Covid-19 Sentry

Contents

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

From Preprints

• Temporal Pattern of Mutation Accumulation in SARS-CoV-2 Proteins: Insights from Whole Genome Sequences Pan-India Using Data Mining Approach -
  Mutation is a fundamental factor that affects host-pathogen biology and consequently viral survival and spread. Close monitoring and observation of such mutation help decipher essential changes in the SARS Cov2 genome. A plethora of mutations have been documented owing to increased whole genomic sequencing. Understanding how conserved the specific mutations are and the temporal pattern of mutation accumulation is of paramount interest. Using an in-house data mining approach, pan-India data was mined and analysed for 26 proteins expressed by SARS-CoV-2 to understand the spread of mutations over 28 months (January 2021- April 2023). It was observed that proteins such as Nsp3, Nsp4, ORF9b, among others, acquired mutations over the period. In contrast, proteins such as Nsp6-10 were highly stable, with no detectable conserved mutations. Further, it was observed that many of the mutations that were highly prevalent in the delta variants were not observed in the omicron variants, which probably influenced the host-pathogen relationship. The study attempts to catalogue and focus on well-conserved mutations across all the SARS-CoV-2 proteins, highlighting the importance of understanding non-spike mutations.
  🖺 Full Text HTML: Temporal Pattern of Mutation Accumulation in SARS-CoV-2 Proteins: Insights from Whole Genome Sequences Pan-India Using Data Mining Approach
• First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects wildlife. Recent studies highlighted that variants of concern (VOC) may expand into novel animal reservoirs with the potential for reverse zoonosis. North American white-tailed deer are the only deer species in which SARS-CoV-2 has been documented, raising the question whether further reservoir species exist as new VOC emerge. Here, we report the first cases of deer SARS-CoV-2 seropositivity in Eurasia, in a city population of fallow deer in Dublin, Ireland. Deer were seronegative in 2020 (circulating variant in humans: Alpha), one animal was seropositive in 2021 (Delta variant), and 57% of animals tested in 2022 were seropositive (Omicron variant). Ex vivo, a clinical isolate of Omicron BA.1 infected fallow deer precision cut lung slice type-2 pneumocytes, also a major target of infection in human lungs. Our findings suggest a change in host tropism as new variants emerged in the human reservoir, highlighting the importance of continued wildlife disease monitoring and limiting human-wildlife contacts.
  🖺 Full Text HTML: First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer
• Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states -
  The ability of a virus to infect a cell type is at least in part determined by the presence of host factors required for the viral life cycle. However, even within cell types that express known factors needed for infection, not every cell is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the most susceptible subsets of cells within a population may reveal additional factors that promote infection. However, because viral infection dramatically alters the state of the cell, new approaches are needed to reveal the state of these cells prior to infection with virus. Here, we used single-cell clone tracing to retrospectively identify and characterize lung epithelial cells that are highly susceptible to infection with SARS-CoV-2. The transcriptional state of these highly susceptible cells includes markers of retinoic acid signaling and epithelial differentiation. Loss of candidate factors identified by our approach revealed that many of these factors play roles in viral entry. Moreover, a subset of these factors exert control over the infectable cell state itself, regulating the expression of key factors associated with viral infection and entry. Analysis of patient samples revealed the heterogeneous expression of these factors across both cells and patients in vivo. Further, the expression of these factors is upregulated in particular inflammatory pathologies. Altogether, our results show that the variable expression of intrinsic cell states is a major determinant of whether a cell can be infected by SARS-CoV-2.
  🖺 Full Text HTML: Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states
• Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections -
  Previous studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.
  🖺 Full Text HTML: Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections
• Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant. -
  Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, the S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production of the recombinant S trimer and, more importantly, its immunogenicity, suggesting that these two parameters are related. However, S-2P still shows some molecular instability and it is produced with low yield. Thus, S-2P production can be further optimized. Here we described a novel set of mutations identified by molecular modelling and located in the S2 region of the Spike that increase S-2P production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 spike mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.
  🖺 Full Text HTML: Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.
• In vitro broad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses -
  The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay. We also evaluated the functional analysis of MIT-001 by JC-1 staining to measure mitochondrial depolarization, total RNA sequencing to investigate gene expression changes, and immunoblot to quantify protein expression levels. The results showed that MIT-001 effectively inhibited the replication of B.1.617.2 and BA.1 strains, Zika virus, Seoul virus, and Vaccinia virus. Treatment with MIT-001 restored the expression of heme oxygenase-1 (HMOX1) and NAD(P)H: quinone oxidoreductase 1 (NqO1) genes, anti-oxidant enzymes reduced by SARS-CoV-2, to normal levels. The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection. Keywords: COVID-19, MIT-001, ROS, HMOX1, NqO1, Broad-spectrum antiviral
  🖺 Full Text HTML: In vitro broad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses
• Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern -

  The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta, and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method, a statistical technique for the detection of aberrations in spatial point processes, applied to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. The application of RaNCover method could rapidly detect outbreaks of future SARS-CoV-2 variants of concern and hence inform optimal spatial interventions.

  🖺 Full Text HTML: Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern
• Long-term symptom profiles after COVID-19 vs other acute respiratory infections: a population-based observational study (COVIDENCE UK) -

  Summary Background: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms. Methods: COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data on 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported in January, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). Findings: We included 10,203 participants (1343 [13.2%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of taste/smell problems and hair loss compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (including 23% of participants with SARS-CoV-2, and 21% with non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of memory problems, difficulty concentrating, hair loss, and taste/smell problems than non-COVID-19 ARI. Interpretation: Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of long-term symptoms. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens. Funding: Barts Charity.

  🖺 Full Text HTML: Long-term symptom profiles after COVID-19 vs other acute respiratory infections: a population-based observational study (COVIDENCE UK)
• Characterising information loss due to aggregating epidemic model outputs -

  Background. Collaborative comparisons and combinations of multiple epidemic models are used as policy-relevant evidence during epidemic outbreaks. Typically, each modeller summarises their own distribution of simulated trajectories using descriptive statistics at each modelled time step. We explored information losses compared to directly collecting a sample of the simulated trajectories, in terms of key epidemic quantities, ensemble uncertainty, and performance against data. Methods. We compared July 2022 projections from the European COVID-19 Scenario Modelling Hub. Using shared scenario assumptions, five modelling teams contributed up to 100 simulated trajectories projecting incidence in Belgium, the Netherlands, and Spain. First, we compared epidemic characteristics including incidence, peaks, and cumulative totals. Second, we drew a set of quantiles from the sampled trajectories for each model at each time step. We created an ensemble as the median across models at each quantile, and compared this to an ensemble of quantiles drawn from all available trajectories at each time step. Third, we compared each trajectory to between 4 and 29 weeks of observed data, using the mean absolute error to weight trajectories in consecutive ensembles. Results. We found that collecting models9 simulated trajectories, as opposed to collecting models9 quantiles at each time point, enabled us to show additional epidemic characteristics, a wider range of uncertainty, and performance against data. Sampled trajectories contained a right-skewed distribution which was poorly captured by an ensemble of models9 quantile intervals. Ensembles weighted by predictive performance narrowed the range of plausible incidence over time, excluding some epidemic shapes altogether. Conclusions. Understanding potential information loss when collecting model projections can support the accuracy, reliability, and communication of collaborative infectious disease modelling efforts. The importance of different information losses may vary with each collaboration9s aims, with lesser impact on short term predictions compared to assessing threshold risks and longer term uncertainty.

  🖺 Full Text HTML: Characterising information loss due to aggregating epidemic model outputs
• Cytokine storm mitigation for exogenous immune agonists -
  Cytokine storm is a life-threatening inflammatory response characterized by hyperactivation of the immune system. It can be caused by various therapies, auto-immune conditions, or pathogens, such as respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease COVID-19. Here we propose a conceptual mathematical model describing the phenomenology of cytokine-immune interactions when a tumor is treated by an exogenous immune cell agonist which has the potential to cause a cytokine storm, such as CAR T cell therapy. Numerical simulations reveal that as a function of just two model parameters, the same drug dose and regimen could result in one of four outcomes: treatment success without a storm, treatment success with a storm, treatment failure without a storm, and treatment failure with a storm. We then explore a scenario in which tumor control is accompanied by a storm and ask if it is possible to modulate the duration and frequency of drug administration (without changing the cumulative dose) in order to preserve efficacy while preventing the storm. Simulations reveal existence of a sweet spot in protocol space (number versus spacing of doses) for which tumor control is achieved without inducing a cytokine storm. This theoretical model, which contains a number of parameters that can be estimated experimentally, contributes to our understanding of what triggers a cytokine storm, and how the likelihood of its occurrence can be mitigated.
  🖺 Full Text HTML: Cytokine storm mitigation for exogenous immune agonists
• SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection -
  A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones whose inhibition impairs infectious particle production without major toxicity to the host. We find that CoV2 non-structural protein Nsp1 selectively enhances virus translation through functional interactions with initiation factor EIF1A. When EIF1A is depleted, more ribosomes initiate translation from an upstream CUG start codon, inhibiting translation of non-structural genes and reducing viral titers. Together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and identifies druggable targets for potential antiviral development.
  🖺 Full Text HTML: SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection
• Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes -

  Background: COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis is a serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. Methods: COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities. Results: A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with a mean age of 63.8 ± 1.6 years, and 32.2% females. Intracardiac thrombosis was present in 0.001% (1,830) patients. Overall, in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. The main factors associated with intracardiac thrombosis were a history of congestive heart failure and coagulopathy. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95% CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95% CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95% CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95% CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95% CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95% CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27). Conclusion: Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there is a high index of suspicion and a confirmed diagnosis respectively.

  🖺 Full Text HTML: Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes
• Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial -

  Background. Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX CoV2373), to assess antibody responses to SARS-CoV-2. Methods. Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. Results. Of participants who received trial vaccine (N=829), those administered NVX-CoV2515 (n=286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n=274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated. Conclusions. NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.

  🖺 Full Text HTML: Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial
• Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases -

  Background: Societal separation of unvaccinated people from public spaces has been a novel and controversial COVID-era public health practice in many countries. Models exploring potential consequences of vaccination-status-based separation have not considered how separation influences the contact frequencies in the separated groups; we systematically investigate implementing effects of separation on person-to-person contact frequencies and show this critically determines the predicted epidemiological outcomes, focusing on the attack rates in the vaccinated and unvaccinated populations and the share of infections among vaccinated people that were due to contacts with infectious unvaccinated people. Methods: We describe a susceptible-infectious-recovered (SIR) two-population model for vaccinated and unvaccinated groups of individuals that transmit an infectious disease by person-to-person contact. The degree of separation between the two groups, ranging from zero to complete separation, is implemented using the like-to-like mixing approach developed for sexually-transmitted diseases [1-3], adapted for presumed SARS-CoV-2 transmission. We allow the contact frequencies for individuals in the two groups to be different and depend, with variable strength, on the degree of separation. Results: Separation can either increase or decrease the attack rate among the vaccinated, depending on the type of separation (isolating or compounding), and the contagiousness of the disease. For diseases with low contagiousness, separation can cause an attack rate in the vaccinated, which does not occur without separation. Interpretation: There is no blanket epidemiological advantage to separation, either for the vaccinated or the unvaccinated. Negative epidemiological consequences can occur for both groups.

  🖺 Full Text HTML: Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases
• The K+/Na+ innate immune system is involved in the susceptibility to and severity of COVID-19: a systematic review and retrospective cohort study -

  Abstract Background: From single-cellular to multicellular organisms, a natural nonspecific immune system, called the K+/Na+ innate immune system, has recently been proposed to play an important role in the process of fighting against viral infection, however, there is little direct research evidence. This study aimed to evaluate whether the changes in serum K+/Na+ concentrations are associated with susceptibility and severity of SARS-CoV-2 infection. Methods: We systematically searched PubMed, the Web of Science Core Collection, MedRxiv and BioRxiv databases for articles published between Jan 1, 2020 and Dec 14, 2022. We extracted the serum K+/Na+ concentration data of patients with COVID-19 from 112 published studies after removing inappropriate articles according to the defined criteria and analyzed the relationship between the serum k+/Na+ concentrations and the illness severity of patients. Then we used a cohort of 244 patients with COVID-19 for a retrospective analysis. Results: The mean serum k+/Na+ concentrations in patients with COVID-19 were 3.99 and 138.0 mmol/L, respectively, which were much lower than the mean levels in the population (4.40 and 142.0, respectively). The mean serum Na+ concentration in severe/critical patients (136.8) was significantly lower than those in mild and moderate patients (139.4 and 138.0, respectively). Such findings were confirmed in a retrospective cohort study, of which the mean serum k+/Na+ concentrations in all patients were 4.0 and 137.5 mmol/L, respectively. The significant differences in serum Na+ concentrations were found between the mild (139.2) and moderate (137.2) patients, and the mild and severe/critical (136.6) patients, which were correlated to the illness severity of patients. Conclusions: These findings may indicate the importance of a natural immune system constructed by intracellular potassium and extracellular sodium ions in the fight against viral infection and provide new ideas for the prevention and treatment of COVID-19.

  🖺 Full Text HTML: The K+/Na+ innate immune system is involved in the susceptibility to and severity of COVID-19: a systematic review and retrospective cohort study

From Clinical Trials

• Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine
  Sponsor:   PT Bio Farma
  Not yet recruiting

• Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Colchicine 0.5 MG;   Drug: Standared managment
  Sponsor:   Ain Shams University
  Completed

• A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-2;   Biological: SCTV01E
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists - Condition:   COVID-19
  Interventions:   Behavioral: Standard implementation webinar and online training;   Behavioral: Virtual facilitation
  Sponsors:   University of North Carolina, Chapel Hill;   University of Arkansas;   University of South Carolina;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients - Conditions:   COVID-19;   Hospitalized COVID-19 Patients
  Interventions:   Drug: Lopinavir / Ritonavir;   Drug: Remdesivir (RDV);   Drug: Tocilizumab;   Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
  Sponsors:   Lebanese University;   Hospital Saydet Zgharta University Medical Center
  Recruiting

• Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+ - Condition:   COVID-19
  Intervention:   Device: Resistance Training
  Sponsor:   Józef Piłsudski University of Physical Education
  Recruiting

• Comprehensive Imaging Exam of Convalesced COVID-19 Patients - Conditions:   COVID-19;   COVID Long-Haul
  Interventions:   Other: Magnetic Resonance Imaging;   Other: Ultra-High Resolution Computed Tomography (CT) Scan
  Sponsors:   Johns Hopkins University;   Canon Medical Systems, USA
  Enrolling by invitation

• Multimodal Long Covid19 - Condition:   Long COVID-19 Syndrome
  Intervention:   Other: Multimodal intervention in Long Covid19
  Sponsors:   Universidad de Magallanes;   Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG;   Clinical Hospital Dr. Lautaro Navarro Avaria
  Active, not recruiting

• UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study) - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults - Condition:   COVID-19
  Interventions:   Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection;   Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection
  Sponsor:   Clover Biopharmaceuticals AUS Pty Ltd
  Not yet recruiting

• The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002 - Condition:   COVID-19
  Interventions:   Biological: LYB002V14;   Biological: LYB002V14A;   Biological: LYB002CA
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2373 (5μg);   Biological: NVX-CoV2601 (5μg);   Biological: NVX-CoV2601(5μg);   Biological: NVX-CoV2601 (35μg);   Biological: NVX-CoV2601(35μg);   Biological: NVX-CoV2601(50μg);   Biological: Bivalent BA.4/5
  Sponsor:   Novavax
  Not yet recruiting

• The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001 - Conditions:   COVID-19;   Vaccine Reaction
  Interventions:   Biological: LYB001;   Biological: CoronaVac
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome - Condition:   Post-Acute COVID-19 Syndrome
  Interventions:   Drug: Placebo;   Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Not yet recruiting

• The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19 - Conditions:   Coronavirus Disease;   COVID-19;   Long Covid-19;   Telerehabilitation
  Interventions:   Device: KNEESUP smart knee assistive device + KNEESUP care APP;   Device: KNEESUP care APP;   Behavioral: Healthy consulation
  Sponsor:   Shang-Lin Chiang
  Recruiting

From PubMed

• Targeting 2-Oxoglutarate-Dependent Dioxygenases Promotes Metabolic Reprogramming That Protects against Lethal SARS-CoV-2 Infection in the K18-hACE2 Transgenic Mouse Model - Dysregulation of host metabolism is a feature of lethal SARS-CoV-2 infection. Perturbations in α-ketoglutarate levels can elicit metabolic reprogramming through 2-oxoglutarate-dependent dioxygenases (2-ODDGs), leading to stabilization of the transcription factor HIF-1α. HIF1-α activation has been reported to promote antiviral mechanisms against SARS-CoV-2 through direct regulation of ACE2 expression (a receptor required for viral entry). However, given the numerous pathways HIF-1α serves to…

• Individuals at risk for severe COVID-19 in whom ritonavir-containing therapies are contraindicated or may lead to interactions with concomitant medications: a retrospective analysis of German health insurance claims data - CONCLUSION: Administering ritonavir-containing COVID-19 therapy can be challenging as thorough medical record review and close monitoring are required. In some cases, ritonavir-containing treatment may not be appropriate due to contraindications, risk of pDDIs, or both. For those individuals, an alternative ritonavir-free treatment should be considered.

• e-Pharmacophore modeling and in silico study of CD147 receptor against SARS-CoV-2 drugs - Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the…

• Investigating theobromine as a potential anti-human coronaviral agent - Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting…

• SARS-CoV-2 Nsp1 mediated mRNA degradation requires mRNA interaction with the ribosome - Nsp1 is a SARS-CoV-2 host shutoff factor that both represses cellular translation and promotes host RNA decay. However, it is unclear how these two activities are connected and interact with normal translation processes. Here, we performed mutational analyses of Nsp1, and these revealed that both the N and C terminal domains of Nsp1 are important for translational repression. Furthermore, we demonstrate that specific residues in the N terminal domain are required for cellular RNA degradation but…

• Repurposing Polyether Ionophores as a New-Class of Anti-SARS-Cov-2 Agents as Adjunct Therapy - The emergence of SARS-CoV-2 and its variants have posed a significant threat to humankind in tackling the viral spread. Furthermore, currently repurposed drugs and frontline antiviral agents have failed to cure severe ongoing infections effectively. This insufficiency has fuelled research for potent and safe therapeutic agents to treat COVID-19. Nonetheless, various vaccine candidates have displayed a differential efficacy and need for repetitive dosing. The FDA-approved polyether ionophore…

• Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current - Remdesivir, approved for the treatment of coronavirus disease (COVID-19), has been associated with QTc interval prolongation and torsade de pointes (TdP) in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related (hERG)-related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney (HEK 293) cells stably expressing hERG…

• The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression - Identification of host determinants of coronavirus infection informs mechanisms of pathogenesis and may provide novel therapeutic targets. Here, we demonstrate that the histone demethylase KDM6A promotes infection of diverse coronaviruses, including SARS-CoV, SARS-CoV-2, MERS-CoV and mouse hepatitis virus (MHV) in a demethylase activity-independent manner. Mechanistic studies reveal that KDM6A promotes viral entry by regulating expression of multiple coronavirus receptors, including ACE2, DPP4…

• Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid protein….

• Conformational response to ligand binding of TMPRSS2, a protease involved in SARS-CoV-2 infection: Insights through computational modeling - Thanks to the considerable research which has been undertaken in the last few years to improve our understanding of the biology and mechanism of action of SARS-CoV-2, we know how the virus uses its surface spike protein to infect host cells. The transmembrane prosthesis, serine 2 (TMPRSS2) protein, located on the surface of human cells, recognizes the cleavage site in the spike protein, leading to the release of the fusion peptide and entry of the virus into the host cells. Because of its role,…

• Respiratory infections in children and adolescents in Germany during the COVID-19 pandemic - CONCLUSIONS: While the measures taken were effective in inhibiting the number of respiratory infections for almost 1.5 years, moderately frequent but rather mild COVID-19 cases occurred when measures were lifted. When Omicron emerged in 2022 COVID-19 became moderately frequent but led predominantly to mild illnesses. For RSV and influenza, the measures resulted in changes in their annual timing and intensity.

• Maternal prenatal attachment during the COVID-19 pandemic: exploring the roles of pregnancy-related anxiety, risk perception, and well-being - Pregnant women have faced novel physical and mental health risks during the pandemic. This situation is remarkable because a parent’s emotional bond with their unborn baby (also known as prenatal attachment) is related to the parent’s mental state. Prenatal attachment helps parents psychologically prepare for the transition into parenthood. Moreover, it plays a pivotal role in the future parentchild relationship and psychosocial development of the baby. Based on the available literature, the…

• Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants - SARS-CoV-2 poses an unprecedented threat to the world as the causative agent of the COVID-19 pandemic. Among a handful of therapeutics developed for the prevention and treatment of SARS-CoV-2 infection, ensitrelvir is the first noncovalent and nonpeptide oral inhibitor targeting the main protease (M^(pro)) of SARS-CoV-2, which recently received emergency regulatory approval in Japan. Here we determined a 1.8-Å structure of M^(pro) in complex with ensitrelvir, which revealed that ensitrelvir…

• Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice - As the COVID-19 pandemic transitions into endemicity, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist…

• Synthesis and characterization of n-phosphonium chitosan and its virucidal activity evaluation against coronavirus - Despite the worldwide vaccination effort against COVID-19, the demand for biocidal materials has increased. One promising solution is the chemical modification of polysaccharides, such as chitosan, which can provide antiviral activity through the insertion of cationic terminals. In this study, chitosan was modified with (4-carboxybutyl) triphenylphosphonium bromide to create N-phosphonium chitosan (NPCS), a quaternized derivative. The resulting NPCS samples with three degrees of substitution…

From Patent Search