Background <br /> The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. <br /> Methods <br /> Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. <br /> Results <br /> 1,298 infections were detected among 9,560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95%CI 0.9 to 23.8) overall; 24.0% (95%CI 8.5 to 36.8) in the first two months post-vaccination, reducing to 10.3% (95%CI -11.4 to 27.8) and 1.7% (95%CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95%CI 46.9 to 75.0) and 29.1% (95%CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. <br /> Conclusions <br /> Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. <br /> Funding <br /> UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, and others.
Researchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Monitoring of air travel provides little benefit in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19.
The COVID-19 pandemic has highlighted the critical role of genomic surveillance for guiding policy and control strategies. Timeliness is key, but rapid deployment of existing surveillance is difficult because current approaches are based in sequence alignment and phylogeny. Millions of SARS-CoV-2 genomes have been assembled, the largest collection of sequence data in history. Phylogenetic methods are ill equipped to handle this sheer scale. We introduce a pan-genomic measure that examines the information diversity of a k-mer library drawn from a country9s complete set of sequenced genomes. Quantifying diversity is central to ecology. Studies that measure the diversity of various environments increasingly use the concept of Hill numbers, or the effective number of species in a sample, to provide a simple metric for comparing species diversity across environments. The more diverse the sample, the higher the Hill number. We adopt this ecological approach and consider each k-mer an individual and each genome a transect in the pan-genome of the species. Applying Hill numbers in this way allows us to summarize the temporal trajectory of pandemic variants by collapsing each day9s assemblies into genomic equivalents. We do this quickly, without alignment or trees, using modern genome sketching techniques to accommodate millions of genomes in one condensed view of pandemic dynamics. Using data from the UK, USA, and South Africa, we trace the ascendence of new variants of concern as they emerge in local populations. This history of emerging variants uses all available data as it is sequenced, intimating variant sweeps to dominance or declines to extinction at the leading edge of the COVID19 pandemic. The surveillance technique we introduce in a SARS-CoV-2 context here can operate on genomic data generated over any pandemic time course and is organism agnostic.
The COVID-19 pandemic has highlighted the need for improved air flow in hospitals, to reduce the transmission of airborne infections such as COVID-19. The aim of this review was to map the existing literature on intervention used to improve air flow in hospitals, understanding challenges in implementation and the findings of any evaluations. We reviewed peer-reviewed articles identified on three databases, MEDLINE, Web of Science and the Cochrane Library with no restriction on date. 5846 articles were identified, 130 were reviewed and 18 were included: ten articles were from databases and eight articles were identified through hand searching. Results were discussed in terms of three categories: (i) concentration of aerosol particles, (ii) changes in/effect of air speed and ventilation and (iii) improvements or reduction in health conditions. Eight studies included an evaluation, the majority only had one comparator condition however three had multiple conditions. The most common device or method that was outlined by researchers was HEPA filters, which can remove particles with a size of 3 microns. Articles outline different interventions to improve air flow and some demonstrate their effectiveness in terms of improving health outcomes for patients, they also suggest either mechanical and natural ventilation are the best methods for dispersing particulate matter as well as perhaps two air cleaning units rather than one. With different methods comes different strengths and weaknesses however, the key finding is that air flow improvement measures reduce the likelihood of nosocomial infections.
Protection against SARS-CoV-2 wanes over time, and booster uptake has been low, in part because of concern about side effects. We examined the relationships between local and systemic symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 364) who received two doses of either BNT162b2 or mRNA-1273. Serum nAB concentration was measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater increases in skin temperature and heart rate after the second dose predicted higher nAB levels at both time points, but skin temperature change was more predictive of durable (6 month) nAB response than of short-term (1 month) nAB response. In the context of low ongoing vaccine uptake, our convergent symptom and biometric findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.
Longitudinal research examining childrens mental health (MH) over the course of the COVID-19 pandemic is scarce. We examined trajectories of depression and anxiety over two pandemic years among children with and without MH disorders. Parents and children 2 to 18 years completed surveys at seven timepoints (April 2020 to June 2022). Parents completed validated measures of depression and anxiety for children 8to 18 years, and validated measures of emotional/behavioural symptoms for children 2 to 7 years old. Children 10 years and older completed validated measures of depression and anxiety. Latent growth curve analysis determined depression and anxiety trajectories, accounting for demographics, child and parent MH. Data were available on 1315 unique children (1259 parent-reports, 550 child-reports). Trajectories were stable across the study period, however individual variation in trajectories was statistically significant. Of included covariates, only initial symptom level predicted symptom trajectories. Among participants with pre-COVID data, a significant increase in depression symptoms relative to pre-pandemic levels was observed. Children and adolescents experienced elevated and sustained levels of depression and anxiety during the two-year period. Findings have direct policy implications in the prioritization and of maintenance of educational, recreational, and social activities with added MH supports in the face of future events.
Study of the Vector Vaccine GamCovidVac-M (Altered Antigenic Composition) - Conditions: COVID-19
Interventions: Biological: GamCovidVac-M vector vaccine for the prevention of COVID-19 with altered antigenic composition
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Study of the Vector Vaccine GamCovidVac for the Prevention of COVID-19 With Altered Antigenic Profile With Participation of Adult Volunteers - Conditions: COVID-19
Interventions: Biological: GamCovidVac vector vaccine for the prevention of COVID-19 (with altered antigenic profile)
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Exercise Interventions in Post-acute Sequelae of Covid-19 - Conditions: COVID-19
Interventions: Behavioral: Exercise
Sponsors: University of Virginia
Not yet recruiting
Effects of Cacao FLAvonoids in LOng Covid Patients (FLALOC) - Conditions: Long Covid19; Fatigue Syndrome, Chronic
Interventions: Dietary Supplement: Flavonoids
Sponsors: Guillermo Ceballos Reyes; Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado
Recruiting
The Efficacy of the 2023-2024 Updated COVID-19 Vaccines Against COVID-19 Infection - Conditions: COVID-19; Vaccine-Preventable Diseases; SARS CoV 2 Infection; Upper Respiratory Tract Infection; Upper Respiratory Disease
Interventions: Biological: Novavax COVID-19 vaccine (2023-2024 formula XBB containing); Biological: Pfizer COVID-19 mRNA vaccine (2023-2024 formula XBB containing)
Sponsors: Sarang K. Yoon, DO, MOH; Westat; Novavax
Not yet recruiting
Motivational Interviewing for Vaccine Uptake in Latinx Adults - Conditions: Vaccine Hesitancy
Interventions: Other: EHR alert; Behavioral: Motivational Interviewing; Behavioral: Warm hand off to nurse
Sponsors: Boston College; East Boston Neighborhood Health Center; Harvard School of Public Health (HSPH); Boston Children’s Hospital; National Institute of Nursing Research (NINR)
Not yet recruiting
Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects - Conditions: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection
Interventions: Combination Product: RQ-001; Other: Placebo
Sponsors: Red Queen Therapeutics, Inc.; PPD
Recruiting
Study of “Sputnik Lite” for the Prevention of COVID-19 With Altered Antigenic Composition. - Conditions: COVID-19
Interventions: Biological: “Sputnik Lite” vaccine for the prevention of COVID-19 with altered antigenic composition
Sponsors: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
Not yet recruiting
Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 - Conditions: COVID-19, SARS-CoV-2
Interventions: Biological: Biological: AZD3152; Biological: Biological: Placebo
Sponsors: AstraZeneca
Not yet recruiting
Examining the Function of Cs4 on Post-COVID-19 Disorders - Conditions: Long COVID
Interventions: Other: Chinese medicine nutritional supplement Cs4
Sponsors: The University of Hong Kong
Recruiting
Amantadine Therapy for Cognitive Impairment in Long COVID - Conditions: Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome
Interventions: Drug: Amantadine
Sponsors: Ohio State University
Not yet recruiting
Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia - Conditions: Parosmia
Interventions: Procedure: Stellate Ganglion Block; Other: Placebo
Sponsors: Lawson Health Research Institute
Not yet recruiting
CPAP Efficacy in Post-COVID Patients With Sleep Apnea - Conditions: COVID-19; Sleep Apnea
Interventions: Device: Continuous positive airway pressure
Sponsors: University of Pittsburgh
Not yet recruiting
Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2) - Conditions: 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
Angiotensin-(1-7) attenuates SARS-CoV2 spike protein-induced interleukin-6 and interleukin-8 production in alveolar epithelial cells through activation of Mas receptor - BACKGROUND: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis.
Antiviral opportunities of Mannich bases derived from triterpenic N-propargylated indoles - Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH-group condensed with the triterpene A-ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin-Darby canine kidney (MDCK) cell culture and SARS-CoV-2 pseudovirus in baby hamster kidney-21-human angiotensin-converting enzyme 2 (BHK-21-hACE2) cells….
Alisol B 23-acetate broadly inhibits coronavirus through blocking virus entry and suppresses proinflammatory T cells responses for the treatment of COVID-19 - CONCLUSION: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.
Universal features of Nsp1-mediated translational shutdown by coronaviruses - Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory…
Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3 - Coronaviruses (CoVs) are a family of the largest RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans, imposing great threats to the public safety and animal health. Porcine deltacoronavirus (PDCoV), a newly emerging enteropathogenic coronavirus, causes severe diarrhea in suckling piglets all over the world and poses potential risks of cross-species transmission. Here, we use PDCoV as a model of CoVs to illustrate the reciprocal regulation between…
Porphyrin-derived carbon dots for an enhanced antiviral activity targeting the CTD of SARS-CoV-2 nucleocapsid - CONCLUSIONS: Therefore, this study comprehensively demonstrated the potential of porphyrin-derived carbon dots to be developed further as a promisingly safe and effective COVID-19 antiviral drug.
The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial - CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season.
Analysis of SARS-CoV-2 spike RBD binding to ACE2 and its inhibition by fungal cohaerin C using surface enhanced Raman spectroscopy - The structure of the SARS-CoV-2 spike RBD and human ACE2 as well as changes in the structure due to binding activities were analysed using surface enhanced Raman spectroscopy. The inhibitor cohaerin C was applied to inhibit the binding between spike RBD and ACE2. Differences and changes in the Raman spectra were determined using deconvolution of the amide bands and principal component analysis. We thus demonstrate a fast and label-free analysis of the protein structures and the differentiation…
Novel designed analogues of quercetin against SARS-CoV2:an in-silico pharmacokinetic evaluation, molecular modeling, MD simulations based study - Here we present the design of the series of quercetin analogues and their molecular docking study involving the binding of quercetin and its analogues with SARS-CoV2 3CLpro. The scientific literature shows that quercetin compound has been successfully used against SARS-CoV by inhibiting the replication of virus in respiratory epithelial cell through the inhibition of the SARS-CoV main protease (3CLpro.) It was suggested that the modification at position 3 in quercetin structure may produce…
Reply to: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection - No abstract
SARS-CoV-2 Spike protein peptides displayed in the Pyrococcus furiosus RAD system preserve epitopes antigenicity, immunogenicity, and virus-neutralizing activity of antibodies - Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in…
Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry - For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute…
Effect of microfibers induced toxicity in marine sedentary polychaete Hydroides elegans: Insight from embryogenesis axis - Presence of surgical face masks in the environment are more than ever before after the COVID-19 pandemic, and it poses a newer threat to aquatic habitats around the world due to microfibers (MFs) and other contaminants that get discharged when these masks deteriorate. The mechanism behind the developmental toxicity of MFs, especially released from surgical masks, on the early life stages of aquatic organisms are not well understood. Toxicity test were developed to examine the effects of MFs…
COVID-19 promotes endothelial dysfunction and thrombogenicity: Role of pro-inflammatory cytokines/SGLT2 pro-oxidant pathway - CONCLUSIONS: In COVID-19 patients, pro-inflammatory cytokines induced a redox-sensitive up-regulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin, appeared as an attractive strategy to restore vascular homeostasis in COVID-19.
SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway - Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leading to pulmonary and extra-pulmonary manifestations due to the development of oxidative stress (OS) and hyperinflammation. The underlying cause for OS and hyperinflammation in COVID-19 may be related to the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidative responses and cellular homeostasis. The Nrf2…