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Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel- group trial. Results of the first interim analysis
Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel- group trial. Results of the first interim analysis
We and others have previously demonstrated that the endothelium is a primary target of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and L-arginine has been shown to improve endothelial dysfunction. However, the effects of L-arginine have never been evaluated in coronavirus disease 2019 (COVID-19). Methods: This is a parallel-group, double-blind, randomized, placebo-controlled trial conducted on patients hospitalized for severe COVID-19. Patients received 1.66 g L-arginine twice a day or placebo, administered orally. The primary efficacy endpoint was a reduction in respiratory support assessed 10 and 20 days after randomization. Secondary outcomes were the length of in-hospital stay, the time to normalization of lym- phocyte number, and the time to obtain a negative real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. This clinical trial had been registered at ClinicalTrials.gov, identifier: NCT04637906. Findings: We present here the results of the initial interim analysis on the first 101 patients. No treatment- emergent serious adverse events were attributable to L-arginine. At 10-day evaluation, 71.1% of patients in the L-arginine arm and 44.4% in the placebo arm (p 0.01) had the respiratory support reduced; however, a significant difference was not detected 20 days after randomization. Strikingly, patients treated with L-argi- nine exhibited a significantly reduced in-hospital stay vs placebo, with a median (interquartile range 25th ,75 th percentile) of 46 days (45,46) in the placebo group vs 25 days (21,26) in the L-arginine group (p 0.0001); these findings were also confirmed after adjusting for potential confounders including age, duration of symptoms, comorbidities, D-dimer, as well as antiviral and anticoagulant treatments. The other secondary outcomes were not significantly different between groups. Interpretation: In this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment.
·thelancet.com·
Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel- group trial. Results of the first interim analysis
Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis
Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis
In this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment.
1.66 g L-arginine twice a day
·thelancet.com·
Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis
Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial - PubMed
Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial - PubMed
Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. …
combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C
·pubmed.ncbi.nlm.nih.gov·
Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial - PubMed
Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Nature Communications - Exponential growth of toxigenic Streptococcus pyogenes M1UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that...
Fig. 1: Trend in S. pyogenes-positive samples, England 2016–2023.Data show absolute numbers of weekly S. pyogenes-positive samples from non-sterile sites (light blue bars, left hand, positive axis) and sterile sites (dark blue bars, right hand, negative axis) recorded by the Second Generation Surveillance System (SGSS) in England, by week and by year. Timing of non-pharmaceutical interventions (NPI) related to COVID-19 in England is indicated by the horizontal bar: red, lockdown periods; orange, legally enforced NPI including no mixing; yellow, non-severe NPI. Schools were closed during lockdown periods and between the two later lockdown periods except for children of key workers and vulnerable children. Source data are provided as a Source Data file Fig. 1.
·nature.com·
Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Can the Japanese Encephalitis Vaccine Reduce Symptoms of Long COVID? - Health Rising
Can the Japanese Encephalitis Vaccine Reduce Symptoms of Long COVID? - Health Rising
As a researcher in international development, travel vaccines for low-income countries are a typical part of my life. But I never expected that once I developed Long COVID, a travel vaccine for Japanese encephalitis might help me make a rapid recovery. Could similar vaccines hold clues to fighting Long COVID? […]
·healthrising.org·
Can the Japanese Encephalitis Vaccine Reduce Symptoms of Long COVID? - Health Rising
Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms
Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms
There have been concerning reports about people experiencing new onset persistent complications (greater than 30 days) following approved SARS-CoV-2 vaccines (BNT162b2 (Pfizer), mRNA-1273 (Moderna), Janssen (Johnson and Johnson), and ChAdOx1 nCoV-19 (AstraZeneca)). We sought to determine the immunologic abnormalities in these patients and to investigate whether the potential etiology was similar to Post-Acute Sequalae of COVID (PASC), or long COVID. We studied 50 individuals who received one of the approved COVID-19 vaccines and who experienced new onset PASC-like symptoms along with 45 individuals post-vaccination without symptoms as controls. We performed multiplex cytokine/chemokine profiling with machine learning as well as SARS-CoV-2 S1 protein detection on CD16+ monocyte subsets using flow cytometry and mass spectrometry. We determined that post-vaccination individuals with PASC- like symptoms had similar symptoms to PASC patients. When analyzing their immune profile, Post-vaccination individuals had statistically significant elevations of sCD40L (p
·medrxiv.org·
Persistence of S1 Spike Protein in CD16+ Monocytes up to 245 Days in SARS-CoV-2 Negative Post COVID-19 Vaccination Individuals with Post-Acute Sequalae of COVID-19 (PASC)-Like Symptoms
SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway - Fluids and Barriers of the CNS
SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway - Fluids and Barriers of the CNS
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with various neurological symptoms, including nausea, dizziness, headache, encephalitis, and epileptic seizures. SARS-CoV-2 is considered to affect the central nervous system (CNS) by interacting with the blood–brain barrier (BBB), which is defined by tight junctions that seal paracellular gaps between brain microvascular endothelial cells (BMECs). Although SARS-CoV-2 infection of BMECs has been reported, the detailed mechanism has not been fully elucidated. Methods Using the original strain of SARS-CoV-2, the infection in BMECs was confirmed by a detection of intracellular RNA copy number and localization of viral particles. BMEC functions were evaluated by measuring transendothelial electrical resistance (TEER), which evaluates the integrity of tight junction dynamics, and expression levels of proinflammatory genes. BMEC signaling pathway was examined by comprehensive RNA-seq analysis. Results We observed that iPSC derived brain microvascular endothelial like cells (iPSC-BMELCs) were infected with SARS-CoV-2. SARS-CoV-2 infection resulted in decreased TEER. In addition, SARS-CoV-2 infection decreased expression levels of tight junction markers CLDN3 and CLDN11. SARS-CoV-2 infection also increased expression levels of proinflammatory genes, which are known to be elevated in patients with COVID-19. Furthermore, RNA-seq analysis revealed that SARS-CoV-2 dysregulated the canonical Wnt signaling pathway in iPSC-BMELCs. Modulation of the Wnt signaling by CHIR99021 partially inhibited the infection and the subsequent inflammatory responses. Conclusion These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.
·fluidsbarrierscns.biomedcentral.com·
SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway - Fluids and Barriers of the CNS
Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study
Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study
A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI).
·thelancet.com·
Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study
Do mobile phone surfaces carry SARS-CoV-2 virus? A systematic review warranting the inclusion of a “6th” moment of hand hygiene in healthcare
Do mobile phone surfaces carry SARS-CoV-2 virus? A systematic review warranting the inclusion of a “6th” moment of hand hygiene in healthcare
Mobile phones, used in billions throughout the world, are high-touch devices subject to a dynamic contamination of microorganisms and rarely considere…
·sciencedirect.com·
Do mobile phone surfaces carry SARS-CoV-2 virus? A systematic review warranting the inclusion of a “6th” moment of hand hygiene in healthcare
Primary care data for public health research
Primary care data for public health research
CPRD collects fully-coded patient electronic health records from GP practices using the Vision® or EMIS® software systems. Due to some differences in structure and clinical coding in these two systems, these data are provided as two separate primary care databases at present with accompanying metadata and advice to enable researchers to make study-specific decisions on how best to pool these data.Our in-house researchers are happy to provide advice on which database to use depending on your research question.
·cprd.com·
Primary care data for public health research
Long COVID-19's impact continues to be felt globally - The World from PRX
Long COVID-19's impact continues to be felt globally - The World from PRX
COVID-19 is still with us. Long COVID-19, where people suffer symptoms for months and years after the infection, affects 400 million people across the globe. Host Marco Werman speaks with Dr. Ziyad al-Aly, chief of research and development at the V.A. St. Louis Health Care System, about what patients experience, how patients endure the virus […]
·theworld.org·
Long COVID-19's impact continues to be felt globally - The World from PRX
Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study
Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study
Objective To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. Design Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. Setting Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom’s health service (NHS). Participants 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study. Main outcome measures The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events. Results The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test. Conclusion Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population. To guarantee the confidentiality of personal and health information only the authors have had access to the data during the study in accordance with the relevant licence agreements.
·bmj.com·
Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study
Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England
Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England
In a population-based cohort study, William Whiteley and colleagues investigate the association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events in England.
·journals.plos.org·
Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England
Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual
Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual
Prime-boost vaccinations can enhance immune responses,1 whereas chronic antigen exposure can cause immune tolerance.2 In humans, the benefits, limitations, and risks of repetitive vaccination remain poorly understood.
·thelancet.com·
Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual
Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway
Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway
Our recent study using data from more than 20 million participants has shown that COVID-19 vaccines consistently prevent long COVID symptoms in adults, with meta-analytic calibrated subdistribution hazard ratio (sHRs) of 0·54 (95% CI 0·44–0·67) in CPRD GOLD, 0·48 (0·34–0·68) in CPRD AURUM, 0·71 (0·55–0·91) in SIDIAP, and 0·59 (0·40–0·87) in CORIVA.1 In addition, when considering post-COVID thromboembolic and cardiovascular complications as outcomes of interest, recently published data have shown that vaccination with any COVID-19 first vaccine dose (ChAdOx1, BNT162b2, and mRNA-1273) is associated with reduced risk of post-acute heart failure (0·45 [0·38–0·53] 0–30 days after SARS-CoV-2 infection; 0·61 [0·51–0·73] 91–180 days after SARS-CoV-2 infection), venous thromboembolism (sHR 0·22 [95% CI 0·17–0·29] 0–30 days after SARS-CoV-2 infection; 0·53 [0·40–0·70] 91–180 days after SARS-CoV-2 infection), and arterial thrombosis (0·53 [0·44–0·63] 0–30 days after SARS-CoV-2 infection; 0·72 [0·58–0·88] 91–180 days after SARS-CoV-2 infection).
We then applied the publicly available scripts to assess the effectiveness of COVID-19 vaccines to prevent long COVID and post-acute complications.
·thelancet.com·
Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway
Optimizing Spatial Distribution of Wastewater-Based Disease Surveillance to Advance Health Equity
Optimizing Spatial Distribution of Wastewater-Based Disease Surveillance to Advance Health Equity
In 2022, the US Centers for Disease Control and Prevention commissioned the National Academies of Sciences, Engineering, and Medicine to assess the role of community-level wastewater-based disease surveillance (WDS) beyond COVID-19. WDS is recognized as a promising mechanism for promptly identifying infectious diseases, including COVID-19 and other novel pathogens. An important conclusion drawn from this initiative is that it is crucial to maintain equity and expand access to maximize the advantages of WDS for marginalized communities. To address this need, we propose an optimization framework that focuses on the strategic allocation of wastewater monitoring resources at the wastewater treatment plant (WWTP) level. The framework's purpose is to obtain a balanced spatial distribution, inclusive population coverage, and efficient representation of vulnerable communities in allocating resources for WDS. This study offers an opportunity to improve wastewater surveillance by tailoring location selection strategies to address specific priorities, improving decision-making in public health responses. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data used in this study were publicly accessible prior to the initiation of the study. Specifically, we sourced data from the California Open Data COVID-19 Wastewater Surveillance dataset, available at https://data.ca.gov/dataset/covid-19-wastewater-surveillance-data-california, and WastewaterSCAN, accessible at https://data.wastewaterscan.org. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.
·medrxiv.org·
Optimizing Spatial Distribution of Wastewater-Based Disease Surveillance to Advance Health Equity