Covid-19 Sentry

Contents

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

From Preprints

• Near-term forecasting of Covid-19 cases and hospitalisations in Aotearoa New Zealand -

  Near-term forecasting of infectious disease incidence and consequent demand for acute healthcare services can support capacity planning and public health responses. Despite well-developed scenario modelling to support the Covid-19 response, Aotearoa New Zealand lacks advanced infectious disease forecasting capacity. We develop a model using Aotearoa New Zealand9s unique Covid-19 data streams to predict reported Covid-19 cases, hospital admissions and hospital occupancy. The method combines a semi-mechanistic model for disease transmission to predict cases with Gaussian process regression models to predict the fraction of reported cases that will require hospital treatment. We evaluate forecast performance against out-of-sample data over the period from 2 October 2022 to 23 July 2023. Our results show that forecast performance is reasonably good over a 1-3 week time horizon, although generally deteriorates as the time horizon is lengthened. The model has been operationalised to provide weekly national and regional forecasts in real-time. This study is an important step towards development of more sophisticated situational awareness and infectious disease forecasting tools in Aotearoa New Zealand.

  🖺 Full Text HTML: Near-term forecasting of Covid-19 cases and hospitalisations in Aotearoa New Zealand
• Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily During a 10.9 month Observation Period within a Pragmatic Randomized Clinical Trial -

  Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Com-parisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups were not statistically different. Vitamin D3 supplementation reduced healthcare utilization in four major cate-gories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate dif-ference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to Covid-19 (rate difference: -8.47X10^-3 per 1000 person-days, 95%-CI: -0.02 to -1.05X10^-3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are rec-ommended for replication of these utilization findings and analysis of cost differences.

  🖺 Full Text HTML: Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily During a 10.9 month Observation Period within a Pragmatic Randomized Clinical Trial
• Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL -

  Patients with B-cell lymphomas have altered cellular components of vaccine responses due to the malignancies and therapies. The optimal timing of vaccine administration relative to chemotherapy and immunotherapy remains unknown. The SARS-CoV-2 vaccine campaign created a unique opportunity to gather insights into vaccine timing because patients were challenged with a novel antigen across multiple phases of lymphoma management. We studied retrospective and prospective cohorts of patients with lymphoma and CLL who received an mRNA-based vaccine and paired serologic response with treatment dates, clinical immune parameters, and deep immunophenotyping. Reduced serologic response was observed more frequently during active therapies but nonresponders were also identified within observation and post-treatment groups. Clinical immunologic profiling demonstrated that total IgA and IgM near the time of vaccination correlated with ability to coordinate vaccine response. In individuals treated with CART-19, high-parameter immunophenotyping demonstrated that nonresponse was associated with reduced participation in B cell clusters and clusters of T follicular helper cells required for vaccine response. Together these data suggest that predictors of vaccine responsiveness vary by disease and therapeutic group. Further studies of immune health during and after cancer therapies will allow clinicians to individualize the timing of vaccines and define immunologic vulnerabilities.

  🖺 Full Text HTML: Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL
• Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort -

  Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

  🖺 Full Text HTML: Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort
• Research ethics review during the COVID-19 pandemic An international study -

  Research ethics review committees (ERCs) worldwide faced daunting challenges during the COVID-19 pandemic. There was a need to balance rapid turnaround with rigorous evaluation of high-risk research protocols in the context of considerable uncertainty. This study explored the experiences and performance of ERCs during the pandemic. We conducted an anonymous, cross-sectional, global online survey of chairs (or their delegates) of ERCs who were involved in the review of COVID-19-related research protocols after March 2020. The survey ran from October 2022 to February 2023 and consisted of 50 items, with opportunities for open text responses. Two hundred and three participants [130 from high-income countries (HICs) and 73 from low- and middle-income countries (LMICs)] completed our survey. Respondents came from diverse entities and organizations from 48 countries (19 HICs and 29 LMICs) in all World Health Organization regions. Responses show little of the increased global funding for COVID-19 research was allotted to the operation of ERCs. Few ERCs had pre-existing internal policies to address operation during public health emergencies, but almost half used existing guidelines. Most ERCs modified existing procedures or designed and implemented new ones but had not evaluated the success of these changes. Participants overwhelmingly endorsed permanently implementing several of them. Few ERCs added new members but non-member experts were consulted; quorum was generally achieved. Collaboration among ERCs was infrequent, but reviews conducted by external ERCs were recognized and validated. Review volume increased during the pandemic, with COVID-19-related studies being prioritized. Most protocol reviews were reported as taking less than three weeks. One-third of respondents reported external pressure on their ERCs from different stakeholders to approve or reject specific COVID-19-related protocols. ERC members faced significant challenges to keep their committees functioning during the pandemic. Our findings can inform ERC approaches towards future public health emergencies. To our knowledge, this is the first international, COVID-19-related study of its kind.

  🖺 Full Text HTML: Research ethics review during the COVID-19 pandemic An international study
• Highly efficient and sensitive membrane-based concentration process allows quantification, surveillance, and sequencing of viruses in large volumes of wastewater. -

  Wastewater-based epidemiology is experiencing exponential development. Despite undeniable advantages compared to patient-centered approaches (cost, anonymity, survey of large populations without bias, detection of asymptomatic infected peoples etc), major technical limitations persist. Among them is the low sensitivity of the current methods used for quantifying and sequencing viral genomes from wastewater. In situations of low viral circulation, during initial stages of viral emergences, or in countries experiencing heavy rains, the extremely low concentrations of viruses in wastewater may fall below the limit of detection of the current methods. The availability and cost of the commercial kits, as well as the requirement of expensive materials, can also present major blocks to the development of wastewater-based epidemiological survey, specifically in low-income countries. Thereby, highly sensitive, low cost and open-access methods are still needed to increase the predictability of the viral emergences, to survey low-circulating viruses and to allow wastewater-based surveillance. Here, we outline and characterize new protocols for concentrating, quantifying, monitoring, and sequencing SARS-CoV-2 from large volumes (500 mL-1L) of raw wastewater. Our nucleic acid extraction technique (the routine C: 5ml method) does not require sophisticated equipment such as automatons and is not reliant on commercial kits, making it readily available to a broader range of laboratories for routine epidemiological survey. Furthermore, we demonstrate the efficiency, the repeatability, and the high sensitivity of a new membrane-based concentration method (MBC: 500 mL method) for enveloped (SARS-CoV-2) and naked (FRNAPH GGII) viruses. We show that the MBC method allows the quantification and the monitoring of viruses in wastewater with a significantly improved sensitivity. In contexts of low viral circulation, we report quantifications of SARS-CoV-2 in wastewater at concentrations below 100 genome copies per liter and as low as 40 genome copies per liter. In highly diluted samples collected in wastewater treatment plants of French Guiana, we confirmed the accuracy of the MBC method compared to the estimations done with the C method. Finally, we demonstrate that both the C and MBC methods are compatible with SARS-CoV-2 sequencing. We show that the quality of the sequence is correlated with the concentration of the extracted viral genome. Of note, the quality of the sequences obtained with some MBC processed wastewater was improved by dilutions or enzyme substitutions suggesting the presence of specific enzyme inhibitors in some wastewater. To the best of our knowledge, our MBC method is the first efficient, sensitive, repeatable, and up-scalable method characterized for SARS-CoV-2 quantification and sequencing from large volumes of wastewater.

  🖺 Full Text HTML: Highly efficient and sensitive membrane-based concentration process allows quantification, surveillance, and sequencing of viruses in large volumes of wastewater.
• Comparative performance of COVID-19 test methods in healthcare workers during the omicron wave -

  Introduction: The COVID-19 pandemic presents unique requirements for accessible, reliable testing, and many testing platforms and sampling techniques have been developed. However, not all test methods have been systematically compared to each other or a common gold standard, and the performance of tests developed in the early epidemic have not been consistently re-evaluated in the context of newly emerging SARS-CoV-2 variants.

  Methods: We conducted a repeated measures study with adult healthcare workers presenting for SARS-CoV-2 testing. Participants were tested using seven test modalities: PCR with samples from the nasopharynx, oropharynx, and saliva; and BinaxNOW and iHealth antigen–based rapid detection tests (AgRDT) sampling the oropharynx and the nares. Test sensitivity was compared using any positive PCR test as the gold standard.

  Results: 325 individuals participated in the study. PCR tests were the most sensitive with saliva PCR at 0.957 ± 0.048, nasopharyngeal PCR at 0.877 ± 0.075, and oropharyngeal PCR at 0.849 ± 0.082. Standard nasal rapid antigen tests were less sensitive but roughly equivalent at 0.613 ± 0.110 for BinaxNOW brand and 0.627 ± 0.109 for iHealth. Oropharyngeal rapid antigen tests were the least sensitive with BinaxNOW and iHealth brands at 0.400 ± 0.111 and 0.311 ± 0.105 respectively.

  Conclusion: PCR remains the most sensitive testing modality for COVID-19, with saliva PCR being significantly more sensitive than oropharyngeal PCR and equivalent to nasopharyngeal PCR. Saliva testing has patient comfort and financial benefits, making it a preferred testing modality. Nasal AgRDTs are less sensitive than PCR though more accessible and convenient.

  🖺 Full Text HTML: Comparative performance of COVID-19 test methods in healthcare workers during the omicron wave
• Impact of COVID-19 Pandemic on Sleep Including HRV and Physical Activity as Mediators: A Causal ML Approach -

  Sleep quality is crucial to both mental and physical well-being. The COVID-19 pandemic, which has notably affected the population9s health worldwide, has been shown to deteriorate people9s sleep quality. Numerous studies have been conducted to evaluate the impact of the COVID-19 pandemic on sleep efficiency, investigating their relationships using correlation based methods. These methods merely rely on learning spurious correlation rather than the causal relations among variables. Furthermore, they fail to pinpoint potential sources of bias and mediators and envision counterfactual scenarios, leading to a poor estimation. In this paper, we develop a Causal Machine Learning method, which encompasses causal discovery and causal inference components, to extract the causal relations between the COVID-19 pandemic (treatment variable) and sleep quality (outcome) and estimate the causal treatment effect, respectively. We conducted a wearable-based health monitoring study to collect data, including sleep quality, physical activity, and Heart Rate Variability (HRV) from college students before and after the COVID-19 lockdown in March 2020. Our causal discovery component generates a causal graph and pinpoints mediators in the causal model. We incorporate the strongly contributing mediators (i.e., HRV and physical activity) into our causal inference component to estimate the robust, accurate, and explainable causal effect of the pandemic on sleep quality. Finally, we validate our estimation via three refutation analysis techniques. Our experimental results indicate that the pandemic exacerbates college students9 sleep scores by 8%. Our validation results show significant p-values confirming our estimation.

  🖺 Full Text HTML: Impact of COVID-19 Pandemic on Sleep Including HRV and Physical Activity as Mediators: A Causal ML Approach
• Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats -

  The COVID-19 pandemic exposed, with few exceptions, a global deficiency in delivering systematic, data-driven guidance to protect citizens and coordinate vaccination programs. At the same time, medical histories are routinely recorded in most healthcare systems and are instantly available for risk assessment. Here, we demonstrate the utility of medical history in determining the risk for 1,883 diseases across clinical specialties and facilitating the rapid response to emerging health threats at the example of COVID-19. We developed a neural network to learn disease-specific risk states from routinely collected health records of 502,460 UK Biobank participants, demonstrating risk stratification for nearly all conditions, and validated this model on 229,830 individuals from the All of US cohort. When integrated into Cox Proportional Hazard Models, we observed significant discriminative improvements over basic demographic predictors for 1,774 (94.3%). After transferring the unmodified risk models to the All of US cohort, the discriminate improvements were replicated for 1,347 (89.8%) of 1,500 investigated endpoints, demonstrating model generalizability across healthcare systems and historically underrepresented groups. We then show that these risk states can be used to identify individuals vulnerable to severe COVID-19 and mortality. Our study demonstrates the currently underused potential of medical history to rapidly respond to emerging health threats by systematically estimating risk for thousands of diseases at once at minimal cost.

  🖺 Full Text HTML: Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats
• The Application of Label-free Detection Using a Tapered Optical Fiber System for Head and Neck Cancer and Infectious Biomolecules -
  Introduction: Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality due to late detection. Tapered optical fiber sensors (TOFS) are biosensors with the potential application as a point-of-care device for detection of HNSCC biomarkers. TOFS uses optical fibers as transduction elements and antigen-antibody binding for the detection of target biomolecules. The present TOFS system was designed to achieve high specificity, sensitivity, and repeatability. To explore its application in HNSCC, we targeted the proinflammatory cytokine IL-8, known for its role in promoting tumorigenicity, metastasis, and angiogenesis in HNSCC. To validate our proof-of-concept experiment, a viral surrogate of SARS-CoV-2, Human Coronavirus OC43 (HCoV-OC43), was also tested. Methods: Our TOFS system contains four main parts: the tapered optical fiber, reservoir (cell), laser light source, and photodetector. The fiber is bitapered with a narrow waist region that anchors antibodies to detect target biomolecules. Light is transduced by the laser to the fiber where it travels through the down-taper region to the tapered waist followed by the up-tapered region and ultimately transmitted to the photodetector. The tapered waist facilitates the transformation of a single mode light to multiple modes, which reverts to a single mode of light as it continues through the up-taper region. Biomolecules introduced to the waist region alter the effective refractive index, which is reflected in the phase change of the wavelength. This is detected by the photodetector and quantified using Fouier analysis. Our tapered fibers were designed with antigen-antibody complexes targeting IL-8 and HCoV-OC43 to validate our TOFS design across two different antigens. Results: TOFS with tethered mouse anti-human IgG (28nm) bound to dissolved IL-8 (14 nm) produces a measurable phase shift. As little as 10pg/ml or 7.1X105 IL-8 molecules/l was detected by the prototype device and the phase change represented in real-time the binding dynamic of IL-8 to the tethered IgG. To validate our proof-of-concept experiment, HCoV-OC43 dissolved in saliva was detected with a sensitivity of 50 viruses/mL. Conclusions: TOFS device is a highly sensitive system capable of detecting proteins, viruses, and other biomolecules. Selectivity of the system is guaranteed by specific antigen-antibody binding, supported by the detection of IL-8 and HCoV-OC43 at the femtomolar level. The long-term goal for TOFS is its application as a point-of-care device used for detection, monitoring, and surveillance of HNSCC as well as detection of other pathogens in the clinical setting.
  🖺 Full Text HTML: The Application of Label-free Detection Using a Tapered Optical Fiber System for Head and Neck Cancer and Infectious Biomolecules
• WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific -
  The authors have withdrawn their manuscript owing to the results of this pre-print being based on experiments performed prior to COVID-19 shutdowns, which required a near complete culling of the mouse colony. Upon re-initiating the colony, the phenotype outlined in the pre-print could no longer be observed and as such we have decided to withdraw the pre-print. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
  🖺 Full Text HTML: WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific
• Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond -
  Importance: The COVID-19 pandemic prompted a surge in telehealth utilization. However, language barriers have emerged as a potential obstacle to effective telemedicine engagement, impacting millions of limited English proficient (LEP) individuals. Understanding the role of English proficiency in telehealth outcomes is critical, particularly in cancer care, where consistent follow-up and communication are vital. Objective: The primary objective of this study is to assess the relationship between telehealth use and clinical outcomes in cancer patients while concurrently exploring the effects of English language proficiency on telehealth utilization. Design: This study utilizes a retrospective cohort design, encompassing cancer patients seen at the Chao Comprehensive Cancer Center between March 1, 2020, and December 31, 2022. The study incorporates both in-person and telehealth visits, examining the association between encounter type and clinical outcomes. Setting: The study took place at an NCI-designated cancer center, offering a controlled setting for assessing telehealth utilization and its consequences in cancer care. Participants: The study includes 7,890 patients with more than one outpatient visit during the study period. The majority of our cohort consists of English, Spanish and Vietnamese-speaking patients. Main Outcome(s) and Measure(s): Primary outcomes include the association between telehealth utilization and clinical outcomes, such as hospitalization rates, duration of hospital admissions, rates of readmission, and patient mortality. Results: There was decreased telehealth utilization in non-English speaking cancer patients throughout the pandemic. Increased telehealth utilization was associated with higher rates of admission, irrespective of cancer type. Additionally, telehealth visits were associated with higher rates of subsequent readmissions and longer duration of subsequent admissions compared to in-person visits. Spanish-speaking patients utilizing telehealth had higher rates of re-admission compared to English speakers utilizing telehealth. Patients who died had higher rates of telehealth utilization compared to patients who survived. Conclusions and Relevance: This study highlights the implications of telehealth usage in healthcare outcomes and the role of language barriers in telehealth engagement among cancer patients. The study underscores the need to optimize telehealth usage and minimize its limitations to enhance the quality of cancer care in a telehealth-driven era.
  🖺 Full Text HTML: Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond
• RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning -
  The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19.
  🖺 Full Text HTML: RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning
• Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain -
  The enzymatic activity of the SARS-CoV-2 Nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N-terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5'-cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated. Here we determine high-resolution cryo-electron microscopy structures of catalytic intermediates for the NMPylation and deRNAylation/capping reactions, revealing diverse nucleotide binding poses and divalent metal ion coordination sites to promote its repertoire of activities. The deRNAylation/capping structure explains why GDP is a preferred substrate for the capping reaction over GTP. Altogether, these findings enhance our understanding of the promiscuous coronaviral NiRAN domain, a therapeutic target, and provide an accurate structural platform for drug development.
  🖺 Full Text HTML: Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain
• Using a function-first “scout fragment”-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes -
  Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity. As a result, helicases are important targets for chemical probes and therapeutics. However, it has been very challenging to develop selective chemical inhibitors for helicases, enzymes with highly dynamic conformations. We envisioned that electrophilic "scout fragments", which have been used for chemical proteomic based profiling, could be leveraged to develop covalent inhibitors of helicases. We adopted a function-first approach, combining enzymatic assays with enantiomeric probe pairs and mass spectrometry, to develop a covalent inhibitor that selectively targets an allosteric site in SARS-CoV-2 nsp13, a superfamily-1 helicase. Further, we demonstrate that scout fragments inhibit the activity of two human superfamily-2 helicases, BLM and WRN, involved in genome maintenance. Together, our findings suggest a covalent inhibitor discovery approach to target helicases and potentially other conformationally dynamic mechanoenzymes.
  🖺 Full Text HTML: Using a function-first “scout fragment”-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes

From Clinical Trials

• 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

• 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

• SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SA55 Injection;   Other: Placebo for SA55 injection
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• 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

• 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

• 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

• 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

• Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2) - Condition:   Systemic Inflammatory Response Syndrome
  Interventions:   Biological: Allogeneic thyTreg 5.000.000;   Biological: Allogeneic thyTreg 10.000.000
  Sponsors:   Hospital General Universitario Gregorio Marañon;   Instituto de Salud Carlos III
  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

• 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

• Amantadine Therapy for Cognitive Impairment in Long COVID - Conditions:   Long COVID;   Post-COVID19 Condition;   Post-Acute COVID19 Syndrome
  Intervention:   Drug: Amantadine
  Sponsor:   Ohio State University
  Not yet recruiting

• Impact of Covid-19 Aerosol Box On Intubation Success Rate - Condition:   Intubation; Difficult or Failed
  Interventions:   Device: Intubation using aerosol box;   Device: Intubation without aerosol box
  Sponsor:   Universiti Kebangsaan Malaysia Medical Centre
  Completed

• Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia - Condition:   Parosmia
  Interventions:   Procedure: Stellate Ganglion Block;   Other: Placebo
  Sponsor:   Lawson Health Research Institute
  Not yet recruiting

From PubMed

• A promising nucleic acid therapy drug: DNAzymes and its delivery system - Based on the development of nucleic acid therapeutic drugs, DNAzymes obtained through in vitro selection technology in 1994 are gradually being sought. DNAzymes are single-stranded DNA molecules with catalytic function, which specifically cleave RNA under the action of metal ions. Various in vivo and in vitro models have recently demonstrated that DNAzymes can target related genes in cancer, cardiovascular disease, bacterial and viral infection, and central nervous system disease. Compared with…

• Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID-19 - Nirmatrelvir, a novel, potent, orally bioavailable SARS-CoV-2 main protease (M^(pro) ) inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID-19 in individuals at increased risk of progression to severe disease. CYP3A4 is the primary metabolic enzyme responsible for nirmatrelvir metabolism; however, when CYP3A4 is inhibited by ritonavir, nirmatrelvir is primarily excreted, unchanged, in urine. Because of intended use…

• Xuanbai Chengqi Decoction alleviates acute lung injury by inhibiting NLRP3 inflammasome - CONCLUSION: The therapeutic mechanism of XCD in ALI treatment may involve alleviating inflammatory responses in lung tissues by inhibiting the activation of the NLRP3 inflammasome-mediated pyroptosis in macrophages.

• Transcriptomics-inferred dynamics of SARS-CoV-2 interactions with host epithelial cells - Virus-host interactions can reveal potentially effective and selective therapeutic targets for treating infection. Here, we performed an integrated analysis of the dynamics of virus replication and the host cell transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using human Caco-2 colon cancer cells as a model. Time-resolved RNA sequencing revealed that, upon infection, cells immediately transcriptionally activated genes associated with…

• B cell responses to membrane-presented antigens require the function of the mechanosensitive cation channel Piezo1 - The demand for a vaccine for coronavirus disease 2019 (COVID-19) highlighted gaps in our understanding of the requirements for B cell responses to antigens, particularly to membrane-presented antigens, as occurs in vivo. We found that human B cell responses to membrane-presented antigens required the function of Piezo1, a plasma membrane mechanosensitive cation channel. Simply making contact with a glass probe induced calcium (Ca^(2+)) fluxes in B cells that were blocked by the Piezo1 inhibitor…

• Host range, transmissibility and antigenicity of a pangolin coronavirus - The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration…

• NETs induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model - BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells and highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, little data is available on the involvement of NETs in secondary events after virus clearance, which can…

• Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2 - The main protease (M^(pro)) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and…

• Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection - Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant…

• Computational study on the mechanisms of inhibition of SARS-CoV-2 M^pro by aldehyde warheads based on DFT - SARS-CoV-2 main protease, M^(pro), plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting M^(pro) at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water…

• Heat shock protein 90 inhibition in the endothelium - No abstract

• Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections - Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1…

• Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…

• Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA - Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts…

• Regulation of human interferon signaling by transposon exonization - Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I…

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