Covid-19 Sentry

Contents

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

From Preprints

• Meisoindigo: An Effective Inhibitor of SARS-CoV-2 Main Protease Revealed by Yeast System -
  The COVID-19 pandemic caused by SARS-CoV-2 has had a significant impact on global health and economy. Despite the availability of vaccines, their limited accessibility and vaccine hesitancy pose challenges in controlling the spread of the disease. Effective therapeutic strategies, including antiviral drugs, are needed to combat the future spread of new SARSCoV- 2 virus variants. The main protease (Mpro) is a critical therapeutic target for COVID-19 medicines, as its inhibition impairs viral replication. However, the use of substances that inhibit Mpro may induce selection pressure. Thus, it is vital to monitor viral resistance to known drugs and to develop new drugs. Here we have developed a yeast system for the identification of Mpro inhibitors as an alternative to costly and demanding high biosecurity procedures. The system is based on stable expression of Mpro and does not require selection media. Yeast can be cultured on a rich carbon source, providing rapid growth and screening results. The designed tool was subsequently used to screen the FDA-Approved Drug Library. Several chemicals with Mpro inhibitory properties were identified. We found that meisoindigo not previously known for its potential to inhibit Mpro, was highly effective. Our results may promote development of new derivatives with therapeutic properties against SARS-CoV-2 and other beta-coronaviruses.
  🖺 Full Text HTML: Meisoindigo: An Effective Inhibitor of SARS-CoV-2 Main Protease Revealed by Yeast System
• Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86 -
  The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86's NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86's transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86's infectivity.
  🖺 Full Text HTML: Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86
• Neutralization of SARS-CoV-2 EG.5/EG.5.1 by sera from ZF2001 RBD-dimer and its next-generation vaccines -
  SARS-CoV-2 Omicron EG.5 and EG.5.1 are surging in several areas of the world, including China. Compared with XBB.1, EG.5 contains additional mutations of F456L and S486P in the spike protein receptor binding domain (RBD) and its subvariant EG.5.1 carries a further spike mutation Q52H. The immune escape potential of EG.5/EG.5.1 is of great concern. In this study, we evaluated the neutralization activities of sera from participants who received COVID-19 inactivated vaccines, protein subunit vaccine ZF2001 or a booster vaccination of Delta-BA.5 RBD-heterodimer protein vaccine, and participants who had a breakthrough infection during a wave of BF.7/BA.5.2 circulation in December 2022. Neutralization profiles elicited by bivalent RBD-heterodimer vaccine candidates containing XBB.1.5 antigen were evaluated in a murine model. We found that EG.5 and EG.5.1 displayed similar immune evasion potential to XBB.1 and XBB.1.5. The Delta-BA.5 RBD-heterodimer booster induced higher neutralizing titers against the tested XBB subvariants, including EG.5 and EG.5.1, than breakthrough infection by BF.7 or BA.5.2. In addition, Delta-XBB.1.5 and BQ.1.1-XBB.1.5 RBD-heterodimer vaccines induced high neutralizing activities against XBB sub-variants in a murine model, suggesting that next-generation COVID-19 vaccines with updated components must be developed to enhance the protection efficacy against the circulating SARS-CoV-2 strains.
  🖺 Full Text HTML: Neutralization of SARS-CoV-2 EG.5/EG.5.1 by sera from ZF2001 RBD-dimer and its next-generation vaccines
• Trapping non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase -
  The RNA dependent RNA polymerase (RdRp) in SARS-CoV-2 is a highly conserved enzyme responsible for viral genome replication/transcription. Here we investigate computationally natural non-cognate vs cognate nucleotide addition cycle (NAC) and intrinsic nucleotide selectivity during the viral RdRp elongation, focusing prechemically from initial nucleotide substrate binding (enzyme active site open) to insertion (active site closed) of RdRp in contrast with one-step only substrate binding process. Current studies have been first carried out using microsecond ensemble equilibrium all-atom molecular dynamics (MD) simulations. Due to slow conformational changes (from the open to closed) accompanying nucleotide insertion and selection, enhanced or umbrella sampling methods have been further employed to calculate free energy profiles of the non-cognate NTP insertion. Our studies show notable stability of noncognate dATP and GTP upon initial binding in the active-site open state. The results indicate that while natural cognate ATP and Remdesivir drug analogue (RDV-TP) are biased to be stabilized in the closed or insertion state, the natural non-cognate dATP and GTP can be well trapped in off-path initial binding configurations. Current work thus presents an intrinsic nucleotide selectivity mechanism of SARS-CoV-2 RdRp for natural substrate fidelity control in viral genome replication.
  🖺 Full Text HTML: Trapping non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase
• Sensitivity of BA.2.86 to prevailing neutralising antibody responses -
  A new SARS-CoV-2 variant, designated BA.2.86, has recently emerged with over 30 spike mutations relative to its parental BA.2, raising questions about its degree of resistance to neutralising antibodies. Using a spike-pseudotyped virus model we characterise neutralisation of BA.2.86 by clinically relevant monoclonal antibodies and by two cohorts of serum sampled from Stockholm, including both a recent cohort, and one sampled prior to the arrival of XBB in Sweden.
  🖺 Full Text HTML: Sensitivity of BA.2.86 to prevailing neutralising antibody responses
• Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19 -
  Background: Accumulating evidence has revealed unexpected phenotypic heterogeneity and diverse functions of neutrophils in several diseases. Coronavirus disease (COVID-19) can alter the leukocyte phenotype based on disease severity, including neutrophil activation in severe cases. However, the plasticity of neutrophil phenotypes and their relative impact on COVID-19 pathogenesis has not been well addressed. This study aimed to identify and validate the heterogeneity of neutrophils in COVID-19 and evaluate the phenotypic alterations for each subpopulation. Methods: We analyzed public single-cell RNA-seq, bulk RNA-seq, and human plasma proteome data from healthy donors and patients with COVID-19 to investigate neutrophil subpopulations and their response to disease pathogenesis. Results: We identified eight neutrophil subtypes, namely C1-C8, and found that they exhibited distinct features, including activation signatures and multiple enriched pathways. The neutrophil subtype C4 (DEFA1/1B/3+) associated with severe and fatal disease. Bulk RNA-seq and proteome dataset analyses using a cellular deconvolution approach validated the relative abundances of neutrophil subtypes and the expansion of C4 (DEFA1/1B/3+) in severe COVID-19 patients. Cell-cell communication analysis revealed representative ligand-receptor interactions among the identified neutrophil subtypes. Notably, the C4 (DEFA1/1B/3+) fraction showed transmembrane receptor expression of CD45 and CAP1 as well as the secretion of pro-platelet basic protein (PPBP). We further demonstrated the clinical potential of PPBP as a novel diagnostic biomarker for severe COVID-19. Conclusion: Our work has great value in terms of both clinical and public health as it furthers our understanding of the phenotypic and functional heterogeneity of neutrophils and other cell populations in multiple diseases.
  🖺 Full Text HTML: Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19
• Reference materials for SARS-CoV-2 molecular diagnostic: validation of encapsulated synthetic RNAs for room temperature storage and shipping -
  The Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate positive controls. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage and costly shipping and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. Here, RNA controls produced by Twist were encapsulated (RNAshells) and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and 6 different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by accelerated aging. The results for a 10-year equivalent storage time at 25C were not significantly different from those for unaged samples. This room temperature RNA stability is a great advantage because it allows the preparation and the distribution of large strategic batches which can be kept for a long time and used for standardization processes between detection sites. Moreover, it makes it possible also to use these controls as single use and in the field where large differences in temperature can occur. In conclusion, these encapsulated RNA controls processed at room temperature can be used as reference materials for SARS-Cov-2 virus and other pathogen detection.
  🖺 Full Text HTML: Reference materials for SARS-CoV-2 molecular diagnostic: validation of encapsulated synthetic RNAs for room temperature storage and shipping
• COVID-19 vaccines and autoimmune disorders: A scoping review protocol -

  Background - Two years into the global vaccination program, important questions about the association between COVID-19 vaccines and autoimmune diseases have arisen. A growing number of reports have documented associations between COVID-19 vaccination and autoimmunity, suggesting, for example, a causal link between vaccination and new-onset and/or relapsing autoimmune disorders such as type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Graves disease, and Hashimoto s thyroiditis. These autoimmune phenomena have occurred with various COVID-19 vaccines and research is required to elucidate the underlying mechanisms and causal directions, for example, whether persons with no history of autoimmune disorders may experience them upon vaccination or persons with autoimmune disorders may experience exacerbation or new adverse events post-vaccination. Methods and analysis - Specific objectives of this scoping review will address the following questions: Can COVID-19 vaccination trigger and/or exacerbate autoimmune disorders? Are persons with autoimmune disorders at higher risk of experiencing additional autoimmune disorders? What are the mechanisms connecting autoimmune disorders with COVID-19 vaccination? Can COVID-19 vaccination interact with immunosuppressive therapy in persons with autoimmune disorders? Does the risk of autoimmune disorders following COVID-19 vaccination differ by vaccine type, age, gender, or other still unidentified characteristics (e.g., SES)? What is the consensus of care concerning COVID-19 vaccination in persons with autoimmune disorders and what evidence informs it? Our review will follow Arksey and O Malley s (2005) framework, enhanced by Levac et al. s team-based approach (2010), and adhering to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. To capture the broadest range of perspectives on the phenomenon of interest, data will be synthesized through numerical summaries describing general characteristics of included studies and thematic analysis. Subgroup analysis of primary outcomes will be performed to compare findings according to 1) the previous existence of autoimmune disorder, 2) the presence of relevant co-morbidities, 3) vaccine type; and other relevant factors that we may encounter as the research proceeds. Significance - COVID-19 has triggered the largest vaccination campaign in history, targeting literally the global human community. Drug safety is a crucial aspect of any medical intervention, critical to a proper assessment of the balance of risks and benefits. Our investigation should yield information useful to improve medical and public health practice in multiple ways, including assisting in clinical decision-making, policy development, and ethical medical practice.

  🖺 Full Text HTML: COVID-19 vaccines and autoimmune disorders: A scoping review protocol
• Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol -
  Responses to COVID-19 in Canadian postsecondary education have overhauled usual norms and practices, with policies of unclear rationale implemented under the pressure of a public health emergency. However, despite the unprecedented nature of these policies and their dramatic impact on millions of lives, the decision-making process leading to them has not been documented or appraised. Drawing from macro and micro theories of public policy, specifically the critical tradition in policy studies exemplified by Carol Bacchi’s approach “What is the problem represented to be” (WPR), we will conduct a scoping review of COVID-19 policies in Canadian postsecondary education, guided by Arksey and O’Malley’s framework for scoping reviews and by the team-based approach of Levan and colleagues. Data will include diverse and publicly available documents to capture multiple stakeholders’ perspectives on the phenomenon of interest, and will be retrieved from university, newsletter, and legal websites through combinations of search terms adapted to specific data types. Two reviewers will independently screen, chart, analyse and synthesize the data and disagreements will be resolved through full team discussion. By identifying, summarizing, and appraising the evidence, our review should inform practices that can contribute to effective and equitable public health policies in postsecondary institutions moving forward.
  🖺 Full Text HTML: Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol
• COVID-19 vaccines and autoimmune disorders: A scoping review protocol -
  Background Two years into the global vaccination program, important questions about the association between COVID-19 vaccines and autoimmune diseases have arisen. A growing number of reports have documented associations between COVID-19 vaccination and autoimmunity, suggesting, for example, a causal link between vaccination and new-onset and/or relapsing autoimmune disorders such as type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Graves disease, and Hashimoto’s thyroiditis. These autoimmune phenomena have occurred with various COVID-19 vaccines and research is required to elucidate the underlying mechanisms and causal directions, for example, whether persons with no history of autoimmune disorders may experience them upon vaccination or persons with autoimmune disorders may experience exacerbation or new adverse events post-vaccination. Methods and analysis Specific objectives of this scoping review will address the following questions: Can COVID-19 vaccination trigger and/or exacerbate autoimmune disorders? Are persons with autoimmune disorders at higher risk of experiencing additional autoimmune disorders? What are the mechanisms connecting autoimmune disorders with COVID-19 vaccination? Can COVID-19 vaccination interact with immunosuppressive therapy in persons with autoimmune disorders? Does the risk of autoimmune disorders following COVID-19 vaccination differ by vaccine type, age, gender, or other still unidentified characteristics (e.g., SES)? What is the consensus of care concerning COVID-19 vaccination in persons with autoimmune disorders and what evidence informs it? Our review will follow Arksey and O’Malley’s (2005) framework, enhanced by Levac et al.’s team-based approach (2010), and adhering to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. To capture the broadest range of perspectives on the phenomenon of interest, data will be synthesized through numerical summaries describing general characteristics of included studies and thematic analysis. Subgroup analysis of primary outcomes will be performed to compare findings according to 1) the previous existence of autoimmune disorder, 2) the presence of relevant co-morbidities, 3) vaccine type; and other relevant factors that we may encounter as the research proceeds. Significance COVID-19 has triggered the largest vaccination campaign in history, targeting literally the global human community. Drug safety is a crucial aspect of any medical intervention, critical to a proper assessment of the balance of risks and benefits. Our investigation should yield information useful to improve medical and public health practice in multiple ways, including assisting in clinical decision-making, policy development, and ethical medical practice.
  🖺 Full Text HTML: COVID-19 vaccines and autoimmune disorders: A scoping review protocol
• Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Quebec, Canada. -

  Objectives. To assess the neutralization activity pre and post Omicron BA.1 emergence in a unique cohort of 280 vaccinated restaurant/bar, grocery and hardware store workers in Quebec, Canada. Methods. Participants were recruited during the emergence of Omicron BA.1 variant. The neutralizing activity of participant sera was assessed by microneutralization assay. Results. Serum neutralizing antibody (NtAb) titers of all participants against the ancestral SARS-CoV-2 strain was comparable with the response against Delta variant, however, their response was significantly reduced against Omicron BA.1, BA2, BA.2.12.1, BA.4 and BA.5. The neutralizing response of each group of workers was similar. Individuals who received 2 doses of vaccine had significantly reduced NtAb titers against all SARS-CoV-2 strains compared to those infected and then vaccinated (≥ 1 dose), vaccinated (≥ 2 doses) and then infected, or those who received 3 doses of vaccine. Participants vaccinated with 2 or 3 doses of vaccine and then infected had the highest NtAb titers against all SARS-CoV-2 strains tested. Conclusion. We assessed for the first time the NtAb response in food and retail workers. Individuals infected after ≥ 2 doses of vaccine had the highest levels of NtAbs against Omicron BA.1, BA.2 and BA.5 variants and might be better protected against reinfection.

  🖺 Full Text HTML: Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Quebec, Canada.
• Integrated antigenic and nucleic acid detection in single virions and virion-infected host-derived extracellular vesicles -

  The coronavirus disease of 2019 (COVID-19) led to the rapid development of novel assays to improve sensitivities for detecting the virion responsible for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite that, there have been over 767 million reported cases and over 6.9 million deaths worldwide. Therefore, tunable, sensitive, and high-throughput assays are warranted to control future outbreaks. Herein, we developed a tunable in situ assay to selectively sort virions and infected host-derived extracellular vesicles (IHD-EVs) and simultaneously detect their antigens and nucleic acid cargo at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA^TM) integrates positive immunoselection and infection dynamics to sort particles, immunofluorescence to detect antigens, and fluorescence in situ hybridization to detect nucleic acids. BARATM enhanced sensitivities by detecting biomolecular signatures at the single-particle level, enabling the detection of virions in asymptomatic patients, and genetic mutations in single SARS-CoV-2 virions. Furthermore, BARA^TM revealed the continued long-term expression of virion-RNA in the IHD-EVs of post-acute sequelae SARS-CoV-2 infection (PASC) patients. BARATM was validated on saliva (30 healthy donors and 33 symptomatic and 20 asymptomatic patients) and nasopharyngeal swabs (19 healthy donors and 40 patients), revealing a highly accurate diagnosis by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA on single SARS-CoV-2 virions with sensitivities of 100 % and 95 %, respectively, and specificities of 100 % for both biofluids. Altogether, the single-particle detection of antigens and virion-RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks.

  🖺 Full Text HTML: Integrated antigenic and nucleic acid detection in single virions and virion-infected host-derived extracellular vesicles
• Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial -

  Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC). Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal PFTs, defined as an abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk testing (6MWT) at the 1-year visit. Results: Sixteen of the 29 one-year survivors consented to the follow up visit. We found that subjects who had originally received dupilumab were less likely to have abnormal PFTs compared to those who received placebo (Fishers exact p=0.011, adjusted p=0.058). We additionally found that 3 out of 19 subjects (16%) in the dupilumab group died by 1 year compared to 8 out of 21 subjects (38%) in the placebo group (log rank p=0.12). We did not find significant differences in neurocognitive testing, symptoms or CT chest imaging between treatment groups but observed evidence of reduced type 2 inflammation in those who received dupilumab. Conclusions: We observed evidence of reduced long-term morbidity and mortality from COVID-19 with dupilumab treatment during acute hospitalization when added to standard of care regimens.

  🖺 Full Text HTML: Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial
• Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations -
  Infographics are an engaging way to share health information with the public, but their relevance and appeal can be improved if they can be tailored to the language, culture, and information needs of their target audience. Digital tools are needed to make such tailoring feasible at scale, and to meet the needs of the community-based organizations (CBOs) that are well-situated to share health information with the public. Here, we describe our progress toward the development of the TailorVis Toolbox, an online system that facilitates infographic tailoring at the level of the CBO and the individual viewer. Incorporated within this project was the participatory design of infographics related to COVID-19 testing and vaccination. The system will be extended to numerous health topics in the future.
  🖺 Full Text HTML: Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations
• Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets -
  After years of the COVID-19 pandemic, over 40 million children worldwide are at risk of measles due to delayed vaccination and temporary SARS-CoV-2 viral dominance. Acute measles has a case-fatality rate of ~1%, but most morbidity and mortality arise post-measles due to destruction of pre-existing immune memory by lymphotropic measles virus (MeV), a paramyxovirus of the Morbillivirus genus. MeV-induced immune amnesia is not mitigated by post-exposure vaccination and the impact of unrelated respiratory virus disease history on measles severity has not been defined. We used a lethal canine distemper virus (CDV)-ferret model as surrogate for human morbillivirus disease and employed the orally efficacious broad-spectrum paramyxovirus polymerase inhibitor GHP-88309 to establish measles treatment paradigms. Applying a receptor tropism-intact recombinant CDV with low lethality, we provide in vivo confirmation of the morbillivirus immune amnesia hypothesis and reveal an 8-day advantage of antiviral treatment versus therapeutic vaccination in preserving immune memory. Infection of ferrets with non-lethal influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks prior to CDV caused exacerbated CDV disease that rapidly advanced to fatal hemorrhagic pneumonia associated with lung onslaught by commensal bacteria. RNAseq of BAL samples and lung tissue identified CDV-induced expression of trefoil factor (TFF) peptides, which was absent in animals pre-infected with IAV, thus highlighting that immune priming by unrelated respiratory viruses influences morbillivirus infection outcome. Non-invasive pulmonary ferret MRI revealed that severe outcomes of consecutive IAV/CDV infections were prevented by oral GHP-88309 treatment even when initiated after peak clinical signs of CDV. These findings validate the morbillivirus immune amnesia hypothesis, define treatment paradigms for measles, identify prior disease history as risk factor for exacerbated morbillivirus disease, and demonstrate that treating morbillivirus infection with direct-acting oral antivirals provides therapeutic benefit regardless of whether the time window to mitigate primary clinical signs of infection has closed.
  🖺 Full Text HTML: Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

From Clinical Trials

• THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL - Condition:   COVID-19
  Intervention:   Dietary Supplement: Neomune
  Sponsors:   Universitas Sriwijaya;   M. Djamil General Hospital
  Completed

• A Phase 2/3 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL - Condition:   COVID-19
  Interventions:   Biological: hAd5-S-Fusion+N-ETSD;   Biological: Placebo (0.9% (w/v) saline)
  Sponsor:   ImmunityBio, Inc.
  Completed

• KAND567 Versus Placebo in Subjects Hospitalized With COVID-19 - Condition:   Covid19
  Interventions:   Drug: KAND567;   Drug: Microcrystalline cellulose
  Sponsor:   Kancera AB
  Terminated

• Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome - Conditions:   Post-COVID-19 Syndrome;   Long-COVID-19 Syndrome
  Intervention:   Behavioral: Aerobic Exercise Training
  Sponsors:   University of Witten/Herdecke;   Institut für Rehabilitationsforschung Norderney
  Completed

• A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection - Condition:   COVID-19
  Interventions:   Drug: Experimental: Primary Cohort;   Other: Placebo Comparator: Primary Cohort - Placebo
  Sponsor:   University of Chicago
  Active, not recruiting

• Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong - Conditions:   Digital Health Literacy;   COVID-19
  Intervention:   Behavioral: Digital health literacy intervention
  Sponsor:   The Hong Kong Polytechnic University
  Not yet recruiting

• Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations - Conditions:   Influenza;   COVID-19;   Influenza Immunogencity;   COVID-19 Immunogenicity
  Interventions:   Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster);   Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster);   Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)
  Sponsors:   Duke University;   Centers for Disease Control and Prevention;   Arizona State University;   University Hospitals Cleveland Medical Center;   University of Pittsburgh;   Washington University School of Medicine;   Valleywise Health;   VA Northeast Ohio Health Care;   Senders Pediatrics
  Not yet recruiting

• Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh - Condition:   Pulmonary Pathology
  Intervention:   Behavioral: Pulmonary Rehabilitation
  Sponsor:   Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  Active, not recruiting

• Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia - Condition:   Bronchoalveolar Lavage
  Intervention:   Procedure: Bronchoalveolar Lavage
  Sponsors:   Mohamed Abd Elmoniem Mohamed;   Marwa Salah Abdelrazek Ghanem;   Mohammad Khairy El-Badrawy;   Tamer Ali Elhadidy;   Dalia Abdellateif Abdelghany
  Completed

• Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19. - Condition:   Nervous System Diseases
  Interventions:   Drug: Tianeptine;   Drug: Placebo
  Sponsors:   Military Institute od Medicine National Research Institute;   ABM Industries
  Recruiting

• Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition - Condition:   Cognitive Behavioral Therapy
  Intervention:   Behavioral: cognitive behavioral therapy
  Sponsor:   Tri-Service General Hospital
  Not yet recruiting

• The Effectiveness of Natural Resources for Reducing Stress - Conditions:   Distress, Emotional;   COVID-19
  Interventions:   Combination Product: Balneotherapy plus complex;   Combination Product: Combined nature resources treatment;   Other: Nature therapy procedure
  Sponsors:   Klaipėda University;   Research Council of Lithuania
  Active, not recruiting

• Complementary and Integrative Medicine as an Online Intervention in Patients With Post-covid Syndrome After COVID-19 - Condition:   Post-COVID Syndrome
  Interventions:   Behavioral: Complementary and Integrative Medicine online intervention, routine care and book;   Behavioral: Routine care and book
  Sponsor:   Charite University, Berlin, Germany
  Not yet recruiting

• Pre-probiotic Supplementation for Post-covid Fatigue Syndrome - Condition:   Long COVID
  Interventions:   Dietary Supplement: Dietary Supplement: Experimental;   Dietary Supplement: Dietary Supplement: Placebo
  Sponsor:   University of Novi Sad, Faculty of Sport and Physical Education
  Active, not recruiting

• A Study of Healthy Microbiome, Healthy Mind - Conditions:   Critical Illness;   COVID-19;   PICS;   Cognitive Impairment;   Mental Health Impairment;   Weakness, Muscle;   Dysbiosis
  Intervention:   Behavioral: Fermented Food Diet
  Sponsor:   Mayo Clinic
  Not yet recruiting

From PubMed

• SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2 - Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 10^(17) molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as…

• High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells - The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2…

• Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication - Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple…

• Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response - Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally,…

• Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients - CONCLUSION: Inhibition of the renin-angiotensin-aldosterone-system had no effect on the mortality of patients with COVID-19 and on their overall disease progression. However, it may be beneficial not to stop these medications as they decrease inflammation in the body and the levels of troponin, which are related to increased stress on the heart.

• Deadly interactions: synergistic manipulations of concurrent pathogen infections potentially enabling future pandemics - Certain monoinfections of influenza viruses and novel coronaviruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are significant threats to human health. Concurrent infections by influenza viruses and coronaviruses increases their threat. Influenza viruses have eight manipulations capable of assisting SARS-CoV-2 and other coronaviruses, and several of these manipulations, which are not specific to viruses, can also directly or indirectly boost dangerous secondary…

• An evolutionarily conserved strategy for ribosome binding and host translation inhibition by β-coronavirus non-structural protein 1 - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Non-structural protein 1 (Nsp1), which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-Coronaviruses (β-CoV) inhibits translation through ribosome binding. The C-terminal domain…

• SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1 - SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated…

• Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review - Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) identified in 2003 infected ∼8000 people in 26 countries with 800 deaths, which was soon contained and eradicated by syndromic surveillance and enhanced quarantine. A closely related coronavirus SARS-CoV-2, the causative agent of COVID-19 identified in 2019, has been dramatically more contagious and catastrophic. It has infected and caused various flu-like symptoms of billions of people in >200 countries, including >6 million…

• Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms - CONCLUSIONS: These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.

• Inhibition of the Cellular Deubiquitinase UCHL1 Suppresses SARS-CoV-2 Replication - No abstract

• Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and Plasmodium - Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus…

• The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses - There is an urgent need for highly effective therapeutic agents to interrupt the continued spread of SARS-CoV-2. As a pivotal protease in the replication process of coronaviruses, the 3CLpro protein is considered as a potential target of drug development to stop the spread and infection of the virus. In this work, molecular dynamics (MD) simulations were used to elucidate the molecular mechanism of a novel and highly effective non-covalent inhibitor, WU-04, targeting the SARS-CoV-2 3CLpro…

• The use of Ephedra herbs in the treatment of COVID-19 - CONCLUSION: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.

• Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019 - CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.

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