Based on early reports of the efficacy of hydroxychloroquine sulfate (HCQS) to inhibit SARS-CoV-2 viral replication in vitro, and since severe pulmonary involvement is the major cause of COVID-19 mortality, we assessed the safety and efficacy of aerosolized HCQS (aHCQS) therapy in animals and humans. In a Phase 1 study of aHCQS in healthy volunteers, doses up to 50 mg were well tolerated and estimated epithelial lining fluid concentrations immediately after inhalation (>2,000 uM) exceeded the in vitro concentrations needed for suppression of viral replication (>=119 uM). A study in rats comparing HCQS solution administered orally (13.3 mg/kg) and by intratracheal installation (IT 0.18 mg/kg, <5% of oral dose) demonstrated that at 2 minutes, IT administration was associated with 5X higher mean hydroxychloroquine (HCQ) concentrations in the lung (IT: 49.5 +/- 6.5 ug HCQ/g tissue, oral: 9.9 +/- 3.4; p<0.01). A subsequent study of IT and intranasal HCQS in the Syrian hamster model of SARS-CoV-2 infection, however, failed to show clinical benefit. We conclude that aHCQS alone is unlikely to be effective for COVID-19, but based on our aHCQS pharmacokinetics and current viral entry data, adding oral HCQS to aHCQS, along with a transmembrane protease inhibitor, may improve efficacy.
Background: Reported changes in antibiotic prescribing during the COVID-19 pandemic have focused on hospital prescribing or community population trends. Community antibiotic prescribing for individuals with COVID-19 are less well described. Methods: Data covering a complete geographic population (~800,000) were utilized. SARS-CoV-2 virus test results from February 1, 2020- March 31, 2022 were included. Anonymized data were linked to prescription data +/-28 days of the test, GP data for high-risk comorbidities, and demographic data. Multivariate binary logistic regression examined associations between patient factors and the odds of antibiotic prescription. Results: Data included 768,206 tests for 184,954 individuals, identifying 16,240 COVID-19 episodes involving 16,025 individuals. There were 3,263 antibiotic prescriptions +/-28 days for 2,385 patients. 35.6% of patients had a prescription only before the test date, 52.5% patients after, and 11.9% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave one, 17.7% in wave two, and 12.0% in wave three. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19,1.45), older (OR 3.02, 95% CI 2.50, 3.68 75+ vs <25 years), having a high-risk comorbidity (OR 1.45, 95% CI 1.31, 1.61), a hospital admission +/-28 days of an episode (OR 1.58, 95% CI 1.42, 1.77), and health board region (OR 1.14, 95% CI 1.03, 1.25, board B versus A) increased the odds of receiving an antibiotic. Conclusion: Community antibiotic prescriptions in COVID-19 episodes were uncommon in this population and likelihood was associated with patient factors. The reduction over pandemic waves may represent increased knowledge regarding COVID-19 treatment and/or evolving symptomatology.
Background: The polymerized type I collagen (PTIC) is a g-irradiated mixture of pepsinized porcine type I collagen and polyvinylpyrrolidone (PVP). It has immunomodulatory properties. However, the receptor and signaling pathway through which it exerts its therapeutic effects has not yet been identified. Aim: To evaluate LAIR-1 as a potential receptor for PTIC and the signaling pathway evoked by ligand-receptor binding. Methods: LAIR-1 binding assay was performed by incubating various concentrations of recombinant human LAIR-1 with native type I collagen or PTIC. Macrophages M1-derived from THP-1 cells were cultured with 2-10% PTIC for 24 h. Cell lysates from THP-1, monocytes-like cells (MLCs), M1, M1+IFN-γ, M1+LPS, and 2 or 10% PTIC treated M1 were analyzed by western blot for the transcription factors NF-κB (p65), p38, STAT-1, and pSTAT-1. Cytokines, Th1 cells, and M1/M2 macrophages were analyzed by luminometry and flow cytometry from blood samples of symptomatic COVID-19 outpatients on treatment with intramuscular administration of PTIC. Results: PTIC binds LAIR-1 with a similar affinity to native collagen. This binding decreases STAT-1 signaling IFN-γ-induced and IL-1β expression in M1 macrophages by down-regulating STAT-1 phosphorylation. Moreover, intramuscular PTIC treatment of symptomatic COVID-19 outpatients decreased at statistically significant levels the percentage of M1 macrophages and cytokines (IP-10, MIF, eotaxin, IL-8, IL-1RA, and M-CSF) associated with STAT-1 transcription factor and increased M2 macrophages and Th1 cells. The downregulation of inflammatory mediators was related to better oxygen saturation and decreased dyspnea, chest pain, cough, and chronic fatigue syndrome in the acute phase of infection and the long term. Conclusion: PTIC is an agonist of LAIR-1 and down-regulates STAT-1 phosphorylation. PTIC could be relevant for treating STAT-1-mediated inflammatory diseases, including COVID-19 and long COVID.
Infections can lead to persistent or long-term symptoms and diseases such as shingles after varicella zoster, cancers after human papillomavirus, or rheumatic fever after streptococcal infections(1,2). Similarly, infection by SARS-CoV-2 can result in Long COVID, a condition characterized by symptoms of fatigue and pulmonary and cognitive dysfunction(3-5). The biological mechanisms that contribute to the development of Long COVID remain to be clarified. We leveraged the COVID-19 Host Genetics Initiative(6,7) to perform a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We identified the first genome-wide significant association for Long COVID at the FOXP4 locus. FOXP4 has been previously associated with COVID-19 severity(6), lung function(8), and cancers(9), suggesting a broader role for lung function in the pathophysiology of Long COVID. While we identify COVID-19 severity as a causal risk factor for Long COVID, the impact of the genetic risk factor located in the FOXP4 locus could not be solely explained by its association to severe COVID-19. Our findings further support the role of pulmonary dysfunction and COVID-19 severity in the development of Long COVID.
Vaccination is considered one of the solutions to the COVID-19 pandemic. However, a small proportion of the population was fully vaccinated in Benin (20.9%) and Senegal (7.6%) by December 2022. This study explores the determinants of intent to vaccinate. This was a cross-sectional, descriptive, and analytical study of 865 Beninese and 607 Senegalese aged 18 years and older. Marginal quota sampling by age, gender and region was adopted. Data collection, using a survey instrument based on the Random Digit Dialing (RDD) method, was conducted from December 24, 2020, to January 16, 2021, in Senegal and from March 29 to May 14, 2021, in Benin. The questionnaire used the Theory of Planned Behavior (TPB) and the Health Belief Model (HBM). The influence of factors was tested using a structural equation model. All analyses were conducted in R. Results show that a good perception of the benefits of vaccination ( =0.33; =0.12), a positive attitude (=0.22; =0.20), and sensitivity to subjective norms ( =0.19; =0.32) positively influence the intention to vaccinate. Low trust in health care providers (=-0.40; =-0.36) amplifies the perceived risk of vaccination (=-0.14; =-0.25), which negatively impacts intention to vaccinate. Perceived vaccine efficacy was affected by perceived risk (=-0.12; =-0.05) of the disease and improved by good apprehension of the benefits of vaccination (=0.60; =0.13). Aspects related to behavioral control, vaccine information seeking, efficacy, or fairness did not appear as correlates of vaccine intention (P>0.05). Beninese and Senegalese public health authorities could develop additional intervention strategies to improve immunization coverage by considering these influencing factors, the basis of which could be better understood through subsequent qualitative studies.
Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID share some clinical and social characteristics. We predicted that this would lead to an increased interaction between pre-pandemic members of a ME/CFS online support community and a long COVID community. We performed a mixed-methods retrospective observational study of the Reddit activity of 7,544 users active on Reddit9s long COVID forum. From among 1600 forums, pre-pandemic activity specifically on a ME/CFS forum is the top predictor of later participation on the long COVID forum versus an acute COVID support forum. In the qualitative portion, motives for this co-participation included seeking mutual support and dual identification with both conditions. Some of this effect may be explained by pre-existing ME/CFS possibly being a risk factor for long COVID and/or SARS-CoV-2 infection being a cause of ME/CFS relapse. The high rate of ME/CFS patients seeking mutual support on a long COVID forum speaks to the long-suffering experience of these patients not feeling heard or respected, and the hope of some ME/CFS patients to gain legitimacy through the public9s growing recognition of long COVID.
Our understanding of SARS-CoV-2 reinfection patterns remains limited. We conducted a longitudinal study using Qatar national SARS-CoV-2 data from February 28, 2020 to June 11, 2023 to investigate incidence of reinfections both prior to and after omicron emergence. The latter analysis excluded individuals with pre-omicron infections. Before omicron introduction, the proportion of incident infections classified as reinfections gradually increased but remained minimal, reaching 1.8% just before omicron emerged. During the first omicron wave, this proportion reached 9.0%, a 5-fold increase. After the conclusion of the first omicron wave, the proportion of incident infections identified as reinfections rapidly increased, reaching 43.3% towards the end of the study. In the pre-omicron era, a total of 3,131 reinfections were documented, of which 99.6% were first reinfections and 0.4% were second reinfections. Meanwhile, a total of 20,962 reinfections were documented after an omicron primary infection of which 99.0% were first reinfections, 1.0% were second reinfections, and 0.01% were third reinfections. Reinfections were rare before omicron9s emergence but became widespread during the omicron era, including among individuals previously infected with omicron. Our findings may indicate accelerated viral evolution in the omicron era aimed at evading population immunity, but with minimal impact on COVID-19 severity, or potentially suggest immune imprinting effects that require further investigation.
Introduction: COVID-19 and tuberculosis (TB) exhibit similar symptomatic presentation and clinical parameters. Common underlying immunological mechanisms also highlight potential routes of immunopathogenic interaction between these diseases during co-infection. To explore immunological similarities, differences and interactions, single-cell RNA-seq (scRNA-seq) was performed on whole blood infected with Mycobacterium tuberculosis (Mtb), SARS-CoV-2, or both pathogens. Methods: Whole blood from four healthy adults, were subjected to ex vivo infection with Mtb and/or SARS-CoV-2 ancestral strain, or were maintained in an uninfected state, for 24 or 96 hours. At each timepoint, for each condition, the four biological replicates were captured, fixed and cryopreserved to be processed for scRNA-seq as a single batch. Following quality control filtering, genotype-based demultiplexing was performed to obtain data from each biological replicate for pseudobulk differential expression analysis. Results: Thirteen distinct clusters of cells were identified based on marker gene expression. Profound differences in the proportions of monocytes, T cells and neutrophils were observed between infection conditions and timepoints. The greatest divergence between pathogen responses occurred within myeloid cells at early timepoints of infection. Co-infection had the greatest synergistic effect 24 hours post-infection with 238 immunological pathways uniquely enriched, including IFN-γ and TNF production, whilst by 96 hours post-infection there was a large overlap of 182 shared pathways between Mtb, SARS-CoV-2 and co-infection. SARS-CoV-2-only infection resulted in widespread cell death by 96 hours post-infection, while Mtb-only and co-infected samples remained enriched for monocyte, T cell and NK cell signatures, sharing negative regulation of extrinsic apoptotic signalling. Distinct from Mtb, SARS-Co-V-2 had unique regulating of αβ T cell activation and differentiation at both time points. Conclusion: These data provide a high-resolution characterisation of distinct and overlapping immunological responses generated by SARS-CoV-2 and Mtb when a single infection or co-infection occurs. This sheds light on the potential effects of novel or existing host-directed therapies that target these pathways, which is particularly crucial for settings where dual presentation is common.
Introduction The COVID-19 pandemic was a major public health threat and posed tremendous pressure to develop a cure for it. Apart from ongoing efforts in developing vaccines, a lot of empirical treatments were recommended, that may have expedited the use of antimicrobials. The main objective of this study was to explore if and how the pandemic posed pressure on antimicrobials in Nepal using semi-structured interviews (SSIs) among patients, clinicians and drug dispensers. Methods A total of 30 stakeholders (10 each among clinicians, dispensers and COVID-19 patients) were identified purposively and were approached for SSIs. Clinicians and dispensers working in three tertiary hospitals in Kathmandu were first approached and were asked for their support to reach out to COVID-19 patients who were on follow-up at their out-patient department. SSIs were audio recorded, translated and transcribed into English, and were analyzed for thematic synthesis. Results Over-the-counter (OTC) uses of antibiotics was widespread during the pandemic, and were mostly rooted to patients attempts to halt the potential severity due to respiratory like illnesses, and the fear of being identified as a COVID-19 patients. Being identified as a COVID-19 patient was feared because of the stigmatization and social isolation. Patients who visited the drug shops and physicians were reported to make demands on specific medicines including antibiotics that may have added pressure among physicians and dispensers. Clinicians reported a degree of uncertainty related to treatment and that may have added pressure to prescribe antimicrobials. All stakeholders, although mostly patients and dispensers with limited understanding of what constitutes antimicrobials and the mechanisms underpinning it reported that the pressure during the pandemic may have added to the adversities such as antimicrobials resistance. Conclusions COVID-19 added a pressure to prescribe, dispense and overuse antimicrobials and may have accentuated the pre-existing OTC use of antimicrobials. Future pandemics including infectious disease outbreaks are major public health incidents that warrant a special caution on inappropriate pressure on antimicrobials. Strict policies related to the use of antimicrobials are urgent to redress their use during normal and pandemic situations.
Probiotic and Colchicine in COVID-19 - Condition: COVID-19
Interventions: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol
Sponsor: Ain Shams University
Completed
A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients - Conditions: COVID-19; Hospitalized COVID-19 Patients
Interventions: Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
Sponsors: Lebanese University; Hospital Saydet Zgharta University Medical Center
Recruiting
Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy - Condition: Post-COVID-19 Syndrome
Interventions: Other: sensory re-education training; Other: traditional treatment
Sponsor: Cairo University
Not yet recruiting
Comprehensive Imaging Exam of Convalesced COVID-19 Patients - Conditions: COVID-19; COVID Long-Haul
Interventions: Other: Magnetic Resonance Imaging; Other: Ultra-High Resolution Computed Tomography (CT) Scan
Sponsors: Johns Hopkins University; Canon Medical Systems, USA
Enrolling by invitation
UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
Interventions: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg
Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia
Recruiting
Evaluate the Safety and Immunogenicity of Different Booster Dose Levels of Monovalent and Bivalent SARS-CoV-2 rS Vaccines in Adults ≥ 50 Years - Condition: COVID-19
Interventions: Biological: NVX-CoV2540 (5, 10, 25 μg); Biological: NVX-CoV2373 (5 μg); Biological: Bivalent BA.4/5 Omicron subvariant
Sponsor: Novavax
Not yet recruiting
Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection. - Conditions: SARS-CoV-2 Infection; COVID-19
Intervention: Drug: Remdesivir
Sponsors: University of Derby; University of Exeter; Peninsula Clinical Trials Unit; University Hospitals of Derby and Burton NHS Foundation Trust
Not yet recruiting
The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19 - Conditions: Coronavirus Disease; COVID-19; Long Covid-19; Telerehabilitation
Interventions: Device: KNEESUP smart knee assistive device + KNEESUP care APP; Device: KNEESUP care APP; Behavioral: Healthy consulation
Sponsor: Shang-Lin Chiang
Recruiting
Open Label Extension of Efgartigimod in Adults With Post-COVID-19 POTS - Condition: Post-COVID Postural Orthostatic Tachycardia Syndrome Postural Orthostatic Tachycardia Syndrome
Intervention: Drug: Efgartigimod
Sponsors: argenx; Iqvia Pty Ltd
Recruiting
Digital Interventions to Understand and Mitigate Stress Response - Conditions: Distress, Emotional; Stress Response Among Nursing Professionals During the COVID-19; Stress Reaction; Acute
Intervention: Behavioral: Digital Intervention Group
Sponsors: Unity Health Toronto; Toronto Metropolitan University; University of Toronto; University of Ontario Institute of Technology; Boston University; University of Ottawa; Western University, Canada; Centre for Addiction and Mental Health
Recruiting
PREPARE-iVAC Trial - Conditions: COVID-19 Vaccines; Varicella Zoster Vaccine; Vaccine Response; Immunosuppression
Intervention: Biological: COVID-19 vaccination
Sponsors: University Medical Center Groningen; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Radboud University Medical Center; Erasmus Medical Center; UMC Utrecht; Leiden University Medical Center; Maastricht University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development
Not yet recruiting
NC Testing in LC & POTS - Conditions: Postural Orthostatic Tachycardia Syndrome; Post Acute Sequelae of SARS CoV 2 Infection
Intervention: Other: IV normal saline (1 Litre)
Sponsor: University of Calgary
Not yet recruiting
To Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID - Condition: Long Covid
Intervention: Drug: BC 007 or matching placebo
Sponsor: Berlin Cures GmbH
Recruiting
Design, Synthesis and Structure-Activity Relationship Studies of Protein Kinase CK2 Inhibitors Containing a Purine Scaffold - Protein kinase CK2 (CK2) is involved in the suppression of gene expression, protein synthesis, cell proliferation, and apoptosis, thus making it a target protein for the development of therapeutics toward cancer, nephritis, and coronavirus disease 2019. Using the solvent dipole ordering-based method for virtual screening, we identified and designed new candidate CK2α inhibitors containing purine scaffolds. Virtual docking experiments supported by experimental structure-activity relationship…
A fish perspective on SARS-CoV-2: toxicity of benzalkonium chloride on Danio rerio - SARS-CoV-2 outbreak lead to an increased marketing of disinfectants, creating a potential environmental problem. For instance, pre-pandemic environmental levels of the disinfectant benzalkonium chloride (BAC) ranging from 0.5 to 5 mgL^(-1) in effluents were expected to further increase threatening aquatic life. Our aim was to characterize potential adverse effects after an acute exposure of zebrafish to different concentrations of BAC. An increase in the overall swimming activity, thigmotaxis…
Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein - Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein-glycan interactions. We hypothesize that polyvalent nano-lectins with flexibly linked…
Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-β - Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19…
Anti-Inflammatory Effects of Dexamethasone in COVID-19 Patients: Translational Population PK/PD Modeling and Simulation - Dexamethasone (DEX) given at a dose of 6 mg once-daily for 10 days is a recommended dosing regimen in patients with COVID-19 requiring oxygen therapy. We developed a population pharmacokinetic and pharmacodynamic (popPK/PD) model of DEX anti-inflammatory effects in COVID-19 and provide simulations comparing the expected efficacy of four dosing regimens of DEX. Nonlinear mixed-effects modeling and simulations were performed using Monolix Suite version 2021R1 (Lixoft, France). Published data for…
The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2 - The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (Momordica charantia), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC50 ~ 0.2 μM) with…
Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease - The SARS-CoV-2 main protease (M^(pro)) plays an essential role in the coronavirus lifecycle by catalyzing hydrolysis of the viral polyproteins at specific sites. M^(pro) is the target of drugs, such as nirmatrelvir, though resistant mutants have emerged that threaten drug efficacy. Despite its importance, questions remain on the mechanism of how M^(pro) binds its substrates. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to evaluate structural and dynamical…
Restriction of SARS-CoV-2 replication by receptor transporter protein 4 (RTP4) - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is subject to restriction by several interferon-inducible host proteins. To identify novel factors that limit replication of the virus, we tested a panel of genes that we found were induced by interferon treatment of primary human monocytes by RNA sequencing. Further analysis showed that one of the several candidates genes tested, receptor transporter protein 4 (RTP4), that had previously been shown to restrict flavivirus replication,…
Characterization of SARS-CoV-2 humoral immune response in a subject with unique sampling: A case report - CONCLUSION: The findings here provide novel insights into humoral immune response characteristics associated with SARS-CoV-2 breakthrough infections.
Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial - CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8.
Endotyping of IgE-mediated polyethylene glycol and/or polysorbate 80 allergy - CONCLUSION: PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whilst PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels and enhanced BAT reactivity. Spherical PEG-exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines.
Hindered visibility improvement despite marked reduction in anthropogenic emissions in a megacity of southwestern China: An interplay between enhanced secondary inorganics formation and hygroscopic growth at prevailing high RH conditions - The PM(2.5)-bound visibility improvement remains challenging in China despite vigorous control on anthropogenic emissions in recent years. One critical issue could exist in the distinct physicochemical properties especially of secondary aerosol components. Taken the COVID-19 lockdown as an extreme case, we focus on the relationship between visibility, emission cuts, and secondary formation of inorganics with changing optical and hygroscopic behaviors in Chongqing, a representative city…
Anthracyclines inhibit SARS-CoV-2 infection - Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks….
Statins: Beneficial Effects in Treatment of COVID-19 - The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important…
mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway - Coronaviruses (CoVs), which pose a serious threat to human and animal health worldwide, need to hijack host factors to complete their replicative cycles. However, the current study of host factors involved in CoV replication remains unknown. Here, we identified a novel host factor, mammalian lethal with sec-13 protein 8 (mLST8), which is a common subunit of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is critical for CoV replication. Inhibitor and knockout (KO) experiments revealed…