comprehensively identify and synthesize research examining the effectiveness of filters within HVAC systems in reducing virus transmission. Twenty-three relevant studies showed that: filtration was associated with decreased transmission; filters removed viruses from the air; increasing filter efficiency (efficiency of particle removal) was associated with decreased transmission, decreased infection risk, and increased viral filtration efficiency (efficiency of virus removal); increasing filter efficiency above MERV 13 was associated with limited benefit in further reduction of virus concentration and infection risk; and filters with the same efficiency rating from different companies showed variable performance. Increasing filter efficiency may mitigate virus transmission; however, improvement may be limited above MERV 13. Adapting HVAC systems to mitigate virus transmission requires a multi-factorial approach and filtration is one factor offering demonstrated potential for decreased transmission.

  🖺 Full Text HTML: The impact of heating, ventilation, and air conditioning design features on the transmission of viruses, including the 2019 novel coronavirus: a systematic review of filtration
• Comparison of adverse events between COVID-19 and Flu vaccines -

  BACKGROUND Among the various driving factors for vaccine hesitancy, confidence in the safety associated with the vaccine constitutes as one of the key factors. This study aimed at comparing the adverse effects of COVID-19 vaccines with the Flu vaccines. METHODS The VAERS data from 01/01/2020 to 08/20/2021 were used. The MedDRA terms coded by VAERS were further aggregated by a clinician into clinically meaningful broader terms. RESULTS Various common adverse events between Flu and COVID-19 vaccines have been identified. Adverse events such as headache and fever were very common across all age groups. Among the common adverse events between Flu and COVID-19 vaccine, the relative risk along with 95% CI indicated that such common adverse events were more likely to be experienced by COVID-19 vaccine users than Flu vaccine users. Our study also quantified the proportion of rare adverse events such as Guillain Barre Syndrome and Gynecological changes in the VAERS database for COVID-19 vaccines. CONCLUSIONS Based on the available data and results, it appears that there were some common adverse events between Flu vaccines and COVID-19 vaccines. These identified common adverse events warrant further investigations based on the relative risk and 95% CI.

  🖺 Full Text HTML: Comparison of adverse events between COVID-19 and Flu vaccines
• One wave or another in the pandemic: Psychological well-being during the third COVID-19 wave -
  After a year from the emergence of the Coronavirus disease (COVID-19) on February 2020, between March and May 2021 Italy faced its third wave of infections. Previous studies have shown that in the first phases of the pandemic certain factors had a protective role against distress. However, as the months in the pandemic went by, people’s feelings and experiences significantly changed and little is known regarding the role of possible protective variables after prolonged pandemic situations. In the present study we aimed to investigate the impact of several behavioral variables on individuals’ mental states and emotions experienced during the third COVID-19 wave in Italy. 454 Italian adults were asked questions regarding the intensity of mental states and emotions experienced, the perceived usefulness of lockdown, the feeling of living a normal life, and the coping strategies implemented to face the pandemic. Using a data driven approach, we calculated the best model on the participation of each factor in explaining participants’ emotions and mental states. Our findings indicate that the presence of acceptance attitudes toward restrictive measures and the implementation of recreational activities helped participants face a prolonged pandemic with positive emotions.

• A Modified Trier Social Stress Test to Investigate Social Anxiety using Videoconferencing Software: A Proof-of- Concept study -
  Social anxiety disorder (SAD) is one of the most common mental disorders and can be significantly disabling. New treatments are needed as the remission rate for SAD is the lowest of all the anxiety disorders. Experimental medicine models, in which features resembling a clinical disorder are experimentally induced, can be a cost-effective and timely approach to explore potential novel treatments for psychiatric disorders. One such model is the Trier Social Stress Test (TSST), which induces social-evaluative threat and subsequent stress responses in participants. However, following the emergence of SARS-CoV-2, there is a need to develop protocols that can be carried out remotely. We developed a novel modified TSST to investigate SAD that can be carried out entirely online (the Internet-based Trier Stress test for Social Anxiety Disorder; iTSSAD). Our protocol involves a naturalistic social interaction task to explore social anxiety symptoms. The observing panel was also artificial which allows the entire protocol to be carried out by a single investigator, reducing costs and improving internal reliability. The iTSSAD induced significant subjective anxiety and reduced positive affect (F’s > 4.41, p’s < 0.02). Further, social anxiety symptoms correlated with anxiety during the social interaction task (r = 0.65, p = 0.0032). This protocol needs further validation with physiological measures. The iTSSAD is a new tool for researchers to investigate mechanisms underlying social anxiety disorder.

• Face processing in early development: a systematic review of behavioral studies and considerations in times of COVID-19 pandemic -
  Human faces are one of the most prominent stimuli infants in the visual environment of young infants and convey critical information for the development of social cognition. During the COVID-19 pandemic, mask wearing has become a common practice outside the home environment. With masks covering nose and mouth regions, the facial cues available to the infant are impoverished. The impact of these changes on development is unknown, but is critical to debates around mask mandates in early childhood settings. As infants grow, they increasingly interact with a broader range of familiar and unfamiliar people outside the home; in these settings, mask wearing could possibly influence social development. In order to generate hypotheses about the effects of mask wearing on infant social development, in the present work we systematically review N=129 studies selected based on the most recent PRISMA guidelines providing a state-of-the-art framework of behavioural studies investigating face processing in early infancy. We focused on identifying sensitive periods during which being exposed to specific facial features or to the entire face configuration has been found to be important for the development of perceptive and socio-communicative skills. For perceptive skills, infants gradually learn to analyze the eyes or the gaze direction within the context of the entire face configuration. This contributes to identity recognition as well as emotional expression discrimination. For socio-communicative skills, direct gaze and emotional facial expressions are crucial for attention engagement while eye-gaze cuing is important for joint attention. Moreover, attention to the mouth is particularly relevant for speech learning. We discuss possible implications of the exposure to masked faces for developmental needs and functions. Providing groundwork for further research, we encourage the investigation of the consequences of mask-wearing for infants’ perceptive and socio-communicative development, suggesting new directions within the research field.
  🖺 Full Text HTML: Face processing in early development: a systematic review of behavioral studies and considerations in times of COVID-19 pandemic
• COVID Feel Good – A Self-Help Virtual Therapeutic Experience for Overcoming the Psychological Distress of the COVID-19 Pandemic: Results from a European Multicentric Trial -
  The primary aim of the present study was to investigate the efficacy of a self-help virtual therapeutic experience (COVID Feel Good) for reducing the psychological burden experienced during the COVID-19 lockdown across different countries. For this purpose, we focused on participants recruited from June 2020 to May 2021 in the context of a European multicenter project including four university/academic sites. Primary outcome measures were depression, anxiety and stress symptoms, perceived stress levels and hopelessness. Secondary outcomes were the experienced social connectedness and the level of fear experienced during the COVID-19 pandemic. To assess the efficacy of the intervention in a multicentric context, we evaluated the strength of evidence supporting the COVID Feel Good computing a single summary estimate of the effect across the different countries. Using separate linear mixed-effect models, the most consistent result across the different countries was an improvement of the perceived stress level after the participation in the COVID Feel Good intervention. By pooling the results of the models using a random-effect meta- analysis, we found that COVID Feel Good intervention was associated a decrease in the perceived general distress [mean standardized effect size for general distress in the treatment groups compared to the control conditions was 0.52 (p = 0.007, 95% CI: 0.14, 0.89] and with an increase the perceived social connection [mean standardized effect size for social connection using COVID Feel Good compared to the control conditions was -0.50 (p = < 0.001, 95% CI: -0.76, -0.25)]. Globally findings suggest the efficacy of the proposed protocol and contribute the growing literature supporting the use of digital psychological interventions to reduce the psychological stress among general population during the COVID-19 crisis.
  🖺 Full Text HTML: COVID Feel Good – A Self-Help Virtual Therapeutic Experience for Overcoming the Psychological Distress of the COVID-19 Pandemic: Results from a European Multicentric Trial

From Clinical Trials

• Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) - Condition:   COVID-19
  Interventions:   Drug: Favipiravir;   Drug: Monoclonal antibodies;   Drug: Ivermectin;   Other: No treatment;   Drug: Remdesivir
  Sponsor:   University of Oxford
  Not yet recruiting

• Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers - Condition:   Covid19
  Intervention:   Biological: AdCLD-CoV19-1
  Sponsor:  
  Cellid Co., Ltd.
  Recruiting

• A Post-Exposure Prophylaxis Study of PF-07321332/Ritonavir in Adult Household Contacts of an Individual With Symptomatic COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Placebo for PF-07321332;   Drug: Placebo for Ritonavir;   Drug: Ritonavir
  Sponsor:   Pfizer
  Recruiting

• Factors Influencing the COVID-19 Vaccine Immune Response According to Age and Presence or Not of a Past History of COVID-19 - Condition:   Covid19
  Interventions:   Biological: COVID-19 vaccine Pfizer (2 doses);   Biological: COVID-19 vaccine Pfizer (1 dose);   Biological: COVID-19 mRNA Vaccine Moderna (2 doses);   Biological: COVID-19 mRNA Vaccine Moderna (1 dose)
  Sponsors:   Centre Hospitalier Universitaire de Saint Etienne;   Sanofi Pasteur, a Sanofi Company;   Bioaster
  Not yet recruiting

• TThe Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine. - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Other: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• The Safety and Efficacy of SCTV01C in Population Aged ≥18 Years Previously Vaccinated With Inactivated COVID-19 Vaccine.Healthy Population Aged ≥18 Years Previously Vaccinated With Adenovirus Vectored or mRNA COVID-19 Vaccine. - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Other: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Heterologous Prime-boost Immunization With an Aerosolised Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Priming With an Inactivated SARS-CoV-2 Vaccine - Condition:   COVID-19
  Interventions:   Biological: inactive SARS-CoV-2 vaccine (Vero cell);   Biological: Low dose aerosolized Ad5-nCoV;   Biological: High dose aerosolized Ad5-nCoV
  Sponsor:   Jiangsu Province Centers for Disease Control and Prevention
  Recruiting

• Combined Antihistaminics Therapy in COVID 19 Patients - Condition:   Covid19
  Interventions:   Drug: Loratadine;   Drug: Famotidine
  Sponsors:   Ain Shams University;   Nasr City Insurance Hospital
  Not yet recruiting

• Relate to the Virus That Causes COVID-19, Known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Condition:   Covid19
  Intervention:   Other: Rapid antigen testing kit
  Sponsors:  
  Mahidol University;   Yuvabadhana foundation;   Zero COVID Thailand
  Not yet recruiting

• Prevention and Treatment of Patient Before, During, and After Covid-19 Infection - Condition:   Covid19
  Intervention:   Drug: AntiCov-220
  Sponsor:  
  Nguyen Thi Trieu, MD
  Active, not recruiting

• Test to Stay in School: COVID-19 Testing Following Exposure in School Communities - Condition:   Covid19
  Intervention:   Other: COVID-19 Testing
  Sponsor:  
  Duke University
  Not yet recruiting

• FLuticasone in cOvid Treatment (FLOT) - Condition:   Covid19
  Intervention:   Drug: Fluticasone Propionate
  Sponsor:  
  University of Medicine and Pharmacy at Ho Chi Minh City
  Recruiting

• Efficacy and Safety of Baricitinib in Patients With Moderate and Severe COVID-19 - Condition:   Covid19
  Interventions:   Drug: Baricitinib;   Drug: Placebo
  Sponsor:  
  Incepta Pharmaceuticals Ltd
  Not yet recruiting

• Efficacy of KOVIR Hard Capsule in the Combination Regimen With Background Treatment in COVID-19 Patients - Condition:   COVID-19
  Intervention:   Dietary Supplement: KOVIR hard capsule combined with background treatment
  Sponsors:   Sunstar Joint Stock Company;   Big Leap Clinical Research Joint Stock Company
  Not yet recruiting

• Safety and Efficacy of KOVIR in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Big Leap Clinical Research Joint Stock Company
  Completed

From PubMed

• Targeting the PI3K/Akt/mTOR pathway: A therapeutic strategy in COVID-19 patients - Some COVID-19 patients suffer complications from anti-viral immune responses which can lead to both a dangerous cytokine storm and development of blood-borne factors that render severe thrombotic events more likely. The precise immune response profile is likely, therefore, to determine and predict patient outcomes and also represents a target for intervention. Anti-viral T cell exhaustion in the early stages is associated with disease progression. Dysregulation of T cell functions, which…

• Mechanisms of Antiviral Immune Evasion of SARS-CoV-2 - Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by a delayed interferon (IFN) response and high levels of proinflammatory cytokine expression. Type I and III IFNs serve as a first line of defense during acute viral infections and are readily antagonized by viruses to establish productive infection. A rapidly growing body of work has interrogated the mechanisms by which SARS-CoV-2 antagonizes both IFN induction and IFN…

• Low molecular weight fucoidan attenuating pulmonary fibrosis by relieving inflammatory reaction and progression of epithelial-mesenchymal transition - Diffuse alveolar injury and pulmonary fibrosis (PF) are the main causes of death of Covid-19 cases. In this study a low molecular weight fucoidan (LMWF) with unique structural was obtained from Laminaria japonica, and its anti- PF and anti- epithelial-mesenchymal transition (EMT) bioactivity were investigated both in vivo and in vitro. After LWMF treatment the fibrosis and inflammatory factors stimulated by Bleomycin (BLM) were in lung tissue. Immunohistochemical and Western-blot results found…

• Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve? - Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc,…

• The Use of Biologics During the COVID-19 Pandemic - During the coronavirus disease 2019 (COVID-19) pandemic, there has been considerable discussion regarding the use of biologics in patients with inflammatory skin conditions, such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. This article discusses clinical trial data, real-world evidence, and guidelines and recommendations for biologics that inhibit tumor necrosis factor, interleukin (IL)-12/23, IL-17, IL-23, and IL-4/13 during the COVID-19 pandemic. Across these inflammatory…

• Cytometric analysis of patients with COVID-19: what is changed in the second wave? - CONCLUSIONS: COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate…

• Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease - We have discovered a family of synthetic oxazole-based macrocycles to be active against SARS-CoV-2. The synthesis, pharmacological properties, and docking studies of the compounds are reported in this study. The structure of the new macrocycles was confirmed by NMR spectroscopy and mass spectrometry. Compounds 13, 14, and 15a-c were evaluated for their anti-SARS-CoV-2 activity on SARS-COV-2 (NRC-03-nhCoV) virus in Vero-E6 cells. Isopropyl triester 13 and triacid 14 demonstrated superior…

• Stem cell-based and mesenchymal stem cell derivatives for coronavirus treatment - Coronavirus disease 2019 (COVID-19) as one of the diseases pneumonia was first reported in Wuhan, China in December

2019. COVID-19 is considered the third most common coronavirus among individuals after acute respiratory syndrome (SARS- CoV) and the Middle East respiratory syndrome (MERS-CoV) in the 20^(th) century. Many studies have shown that cell therapy and regenerative medicine approaches have an impressive effect on different dangerous diseases in a way that using a cell-based experiment…

• Effective SARS-CoV-2 antiviral activity of hyperbranched polylysine nanopolymers - The coronavirus pandemic (COVID-19) had spread rapidly since December 2019, when it was first identified in Wuhan, China. As of April 2021, more than 130 million cases have been confirmed, with more than 3 million deaths, making it one of the deadliest pandemics in history. Different approaches must be put in place to confront a new pandemic: community- based behaviours (i.e., isolation and social distancing), antiviral treatments, and vaccines. Although behaviour-based actions have produced…

• Natural Compounds With Antimicrobial and Antiviral Effect and Nanocarriers Used for Their Transportation - Due to the increasing prevalence of life-threatening bacterial, fungal and viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compunds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable compounds for this task are usually derived from natural sources (animal, plant or even microbial). In this review article, the latest and…

• TLR-4 Agonist Induces IFN-γ Production Selectively in Proinflammatory Human M1 Macrophages through the PI3K-mTOR- and JNK-MAPK-Activated p70S6K Pathway - IFN-γ, a proinflammatory cytokine produced primarily by T cells and NK cells, activates macrophages and engages mechanisms to control pathogens. Although there is evidence of IFN-γ production by murine macrophages, IFN-γ production by normal human macrophages and their subsets remains unknown. Herein, we show that human M1 macrophages generated by IFN-γ and IL-12- and IL-18-stimulated monocyte-derived macrophages (M0) produce significant levels of IFN-γ. Further stimulation of IL-12/IL-18-primed…

• Semi-continuous propagation of influenza A virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy - Defective interfering particles (DIPs) of influenza A virus (IAV) are naturally occurring mutants that comprise an internal deletion in one of their eight viral RNA (vRNA) segments, rendering them propagation-incompetent. Upon co- infection with infectious standard virus (STV), DIPs interfere with STV replication through competitive inhibition. Thus, DIPs are proposed as potent antivirals for treatment of the influenza disease. To select corresponding candidates, we studied de novo generation of…

• Inhibition of autophagy suppresses SARS-CoV-2 replication and ameliorates pneumonia in hACE2 transgenic mice and xenografted human lung tissues - Autophagy is thought to be involved in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, how SARS-CoV-2 interferes with the autophagic pathway and whether autophagy contributes to virus infection in vivo is unclear. Here, we identified SARS-CoV-2-triggered autophagy in animal models including the long tailed or crab eating macaque (Macaca fascicularis), hACE2 transgenic mice and xenografted human lung tissues. In Vero E6 and Huh-7 cells, SARS-CoV-2 induces…

• Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities - At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper…

• Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis - CONCLUSIONS: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided…

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• 一种S1F-AXL复合物、试剂盒和检测该复合物的方法及应用 - 本发明公开了一种S1F‑AXL复合物、试剂盒和检测该复合物的方法及应用。所述试剂盒包含S1F多肽和AXL多肽，以S1F多肽、AXL多肽中的一种作为包被底物；所述S1F多肽和所述AXL多肽中至少一种为具有缀合标签的糖基化多肽，还包括具有微孔的微量滴定板、标记底物标记的抗标签特异性抗体、HRP偶联的二抗、洗涤缓冲液、标记底物反应液、反应终止液。所述检测S1F‑AXL复合物的试剂盒，通过测量标记的信号特征，检测S1F‑AXL复合物的结合亲和力，还可以用于检测来自怀疑感染了SARS‑CoV‑2(Covid‑19)的受试者的生物样品中的病毒。 - link

• 一种检测新型冠状病毒的引物探针组合及其应用 - 本发明提供了一种检测新型冠状病毒的引物探针组合及其应用，所述检测新型冠状病毒的引物探针组合包括特异性扩增并检测2019‑nCoV的ORF1ab基因、核壳蛋白N基因和刺突蛋白S基因N501Y突变位点的特异性引物对和探针。本发明还提供了一种检测新型冠状病毒的试剂盒及其以非疾病诊断和/或治疗为目的的使用方法。本发明所述检测新型冠状病毒的引物探针组合具有良好的特异性与灵敏度，配合优化后的检测体系，可以对待测样本进行快速准确的检测，并可以对整个实验流程进行监控，降低假阳性以及假阴性检测结果的出现概率，具有重要的意义。 - link

• SARS-COV-2 BINDING PROTEINS - - link

• COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link