Background: COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although generally considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vector vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve the vaccine safety profile. Methods: We assessed changes to biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet-activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n=58) was analyzed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. Results: We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose-2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in PAI post-prime dose. Conclusions: Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. These findings suggest that a role of persistent endothelial activation following COVID-19 vaccination warrants further investigation.
Objective: This Phase IV prospective observational study aimed to evaluate the safety and monitor adverse events following immunization (AEFI) associated with CoronaVac, an inactivated SARS-CoV-2 vaccine, in Brazilian adult (18-59 years) and elderly (≥60 years) populations. Methods: Participants (n=538; 487 adults and 51 elderly) were enrolled from three public health services in São Paulo, Brazil. A two-dose vaccination regimen, administered 14 days apart, was used. The study assessed Adverse Reactions (AR) necessitating medical attention within seven days post-vaccination dose and monitored AEFI for a period of 42 days. Safety was monitored through a review of participant diary cards, telephone contacts, and on-site study visits. Results: Among adults, the most frequently reported local AR after the first and second dose was pain (256[52.6%] and 129 [29.5], respectively), while the most common systemic reaction was a headache (158[34.5%] and 51 [11.6%], respectively). Most local and systemic solicited ARs were of Grade 1 or 2, with these reactions being more prevalent in adults after the first dose. One serious adverse event possibly related to the vaccine was reported among adults, but there were no fatalities. Nine adult participants experienced adverse events of special interest, which included five cases of Covid-19. Conclusion: CoronaVac demonstrated safety and tolerability in the observed population. Ongoing post-marketing surveillance is crucial for the identification of rare adverse events and further affirmation of the vaccine’s safety profile.
Understanding and monitoring the major influences on SARS-CoV-2 prevalence is essential to inform policy making and devise appropriate packages of non-pharmaceutical interventions (NPIs). Through evaluating community level influences on the prevalence of SARS-CoV-2 infection and their spatiotemporal variations in England, this study aims to provide some insights into the most important risk parameters. We used spatial clusters developed in Jahanshahi and Jin, 2021 as geographical areas with distinct land use and travel patterns. We also segmented our data by time periods to control for changes in policies or development of the disease over the course of the pandemic. We then used multivariate linear regression to identify influences driving infections within the clusters and to compare the variations of those between the clusters. Our findings demonstrate the key roles that workplace and commuting modes have had on some of the sections of the working population after accounting for several interrelated influences including mobility and vaccination. We found communities of workers in care homes and warehouses and to a lesser extent textile and ready meal industries and those who rely more on public transport for commuting tend to carry a higher risk of infection across all residential area types and time periods.
SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell dataset of peripheral blood of patients with acute COVID-19 and of healthy volunteers before and after receiving the SARS-CoV-2 mRNA vaccine and booster. We compared host immune responses to the virus and vaccine using transcriptional profiling, coupled with B/T cell receptor repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. These findings were validated in an independent dataset. Analysis of B and T cell repertoires revealed that, while the majority of clonal lymphocytes in COVID-19 patients were effector cells, clonal expansion was more evident among circulating memory cells in vaccine recipients. Furthermore, while clonal αβ T cell responses were observed in both COVID-19 patients and vaccine recipients, dramatic expansion of clonal γδT cells was found only in infected individuals. Our dataset enables comparative analyses of immune responses to infection versus vaccination, including clonal B and T cell responses. Integrating our data with publicly available datasets allowed us to validate our findings in larger cohorts. To our knowledge, this is the first dataset to include comprehensive profiling of longitudinal samples from healthy volunteers pre/post SARS-CoV-2 vaccine and booster.
We present compelling evidence for the existence of an extended innate viperin dependent pathway which provides crucial evidence for an adaptive response to viral agents like SARS-CoV-2. We show the in vivo biosynthesis of a family of endogenous cytosine metabolites with potential antiviral activity. Two dimensional Nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase. Mass spectrometry additionally allowed the characterization and quantification of the most abundant serum metabolites showing potential diagnostic value of the compounds for viral infections. In total, we unveiled ten nucleoside (cytosine and uracil based) analogue structures, eight of which were previously unknown in humans. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defence mechanism against viral infection.
Rationale: In the upper respiratory tract replicating (culturable) SARS-CoV-2 is recoverable for ~ 4 to 8 days after symptom onset, however, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (i.e. the human lung). Objectives: We undertook lung tissue sampling (needle biopsy), shortly after death, in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patents served as a control group. Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling and immunohistochemistry. Results: 38% (16/42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 weeks) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (p<0.05). Nasopharyngeal culture was negative in 23.1% (6/26) of decedents despite lung culture positivity. This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary pro-inflammatory response but with concurrent viral culture positivity. Conclusions: Concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe COVID-19 disease.
During Covid-19, the Defense Health Agency9s TRICARE insurance plan expanded its coverage to include 30.1% additional civilian healthcare providers. The DHA9s Annual Report, however, states that TRICARE9s provider directories are only 80% accurate. Although the DHA9s 9.6 million beneficiaries need expanded access to care, they also require protection from misleading information, medical fraud, patient abuse, and identity theft. Since 2013, the Department of Health and Human Services9 Office of the Inspector General has excluded 17,706 physicians from federal health programs due to misconduct. Patients who receive care from excluded providers experience worse medical outcomes. To determine if any excluded provider names were found on TRICARE9s website, we performed background checks on TRICARE West9s healthcare provider directory between January 1 and March 2023. Out of 39,463 provider names sampled from 22 states, there were 2,398 matches (6.08%) with individuals and businesses found in the OIG List of Excluded Individuals and Entities (OIG-LEIE), the GSA-SAM, the HHS HIPAA Breach Report, the International Trade Administration9s Consolidated Screening List, the OIG-HHS Fugitive List, the FBI9s January 6th Capitol Violence List of Charged Defendants, State Medicaid Exclusion Lists, and FDA Debarment Lists. Our study includes demographic analysis of the matching names and recommendations for an Insider Threat Management model. We recommend that DHA officials publish the National Provider Identification (NPI) numbers of all TRICARE providers. NPI numbers facilitate more accurate background checks of healthcare providers.
Objectives: To establish a SARS-CoV-2 PCR testing programme in an academic institution to analyze saliva samples collected from asymptomatic staff and students. Design: PCR to detect SARS-CoV-2 RNA in saliva self-collected by asymptomatic students and staff members from King′s College London, and their household contacts. Standards for diagnostics testing set by the DHSC (UK) were followed to develop an automated saliva PCR service for SARS-CoV-2 detection. Prospective study that run from December 2020 until July 2022. Setting: Testing took place in an academic institution including 18 different locations in London (UK). Participants: There were no selection criteria; asymptomatic participants were encouraged to test regularly (twice weekly when on campus). Main outcome measures: Number of tests, number of participants and positive rate. Results: 158,277 PCR tests were carried out on saliva, of which 2,989 were positive (1.89%), collected by 20,186 participants. Between 10-30% of campus footfall were tested. The positive rate was equivalent to that reported by the Office for National Statistics (UK), except for the period encompassing the delta variant; this wave was nearly absent in our cohort. We employed non-commercial reagents and an open source-inspired automated pipeline for sample processing. This rapidly developed service was awarded UKAS accreditation under the ISO15189 standard. Conclusions: Including academic institutions in pandemic preparedness is a critical consideration, considering the experience in developing, validating, and implementing economic and scalable testing solutions. Given the joint ventures in hospital pathology departments across the UK and the move to centralised, automated, commercial tests, focusing on academic centres that can carry out research and development to test for novel and re-emerging pathogens should be a top priority.
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
Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition: COVID-19
Intervention: Drug: Obeldesivir
Sponsor: Gilead Sciences
Not yet recruiting
Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A COVID-19 Preventive Vaccine in Healthy Volunteers - Conditions: COVID-19; Vaccines
Interventions: Biological: AdCLD-CoV19-1 OMI; Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)
Sponsor: Cellid Co., Ltd.
Not yet recruiting
Using Text Messages to Boost COVID-19 Vaccine Booking Rate - Conditions: Vaccination Hesitancy; COVID-19
Interventions: Behavioral: Behavioural science-informed text messages; Behavioral: Control
Sponsors: The Behavioural Insights Team; Public Health England; Department of Health and Social Care; NHS England and NHS Improvement
Completed
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
Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: Ivermectin; Drug: Placebo
Sponsor: Insud Pharma
Terminated
Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS) - Condition: Post-COVID-19 Syndrome
Intervention: Drug: Methylprednisolone
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy
Intervention: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
Sponsors: Duke University; American Society of Hematology
Not yet recruiting
Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions: Mental Health; COVID-19; Misinformation
Interventions: Behavioral: Card-Sorting Activity (Pre-intervention design); Behavioral: SMS Crafting (Pre-intervention design); Behavioral: SMS Messaging
Sponsors: Harvard Medical School (HMS and HSDM); Partners in Health
Active, not 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
A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Biological: BNT162b2 (Omi XBB.1.5)
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Pulmonary Artery Pressure in COVID-19 Survivors - Condition: Pulmonary Hypertension Secondary
Intervention: Diagnostic Test: right heart catheterization (RHC).
Sponsor: Mansoura University Hospital
Enrolling by invitation
Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic - Conditions: Cardiovascular Health; Physical Function
Intervention: Behavioral: Golden Circle
Sponsor: University of Illinois at Urbana-Champaign
Completed
Study of LAU-7b for the Treatment of Long COVID in Adults - Condition: Long COVID
Interventions: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles
Sponsor: Laurent Pharmaceuticals Inc.
Not yet 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
Dexamethasone attenuates interferon-related cytokine hyperresponsiveness in COVID-19 patients - CONCLUSION: We describe the anti-inflammatory impact of dexamethasone on the pathways contributing to cytokine hyperresponsiveness observed in severe manifestations of COVID-19, including type I/II IFN signaling. Dexamethasone could have adverse effects in COVID-19 patients with mild symptoms by inhibiting IFN responses in early stages of the disease, whereas it exhibits beneficial effects in patients with severe clinical phenotypes by efficiently diminishing cytokine hyperresponsiveness.
Investigation of Iminosugars as Antiviral Agents against SARS-CoV-2 Main Protease: Inhibitor Design and Optimization, Molecular Docking, and Molecular Dynamics Studies to Explore Potential Inhibitory Effect of 1-Deoxynojirmycin Series - CONCLUSION: The present findings confer opportunities for compounds 17a, 7, and 8 that could be developed as new therapeutic agents against COVID-19. These compounds are suggested on the basis of pharmacokinetic parameters as well as therapeutic importance and hence could be tested in-vitro.
A complement atlas identifies interleukin-6-dependent alternative pathway dysregulation as a key druggable feature of COVID-19 - Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the…
The S1’-S3’ Pocket of the SARS-CoV-2 Main Protease Is Critical for Substrate Selectivity and Can Be Targeted with Covalent Inhibitors - The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a well-characterized target for antiviral drug discovery. To date, most antiviral drug discovery efforts have focused on the S4-S1’ pocket of Mpro; however, it is still unclear whether the S1’-S3’ pocket per se can serve as a new site for drug discovery. In this study, the S1’-S3’ pocket of Mpro was found to differentially recognize viral peptidyl substrates; for instance, S3’ in Mpro strongly favors Phe…
Cyclotheonellazoles D-I, Potent Elastase Inhibitory Thiazole-Containing Cyclic Peptides from Theonella sp. (2131) - Six new thiazole-containing cyclic peptides, the cyclotheonellazoles D-I (1-6), were isolated from the Australian marine sponge Theonella sp. (2131) with their structures assigned by comprehensive 1D and 2D NMR spectroscopic and MS spectrometric analyses, Marfey’s derivatization studies, and comparison with time-dependent density functional theory (TDDFT) calculated ECD data. The Type 2 azole-homologated peptides herein comprise up to five nonproteinogenic amino acids, including the protease…
Assessment of efficacy and safety of endoscopic lung volume reduction with one-way valves in patients with a very low FEV1 - CONCLUSION: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV(1), as these patients experienced significant improvements in FEV(1), 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients.
Prevalence of oral complications in the course of severe SARS-CoV-2 infection under mechanical non-invasive ventilation - CONCLUSIONS: COVID-19 hospitalised patients with severe symptoms crossing with poor oral health-related conditions. This may exacerbate a response for COVID infection, and play a role in cytokine storm. For Covid-19 management, to inhibit extraoral/intraoral complications, it is recommended to adjust oral hygiene procedures, including antibacterial, protective, moisturising agents after individual oral health assessment.
The Possible Mechanisms of Cu and Zn in the Treatment and Prevention of HIV and COVID-19 Viral Infection - Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic…
SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b - The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that…
A Mixture of Essential Oils from Three Cretan Aromatic Plants Inhibits SARS-CoV-2 Proliferation: A Proof-of-Concept Intervention Study in Ambulatory Patients - INTRODUCTION: The need for effective therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remained largely unmet. Previous work has shown that a combination of three aromatic plants’ essential oils (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticose Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care settings.
Peptide foldamer-based inhibitors of the SARS-CoV-2 S protein-human ACE2 interaction - The entry of the SARS-CoV-2 virus into a human host cell begins with the interaction between the viral spike protein (S protein) and human angiotensin-converting enzyme 2 (hACE2). Therefore, a possible strategy for the treatment of this infection is based on inhibiting the interaction of the two abovementioned proteins. Compounds that bind to the SARS-CoV-2 S protein at the interface with the alpha-1/alpha-2 helices of ACE2 PD Subdomain I are of particular interest. We present a stepwise…
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis - Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and…
Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-modifying Therapies - Respiratory virus infections initiate and transmit from the upper respiratory tract (URT). Coronaviruses, including OC43, are a major cause of respiratory infection and disease. Failure to mount an effective anti-viral immune response in the nasal mucosa increases the risk of severe disease and person to person transmission highlighting the need for URT infection models to support development of nasal treatments that improve coronavirus anti-viral immunity. We aimed to determine if OC43…
The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community - SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in…
Management of chronic myelogenous leukemia with COVID-19 and hepatitis B - The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and…