Covid-19 Sentry

Contents

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

From Preprints

• Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2 -
  Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fc{gamma}-receptor (Fc{gamma}R)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (PV) assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of Fc{gamma}RIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include Fc{gamma}R activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.
  🖺 Full Text HTML: Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2
• Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, Against SARS-CoV-2 Challenge in Nonhuman Primates -
  TNX-1800 is a synthetically derived live chimeric Horsepox Virus (rcHPXV) vaccine expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated, as indicated by the lack of serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated robust humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In Cynomolgus Macaques, a single dose of TNX-1800 induced a strong interferon-gamma (IFN-{gamma}) mediated T cell response, promoting both pathogen clearance in the upper and lower airways and generation of systemic neutralizing antibody response against WA strain SARS-CoV-2. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.
  🖺 Full Text HTML: Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, Against SARS-CoV-2 Challenge in Nonhuman Primates
• Adapting COVID-19 research infrastructure to capture Influenza and Respiratory Syncytial Virus alongside SARS-CoV-2 in UK healthcare workers Winter 2022/23 and beyond: protocol for a pragmatic sub-study -

  Introduction: During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2, however important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022-2023 with simultaneous circulation of SARS-CoV2 and Respiratory Syncytial Virus (RSV) is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers (HCW), the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis: This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of SIREN, which focuses on hospital staff in the UK. Participants undergo fortnightly Nucleic Acid Amplification Testing (NAAT) on a multiplex assay including SARS-CoV-2, Influenza A&B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants influenza vaccine status. The SIREN Participant Involvement Panel (PIP) shaped the aims and methods for the study, highlighting its acceptability. UK Devolved Administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage; assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination: The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent.

  🖺 Full Text HTML: Adapting COVID-19 research infrastructure to capture Influenza and Respiratory Syncytial Virus alongside SARS-CoV-2 in UK healthcare workers Winter 2022/23 and beyond: protocol for a pragmatic sub-study
• Continued selection on cryptic SARS-CoV-2 observed in Missouri wastewater -

  Deep sequencing of wastewater to detect SARS-Cov-2 has been used during the COVID-19 pandemic to monitor viral variants as they appear and circulate in communities. SARS-CoV-2 lineages of an unknown source that have not been detected in clinical samples, referred to as cryptic lineages, are sometimes repeatedly detected in specific locations. We have continued to detect one such lineage previously seen in a Missouri site. This cryptic lineage has continued to evolve, indicating continued selective pressure similar to that observed in Omicron lineages.

  🖺 Full Text HTML: Continued selection on cryptic SARS-CoV-2 observed in Missouri wastewater
• Analysis of SARS-CoV-2 Ig seroprevalence in Northern Ireland -

  Background: With the impact of SARS-CoV-2 upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy. Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 immunoglobulins (Ig). Samples were assessed using an Elecsys anti-SARS-CoV-2 or anti-SARS-CoV-2 S ECLIA (Roche) on an automated Cobas-e-analyser. Samples were also assessed via ELISA (Euroimmun). A subset of samples assessed via Roche Elecsys anti-SARS-CoV-2 IgG assay were subsequently analysed in an ACE2 pseudoneutralisation assay using a V-PLEX SARS-CoV-2 Panel 7 for IgG and ACE2 by MesoScale Diagnostics Inc. Results: Across three testing rounds (June-July 2020, November-December 2020 and June-July 2021 (rounds 1-3 respectively)), 4844 residual sera/plasma specimens were assayed for SARS-CoV-2 Ig. Seropositivity rates increased across the study, peaking at 11.6% during round 3. Varying trends in SARS-CoV-2 seropositivity were noted based on demographic factors. For instance, highest rates of seropositivity shifted from older to younger demographics across the study period. In round 3, alpha (B.1.1.7) variant neutralising antibodies were most frequently detected across age groups, with median concentration of anti-spike protein antibodies elevated in 50-69 year olds and anti-S1 RBD antibodies elevated in over 70s, relative to other age groups. Conclusions: With seropositivity rates of <15% across the assessment period, it can be concluded that the significant proportion of the Northern Ireland population had not yet naturally contracted the virus by mid-2021.

  🖺 Full Text HTML: Analysis of SARS-CoV-2 Ig seroprevalence in Northern Ireland
• Automatic Population of the Case Report Forms for an International Multifactorial Adaptive Platform Trial Amid the COVID-19 Pandemic -

  Objectives: To automatically populate the case report forms (CRFs) for an international, pragmatic, multifactorial, response-adaptive, Bayesian COVID-19 platform trial. Methods: The locations of focus included 27 hospitals and 2 large electronic health record (EHR) instances (1 Cerner Millennium and 1 Epic) that are part of the same health system in the United States. This paper describes our efforts to use EHR data to automatically populate four of the trial9s forms: baseline, daily, discharge, and response-adaptive randomization. Results: Between April 2020 and May 2022, 417 patients from the UPMC health system were enrolled in the trial. A MySQL-based extract, transform, and load pipeline automatically populated 499 of 526 CRF variables. The populated forms were statistically and manually reviewed and then reported to the trial9s international data coordinating center. Conclusions: We accomplished automatic population of CRFs in a large platform trial and made recommendations for improving this process for future trials.

  🖺 Full Text HTML: Automatic Population of the Case Report Forms for an International Multifactorial Adaptive Platform Trial Amid the COVID-19 Pandemic
• CommunityClick-Virtual: Multi-Modal Interactions for Enhancing Participation in Virtual Meetings -
  Government officials often rely on public engagements to gauge people’s perspectives on civic issues and gather feedback to make informed policy decisions. Traditional public engagement methods are often face-to-face, such as town halls, public forums, and workshops. However, during the COVID-19 pandemic, these approaches were rendered ineffective due to health risks and the engagement process saw a shift towards virtual meetings. While accessible to a broader audience, virtual public meetings introduced challenges around limited time and opportunity for attendees to share feedback. Furthermore, attendees were often required to identify themselves, potentially discouraging reticent attendees from speaking up and risking confrontations with other attendees. To mitigate this issue, we designed and developed CommunityClick-Virtual, a multi-modal companion web application that allows virtual meeting participants to provide feedback on meeting discussions silently and anonymously using six customizable options or through chat messages without the need to speak up. The organizers have access to all attendee feedback channels where they can use synchronized coordinated visualizations to gather a more holistic understanding of people’s perspectives. The field deployments of CommunityClick-Virtual demonstrated its efficacy in increasing participation and enabling organizers to identify insights that could help them make more informed decisions. We argue that multi-modal systems such as Communityclick-Virtual can be pertinent in enhancing participation in both professional and educational environments.
  🖺 Full Text HTML: CommunityClick-Virtual: Multi-Modal Interactions for Enhancing Participation in Virtual Meetings
• Global Preparedness for the Next Disease X: A Current and Prospective Situation Analysis -
  COVID-19 has strongly struck the world and damaged its global lifestyle in an unprecedented manner, at least in our modern age. Thus, it’s of utmost importance to prepare for the next inevitable pandemic regardless of its origin; whether naturally, rouge gain of function research or even planned bioterrorism. In this short note, the most probable upcoming pandemics according to the WHO shortlist of prioritized potentially fatal diseases and other potential ones are being discussed together with the role of climate change. Notably, in Africa we adopted a different scientific strategy to confront COVID-19 which was different from the one adopted in developed countries, we chose early treatment not mass vaccination nor mandates, and the results on the ground are obvious to all. It’s wise and vigilant to learn from Africa and the Egyptian immune-modulatory broad spectrum antiviral immune-modulatory Kelleni’s protocol if we are sincerely determined to avoid loss of more millions of lives.
  🖺 Full Text HTML: Global Preparedness for the Next Disease X: A Current and Prospective Situation Analysis
• ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection -
  A large body of research accumulated over the past three years dedicated to our understanding and fighting COVID-19. Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics. In this study, we developed ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. These ACE2-VLPs exhibited high neutralization capacity even when applied at low doses, and displayed superior efficacy compared to extracellular vesicles carrying ACE2, in the in vitro pseudoviral assays. ACE2-VLPs were stable under different environmental temperatures, and they were effective in blocking all tested variants of concern in vitro. Finally, ACE2-VLPs displayed marked neutralization capacity against Omicron BA.1 in the Vero E6 cells. Based on their superior efficacy compared to extracellular vesicles, and their demonstrated success against live virus, ACE2-VLPs can be considered as vital candidates for treating SARS-CoV-2. This novel therapeutic approach of VLP coating with receptor particles can serve as proof-of-concept for designing effective neutralization strategies for other viral diseases in the future.
  🖺 Full Text HTML: ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection
• High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody -
  Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody ("nano-synbody") based on a three-helix bundle DNA nanostructure with one, two, or three identical arms terminating in a mini-binder protein that targets the SARS-CoV-2 spike protein. The nano-synbody was designed to match the valence and distance between the three receptor binding domains (RBDs) in the spike trimer, in order to enhance affinity. The protein-DNA nano-synbody shows tight binding to the wild-type, Delta, and several Omicron variants of the SARS-CoV-2 spike trimer, with affinity increasing as the number of arms increases from one to three. The effectiveness of the nano-synbody was also verified using a pseudovirus neutralization assay, with the three-arm nanostructure inhibiting two Omicron variants against which the structures with only one or two arms are ineffective. The structure of the three-arm nano-synbody bound to the Omicron variant spike trimer was solved by negative-stain transmission electron microscopy reconstruction, and shows the protein-DNA nanostructure with all three arms attached to the RBD domains, confirming the intended trivalent attachment. The ability to tune the size and shape of the nano-synbody, as well as its potential ability to attach two or more different binding ligands, will enable the high-affinity targeting of a range of proteins not possible with traditional antibodies.
  🖺 Full Text HTML: High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody
• Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner -

  Post-acute Sequelae of COVID-19 (PASC), also known as Long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19 infection. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. Using a sample of 55,257 participants from the National COVID Cohort Collaborative, as part of the NIH Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal, AUC-maximizing combination of gradient boosting and random forest algorithms. We were able to predict individual PASC diagnoses accurately (AUC 0.947). Temporally, we found that baseline characteristics were most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after COVID-19 infection. This finding supports the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients prior to acute COVID diagnosis, which could improve early interventions and preventive care. We found that medical utilization, demographics, anthropometry, and respiratory factors were most predictive of PASC diagnosis. This highlights the importance of respiratory characteristics in PASC risk assessment. The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings.

  🖺 Full Text HTML: Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner
• Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals -
  The bidirectional interaction between the immune system and the gut microbiota is a key contributor to various host physiological functions. Immune-associated diseases such as cancer and autoimmunity, as well as the efficacy of immunomodulatory therapies, have been linked to microbiome variation. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunosuppressive therapy. We find that the gut microbiome, assessed using shotgun metagenomics, remained stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all tested levels including phylum, species, and functional capacity. Our results show the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes.
  🖺 Full Text HTML: Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals
• Developmental progression of the nasopharyngeal microbiome during childhood and association with the lower airway microbiome -

  Background The upper (URT) and lower (LRT) respiratory tract feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the URT and LRT and explore their relationship with development during childhood. Methods We employed V4 16S rDNA sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 183 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures at the Children9s Hospital of Philadelphia over the course of 20 weeks in 2020, from otherwise healthy subjects enrolled in a study investigating potential reservoirs of SARS-CoV-2. Findings After extraction, sequencing, and quality control, we studied the remaining 124 nasopharyngeal swabs and 98 tracheal aspirates, including 85 subject-matched pairs of samples. V4 16S rDNA sequencing revealed that the nasopharynx is colonized by few, highly-abundant taxa, while the tracheal aspirates feature a diverse assembly of microbes. While no taxa co-occur in the URT and LRT of the same subject, clusters of microbiomes in the URT correlate with clusters of microbiomes in the LRT. The clusters identified in the URT correlate with subject age across childhood development. Interpretations The correlation between clusters of taxa across sites may suggest a mutual influence from either a third site, such as the oropharynx, or host-extrinsic, environmental features. The identification of a pattern of upper respiratory microbiota development across the first 18 years of life suggests that the patterns observed in early childhood may extend beyond the early life window. Funding Research reported in this publication was supported by NIH T32 GM007200 (AJH), F30 DK127584 (AJH), NIH/NIAID R21AI154370 (AOJ, ALK), NIH/NICHD R01HD109963 (AOJ, ALK), and NIH/NICHD R33HD105594 (AOJ). Dr. John is an Investigator in the Pathogenesis of Infectious Diseases of the Burroughs Welcome Fund.

  🖺 Full Text HTML: Developmental progression of the nasopharyngeal microbiome during childhood and association with the lower airway microbiome
• Сan we start to ignore the SARS-CoV-2 disease? -

  Current WHO reports claim a decline in COVID-19 testing. Many countries are reporting no new infections. In particular, USA, China and Japan have registered no cases and COVID-19 related deaths since May 15, 2023. To discuss consequences of ignoring SARS-CoV-2 infection, we compare endemic characteristics of the disease in 2023 with ones estimated before using 2022 datasets. The accumulated numbers of cases and deaths reported to WHO by 10 most infected countries and global figures were used to calculate the average daily numbers of cases and deaths per capita (DCC and DDC) and case fatality rates (CFR) for two periods in 2023. The average values of daily deaths per million still vary between 0.12 and 0.41. It means that annual global number of COVID-19 related deaths is still approximately twice higher than the seasonal influenza mortality. Increase of CFR values in 2023 show that SARS-CoV-2 infection is still dangerous despite of increasing the vaccination level. Very low CFR figures in South Korea and very high ones in the UK 4 need further investigations.

  🖺 Full Text HTML: Сan we start to ignore the SARS-CoV-2 disease?
• Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants -
  SARS-CoV-2 adaptation to humans is evidenced by the emergence of variants of concern (VOCs) with distinct genotypes and phenotypes that facilitate immune escape and enhance transmission frequency. Most recently Omicron subvariants have emerged with heavily mutated spike proteins which facilitate re-infection of immune populations through extensive antibody escape driving replacement of previously-dominant VOCs Alpha and Delta. Interestingly, Omicron is the first VOC to produce distinct subvariants. Here, we demonstrate that later Omicron subvariants, particularly BA.4 and BA.5, have evolved an enhanced capacity to suppress human innate immunity when compared to earliest subvariants BA.1 and BA.2. We find that, like previously dominant VOCs, later Omicron subvariants tend to increase expression of viral innate immune antagonists Orf6 and nucleocapsid. We show Orf6 to be a key contributor to enhanced innate immune suppression during epithelial replication by BA.5 and Alpha, reducing innate immune signaling through IRF3 and STAT1. Convergent VOC evolution of enhanced innate immune antagonist expression suggests common pathways of adaptation to humans and links VOC, and in particular Omicron subvariant, dominance to improved innate immune evasion.
  🖺 Full Text HTML: Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants

From Clinical Trials

• A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: HH-120;   Drug: placebo
  Sponsor:   Huahui Health
  Completed

• Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Condition:   Post-COVID-19 Syndrome
  Interventions:   Behavioral: Exercise Therapy;   Behavioral: Psychotherapy
  Sponsors:   Hannover Medical School;   Health Insurance Audi BKK;   occupational health service Volkswagen AG;   Helmholtz Centre for Infection Research
  Not yet recruiting

• A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions:   COVID-19;   SARS-CoV-2
  Interventions:   Drug: VYD222;   Drug: Normal saline
  Sponsor:   Invivyd, Inc.
  Recruiting

• Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Condition:   COVID-19
  Interventions:   Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells);   Biological: Placebo
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Not yet recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Condition:   Covid19
  Interventions:   Other: Placebo;   Drug: Metformin
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Recruiting

• Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations - Conditions:   Immunosuppression;   COVID-19
  Intervention:   Biological: NVX-CoV2372
  Sponsors:   University of Wisconsin, Madison;   Novavax
  Not yet recruiting

• Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration
  Interventions:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention
  Sponsors:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: LEM-mR203;   Biological: Placebo
  Sponsor:   Lemonex
  Not yet recruiting

• Non-pharmacological and TCM-based Treatment for Long COVID Symptoms - Condition:   Long Covid19
  Intervention:   Behavioral: Acupuncture and TCM-based lifestyle management
  Sponsor:   The Hong Kong Polytechnic University
  Not yet recruiting

• SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Condition:   COVID-19
  Intervention:   Drug: SA55 nasal spray
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Condition:   COVID-19
  Intervention:   Drug: STI-1558
  Sponsor:   Zhejiang ACEA Pharmaceutical Co. Ltd.
  Not yet recruiting

• A Study to Determine the Tolerability of Intranasal LMN-301 - Condition:   COVID-19
  Intervention:   Biological: LMN-301
  Sponsor:   Lumen Bioscience, Inc.
  Not yet recruiting

• Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults - Condition:   SARS-CoV-2 Infection
  Intervention:   Biological: B/HPIV3/S-6P
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)
  Recruiting

• Mind Body Intervention for Long COVID - Conditions:   Long COVID;   Post-Acute Sequelae of COVID-19;   COVID Long-Haul
  Intervention:   Behavioral: Mind Body Intervention #1
  Sponsor:   Beth Israel Deaconess Medical Center
  Not yet recruiting

• Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions:   Fever After Vaccination;   Fever;   Seizures Fever
  Interventions:   Biological: Pfizer-BioNTech COVID-19 Vaccine;   Biological: Routine Childhood Vaccinations
  Sponsors:   Duke University;   Kaiser Permanente;   Columbia University;   Children’s Hospital Medical Center, Cincinnati;   Centers for Disease Control and Prevention
  Not yet recruiting

From PubMed

• Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm - CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.

• SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression - Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5´-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for…

• De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain - Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus’s spike protein and the host’s angiotensin converting enzyme…

• Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers - An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT(50) values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential…

• Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment - CONCLUSION: Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.

• Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors - A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2’-O-methyltransferase using a high throughput screening approach with the potential to reveal new inhibition strategies. This screen yielded compound 5a, a ligand possessing an electron-deficient double bond, as an inhibitor of SARS-CoV-2 nsp16 activity. Surprisingly, X-ray crystal structures revealed that 5a covalently binds within a previously unrecognized cryptic pocket…

• Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells - Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The…

• How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…

• Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection - TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to…

• Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation - SARS-CoV-2 infection causes spike-dependent fusion of infected cells with ACE2 positive neighboring cells, generating multi-nuclear syncytia that are often associated with severe COVID. To better elucidate the mechanism of spike-induced syncytium formation, we combine chemical genetics with 4D confocal imaging to establish the cell surface heparan sulfate (HS) as a critical stimulator for spike-induced cell-cell fusion. We show that HS binds spike and promotes spike-induced ACE2 clustering,…

• Prostaglandin E₂ and myocarditis; friend or foe? - This review article summarizes the role of prostaglandin E(2) (PGE(2)) and its receptors (EP1-EP4) as it relates to the inflammatory cardiomyopathy, myocarditis. During the COVID-19 pandemic, the onset of myocarditis in a subset of patients prompted a debate on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, which act to inhibit the actions of prostaglandins. This review aims to further understanding of the role of PGE(2) in the pathogenesis or protection of the…

• SADS-CoV nsp1 inhibits the IFN-β production by preventing TBK1 phosphorylation and inducing CBP degradation - Swine acute diarrhea syndrome (SADS) is first reported in January 2017 in Southern China. It subsequently causes widespread outbreaks in multiple pig farms, leading to economic losses. Therefore, it is an urgent to understand the molecular mechanisms underlying the pathogenesis and immune evasion of Swine acute diarrhea syndrome coronavirus (SADS-CoV). Our research discovered that SADS-CoV inhibited the production of interferon-β (IFN-β) during viral infection. The nonstructural protein 1 (nsp1)…

• Bioprospecting the potential of metabolites from a Saharan saline soil strain Nocardiopsis dassonvillei GSBS4 - Saharan soil samples collected in El-Oued province have been investigated for actinobacteria as a valuable source for the production of bioactive metabolites. A total of 273 isolates were obtained and subjected to antagonistic activity tests against human pathogenic germs. A strain with a broad-spectrum antimicrobial activity was selected and identified as Nocardiopsis dassonvillei GSBS4, with high sequence similarities to N. dassonvillei subsp. dassonvillei^(T) X97886.1 (99%) based on…

• Cholesterol and Ceramide Facilitate Membrane Fusion Mediated by the Fusion Peptide of the SARS-CoV-2 Spike Protein - SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together and its fusion peptide (FP) that interacts with and perturbs the membrane structure to trigger fusion….

• Live imaging of the airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread - SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, and…

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