Covid-19 Sentry

Contents

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

From Preprints

• Who are the Masked Unvaccinated and the Unmasked Vaccinated? Concern, Trust, and Demographic Features relating to Mask-wearing and Vaccination Status -
  In mid-August 2021, the Centers for Disease Control and Prevention (C.D.C.) issued a recommendation for both vaccinated and unvaccinated Americans to begin wearing masks in public again, particularly in places experiencing outbreaks of COVID-19, driven by the Delta variant. Further compounding this concern is the lower propensity of unvaccinated individuals to wear masks. For example, a report from July 2021 found that unvaccinated Americans, on average, tended to wear masks less than vaccinated Americans by a margin of 25 percentage points. Given the link between mask-wearing and vaccination, discussions of behaviors relating to COVID-19 often lump people into two categories: those who behave in ways that prevent the spread of COVID-19 and those who do not. However, doing so misses the complexity of who engages or doesn’t engage in behaviors that stem the spread of COVID-19, or why they do so. Vaccination and mask-wearing are two different means to the same end: preventing infection. They are, in part, driven by the same factor, concern over infection. But they are also partial substitutes, aimed at the same target, preventing infection. In our data, we find that 30% of the population is either vaccinated and unmasked; or unvaccinated and masked. Indeed, most unvaccinated individuals report wearing masks. Understanding this complexity is significant in getting people vaccinated, and in getting people to wear masks - particularly those who are unvaccinated. In this report, we divide Americans into four categories and investigate the tendencies of each group: (1) those who report wearing masks and who are unvaccinated (“the masked unvaccinated”), (2) those who report wearing masks and who are vaccinated (“the masked vaccinated”), (3) those who report not wearing masks and who are unvaccinated (“the unmasked unvaccinated”), and (4) those who report not wearing masks and who are vaccinated (“the unmasked vaccinated”).

• Heterologous SARS-CoV-2 Booster Vaccinations: Preliminary Report -

  Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x10¹⁰ virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

  🖺 Full Text HTML: Heterologous SARS-CoV-2 Booster Vaccinations: Preliminary Report
• The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission -

  Background Pre-Delta, vaccination reduced SARS-CoV-2 transmission from individuals infected despite vaccination, potentially via reducing viral loads. While vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated individuals infected with Delta question how much vaccination prevents transmission. Methods We performed a retrospective observational cohort study of adult contacts of SARS-CoV-2-infected adult index cases using English contact testing data. We used multivariable Poisson regression to investigate associations between transmission and index case and contact vaccination, and how these vary with Alpha and Delta variants (classified using S-gene detection/calendar trends) and time since second vaccination. Results 54,667/146,243(37.4%) PCR-tested contacts of 108,498 index cases were PCR-positive. Two doses of BNT162b2 or ChAdOx1 vaccines in Alpha index cases were independently associated with reduced PCR-positivity in contacts (aRR, adjusted rate ratio vs.  unvaccinated=0.32[95%CI 0.21-0.48] and 0.48[0.30-0.78] respectively). The Delta variant attenuated vaccine- associated reductions in transmission: two BNT162b2 doses reduced Delta transmission (aRR=0.50[0.39-0.65]), more than ChAdOx1 (aRR=0.76[0.70-0.82]). Variation in Ct values (indicative of viral load) explained 7-23% of vaccine- associated transmission reductions. Transmission reductions declined over time post-second vaccination, for Delta reaching similar levels to unvaccinated individuals by 12 weeks for ChAdOx1 and attenuating substantially for BNT162b2. Protection in contacts also declined in the 3 months post-second vaccination. Conclusions Vaccination reduces transmission of Delta, but by less than the Alpha variant. The impact of vaccination decreased over time. Factors other than PCR Ct values at diagnosis are important in understanding vaccine-associated transmission reductions. Booster vaccinations may help control transmission together with preventing infections.

  🖺 Full Text HTML: The impact of SARS-CoV-2 vaccination on Alpha and Delta variant transmission
• Soluble angiotensin-converting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2 -

  Background: There is a need for better prediction of disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble angiotensin-converting enzyme 2 (sACE2) arises from shedding of membrane ACE2 (mACE2) that is known to be a receptor for the spike protein of SARS-CoV-2; however, its value as a biomarker for disease severity is unknown. This study evaluated the predictive value of sACE2 in the context of other known biomarkers of inflammation and tissue damage (C-reactive protein [CRP], growth/differentiation factor-15 [GDF-15], interleukin-6 [IL-6], and soluble fms-like tyrosine kinase-1 [sFlt-1]) in patients with and without SARS-CoV-2 with different clinical outcomes. Methods: For univariate analyses, median differences between biomarker levels were calculated for the following patient groups classified according to clinical outcome: reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 positive (Groups 1 – 4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and RT-PCR-confirmed SARS-CoV-2 negative controls (Group 7). Results: Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in patients with SARS-CoV-2 who were admitted to hospital compared with patients who were discharged (all p<0.001), whereas levels of sACE2 were significantly lower (p<0.001). Receiver operating characteristic curve analysis of sACE2 provided cut-offs for the prediction of hospital admission of ≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%). Conclusion: These findings support further investigation of sACE2, either as a single biomarker or as part of a panel, to predict hospitalisation risk and disease severity in patients infected with SARS-CoV-2.

  🖺 Full Text HTML: Soluble angiotensin-converting enzyme 2 as a prognostic biomarker for disease progression in patients infected with SARS-CoV-2
• ONTdeCIPHER: An amplicon-based nanopore sequencing pipeline for tracking pathogen variants -
  Motivation: Amplicon-based nanopore sequencing is increasingly used for molecular surveillance during epidemics (e.g. ZIKA, EBOLA) or pandemics (e.g. SARS-CoV-2). However, there is still a lack of versatile and easy-to-use tools that allow users with minimal bioinformatics skills to perform the main steps of downstream analysis, from quality testing to SNPs effect to phylogenetic analysis. Results: Here, we present ONTdeCIPHER, an amplicon-based Oxford Nanopore Technology (ONT) sequencing pipeline to analyze the genetic diversity of SARS-CoV-2 and other pathogenes. Our pipeline integrates 13 bioinformatics tools. With a single command line and a simple configuration file, users can pre- process their data and obtain the sequencing statistics, reconstruct the consensus genome, identify variants and their effects for each viral isolate, infer lineage and, finally perform multi-sequence alignments and phylogenetic analyses.
  🖺 Full Text HTML: ONTdeCIPHER: An amplicon-based nanopore sequencing pipeline for tracking pathogen variants
• Disparities in SARS-CoV-2 exposure: evidence from a citywide seroprevalence study in Holyoke, Massachusetts, USA -

  Background: Seroprevalence studies are important tools to estimate the prevalence of prior or recent SARS-CoV-2 infections, identifying hotspots and high-risk groups and informing public health responses to the COVID-19 pandemic. We conducted a city-level seroprevalence study in Holyoke, Massachusetts, USA to estimate the seroprevalence of SARS-CoV-2 antibodies and risk factors for seropositivity. Methods: We invited inhabitants of 2,000 randomly sampled addresses between November 5 and December 31, 2020. Participants completed questionnaires measuring sociodemographic and health characteristics, and COVID-19 exposure history, and provided dried blood spots for measurement of SARS-CoV-2 IgG and IgM antibodies. We calculate total and subgroup seroprevalence estimates based on presence of IgG antibodies using a Bayesian procedure that incorporates uncertainty in antibody test sensitivity and specificity. We account for clustering by household and weighting based on demographic characteristics to ensure estimates represented the citys population. Findings: We enrolled 280 households including 472 individuals. 328 underwent antibody testing. The citywide seroprevalence estimate of SARS-CoV-2 IgG was 13.1% (95%CI 6.9-22.3) compared to 9.8% based on publicly reported case counts. Seroprevalence was 16.1% (95%CI 6.2-31.8) among individuals identifying as Hispanic compared to 9.4% (95%CI 4.6-16.4) among those identifying as non-Hispanic white. Seroprevalence was higher among Spanish speaking households (21.9%; 95% CI 8.3-43.9) compared to English speaking households (10.2%; 95% CI 5.2-18.0) and among individuals living in high vulnerability areas (14.4%; 95% CI 7.1-25.5) compared to low vulnerability areas (8.2%; 95% CI 3.1-16.9). Interpretation: The measured SARS-CoV-2 seroprevalence of IgG antibodies in Holyoke was only 13.1% during the second surge of SARS-CoV-2 in this region, far from accepted thresholds for herd immunity. Already vulnerable communities were at highest risk of prior infection. Implementation of local serosurveys in tandem with proactive public health interventions that address disparities in SARS-CoV-2 exposure are crucial to ensure at-risk communities have appropriate educational materials and access to vaccines, testing, and timely treatment.

  🖺 Full Text HTML: Disparities in SARS-CoV-2 exposure: evidence from a citywide seroprevalence study in Holyoke, Massachusetts, USA
• Mechanism of optimal time-course COVID-19 vaccine prioritization based on non-Markovian steady-state prediction -

  Vaccination is essential for controlling the coronavirus disease (COVID-19) pandemic. An effective time-course strategy for the allocation of COVID-19 vaccines is crucial given that the global vaccine supply will still be limited in some countries/regions in the near future and that mutant strains have emerged and will continue to spread worldwide. Both asymptomatic and symptomatic transmission have played major roles in the COVID-19 pandemic, which can only be properly described as a typical non-Markovian process. However, the prioritization of vaccines in the non-Markovian framework still lacks sufficient research, and the underlying mechanism of the time-course vaccine allocation optimization has not yet been uncovered. In this paper, based on an age-stratified compartmental model calibrated through clinical and epidemiological data, we propose optimal vaccination strategies (OVS) through steady-state prediction in the non-Markovian framework. This OVS outperforms other empirical vaccine prioritization approaches in minimizing cumulative infections, cumulative deaths, or years of life lost caused by the pandemic. We found that there exists a fast decline in the prevention efficiency of vaccination if vaccines are solely administered to a selected age group, which indicates that the widely adopted strategy to continuously vaccinate high-risk group is not optimal. Through mathematical analysis of the model, we reveal that dynamic vaccine allocations to combinations of different age groups is necessary to achieve optimal vaccine prioritization. Our work not only provides meaningful references for vaccination in countries currently lacking vaccines and for vaccine allocation strategies to prevent mutant strains in the future, but also reveals the mechanism of dynamic vaccine allocation optimization, forming a theoretical and modelling framework empirically applicable to the optimal time-course prioritization.

  🖺 Full Text HTML: Mechanism of optimal time-course COVID-19 vaccine prioritization based on non-Markovian steady-state prediction
• A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses -
  The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS- CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.
  🖺 Full Text HTML: A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses
• Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection. -
  The COVID-19 disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has two characteristics that distinguish it from other viral infections. It affects more severely people with pre-existing comorbidities and viral load peaks prior to the onset of the symptoms. Investigating factors that could contribute to these characteristics, we found increased mTOR signaling and suppressed genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2. Transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients revealed that COVID-19 severity is associated with increased expression of genes related to mTOR signaling and decreased expression of genes related to au-tophagy, lysosome function, and vesicle fusion. SARS- CoV-2 infection in Vero E6 cells also re-sulted in virus retention inside the cells and trafficking of virus-bearing vesicles between neighboring cells. Our findings support a scenario where SARS-CoV-2 benefits from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling, which might relate to undetectable proliferation and evasion of the immune system.
  🖺 Full Text HTML: Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection.
• Variable inhibition of unwinding rates of DNA catalyzed by the SARS-Cov-2 (COV19) helicase nsp13 by structurally distinct single DNA lesions. -
  The SARS 2 (Covid 19) helicase nsp13 plays a critically important role in the replication of the Corona virus by unwinding double-stranded RNA (and DNA) with a 5 prime to 3 prime strand polarity. Here we explored the impact of single, structurally defined covalent DNA lesions on the helicase activity of nsp13 in aqueous solutions, The objectives were to derive mechanistic insights into the relationships between the structures of DNA lesions, the DNA distortions that they engender, and the inhibition of helicase activity. The lesions included two bulky stereoisomeric N2-guanine adducts derived from the reactions of benzo[a]pyrene diol epoxide with DNA. The trans-adduct assumes a minor groove conformation, while the cis-product adopts a base-displaced intercalated conformation. The non-bulky DNA lesions included the intra-strand cross-linked thymine dimers, the cis-syn-cyclobutane pyrimidine dimer, and the pyrimidine (6-4) pyrimidone photoproduct. All four lesions strongly inhibit the helicase activity of nsp13, The UV photolesions feature a 2 - 5-fold smaller inhibition of the nsp13 unwinding activity than the bulky DNA adducts, and the kinetics of these two pairs of DNA lesions are also different. The connections between the structural features of these four DNA lesions and their impact on nsp13 unwinding efficiencies are discussed.
  🖺 Full Text HTML: Variable inhibition of unwinding rates of DNA catalyzed by the SARS-Cov-2 (COV19) helicase nsp13 by structurally distinct single DNA lesions.
• Which anxious adolescents are most impacted by the COVID-19 pandemic? -
  Although the COVID-19 pandemic caused significant stress and anxiety among many, individuals’ experiences varied. We examined if specific forms of anxiety predicted distinct trajectories of anxiety, perceived stress, and COVID-related worries during three early months of the pandemic. In a longitudinal study (N = 291), adolescents’ (n = 194) social and generalized anxiety levels were assessed via parent- and self-reports and clinical diagnostic interviews. In young adulthood (n = 164), anxiety, stress, and COVID-related worries were assessed thrice during the pandemic. Pre- pandemic generalized anxiety predicted higher initial levels and maintenance of anxiety, stress, and COVID-related worries during the pandemic. In contrast, pre-pandemic social anxiety predicted lower initial levels of anxiety, stress, and COVID-related worries, but this initial effect on anxiety and stress was offset over time by social anxiety’s positive effect on the slope. Our results highlight the importance of understanding how pre-pandemic factors influence individuals’ experiences during the pandemic.
  🖺 Full Text HTML: Which anxious adolescents are most impacted by the COVID-19 pandemic?
• Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021 -

  National data on COVID-19 vaccine breakthrough infections is inadequate but urgently needed to determine U.S. policy during the emergence of the Delta variant. We address this gap by comparing SARS CoV-2 infection by vaccination status from February 1, 2021 to August 13, 2021 in the Veterans Health Administration, covering 2.7% of the U.S. population. Vaccine protection declined by mid-August 2021, decreasing from 91.9% in March to 53.9% (p<0.01, n=619,755). Declines were greatest for the Janssen vaccine followed by PfizerBioNTech and Moderna. Patterns of breakthrough infection over time were consistent by age, despite rolling vaccine eligibility, implicating the Delta variant as the primary determinant of infection. Findings support continued efforts to increase vaccination and an immediate, national return to additional layers of protection against infection.

  🖺 Full Text HTML: Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021
• Modelling airborne transmission of SARS-CoV-2 using CARA: Risk assessment for enclosed spaces -

  The global crisis triggered by the COVID-19 pandemic has highlighted the need for a proper risk assessment of respiratory pathogens in indoor settings. This paper documents the COVID Airborne Risk Assessment (CARA) methodology, to assess the potential exposure of airborne SARS-CoV-2 viruses, with an emphasis on the effect of certain virological and immunological factors in the quantification of the risk. The proposed model is the result of a multidisciplinary approach linking physical, mechanical and biological domains, benchmarked with clinical and experimental data, enabling decision makers or facility managers to perform risk assessments against airborne transmission. The model was tested against two benchmark outbreaks, showing good agreement. The tool was also applied to several everyday-life settings, in particular for the cases of a shared office, classroom and ski cabin. We found that 20% of infected hosts can emit approximately 2 orders of magnitude more viral-containing particles, suggesting the importance of super-emitters in airborne transmission. The use of surgical-type masks provides a 5-fold reduction in viral emissions. Natural ventilation through the opening of windows at all times are effective strategies to decrease the concentration of virions and slightly opening a window in the winter has approximately the same effect as a full window opening during the summer. Although vaccination is an effective protection measure, non-pharmaceutical interventions, which significantly reduce the viral density in the air (ventilation, masks), should be actively supported and included early in the risk assessment process. We propose a critical threshold value approach which could be used to define an acceptable risk level in a given indoor setting.

  🖺 Full Text HTML: Modelling airborne transmission of SARS-CoV-2 using CARA: Risk assessment for enclosed spaces
• Effects of Side-Effect Risk Framing Strategies on COVID-19 Vaccine Intentions in the United States and the United Kingdom: A Randomized Controlled Trial -

  Vaccination rates have stagnated in the United States and the United Kingdom leading to the continuing spread of COVID-19. Fear and concern over vaccine side-effects is one of the main drivers of hesitancy. Drawing from behavioral science and health communication theory, we conducted a randomized controlled trial among 8998 adults to determine whether the way COVID-19 vaccine side-effects are framed and presented to individuals can influence their willingness to take a vaccine. We presented participants information on a hypothetical future COVID-19 vaccine – including information on its side-effect rate – and then examined the effect of three side-effect framing strategies on individuals stated willingness to take this vaccine: adding a qualitative risk label next to the numerical risk, adding comparison risks, and for those presented with comparisons, framing the comparison in relative rather than absolute terms. Based on a pre-registered and published analysis plan, we found that adding a simple descriptive risk label (very low risk) next to the numerical side-effect increased participants9 willingness to take the COVID-19 vaccine by 3.0 percentage points (p = 0.003). Providing a comparison to motor vehicle mortality increased COVID-19 vaccine willingness by 2.4 percentage points (p = 0.051). These effects were independent and additive: participants that received both a qualitative risk label and comparison to motor-vehicle mortality were 6.1 percentage points (p < 0.001) more likely to report willingness to take a vaccine compared to those who did not receive a label or comparison. Taken together, our results reveal that despite increasingly strong vaccination hesitancy and exposure to large amounts of vaccine misinformation, low-cost side-effect framing strategies can meaningfully affect vaccination intentions at a population level.

  🖺 Full Text HTML: Effects of Side-Effect Risk Framing Strategies on COVID-19 Vaccine Intentions in the United States and the United Kingdom: A Randomized Controlled Trial
• Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution -

  Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii).

  🖺 Full Text HTML: Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution

From Clinical Trials

• Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: AD17002;   Biological: Placebo (Formulation buffer)
  Sponsor:   Advagene Biopharma Co. Ltd.
  Not yet recruiting

• Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition:   Covid19
  Intervention:   Device: Inspiratory muscle training
  Sponsor:  
  Universidade Federal do Rio Grande do Norte
  Recruiting

• Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition:   COVID-19
  Interventions:   Other: Lymphatic OMM;   Other: Light Touch
  Sponsor:   Rowan University
  Not yet recruiting

• Efficacy and Safety of Ergoferon for COVID-19 Prevention During Vaccination Against SARS-CoV-2 - Condition:   Immunization Against COVID-19
  Interventions:   Drug: Ergoferon;   Drug: Placebo
  Sponsor:   Materia Medica Holding
  Recruiting

• Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine;   Biological: SARS-CoV-2 Inactivated Vaccine
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Not yet recruiting

• A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Drug: VXA-CoV2-1.1-S;   Other: Placebo Tablets
  Sponsor:   Vaxart
  Recruiting

• Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition:   COVID-19
  Intervention:   Diagnostic Test: diaphragm ultrasonography
  Sponsor:   University Hospital, Limoges
  Not yet recruiting

• A Safety and Tolerability Study of BDB-001 in Mild, Moderate COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: BDB-001 injection
  Sponsors:  
  Staidson (Beijing) Biopharmaceuticals Co., Ltd;   Beijing Defengrui Biotechnology Co. Ltd
  Completed

• Acetylsalicylic Acid in COVID-19 (ASA-SARS) - Conditions:   SARS-CoV2 Infection;   Covid19
  Interventions:   Drug: Low-dose acetylsalicylic acid;   Drug: Placebo
  Sponsors:   Barcelona Institute for Global Health;   Hospital Universitario de Torrejón,Madrid;   Hospital Universitario Infanta Leonor;   Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau;   Hospital del Mar;   Hopsital Central de Maputo, Mozambique
  Not yet recruiting

• Telerehabilitation in COVID-19 Survivors - Conditions:   COVID-19;   Telerehabilitation
  Interventions:   Other: telerehabilitation;   Other: home exercise program;   Other: informed program
  Sponsor:   Bandırma Onyedi Eylül University
  Recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells,NVSI-06-08) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08);   Biological: COVID-19 vaccine (Vero cells);   Biological: 3 doses Recombinant COVID-19 Vaccine (CHO cell，NVSI-06-08)
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Phase 3 Booster Vaccination Against SARS-CoV-2 - Conditions:   COVID-19;   Sars-CoV-2 Infection
  Intervention:   Biological: CoronaVac
  Sponsor:   Health Institutes of Turkey
  Recruiting

• SARS-CoV-2 Buccal Screening Evaluation Using an RT-PCR Assay and a Rapid ELISA Test Among Symptomatic and Asymptomatic Patients - Conditions:   SARS-CoV-2;   COVID-19
  Intervention:   Diagnostic Test: ELISA POCT vs RT-PCR
  Sponsors:   Centre Scientifique de Monaco;   Department of Health Affairs, Monaco
  Recruiting

• Study on COVID-19 Vaccine Effectiveness Among Health Workers in Azerbaijan - Conditions:   Vaccine Refusal;   Covid19
  Intervention:   Biological: COVID-19 vaccine Observation of individuals who receive the COVID-19 vaccine
  Sponsors:   Public health and reforms Center of Ministry of Health;   World Health Organization;   Ministry of Health of Azerbaijan Republic
  Recruiting

From PubMed

• Integrin activation is an essential component of SARS-CoV-2 infection - SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS- CoV-2^(R18) particles engage…

• Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review - Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a…

• Possible Benefits of Zinc supplement in CVD and COVID-19 Comorbidity - As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead…

• Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life- threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited…

• Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19 - [Figure: see text].

• Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins - SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin’s help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface…

• Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition - Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles (“cellular nanosponges”) mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that…

• Inhibition of Receptor-Binding Domain - ACE2 interaction after two doses of Sinovac’s CoronaVac or AstraZeneca/Oxford’s AZD1222 SARS-CoV-2 vaccines - Practical laboratory proxies that correlate to vaccine efficacy may facilitate trials, identify non-responders and inform about boosting strategies. Among clinical and laboratory markers, assays that evaluate antibodies that inhibit receptor-binding domain ligation to angiotensin-converting enzyme-2 receptor (RBI) may provide a surrogate for viral neutralization assays. We evaluated RBI before and after a median of 34 days (IQR 33-40) of the second dose of SARS- CoV-2 Sinovac’s CoronaVac (CN) or…

• Computational and in vitro experimental analyses of the anti-COVID-19 potential of Mortaparib and MortaparibPlus - Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a global health emergency. Although new vaccines have been generated and being implicated, discovery and application of novel preventive and control measures are warranted. We aimed to identify compounds that may possess the potential to either block the entry of virus to host cells or attenuate its replication upon infection. Using host cell surface receptor…

• Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19 - The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being…

• Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction - The emergence and rapid spread of SARS-CoV-2 have caused a worldwide public health crisis. Designing small molecule inhibitors targeting SARS-CoV-2 S-RBD/ACE2 interaction is considered as a potential strategy for the prevention and treatment of SARS-CoV-2. But to date, only a few compounds have been reported as SARS-CoV-2 S-RBD/ACE2 interaction inhibitors. In this study, we described the virtual screening and experimental validation of two novel inhibitors (DC- RA016 and DC-RA052) against…

• Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone - In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate…

• Lessons in self-defence: inhibition of virus entry by intrinsic immunity - Virus entry, consisting of attachment to and penetration into the host target cell, is the first step of the virus life cycle and is a critical ‘do or die’ event that governs virus emergence in host populations. Most antiviral vaccines induce neutralizing antibodies that prevent virus entry into cells. However, while the prevention of virus invasion by humoral immunity is well appreciated, considerably less is known about the immune defences present within cells (known as intrinsic immunity)…

• Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti- Inflammatory Therapeutic Responses - Many patients with coronavirus disease 2019 in intensive care units suffer from cytokine storm. Although anti- inflammatory therapies are available to treat the problem, very often, these treatments cause immunosuppression. Because angiotensin-converting enzyme 2 (ACE2) on host cells serves as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to delineate a SARS-CoV-2-specific anti-inflammatory molecule, we designed a hexapeptide corresponding to the spike…

• Correction: Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition - No abstract

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