- Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells -
The fight against COVID-19 pandemic has gained a strong consensus about the importance of developing mRNA vaccines to rapidly respond to an outbreak. Several studies have shown that mRNA vaccines formulated as mRNA-lipid nanoparticles (LNPs) for vaccination can elicit a robust and efficient immune response. In this study, we report the preparation of mRNA-bifunctional lipid nanoparticles (mRNA-BLNPs) as vaccines for targeted delivery to dendritic cells (DCs) to improve safety and enhance immune response. Using this DC-targeted delivery system, mice immunized with SARS-CoV-2 spike mRNA-BLNP vaccine elicited a stronger immune response with higher titer of neutralizing IgG antibody response than the LNP-formulated vaccine against SARS-CoV-2. In addition, the spike mRNA-BLNP vaccine with deletion of glycosites in the stem elicited a broadly protective immune response against SARS-CoV-2 and variants. These findings suggest the importance and potential of developing DC-targeted mRNA vaccines to elicit broadly protective immune responses against human viruses.
- The base media formulation impacts the efficiency of ex-vivo erythropoiesis of primary human hematopoietic stem cells -
During the COVID-19 pandemic, there was a disruption in the supply of the widely used erythroid differentiation media product, Iscove’s Modified Dulbecco’s Medium, manufactured by Biochrom AG. IMDM is a critical component of ex vivo erythropoiesis protocols used to generate genetically modified red blood cells for the study of malaria host factors. Therefore, we set out to identify the best alternative IMDM product for efficient erythroid differentiation of hematopoietic stem cells into enucleated red blood cells for use in our research. We tested other IMDM products, including I2911 (from Millipore Sigma), P04-20450 (from Pan Biotech) and EP-CM-L0216 (from ElabScience Technologies) which are all marketed specifically as replacements for the Biochrom AG product. We found that while FG0465, I2911, and P04-20450 were all sufficient for ex-vivo erythropoiesis, FG0465 IMDM was superior to other products tested in supporting maximal erythroid cell proliferation and enucleation.
- Motorhomes as a Housing Alternative for the Indonesian Millennial Generation -
Motorhomes/campervans are a long-standing fad that is currently making a resurgence in all parts of the world. Because of the versatility of the motorhome, this lifestyle has grown in popularity, not only among hippies, but also among families who wish to have fun or live a nomadic (moving) existence, especially with the rapid rise of the Internet of Things. We can learn from the Covid-19 pandemic that work and study can be done anywhere, whether at home, in recreational spaces, in third rooms, and so on. Motorhomes can now be purchased at reasonable costs. Furthermore, the motorhome can be customized to meet your specific demands and functions. Motorhomes can be created from simple automobiles using any car foundation, such as an MPV, Van, SUV, Middle Size Bus, Full Size Bus, or even a sedan, rather than full size RVs with big proportions and luxurious equipment. The purpose of this study is to define the motorhome/campervan concept and its potential as an alternative housing type. Furthermore, the potential is fairly large for Indonesian millennials, who appear to have a lot of issues on housing ownership mostly because the affrodability (economic) aspect and also considering the raising on nomadic and flexible lifestyle. Motorhomes are an excellent option to economical housing since they are mobile, have flexible layouts, and provide a comfortable living space especially for Youth Indonesia’s Millenial who’s carving for a unique experience.
- CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research -
Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale. Study Design: Quasi-experimental. Setting: Virtual. Methods: CompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform's flexibility in experimental design and its wide range of applications in sound processing research. Results: Performance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com). Conclusion: The CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.
- Long Covid Perspectives: history, paradigm shifts, global challenges -
The Covid-19 pandemic is one of the most devastating health disasters in recorded history. In addition to the significant death toll, the pandemic is leaving behind a long tail of prolonged disease and disability. The long-term symptoms, clinical signs and sequelae of SARS-CoV-2 infection are collectively known as Long Covid – a patient-made term that was created and gained consistency in just a few months in Spring to Summer 2020. Long Covid was openly recognized by the World Health Organization (WHO) in August 2020, following intense advocacy by Covid-19 survivors. Long Covid has been described as the first illness identified, named and defined by patients finding one other on social media such as Twitter. As a disease entity named and defined collectively by patients, Long Covid has the potential to change knowledge building in medicine, while centring patient expertise within the biomedical community. This paper will, first, explore the rise of Long Covid as patient-made term, clinical entity and collective, grassroots, international advocacy–research movement in early 2020 and beyond. This happened while people with Covid-19 suffered abandonment and lack of care in the pandemic’s disaster context. Second, I will discuss some key paradigm shifts triggered by this ground-breaking patient-driven, collective advocacy–research, while sketching links with earlier patient movements, such as around HIV/AIDS. Then, I will explore the role of Long Covid advocacy–research in our digital era. This advocacy took place during a pandemic when digital spaces such as Twitter and Facebook were often the only arenas available to Covid-19 survivors. Moreover, I will raise some pressing issues around epistemic injustice in relation to the use of patient-produced data and the recognition of patient contributions to knowledge. Finally, I will address the need to fully acknowledge the nature, scope, and severity of Long Covid, which are detailed in thousands of scientific publications, including in relation to the ongoing spread of SARS-CoV-2.
- Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic -
Genomic analyses of bacterial isolates are necessary to monitor the prevalence of antibiotic resistance genes and virulence determinants. Herein, we provide a comprehensive genomic description of a collection of 339 Staphylococcus aureus strains isolated from patients with bacteremia between 2014 and 2022. Nosocomial acquisition accounted for 56.6% of episodes, with vascular catheters being the predominant source of infection (31.8%). Cases of fatality (27.4%), persistent bacteremia (19.5%) and diagnosis of septic emboli (24.2%) were documented. During the COVID-19 pandemic, we observed a 140% increase of the episodes of S. aureus bacteremia per year, with a concomitant increase of the cases from nosocomial origin. This prompted us to investigate the existence of genetic features associated with S. aureus isolates from the COVID-19 pandemic. While genes conferring resistance to {beta}-lactams (blaI-blaR-blaZ), macrolides (ermA, ermC, ermT, mphC, msrA) and aminoglycosides (ant(4')-Ia, ant(9)-Ia, aph(3')-IIIa, aph(2'')-Ih) were prevalent in our collection, detection of the msrA and mphC genes increased significantly in pandemic S. aureus isolates. Similarly, we observed a higher prevalence of isolates carrying the genes encoding the Clumping Factors A and B, involved in fibrinogen binding. Of note, macrolides were extensively used as accessory therapy for COVID-19 and fibrinogen levels were usually elevated upon SARS-CoV-2 infection. Therefore, our results reveal a remarkable adaptation of the S. aureus isolates to the COVID-19 pandemic context and demonstrates the potential of whole-genome sequencing to conduct molecular epidemiology studies.
- Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants -
The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S.
- The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022) -
Background-COVID-19 pandemic increased the risk of CVD (cardiovascular disease). There is lack of comparative assessment on the incidence of sudden death due to MI during and before COVID-19. This study aimed to quantify this assessment. Another quest to start this study is that several studies have reported COVID-19 vaccine-associated myocarditis/cardiomyopathy. Methods and results-This study was based on NCRB data from all states and UTs of India who died suddenly due to MI between 1 January 2018 and 31 December 2022. 5 coastal states of India accounts for about 70 % of all MI cases related sudden death. The base year 2018 is having least whereas the last year 2022 is having the largest number of total new MI cases related mortality detected in one individual year. The largest and noteworthy percent change in sudden death due to MI in males is found in 2022 when it increased by 14.26% (is it due to delayed cardiomyopathy due to COVID-19 or its due to Vaccine? This will be a matter of research in coming era). This study revealed that there is 25.80 percent increase in total number of new MI cases related mortality in 2022 in comparison to pre-COVID-19 year of 2018. There is an overall increase of 11.24 percent in sudden death due to MI cases in males during the COVID-19 period. The Male-Sudden death due to Myocardial Infarction increased during COVID-19 year 2022 by 26.71 percent in comparison to 2018 pre- COVID-19 year. Conclusion-Sudden death due to MI increased during COVID-19.
- MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity. -
BackgroundDespite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics. MethodsIn this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi- omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients. ResultsAs COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods. ConclusionsThis approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
- Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data -
Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic novel lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.
- Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics -
Introduction: The transcriptional heterogeneity of activated platelets, play a significant role in contributing to negative outcomes in sepsis, COVID-19, and autoimmune diseases such as systemic lupus erythematosus (SLE). Despite this, our understanding of these heterogeneous platelet responses remains limited. In this study, we aim to investigate the diverse transcriptional profiles of activated platelets in these diseases, with the goal of deciphering this platelet heterogeneity for new therapeutic strategies to target abnormal and pathogenic platelet subtypes. Materials and methods: We obtained the single cell transcriptional profiles of blood platelets from patients with COVID-19, sepsis, and SLE. Utilizing machine learning algorithms, Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB), we discerned the distinct transcriptomic signatures indicative of fatal versus survival clinical outcomes. Our methodological framework incorporated source data annotations and platelet markers and used SingleR and Seurat for detailed profiling. Additionally, we implemented Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization, aiding in the detection of various platelet subtypes and their correlation with disease status and patient outcomes. Results: Our study identified distinct platelet subpopulations that are associated with disease severity. We demonstrated that alterations in platelet transcription patterns can exacerbate endotheliopathy, potentially heightening the risk of coagulation in fatal patients. Moreover, these changes can also influence lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. Conclusions: Enhanced transcriptional heterogeneity in activated platelets is linked to adverse outcomes in conditions such as sepsis, COVID-19, and autoimmune diseases. The discovery of these unique platelet subpopulations paves the way for innovative therapeutic strategies targeting platelet activation, which could potentially improve patient outcomes.
- Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro -
Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ~20% of the treated cases. The persistence of an intermediary form of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious intermediate decayed slowly with a half-life of ~1 day, suggesting that its persistence could outlive the treatment course to re-ignited SARS-CoV-2 infection as the drug is eliminated. Additional studies are needed to define the nature of this viral intermediate, but our findings point to a particular direction for future investigation and offer a specific treatment recommendation that should be tested clinically.
- Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster -
Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characterize the antibody responses following vaccination, particularly in the elderly. Here, we show that the monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a panel of variants, including BA.2.86, in an older population with four or more previous vaccine doses. Furthermore, neutralizing antibody titers to XBB.1.5 and BA.2.86 were boosted more strongly than titers to historical variants were. Our findings thereby suggest increased vaccine induced protection against both antigenically matched variants, as well as the more distant BA.2.86 variant, and support current vaccine policies recommending a monovalent XBB.1.5 booster dose to older individuals.
- Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol -
Responses to COVID-19 in Canadian postsecondary education have overhauled usual norms and practices, with policies of unclear rationale implemented under the pressure of a public health emergency. However, despite the unprecedented nature of these policies and their dramatic impact on millions of lives, the decision-making process leading to them has not been documented or appraised. Drawing from macro and micro theories of public policy, specifically the critical tradition in policy studies exemplified by Carol Bacchi’s approach “What is the problem represented to be” (WPR), we will conduct a scoping review of COVID-19 policies in Canadian postsecondary education, guided by Arksey and O’Malley’s framework for scoping reviews and by the team-based approach of Levan and colleagues. Data will include diverse and publicly available documents to capture multiple stakeholders’ perspectives on the phenomenon of interest, and will be retrieved from university, newsletter, and legal websites through combinations of search terms adapted to specific data types. Two reviewers will independently screen, chart, analyse and synthesize the data and disagreements will be resolved through full team discussion. By identifying, summarizing, and appraising the evidence, our review should inform practices that can contribute to effective and equitable public health policies in postsecondary institutions moving forward.
- Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating -
The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
Safety and Immunogenicity of a Booster Vaccination With an Adapted Vaccine - Conditions: SARS-CoV2 Infection
Interventions: Biological: PHH-1V81; Biological: Comirnaty Omicron XBB1.5
Sponsors: Hipra Scientific, S.L.U
Active, not recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza. - Conditions: Influenza; COVID-19
Interventions: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Transcranial Pulse Stimulation (TPS) in Post-COVID-19 - Conditions: Post-COVID-19 Syndrome; Fatigue
Interventions: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham
Sponsors: Medical University of Vienna; Campus Bio-Medico University
Not yet recruiting
Evaluate the Efficacy and Safety of “Formosa 1-Breath Free (NRICM101)” in Subjects With the Symptoms of COVID-19 or Influenza-like Disease - Conditions: Influenza Viral Infections; COVID-19
Interventions: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug
Sponsors: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd.
Not yet recruiting
A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell) - Conditions: COVID-19
Interventions: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo
Sponsors: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd.
Not yet recruiting
Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID - Conditions: Long Covid19; Exercise Intolerance, Riboflavin-Responsive
Interventions: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises
Sponsors: Columbia University; New York University
Recruiting
A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues - Conditions: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission
Interventions: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary
Sponsors: University of Chicago
Not yet recruiting
Safety and Immunogenicity of Recombinant COVID-19 Trivalent Protein Vaccine （CHO Cell）LYB002V14 in Booster Vaccination - Conditions: SARS-CoV-2; COVID-19 Vaccine
Interventions: Biological: 30μg dose of LYB002V14; Biological: 60μg dose of LYB002V14; Biological: placebo
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
Exercise Training Using an App on Physical Cardiovascular Function Individuals With Post-covid-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Exercise; Behavioral: Control
Sponsors: University of Nove de Julho
Not yet recruiting
COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research - Conditions: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor
Interventions: Biological: Any Chinese government-recommended COVID-19 booster vaccine
Sponsors: Peking Union Medical College Hospital
Recruiting
Excessive daytime sleepiness is associated with impaired antibody response to influenza vaccination in older male adults - CONCLUSION: Our results provide an additional and easily measured variable explaining poor vaccine effectiveness in older adults. Our results support that gaining sufficient sleep is a simple non-vaccine interventional approach to improve influenza immune responses in older adults. Our findings extend the literature on the negative influence of excessive daytime sleepiness on immune responses to influenza vaccination in older male adults.
Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS) - CONCLUSIONS: Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.
Sutimlimab suppresses SARS-CoV-2 mRNA vaccine-induced hemolytic crisis in a patient with cold agglutinin disease - Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2…
COVID-19 in Dental Practice Is Prevented by Eugenol Responsible for the Ambient Odor Specific to Dental Offices: Possibility and Speculation - Dental professionals routinely work in proximity to patients even when either or both of them have suspected or confirmed COVID-19. The oral cavity also serves as a reservoir for SARS-CoV-2 because the virus is present in and replicates in oral secretions (saliva and gingival crevicular fluid), oral tissues (salivary gland and periodontal tissue), and oral microenvironments (gingival sulcus and periodontal pocket). Despite a high risk of SARS-CoV-2 infection, the prevalence of COVID-19 in…
Inhibition of Porcine Deltacoronavirus Entry and Replication by Cepharanthine - Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The…
Does denosumab exert a protective effect against COVID-19? Results of a large cohort study - CONCLUSION: Our study confirms that denosumab may be safely continued in COVID-19 patients. RANK/RANKL inhibition seems associated with a reduced incidence of symptomatic COVID-19, particularly among the elderly.
Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques - Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P was…
Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there’s no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers…
Comparative transcriptome analysis of SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E identifying potential IFN/ISGs targets for inhibiting virus replication - INTRODUCTION: Since its outbreak in December 2019, SARS-CoV-2 has spread rapidly across the world, posing significant threats and challenges to global public health. SARS-CoV-2, together with SARS-CoV and MERS-CoV, is a highly pathogenic coronavirus that contributes to fatal pneumonia. Understanding the similarities and differences at the transcriptome level between SARS-CoV-2, SARS-CoV, as well as MERS-CoV is critical for developing effective strategies against these viruses.
Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity - The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize…
Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development - Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia, but specific interventions preventing autoimmune aPL development are an unmet clinical need. While autoimmune aPL cross-react with various coagulation regulatory proteins, lipid-reactive and COVID-19 patient-derived aPL recognize the endo-lysosomal phospholipid lysobisphosphatidic acid (LBPA) presented by the cell surface expressed endothelial protein C receptor…
Tissue factor binds to and inhibits interferon-α receptor 1 signaling - Tissue factor (TF), which is a member of the cytokine receptor family, promotes coagulation and coagulation-dependent inflammation. TF also exerts protective effects through unknown mechanisms. Here, we showed that TF bound to interferon-α receptor 1 (IFNAR1) and antagonized its signaling, preventing spontaneous sterile inflammation and maintaining immune homeostasis. Structural modeling and direct binding studies revealed binding of the TF C-terminal fibronectin III domain to IFNAR1, which…
Avian coronavirus infectious bronchitis virus Beaudette strain NSP9 interacts with STAT1 and inhibits its phosphorylation to facilitate viral replication - Avian coronavirus, known as infectious bronchitis virus (IBV), is the causative agent of infectious bronchitis (IB). Viral nonstructural proteins play important roles in viral replication and immune modulation. IBV NSP9 is a component of the RNA replication complex for viral replication. In this study, we uncovered a function of NSP9 in immune regulation. First, the host proteins that interacted with NSP9 were screened. The immune-related protein signal transducer and activator of transcription…
Cholesterol depletion inhibits rabies virus infection by restricting viral adsorption and fusion - Rabies is an ancient zoonotic disease caused by the rabies virus (RABV), and a sharp increase in rabies cases and deaths were observed following the COVID-19 pandemic, indicating that it still poses a severe public health threat in most countries in the world. Cholesterol is one of the major lipid components in cells, and the exact role of cholesterol in RABV infection remains unclear. In this study, we initially observed that cellular cholesterol levels were significantly elevated in RABV…
Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants - Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition…