Covid-19 Sentry

Contents

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

From Preprints

• Introduction to Qualitative Evidence Synthesis as a Methodology -
  The outbreak of COVID-19 has disrupted research methods just as it had to all other sectors of education across the globe. Many institutions and organisations, including researchers sought to find ways to deal with research while observing the requirement for remote interactions. While many options have been implemented, the use of systematic reviews, and in particular, Qualitative Evidence Synthesis (QES) have not been explored. QES, as a research method, offers a high level of evidence through the synthesis of primary qualitative studies, using established and endorsed critical appraisal methods such as PRISMA Workflow charts or COREQ, CASP (the latter is commonly used in QES), and many more that are suitable based on the nature of the study design. The other beneficial quality of QES is the ability to preserve research, use and embellish primary research and provide formidable networks among researchers. This presentation was first presented at a workshop organized by the National Center for Research Methods and the University of Manchester (UK) in October 2021 and later on at the 6th World Conference on Qualitative Research (Spain) in January 2022.
  🖺 Full Text HTML: Introduction to Qualitative Evidence Synthesis as a Methodology
• COVIDpro: Database for mining protein dysregulation in patients with COVID-19 -
  Background: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still has limited treatment options partially due to our incomplete understanding of the molecular dysregulations of the COVID-19 patients. We aimed to generate a repository and data analysis tools to examine the modulated proteins underlying COVID-19 patients for the discovery of potential therapeutic targets and diagnostic biomarkers. Methods: We built a web server containing proteomic expression data from COVID-19 patients with a toolset for user-friendly data analysis and visualization. The web resource covers expert-curated proteomic data from COVID-19 patients published before May 2022. The data were collected from ProteomeXchange and from select publications via PubMed searches and aggregated into a comprehensive dataset. Protein expression by disease subgroups across projects was compared by examining differentially expressed proteins. We also visualize differentially expressed pathways and proteins. Moreover, circulating proteins that differentiated severe cases were nominated as predictive biomarkers. Findings: We built and maintain a web server COVIDpro (https://www.guomics.com/covidPro/) containing proteomics data generated by 41 original studies from 32 hospitals worldwide, with data from 3077 patients covering 19 types of clinical specimens, the majority from plasma and sera. 53 protein expression matrices were collected, for a total of 5434 samples and 14,403 unique proteins. Our analyses showed that the lipopolysaccharide-binding protein, as identified in the majority of the studies, was highly expressed in the blood samples of patients with severe disease. A panel of significantly dysregulated proteins was identified to separate patients with severe disease from non-severe disease. Classification of severe disease based on these proteomic signatures on five test sets reached a mean AUC of 0.87 and ACC of 0.80. Interpretation: COVIDpro is an online database with an integrated analysis toolkit. It is a unique and valuable resource for testing hypotheses and identifying proteins or pathways that could be targeted by new treatments of COVID-19 patients.
  🖺 Full Text HTML: COVIDpro: Database for mining protein dysregulation in patients with COVID-19
• IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding -
  The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded, and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 strain of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality, but also for binding and neutralization of antigenically drifted viruses.
  🖺 Full Text HTML: IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding
• Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19 -
  SARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). Serine proteases, such as TMPRSS2 and trypsin, promote viral entry. In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, infectivity of clinical specimens containing culture supernatants of Fusobacterium necrophorum was increased from several- to 10-fold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection.
  🖺 Full Text HTML: Activation of SARS-CoV-2 by trypsin-like proteases in the clinical specimens of patients with COVID-19
• Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in Syrian hamsters -
  The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic target for the treatment of COVID-19. Nirmatrelvir is the only the 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization; other 3Lpro inhibitors are in development. We recently repored on the in vitro selection of a SARS-CoV2 3CLpro (L50F-E166A-L167F; short 3CLprores) virus that is cross-resistant with nirmatrelvir and yet other 3CLpro inhibitors. Here, we demonstrate that the resistant virus replicates efficiently in the lungs of intranassaly infected hamsters and that it causes a lung pathology that is comparable to that caused by the WT virus. Moreover, 3CLprores infected hamsters transmit the virus efficiently to co-housed non-infected contact hamsters. Fortunately, resistance to Nirmatrelvir does not readily develop (in the clinical setting) since the drug has a relatively high barrier to resistance. Yet, as we demonstrate, in case resistant viruses emerge, they may easily spread and impact therapeutic options for others. Therefore, the use of SARS-CoV-2 3CLpro protease inhibitors in combinations with drugs that have a different mechanism of action, may be considered to avoid the development of drug-resistant viruses in the future.
  🖺 Full Text HTML: Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in Syrian hamsters
• Mutational spectra distinguish SARS-CoV-2 replication niches -
  Exposure to different mutagens leaves distinct mutational patterns that can allow prediction of pathogen replication niches (Ruis 2022). We therefore hypothesised that analysis of SARS-CoV-2 mutational spectra might show lineage-specific differences, dependant on the dominant site(s) of replication and onwards transmission, and could therefore rapidly infer virulence of emergent variants of concern (VOC; Konings 2021). Through mutational spectrum analysis, we found a significant reduction in G>T mutations in Omicron, which replicates in the upper respiratory tract (URT), compared to other lineages, which replicate in both upper and lower respiratory tracts (LRT). Mutational analysis of other viruses and bacteria indicates a robust, generalisable association of high G>T mutations with replication within the LRT. Monitoring G>T mutation rates over time, we found early separation of Omicron from Beta, Gamma and Delta, while the mutational burden in Alpha varied consistent with changes in transmission source as social restrictions were lifted. This supports the use of mutational spectra to infer niches of established and emergent pathogens.
  🖺 Full Text HTML: Mutational spectra distinguish SARS-CoV-2 replication niches
• Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome -
  Interactions between proteins from intracellular pathogens and host proteins in an infected cell are often mediated by post-translational modifications encoded in the host proteome. Identifying protein modifications, such as phosphorylation, that dictate these interactions remains a defining challenge in unraveling the molecular mechanisms of pathogenesis. We have developed a platform in engineered bacteria that displays over 110,000 phosphorylated human proteins coupled to a fluorescent reporter system capable of identifying the host-pathogen interactome of phosphoproteins (H-PIP). This resource broadly enables cell-type independent interrogation and discovery of proteins from intracellular pathogens capable of binding phosphorylated human proteins. As an example of the H-PIP platform, we generated a unique, high-resolution SARS-CoV-2 interaction network which expanded our knowledge of viral protein function and identified understudied areas of host pathology.
  🖺 Full Text HTML: Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome
• Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States -
  The spread and transmission dynamics of directly transmitted airborne pathogens, such as SARS-CoV-2, are fundamentally determined by in-person contact patterns. Reliable quantitative estimates of contact patterns are critical to modeling and reducing the spread of directly transmitted infectious diseases. While national-level contact data are available in many countries, including the United States, local-level estimates of age-specific contact patterns are key since disease dynamics and public health policy vary by geography. However, collecting contact data for each state would require a very large sample and be prohibitively expensive. To overcome this challenge, we develop a flexible model to estimate age-specific contact patterns at the subnational level using national-level interpersonal contact data. Our model is based on dynamic multilevel regression with poststratification. We apply this approach to a national sample of interpersonal contact data collected by the Berkeley Interpersonal Contact Study (BICS). Results illustrate important state-level variation in levels and trends of contacts across the US.
  🖺 Full Text HTML: Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States
• Morinda citrifolia (noni) fruit juice inhibits SARS-CoV-2 spike protein binding of angiotensin receptor type 2 -
  Covid-19 is a global pandemic that has claimed millions of lives. This disease is caused by a coronavirus, SARS-CoV-2, which requires the binding of its spike protein to angiotensin-converting enzyme 2 (ACE2) for infection of the host cell. Morinda citrifolia (noni) fruit juice has antiviral activity that involves enhancement of immune system function. SARS-CoV-2 spike-ACE2 interaction experiments were carried out to further investigate the antiviral properties of noni juice and its major iridoids. Noni juice inhibited binding by approximately 69%. Scandoside was the most active of the three iridoids evaluated, reducing average spike protein-ACE2 interaction by 79.25%. The iridoids worked synergistically towards inhibiting spike protein binding when assayed together, improving activity by more than 22% above the expected level. But the modest activity of the most abundant iridoid, deacetylasperulosidic acid, indicates that other phytochemicals (i.e. scopoletin, quercetin, rutin and kaempferol) are also involved. Our results suggest that the presence of several biological active phytochemicals in noni juice enhances resistance to SARS-CoV-2 by interfering with its ability to bind ACE2. This is a new and significant anti-viral mechanism of noni juice that does not directly involve its immunomodulatory properties.
  🖺 Full Text HTML: Morinda citrifolia (noni) fruit juice inhibits SARS-CoV-2 spike protein binding of angiotensin receptor type 2
• Explanation of Hand, Foot, and Mouth Disease Cases in Japan Using Google Trends Before and During the COVID-19: Infodemiology Study -

  Background: COVID-19 pandemic affected common disease infections, while the impact on hand, foot, and mouth disease (HFMD) is unclear. Google Trends data is beneficial in approximately real-time statistics and easily accessed, expecting to be used for infection explanation from information-seeking behavior perspectives. We aimed to explain HFMD cases before and during COVID-19 using Google Trends data. Methods: HFMD cases were obtained from the National Institute of Infectious Disease, and Google search data from 2009 to 2021 was downloaded using Google Trends in Japan. Pearson correlation coefficients were calculated between HFMD cases and the search topic “HFMD” from 2009 to 2021. Japanese tweets containing “HFMD” were retrieved to select search terms for further analysis. Search terms were retained with counts larger than 1000 and belonging to ranges of infection sources, susceptible sites, susceptible populations, symptoms, treatment, preventive measures, and identified diseases. Cross-correlation analyses were conducted to detect lag changes between HFMD cases and HFMD search terms before and during COVID-19. Multiple linear regressions with backward elimination processing were used to identify the most significant terms for HFMD explanation. Results: HFMD cases and Google search volume peaked around July in most years without 2020 and 2021. The search topic “HFMD” presented strong correlations with HFMD cases except in 2020 when COVID-19 outbroke. In addition, differences in lags for 73 (72.3%) search terms were negative, might indicating increasing public awareness of HFMD infections during the COVID-19 pandemic. Results of multiple linear regression demonstrated that significant search terms contained the same meanings but expanded informative search content during COVID-19. Conclusions: Significant terms for HFMD cases explanation before and during COVID-19 were different. The awareness of HFMD infection in Japan may improve during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. Public interest reflected in information-seeking behavior can be helpful for public health surveillance.

  🖺 Full Text HTML: Explanation of Hand, Foot, and Mouth Disease Cases in Japan Using Google Trends Before and During the COVID-19: Infodemiology Study
• Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination -

  Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundant breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection.

  🖺 Full Text HTML: Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination
• Fairness and efficiency considerations in COVID-19 vaccine allocation strategies: a case study comparing front-line workers and 65-74 year olds in the United States -

  The COVID-19 epidemic in the United States has been characterized by two stark disparities. COVID-19 burden has been unequally distributed among racial and ethnic groups and at the same time the mortality rates have been sharply higher among older age groups. These disparities have led some to suggest that inequalities could be reduced by vaccinating front-line workers before vaccinating older individuals, as older individuals in the US are disproportionately Non-Hispanic White. We compare the performance of two distribution policies, one allocating vaccines to front-line workers and another to older individuals aged 65-74-year-old. We estimate both the number of lives saved and the number of years of life saved under each of the policies, overall and in every race/ethnicity groups, in the United States and every state. We show that prioritizing COVID-19 vaccines for 65-74-year-olds saves both more lives and more years of life than allocating vaccines front-line workers in each racial/ethnic group, in the United States as a whole and in nearly every state. When evaluating fairness of vaccine allocation policies, the overall benefit to impact of each population subgroup should be considered, not only the proportion of doses that is distributed to each subgroup. Further work can identify prioritization schemes that perform better on multiple equity metrics.

  🖺 Full Text HTML: Fairness and efficiency considerations in COVID-19 vaccine allocation strategies: a case study comparing front-line workers and 65-74 year olds in the United States
• ARDSFlag: An NLP/Machine Learning Algorithm to Visualize and Detect High-Probability ARDS Admissions Independent of Provider Recognition and Billing Codes -

  Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by bilateral pulmonary infiltrates that cannot be explained entirely by cardiogenic pulmonary edema. ARDS is the primary cause of mortality in COVID-19 patients and one of the leading causes of morbidity and mortality in ICUs. Despite its significance and prevalence, the detection of ARDS remains highly variable and inconsistent. In this work, we develop a tool to automate the diagnosis of ARDS based on the Berlin definition to increase the accuracy of ARDS detection using electronic health record (EHR) fields. ARDSFlag applies machine learning (ML) and natural language processing (NLP) techniques to evaluate Berlin criteria by incorporating structured and unstructured data. The output is the ARDS diagnosis, onset time, and severity. We have also developed a visualization that helps clinicians efficiently assess ARDS criteria retrospectively and in real time. The method includes separate text classifiers trained using large training sets to find evidence of bilateral infiltrates in radiology reports (accuracy of 91.9%+-0.5%) and heart failure/fluid overload in radiology reports (accuracy 86.1%+-0.5%) and echocardiogram notes (accuracy 98.4%+-0.3%). A holdout set of 300 cases, which was blindly and independently labeled for ARDS by two groups of clinicians, shows that the algorithm generates an overall accuracy of 89.0%, with a specificity of 91.7%, recall of 80.3%, and precision of 75.0%. Compared with two other ARDS identification methods used in the literature, ARDSFlag shows higher performance in all accuracy measures (an increase of 25.5% in overall accuracy, 6.5% in specificity, 44.2% in recall, 31.7% in precision, and 38.20% in F1-score over the best of the two detection methods).

  🖺 Full Text HTML: ARDSFlag: An NLP/Machine Learning Algorithm to Visualize and Detect High-Probability ARDS Admissions Independent of Provider Recognition and Billing Codes
• Comparative adverse effects, perceptions and attitudes related to BNT162b2, mRNA1273, or JNJ-78436735 SARS-CoV-2 vaccines: A population-based longitudinal cohort -

  Importance: Long-term control of SARS-CoV-2 requires effective vaccination strategies. This has been challenged by public mistrust and spread of misinformation regarding vaccine safety. Hence, better understanding and communication on the longer-term and comparative experiences of general population individuals following SARS-CoV-2 vaccination are required. Objective: To evaluate and compare self-reported adverse effects following SARS-CoV-2 vaccination, participants perceptions regarding vaccinations and their compliance with recommended public health measures. Design, Setting and Participants: Population-based longitudinal cohort of 575 adults, randomly selected from all individuals presenting to the reference vaccination center of the Canton of Zurich, Switzerland, for receipt of BNT162b2, mRNA1273, or JNJ-78436735. Exposures: BNT162b2, mRNA1273, or JNJ-78436735 vaccines. Main Outcomes and Measures: Primary outcomes included period prevalence, onset, duration, and severity of self-reported adverse effects over 12 weeks following vaccination with a specific focus on the proportion of participants reporting allergic reactions, menstrual irregularities, or cardiac adverse effects, or requiring hospitalization. Secondary outcomes included risk factors associated with reporting adverse effects, perception of vaccine importance, trust in public health authorities and pharmaceutical companies, and compliance with recommended public health measures. Results: 454 (79.0%) participants reported at least one adverse effect during 12 weeks after vaccination. Prevalence was highest among mRNA-1273 recipients (88.7% vs. 77.3% after BNT162b2, 69.1% after JNJ-78436735). Most adverse effects were systemic (72%), occurred within 24 hours (67.9%), and resolved in less than three days (76.3%). 85.2% were reported as mild or moderate. Allergic reactions were reported by 0.3% of participants, hospitalizations by 0.7%, cardiac adverse effects by 1.4%. Menstrual irregularities were reported by 9% of female participants younger than 50 years. Female sex, younger age, higher education, and receipt of mRNA-1273 were associated with reporting adverse effects. Compared to JNJ-78436735 recipients, a higher proportion of mRNA vaccine recipients agreed that vaccination is important (87.5% vs. 28.5%), and trusted public health authorities (80.2% vs. 30.3%) and pharmaceutical companies (71.7% vs. 23.6%). Conclusions and Relevance: Our population-based cohort provided real-world data on self-reported adverse effects following SARS-CoV-2 vaccination and highlights the importance of transparent communication regarding adverse effects and building trust in public health authorities to ensure successful future vaccination campaigns.

  🖺 Full Text HTML: Comparative adverse effects, perceptions and attitudes related to BNT162b2, mRNA1273, or JNJ-78436735 SARS-CoV-2 vaccines: A population-based longitudinal cohort
• Impact of Differential Vaccine Effectiveness on COVID-19 Hospitalization Cases: Projections for 10 Developed Countries where Booster Vaccines were Recommended -

  Background & Objectives: In a previous analysis, a decision-analytic model was used to analyze the clinical and economic impact of the differences in effectiveness between the two licensed mRNA COVID-19 booster vaccines, mRNA-1273 and BNT162b2, in 2022 for adults aged 18 years and older in the United States (US). In this analysis, the same model was used to estimate the impact that administering first booster doses with mRNA-1273 could have had on COVID-related hospitalizations and costs over a 6-month period in 10 developed countries (Australia, Canada, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom [UK], and US), considering updated effectiveness data. Methods: The model was used to estimate number of hospitalizations and related costs using the actual vaccine distribution for the first COVID-19 booster from each country. These estimates were compared to a scenario where 100% of doses for that 6-month period was assumed to be mRNA-1273. The effectiveness of mRNA-1273 compared to BNT162b2 was estimated from real world data from the UK. Results: The total number of doses switched to the mRNA-1273 booster would range from 4.3 million in Spain to 39.4 million in Japan. The number of hospitalizations and associated hospitalization costs would be expected to fall in all countries, with the proportional decrease ranging from 1.1% (16,800 fewer) in Germany to 8.8% (25,100 fewer) in Australia. Conclusions: Real-world effectiveness data suggest that a booster dose of the mRNA-1273 vaccine may be more effective compared to other vaccines used for booster doses. Given this difference in effectiveness, results of this analysis demonstrate that switching to 100% mRNA-1273 boosters would have reduced the number of hospitalizations and associated costs in each country during the first 6 months of the omicron period.

  🖺 Full Text HTML: Impact of Differential Vaccine Effectiveness on COVID-19 Hospitalization Cases: Projections for 10 Developed Countries where Booster Vaccines were Recommended

From Clinical Trials

• The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: TADIOS;   Drug: Placebo
  Sponsor:   Helixmith Co., Ltd.
  Completed

• COVID-19 Fourth Dose Study in Australia - Condition:   COVID-19
  Interventions:   Biological: Tozinameran;   Biological: Elasomeran;   Biological: Bivalent Pfizer-BioNTech;   Biological: Bivalent Moderna
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg;   Biological: BNT162b4 5 µg;   Biological: BNT162b4 10 µg;   Biological: BNT162b4 15 µg
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PBI-0451;   Drug: Placebo
  Sponsor:   Pardes Biosciences, Inc.
  Recruiting

• Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AD17002 + Formulation buffer;   Biological: Placebo
  Sponsors:   Advagene Biopharma Co. Ltd.;   Gadjah Mada University
  Not yet recruiting

• Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia - Conditions:   Olfactory Disorder;   COVID-19
  Intervention:   Drug: Simvastatin
  Sponsors:   Washington University School of Medicine;   Duke University
  Not yet recruiting

• COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Device: iCura COVID-19 Antigen Rapid Home Test;   Diagnostic Test: RT-PCR Test
  Sponsors:   EDP Biotech;   Paragon Rx Clinical, Inc.;   iCura Diagnostics, LLC
  Recruiting

• FMT for Post-acute COVID-19 Syndrome - Conditions:   Post-Acute COVID19 Syndrome;   COVID-19
  Intervention:   Procedure: Faecal Microbiota Transplantation
  Sponsor:   Chinese University of Hong Kong
  Recruiting

• Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations - Condition:   COVID-19
  Intervention:   Behavioral: Active Intervention Group
  Sponsor:   Pennington Biomedical Research Center
  Not yet recruiting

• Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community - Condition:   COVID-19 Pandemic
  Intervention:   Device: STANDARD Q COVID-19 Ag Test
  Sponsor:   University of Oxford
  Active, not recruiting

• Evaluation of the Efficacy of Mouth Rinses With Commercial Mouthwashes to Decrease Viral Load in Saliva in COVID-19 Patients - Condition:   covid19
  Interventions:   Drug: Lacer Clorhexidina Colutorio;   Drug: Lacer Clorhexidine 0.20% Colutorio;   Drug: Gingilacer Encías Delicadas Colutorio;   Drug: Distilled water
  Sponsors:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario Infanta Elena
  Completed

• Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: low-dose LYB001;   Biological: Recombinant COVID-19 Vaccine (CHO Cell);   Biological: high-dose LYB001
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Recruiting

• Long COVID-19 Syndrome in Primary Care: A Novel Protocol of Exercise Intervention “CON-VIDA Clinical Trial” - Conditions:   COVID-19;   Long COVID;   Post-COVID-19 Syndrome
  Intervention:   Behavioral: EXERCISE
  Sponsor:   Universidad San Jorge
  Active, not recruiting

• The Efficacy and Safety of BioBlock® Intranasally Administered Virus-Neutralizing Bovine Colostrum Nasal Spray in Preventing of COVID-19 (Coronavirus Disease-19) Infection in Healthy Volunteer Individuals - Condition:   SARS CoV 2 Infection
  Intervention:   Biological: BioBlock® antiviral nasal spray
  Sponsor:   Chemi-Pharm AS
  Recruiting

• Spikogen Booster Study - Condition:   COVID-19
  Intervention:   Biological: SpikoGen vaccine
  Sponsors:   Vaxine Pty Ltd;   Australian Respiratory and Sleep Medicine Institute Ltd;   Cinnagen
  Not yet recruiting

From PubMed

• A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19) - CONCLUSION: Cytotoxic test of Fe(II) isoleucine dithiocarbamate showed moderate anticancer activity on MCF-7 cancer cells and showed antiviral activity against SARSCOV-2 by interfering with spike glycoprotein -ACE2 receptors, and inhibiting major proteases and 3Clpro.

• IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques - The pro- and anti-inflammatory pathways that determine the balance of inflammation and viral control during SARS-CoV-2 infection are not well understood. Here we examine the roles of IFNγ and IL-10 in regulating inflammation, immune cell responses and viral replication during SARS-CoV-2 infection of rhesus macaques. IFNγ blockade tended to decrease lung inflammation based on ^(18) FDG-PET/CT imaging but had no major impact on innate lymphocytes, neutralizing antibodies, or antigen-specific T…

• Flap structure within receptor binding domain of SARS-CoV-2 spike periodically obstructs hACE2 Binding subdomain bearing similarities to HIV-1 protease flap - The SARS-CoV-2 prefusion spike protein is characterized by a high degree of flexibility and temporal transformations associated with its multifunctional behavior. In this study, we have examined the dynamics of the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein in detail. Its primary, binding subdomain with human Angiotensin Covering Enzyme II includes a highly conspicuous flap or loop that is part of a beta hairpin loop structural motif. Dynamic details of the RBD obtained…

• Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure-Activity Relationship Insights and Evolution Perspectives - The viral main protease is one of the most attractive targets among all key enzymes involved in the SARS-CoV-2 life cycle. Covalent inhibition of the cysteine^(145) of SARS-CoV-2 M^(PRO) with selective antiviral drugs will arrest the replication process of the virus without affecting human catalytic pathways. In this Perspective, we analyzed the in silico, in vitro, and in vivo data of the most representative examples of covalent SARS-CoV-2 M^(PRO) inhibitors reported in the literature to date….

• The inhibition of MDM2 slows cell proliferation and activates apoptosis in ADPKD cell lines - CONCLUSIONS: Our results indicate that several inflammatory proteins remain aberrantly dysregulated in COVID-19 survivors and CXCL10 might serve as a potential biomarker to typify COV-LH. Further characterization of these signature inflammatory molecules might improve the understanding of the long-term impacts of COVID-19 and provide new targets for the diagnosis and treatment of COVID-19 survivors with PASC.

• Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction - Postviral bacterial infections are a major health care challenge in coronavirus infections, including COVID-19; however, the coronavirus-specific mechanisms of increased host susceptibility to secondary infections remain unknown. In humans, coronaviruses, including SARS-CoV-2, infect lung immune cells, including alveolar macrophages, a phenotype poorly replicated in mouse models of SARS-CoV-2. To overcome this, we used a mouse model of native murine β-coronavirus that infects both immune and…

• Longitudinal Characterization of Phagocytic and Neutralization Functions of Anti-Spike Antibodies in Plasma of Patients after Severe Acute Respiratory Syndrome Coronavirus 2 Infection - Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and role remain to be fully elucidated. In this study of 62 acute and convalescent patients, we found that patients with acute coronavirus disease 2019 can…

• Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence - Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19),…

• CLL-050 Induction of Neutralizing Antibodies in Chronic Lymphocytic Leukemia Patients After SARS-CoV-2 mRNA Vaccination: A Monocentric Experience - CONCLUSIONS: Only around half of vaccinated CLL patients acquire detectable anti-RBD and neutralizing antibodies, according to our findings. Furthermore, we discovered a substantial difference in the rates of detectable anti-SARS-CoV-2 antibodies between patients who were treatment-naïve/in clinical remission and those on CLL-directed treatment. The persistence and burden of disease represent a surrogate of vaccine failure, probably due to the persistence of immune dysfunction.

• SARS-CoV-2 ORF3a inhibits cGAS-STING-mediated autophagy flux and antiviral function - Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity are essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral…

• Preventing SARS-CoV-2 Infection Using Anti-spike Nanobody-IFN-β Conjugated Exosomes - CONCLUSION: Exosomes conjugated with nanobody-IFN-β may provide potential benefits in the treatment of COVID-19 because of the cooperative anti-viral effects of the anti-spike nanobody and the IFN-β.

• Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria - Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the…

• An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension - The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy and reduce cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma…

• The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses - Genome-wide screens are powerful approaches to unravel regulators of viral infections. Here, a CRISPR screen identifies the RNA helicase DDX42 as an intrinsic antiviral inhibitor of HIV-1. Depletion of endogenous DDX42 increases HIV-1 DNA accumulation and infection in cell lines and primary cells. DDX42 overexpression inhibits HIV-1 infection, whereas expression of a dominant-negative mutant increases infection. Importantly, DDX42 also restricts LINE-1 retrotransposition and infection with other…

• Remdesivir in treating hospitalized patients with COVID-19: A renewed review of clinical trials - Since December 2019, COVID-19 has spread across the world almost through 2.5 years. As of 16 June 2022, the cumulative number of confirmed cases of COVID-19 worldwide has reached 542.62 million, and the death toll has risen to 6.33 million. With the increasing number of deaths, it is urgent to find effective treatment drugs. Remdesivir, an investigational broad-spectrum antiviral drug produced by Gilead has been shown to inhibit SARS-CoV-2, in vitro and in vivo. This review is aimed to analyze…

From Patent Search