Covid-19 Sentry

Contents

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

From Preprints

• Structural basis of Omicron neutralization by affinity-matured public antibodies -
  The SARS-CoV-2 Omicron Variant of Concern (B.1.1.529) has spread rapidly in many countries. With a spike that is highly diverged from that of the pandemic founder, it escapes most available monoclonal antibody therapeutics and erodes vaccine protection. A public class of IGHV3-53-using SARS-CoV-2 neutralizing antibodies typically fails to neutralize variants carrying mutations in the receptor-binding motif, including Omicron. As antibodies from this class are likely elicited in most people following SARS-CoV-2 infection or vaccination, their subsequent affinity maturation is of particular interest. Here, we isolated IGHV3-53-using antibodies from an individual seven months after infection and identified several antibodies capable of broad and potent SARS-CoV-2 neutralization, extending to Omicron without loss of potency. By introducing select somatic hypermutations into a germline-reverted form of one such antibody, CAB-A17, we demonstrate the potential for commonly elicited antibodies to develop broad cross-neutralization through affinity maturation. Further, we resolved the structure of CAB-A17 Fab in complex with Omicron spike at an overall resolution of 2.6 angstroms by cryo-electron microscopy and defined the structural basis for this breadth. Thus, public SARS-CoV-2 neutralizing antibodies can, without modified spike vaccines, mature to cross-neutralize exceptionally antigenically diverged SARS-CoV-2 variants.
  🖺 Full Text HTML: Structural basis of Omicron neutralization by affinity-matured public antibodies
• Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction -
  Since SARS-CoV-2 Omicron variant (B.1.1.529) was reported in November 2021, it has quickly spread to many countries and outcompeted the globally dominant Delta variant in several countries. The Omicron variant contains the largest number of mutations to date, with 32 mutations located at spike (S) glycoprotein, which raised great concern for its enhanced viral fitness and immune escape[1-4]. In this study, we reported the crystal structure of the receptor binding domain (RBD) of Omicron variant S glycoprotein bound to human ACE2 at a resolution of 2.6 angstrom. Structural comparison, molecular dynamics simulation and binding free energy calculation collectively identified four key mutations (S477N, G496S, Q498R and N501Y) for the enhanced binding of ACE2 by the Omicron RBD compared to the WT RBD. Representative states of the WT and Omicron RBD-ACE2 systems were identified by Markov State Model, which provides a dynamic explanation for the enhanced binding of Omicron RBD. The effects of the mutations in the RBD for antibody recognition were analyzed, especially for the S371L/S373P/S375F substitutions significantly changing the local conformation of the residing loop to deactivate several class IV neutralizing antibodies.
  🖺 Full Text HTML: Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction
• A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron -
  Bispecific antibodies have emerged as a promising strategy for curtailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape. This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.
  🖺 Full Text HTML: A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron
• Maternal cytokine response after SARS-CoV-2 infection during pregnancy -
  Objective: Dysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels. Study design: We conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured. Results: Individual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy. Conclusion: Our findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy.
  🖺 Full Text HTML: Maternal cytokine response after SARS-CoV-2 infection during pregnancy
• A framework for reconstructing SARS-CoV-2 transmission dynamics using excess mortality data -

  Detailed reconstruction of the SARS-CoV-2 transmission dynamics and assessment of its burden in several parts of the world has still remained largely unknown due to the scarcity of epidemiological analyses and limited testing capacities of different countries to identify cases and deaths attributable to COVID-19 [1-4]. Understanding the true burden of the Iranian COVID-19 epidemic is subject to similar challenges with limited clinical and epidemiological studies at the subnational level [5-9]. To address this, we develop a new quantitative framework that enables us to fully reconstruct the transmission dynamics across the country and assess the level of under-reporting in infections and deaths using province-level, age-stratified all-cause mortality data. We show that excess mortality aligns with seroprevalence estimates in each province and subsequently estimate that as of 2021-10-22, only 48% (95% confidence interval: 43-55%) of COVID-19 deaths in Iran have been reported. We find that in the most affected provinces such as East Azerbaijan, Qazvin, and Qom approximately 0.4% of the population have died of COVID-19 so far. We also find significant heterogeneity in the estimated attack rates across the country with 11 provinces reaching close to or higher than 100% attack rates. Despite a relatively young age structure in Iran, our analysis reveals that the infection fatality rate in most provinces is comparable to high-income countries with a larger percentage of older adults, suggesting that limited access to medical services, coupled with undercounting of COVID-19-related deaths, can have a significant impact on accurate estimation of COVID-19 fatalities. Our estimation of high attack rates in provinces with largely unmitigated epidemics whereby, on average, between 10% to 25% individuals have been infected with COVID-19 at least twice over the course of 20 months also suggests that, despite several waves of infection, herd immunity through natural infection has not been achieved in the population.

  🖺 Full Text HTML: A framework for reconstructing SARS-CoV-2 transmission dynamics using excess mortality data
• Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332) -
  The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic nirmatrelvir (PF-07321332). We expressed Mpro of six SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, B.1.1.529 Omicron, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, P132H, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that nirmatrelvir has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of the specific Mpro inhibitor nirmatrelvir is not compromised in current COVID-19 variants.
  🖺 Full Text HTML: Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir (PF-07321332)
• Identification of ACE2 mutations that modulate SARS-CoV-2 spike binding across multiple mammalian species -
  Understanding how SARS-CoV-2 interacts with different mammalian angiotensin-converting enzyme II (ACE2) cell entry receptors elucidates determinants of virus transmission and facilitates development of vaccines for humans and animals. Yeast display-based directed evolution identified conserved ACE2 mutations that increase spike binding across multiple species. Gln42Leu increased ACE2-spike binding for human and four of four other mammalian ACE2s; Leu79Ile had a effect for human and three of three mammalian ACE2s. These residues are highly represented, 83% for Gln42 and 56% for Leu79, among mammalian ACE2s. The above findings can be important in protecting humans and animals from existing and future SARS-CoV-2 variants.
  🖺 Full Text HTML: Identification of ACE2 mutations that modulate SARS-CoV-2 spike binding across multiple mammalian species
• Evaluation of the Implementation of the 4C Mortality Score in United Kingdom hospitals during the second pandemic wave -

  ABSTRACT The 4C Mortality Score (4C Score) was designed to risk stratify hospitalised patients with COVID-19. We assessed inclusion of 4C Score in COVID-19 management guidance and its documentation in patients9 case notes in January 2021 in UK hospitals. 4C Score was included within guidance by 50% of sites, though score documentation in case notes was highly variable. Higher documentation of 4C Score was associated with score integration within admissions proformas, inclusion of 4C Score variables or link to online calculator, and management decisions. Integration of 4C Score within clinical pathways may encourage more widespread use.

  🖺 Full Text HTML: Evaluation of the Implementation of the 4C Mortality Score in United Kingdom hospitals during the second pandemic wave
• Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant SARS-CoV-2 isolates -
  The SARS-CoV-2 Omicron variant is currently causing a large number of infections in many countries. A number of antiviral agents are approved or in clinical testing for the treatment of COVID-19. Despite the high number of mutations in the Omicron variant, we here show that Omicron isolates display similar sensitivity to eight of the most important anti-SARS-CoV-2 drugs and drug candidates (including remdesivir, molnupiravir, and PF-07321332, the active compound in paxlovid), which is of timely relevance for the treatment of the increasing number of Omicron patients. Most importantly, we also found that the Omicron variant displays a reduced capability of antagonising the host cell interferon response. This provides a potential mechanistic explanation for the clinically observed reduced pathogenicity of Omicron variant viruses compared to Delta variant viruses.
  🖺 Full Text HTML: Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant SARS-CoV-2 isolates
• The SARS-CoV-2 infection in Thailand: analysis of spike variants complemented by protein structure insights -
  Thailand was the first country outside China to officially report COVID-19 cases. Despite the strict regulations for international arrivals, up until February 2021, Thailand had been hit by two major outbreaks. With a large number of SARS-CoV-2 sequences collected from patients, the effects of many genetic variations, especially those unique to Thai strains, are yet to be elucidated. In this study, we analysed 439,197 sequences of the SARS-CoV-2 spike protein collected from NCBI and GISAID databases. 595 sequences were from Thailand and contained 52 variants, of which 6 had not been observed outside Thailand (p.T51N, p.P57T, p.I68R, p.S205T, p.K278T, p.G832C). These variants were not predicted to be of concern. We demonstrate that the p.D614G, although already present during the first Thai outbreak, became the prevalent strain during the second outbreak, similarly to what was described in other countries. Moreover, we show that the most common variants detected in Thailand (p.A829T, p.S459F and p.S939F) do not appear to cause any major structural change to the spike trimer or the spike-ACE2 interaction. Among the variants identified in Thailand was p.N501T. This variant, which involves an asparagine critical for spike-ACE2 binding, was not predicted to increase SARS-CoV-2 binding, thus in contrast to the variant of global concern p.N501Y. In conclusion, novel variants identified in Thailand are unlikely to increase the fitness of SARS-CoV-2. The insights obtained from this study could aid SARS-CoV-2 variants prioritisations and help molecular biologists and virologists working on strain surveillance.
  🖺 Full Text HTML: The SARS-CoV-2 infection in Thailand: analysis of spike variants complemented by protein structure insights
• Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial -

  Background: The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. Methods: This study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged ≥18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or ≥6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate (≥4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. Findings: A total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20.47%) participants in the heterologous boost groups and 177 (19.64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89.96% - 97.52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36.80% - 81.75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21.01 - 63.85 folds from baseline to 28 days post-boosting vaccination, whereas only 4.20 - 16.78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37.91 (95%CI, 30.35-47.35), however, a significantly higher level of neutralizing antibodies with GMT 292.53 (95%CI, 222.81-384.07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. Interpretation: Our findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV.

  🖺 Full Text HTML: Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial
• E.PAGE: A curated database and enrichment tool to predict modules associated with gene-environment interactions -
  Aims/hypothesis: The purpose of this study is to manually and semi-automatically curate a database and develop an R package that will act as a comprehensive resource to understand how biological processes are dysregulated due to interactions with environmental factors. Methods: We followed a two-step process to achieve the objectives of this study. First, we conducted a systematic review of the existing gene expression datasets to identify the integrated genomic and environmental factors used in available studies. This enabled us to curate a comprehensive genomic- environmental database for four key environmental factors (smoking, diet, infections and toxic chemicals) associated with various autoimmune and chronic conditions. Second, we developed a statistical analysis package that allows users to understand the relationships between differentially expressed genes and environmental factors under different disease conditions. Results: The initial database search run on the Gene Expression Omnibus (GEO) and the Molecular Signature Database (MSigDB) retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 186 studies were selected. From those, 243 individual sets of genes, or gene modules, were obtained. We then curated a database containing four environmental factors, namely cigarette smoking, diet, infections and toxic chemicals, along with a total of 25789 genes that had an association with one or more of these factors. In 6 case studies, the database and statistical analysis package were then tested with lists of differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, cobalt exposure, COVID-19 and smoking. On testing, we uncovered statistically enriched biological processes, which could help us understand the pathways associated with environmental factors and gene modules. Conclusions: A novel curated database and software tool is provided as an R Package. Users can enter a list of genes to discover associated environmental factors under various disease conditions.
  🖺 Full Text HTML: E.PAGE: A curated database and enrichment tool to predict modules associated with gene-environment interactions
• Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern. -

  Purpose: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. Methods: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. Results: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. Conclusions: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

  🖺 Full Text HTML: Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.
• Early signals of significantly increased vaccine breakthrough, decreased hospitalization rates, and less severe disease in patients with COVID-19 caused by the Omicron variant of SARS-CoV-2 in Houston, Texas -

  Genetic variants of SARS-CoV-2 continue to dramatically alter the landscape of the COVID-19 pandemic. The recently described variant of concern designated Omicron (B.1.1.529) has rapidly spread worldwide and is now responsible for the majority of COVID-19 cases in many countries. Because Omicron was recognized very recently, many knowledge gaps exist about its epidemiology and clinical severity and disease course. A comprehensive genome sequencing study of SARS- CoV-2 in the Houston Methodist healthcare system identified 862 symptomatic patients with infections caused by Omicron from late November 2021 through December 18, 2021. Omicron very rapidly increased in only three weeks to cause 90% of all new COVID-19 cases. Compared to patients infected with either Alpha or Delta variants in our healthcare system, Omicron patients were significantly younger, had significantly increased vaccine breakthrough rates, and were significantly less likely to be hospitalized. Omicron patients required less intense respiratory support and had a shorter length of hospital stay, consistent with decreased disease severity. Although the number of Omicron patients we studied is relatively small, in the aggregate the data document the unusually rapid spread and increased occurrence of COVID-19 caused by the Omicron variant in metropolitan Houston, and provide information about disease character.

  🖺 Full Text HTML: Early signals of significantly increased vaccine breakthrough, decreased hospitalization rates, and less severe disease in patients with COVID-19 caused by the Omicron variant of SARS-CoV-2 in Houston, Texas
• The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC- COV1901: An extension to an open-label, dose-escalation, and non-randomized phase 1 study -

  The waning antibody levels after immunization and the emergence of SARS-CoV-2 variants of concern (VoC) negatively impact the vaccine-induced neutralization of SARS-CoV-2. In this extension to the phase 1 clinical study, we report the antibody durability until 180 days after the second dose of MVC-COV1901, and examined the reactogenicity and immunogenicity followed by a booster shot MVC-COV1901 administered to 45 healthy adults from 20 to 49 years of age on day 209. Adverse reactions after the booster dose were mostly mild and comparable to that of the first two doses. Neutralizing antibodies remained detectable on day 209 at 59.4, 79.4, and 113.2 (IU/mL) for low dose (LD), middle dose (MD), and high dose (HD) groups, respectively. At four weeks after the booster dose, neutralizing titers increased to 1719.6, 818.3, and 1345.6 for LD, MD, and HD groups, respectively. Our data also showed that three doses of MVC- COV1901-induced antibodies were still effective, albeit lowered neutralizing titers, against the Omicron variant.

  🖺 Full Text HTML: The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC-COV1901: An extension to an open-label, dose-escalation, and non-randomized phase 1 study

From Clinical Trials

• Phase III Study of Novaferon in Non-hospitalized Adult Patients With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: Novaferon;   Biological: Placebo
  Sponsors:   Genova Inc.;   Tokyo Shinagawa Hospital
  Recruiting

• Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients - Condition:   COVID-19
  Interventions:   Biological: Human COVID-19 immunoglobulin (pH4) for intravenous injection;   Drug: Placebo
  Sponsors:   Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd.;   China National Biotec Group Company Limited;   Beijing Tiantan Biological Products Co., Ltd.
  Not yet recruiting

• A Telemedicine Brief Mindfulness Intervention in Post-COVID-19 - Condition:   Post COVID-19
  Intervention:   Other: Mindfulness
  Sponsors:  
  Fondazione Don Carlo Gnocchi Onlus;   Catholic University of the Sacred Heart
  Recruiting

• Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: Saline placebo
  Sponsors:   Cinnagen;   Vaxine Pty Ltd
  Active, not recruiting

• A Safety, Tolerability, and Efficacy Study of IBI314 in Mild to Moderate Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: IBI314(low dose);   Biological: IBI314(high dose);   Biological: IBI314(medium dose);   Other: Placebo
  Sponsor:  
  Innovent Biologics (Suzhou) Co. Ltd.
  Not yet recruiting

• PTX-COVID19-B, an mRNA Humoral Vaccine, Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Demonstrate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B in Comparison to the Pfizer- BioNTech COVID-19 Vaccine. - Condition:   Covid19 Vaccine
  Interventions:   Biological: PTX-COVID19-B;   Biological: Pfizer- BioNTech COVID-19 vaccine;   Biological: Placebo
  Sponsor:   Providence Therapeutics Holdings Inc.
  Active, not recruiting

• CONFIDENT: Supporting Long-term Care Workers During COVID-19 - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccine Confidence
  Interventions:  
  Behavioral: Dialogue-Based Webinar;   Behavioral: Social Media Website;   Other: Enhanced Usual Practice
  Sponsors:   Dartmouth-Hitchcock Medical Center;   National Association of Health Care Assistants;   Institute for Healthcare Improvement;   East Carolina University
  Not yet recruiting

• Quality of Life and Lung Function on Post Covid-19 Patient - Condition:   COVID-19
  Intervention:   Other: breathing exercise, Aerobic exercises
  Sponsor:   Qassim University
  Recruiting

• A Study to Evaluate the Ability of UB-612 COVID-19 Vaccine to Boost Immunity of Heterologous COVID-19 Vaccines. - Condition:   COVID-19; SARS-CoV-2
  Intervention:   Biological: UB-612
  Sponsor:  
  United Biomedical Inc., Asia
  Not yet recruiting

• Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients. - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: Raloxifene;   Other: Placebo
  Sponsor:   Dompé Farmaceutici S.p.A
  Completed

• Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell) - Condition:   COVID-19
  Intervention:   Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated
  Sponsor:   PT. Kimia Farma (Persero) Tbk
  Not yet recruiting

• Brequinar Combined With Dipyridamole in Patients With Mild to Moderate SARS-CoV-2 Infection. - Condition:   COVID-19
  Interventions:   Drug: Brequinar Sodium;   Drug: Dipyridamole 75 MG;   Drug: Placebo
  Sponsor:   Clear Creek Bio, Inc.
  Not yet recruiting

• Spa Rehabilitation, Antioxidant and Bioenergetic Supportive Treatment of Patients With Post-Covid-19 Syndrome - Condition:   COVID-19 Respiratory Infection
  Interventions:   Dietary Supplement: ubiquinol (reduced coenzyme Q10);   Other: mountain spa rehabilitation;   Diagnostic Test: 2x14 ml of peripheral blood collected in a tube with anticoagulant
  Sponsors:   Comenius University;   Sanatórium of Dr. Guhr, n.o.
  Completed

• Study to Evaluate the Effect of Nicotinamide Mononucleotide (NMN) As an Adjuvant to Standard of Care (SOC) On Fatigue Associated With COVID-19 Infection - Condition:   COVID-19 Infection
  Interventions:   Other: Nicotinamide Mononucleotide;   Other: Nicotinamide Mononucleotide with L-Leucine;   Other: Placebo
  Sponsor:  
  Vedic Lifesciences Pvt. Ltd.
  Recruiting

• The Effectiveness of RPSG Intervention for Nurses During the COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Interventions:   Behavioral: RPSG;   Behavioral: AVMBM
  Sponsor:   National Taiwan University Hospital
  Not yet recruiting

From PubMed

• SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterol- increased endosomal pH of alveolar macrophages - Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but…

• Thymoquinone: A Review of Pharmacological Importance, Oxidative Stress, COVID-19, and Radiotherapy - Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties such as antioxidant, anti-inflammatory, antiviral, and…

• Unravelling multiple removal pathways of oseltamivir in wastewater by microalgae through experimentation and computation - Increased worldwide consumption of antiviral drugs (AVDs) amid COVID-19 has induced enormous burdens to the existing wastewater treatment systems. Microalgae-based bioremediation is a competitive alternative technology due to its simultaneous nutrient recovery and sustainable biomass production. However, knowledge about the fate, distribution, and interaction of AVDs with microalgae is yet to be determined. In this study, a concentration-determined influence of AVD oseltamivir (OT) was observed…

• The Type 2 Asthma Mediator IL-13 Inhibits SARS-CoV-2 Infection of Bronchial Epithelium - Asthma is associated with chronic changes in the airway epithelium, a key target of SARS-CoV-2. Many epithelial changes, including goblet cell metaplasia, are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. We found that IL-13 stimulation of differentiated human bronchial epithelial cells (HBECs) cultured at air-liquid interface reduced viral RNA recovered from SARS-CoV-2 infected cells and decreased dsRNA, a marker of viral replication, to…

• Engineered small extracellular vesicles displaying ACE2 variants on the surface protect against SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID-19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly…

• Modeling and Evaluation of the Joint Prevention and Control Mechanism for Curbing COVID-19 in Wuhan - The spread of COVID-19 in Wuhan was successfully curbed under the strategy of “Joint Prevention and Control Mechanism.” To understand how this measure stopped the epidemics in Wuhan, we establish a compartmental model with time-varying parameters over different stages. In the early stage of the epidemic, due to resource limitations, the number of daily reported cases may lower than the actual number. We employ a dynamic-based approach to calibrate the accumulated clinically diagnosed data with a…

• A Scoping Review on the Medical and Recreational Use of Cannabis During the COVID-19 Pandemic - Background/Introduction: The shelter-in-place orders and social distancing regulations on account of the COVID-19 pandemic have impacted lifestyles, including the use of cannabis. The purpose of this scoping review is to summarize both the gray and academic literature on the use of cannabis during the pandemic. Materials and Methods: A total of 11 databases, including 2 medical databases, 7 social science databases, and 2 gray literature databases were searched resulting in 316 titles and…

• Design and Evaluation of a Novel Peptide-Drug Conjugate Covalently Targeting SARS-CoV-2 Papain-like Protease - Coronavirus disease 2019 (COVID-19) pandemic, a global health threat, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 papain-like cysteine protease (PLpro) was recognized as a promising drug target because of multiple functions in virus maturation and antiviral immune responses. Inhibitor GRL0617 occupied the interferon-stimulated gene 15 (ISG15) C-terminus-binding pocket and showed an effective antiviral inhibition. Here, we described a novel…

• Structural insights into pixatimod (PG545) inhibition of heparanase, a key enzyme in cancer and viral infections - Pixatimod (PG545), a heparan sulfate (HS) mimetic and anticancer agent currently in clinical trials, is a potent inhibitor of heparanase. Heparanase is an endo -β-glucuronidase that degrades HS in the extracellular matrix and basement membranes and is implicated in numerous pathological processes such as cancer and viral infections, including SARS-CoV-2. To understand how PG545 interacts with heparanase, we firstly carried out a conformational analysis through a combination of NMR experiments…

• Inhibitory effect of whey protein concentrate on SARS-CoV-2-targeted furin activity and spike protein-ACE2 binding in methotrexate-induced lung damage - This study aims to investigate the effects of whey proteins on SARS CoV-2 in methotrexate-induced lung tissue damage in rats. To determine the possible effects, rats were divided into four groups as control, control + whey, methotrexate (20 mg/kg, i.p.) and methotrexate + whey. Whey protein concentrate (2 g/kg, oral gavage) was administered for 10 days. Cytokine levels were measured and protein electrophoresis was carried out in serum samples. Lipid peroxidation, nitric oxide and glutathione…

• Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination - CONCLUSIONS: The data suggest that human milk SARS-CoV-2-specific antibodies may be available to milk-fed infants for up to 6 months. In addition, donor milk from vaccinated mothers retain IgG and neutralizing activity.

• Vandetanib Reduces Inflammatory Cytokines and Ameliorates COVID-19 in Infected Mice - The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib) or in advanced clinical trials. We have tested 45 FDA- approved kinase inhibitors in vitro against murine hepatitis virus (MHV) as a model of SARS-CoV-2 replication and identified 12 showing inhibition in the delayed brain tumor (DBT) cell line. Vandetanib, which targets the vascular endothelial growth factor receptor (VEGFR),…

• The N -Terminal Carbamate is Key to High Cellular and Antiviral Potency for Boceprevir-Based SARS-CoV-2 Main Protease Inhibitors - Boceprevir is an HCV NSP3 inhibitor that has been explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (M ^(Pro) ) and contains an α-ketoamide warhead, a P1 β-cyclobutylalanyl moiety, a P2 dimethylcyclopropylproline, a P3 tert -butyl-glycine, and a P4 N -terminal tert -butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based M ^(Pro) inhibitors including PF-07321332 and characterized their M ^(Pro) inhibition potency…

• A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors - Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high- throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based…

• ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection - Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are…

From Patent Search

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• METHODS OF TREATING SARS-COV-2 INFECTION - - link

• 피라졸 유도체의 폐섬유증 치료제 - 본 발명은 피라졸 유도체인 하기 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는, 폐섬유증 치료용 약학적 조성물 또는 항바이러스제를 제공한다 <화학식 1>

(상기 화학식 1에서 R은 발명의 설명에서 정의한 바와 같다.).

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      66 - [link](https://patentscope.wipo.int/search/en/detail.jsf?docId=KR345008871)

• 一种疾病相关标志物的筛选方法、应用及试剂盒 - 本发明公开了一种疾病相关标志物的筛选方法、应用及试剂盒。筛选方法包括：使用能够结合免疫球蛋白（Ig）的物质，分别从第一批健康样本血清和患病样本血清中纯化出Ig复合物；将与Ig相结合的蛋白进行蛋白质谱测序分析，比较健康样本与患病样本的差异，找到只出现在患病样本中的差异蛋白，即为该疾病相关潜在标志物。另外还可以通过以下步骤进一步验证该潜在标志物：使用第二批健康样本和患病样本的血清（扩大病例），纯化获得Ig复合物，利用差异蛋白的特异性抗体进行进一步鉴定。该方法先从血清中获得Ig复合物（而不是全血清），再将与Ig相结合的蛋白进行蛋白质谱测序联合特异性抗体分析，能够快速有效地筛选出疾病相关标志物。 - link

• 一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用 - 本发明提供一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用，属于疾病预后和分子生物学技术领域。本发明采用高通量测序的慢性淋巴细胞白血病(CLL)表达谱，进一步证实CLL的异质性，验证基于CLL细胞分化的CLL患者分类，预测患者预后。本发明将CLL细胞按分化状态分为两组，并对CLL细胞分化相关基因进行鉴定。最后，选择4个最具预后意义的CLL细胞分化相关基因，建立基于CLL细胞分化相关基因的SSCR风险评分模型，经验证该风险评分模型对CLL患者总生存期及首次治疗时间预测具有良好的可靠性。该评分系统可以帮助医生根据CLL细胞分化状况预测患者的预后，选择最佳的治疗方案，具有良好的实际应用价值。 - link

• 一种流感新冠联合疫苗及其制备方法 - 本发明公开了一种流感新冠联合疫苗，包括以下质量浓度的原料：含RBD‑Fc融合蛋白的重组新冠疫苗1‑100μg/mL；含H1N1型流感病毒的流感亚单位疫苗1‑50μg/mL；含H3N2型流感病毒的流感亚单位疫苗1‑50μg/mL；含B型流感病毒的流感亚单位疫苗1‑50μg/mL；氢氧化铝溶液，其中铝离子在流感新冠联合疫苗中的终浓度为0.5‑2.0mg/mL；余量为PBS磷酸缓冲液。制备方法：称取各原料；将四种疫苗分别用PBS磷酸缓冲液稀释后与氢氧化铝溶液混合；按照等体积比例混合，即得。本发明为含铝佐剂的新型冠状病毒疫苗和含铝佐剂的流感亚单位疫苗的联合疫苗，联合后，两种抗原组分疫苗之间没有相互抑制，能很好兼容。 - link

• REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link

• 一种瑞德西韦的合成方法 - 本发明涉及一种瑞德西韦的合成方法，包括以下步骤：将(2R,3R,4S,5R)‑2‑(4‑氨基吡咯[2,1‑f][1,2,4]三嗪‑7‑基)‑3,4‑二羟基‑5‑(羟甲基)四氢呋喃‑2‑碳腈、2,2‑二甲氧基丙烷和第一酸催化剂加入第一溶剂中，搅拌，经2,2‑二甲氧基丙烷保护邻二羟基合成中间体4，反应完毕后调碱降温；将无水氯化镁和中间体7加入反应中，通氮气流保护，搅拌均匀后滴加碱催化剂，升温搅拌，合成中间体5，反应完毕后进行提取分液；向反应中滴加第二酸催化剂，搅拌，经过后处理得到瑞德西韦粗品。本发明的三步反应均以第一溶剂为介质进行反应，仅在三步反应完成后进行后处理浓缩溶剂，减少浓缩溶剂的次数，降低工业成本。 - link

• 一种基于宏基因组学的病原微生物检测方法及装置 - 本发明公开了一种基于宏基因组学的病原微生物检测方法及装置，包括：获取待检测样本的宏基因组测序数据；对宏基因组测序数据进行预处理，得到目标数据；对目标数据进行筛选，得到目标序列；对目标序列进行聚类分析，获得待测样本的候选物种类别；将目标数据与非冗余参考基因集进行比对，并计算每个基因在单个样本中的丰度，得到待测样本的目标物种分类信息；将目标数据与病原微生物可检测数据库中的信息进行比对，获得待测样本的耐药基因和毒性元件信息；将目标物种分类信息、耐药基因和毒性元件信息，确定为待检测样本的检测结果。本发明提升了病原微生物检测适用性范围和病原检测准确性。 - link

• CONJUNTO DE ESCOBILLA Y ESCOBILLERO CON AUTOLIMPIEZA - - link