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A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

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Cellular & Molecular Immunology 2021年第2期18卷 318-327页

作者： Vincent Legros Solène Denolly Manon Vogrig Bertrand Boson Eglantine Siret Josselin Rigaill Sylvie Pillet Florence Grattard Sylvie Gonzalo paul Verhoeven Omran Allatif Philippe Berthelot Carole Pélissier Guillaume Thiery Elisabeth Botelho-Nevers Guillaume Millet Jérôme Morel Stéphane paul Thierry Walzer François-Loïc Cosset thomas Bourlet Bruno Pozzetto CIRI–Centre International de Recherche en Infectiologie Team EVIRUniv LyonUniversitéClaude Bernard Lyon 1InsermU1111CNRSUMR5308ENS Lyon46 allée d’ItalieF-69007LyonFrance Universitéde Lyon VetAgro SupMarcy-l’ÉtoileFrance Department of Infectious Agents and Hygiene University-Hospital of Saint-EtienneSaint-EtienneFrance Department of Immunology University-Hospital of Saint-EtienneSaint-EtienneFrance CIRI–Centre International de Recherche en Infectiologie Team GIMAPUniv LyonUniversitéClaude Bernard Lyon 1InsermU1111CNRSUMR5308ENS Lyon46 allée d’ItalieF-69007LyonFrance Department of Infectious Diseases University-Hospital of Saint-EtienneSaint-EtienneFrance Department of Occupational Medicine University-Hospital of Saint-EtienneSaint-EtienneFrance Department of Intensive Care and Resuscitation(Réanimation G) University-Hospital of Saint-EtienneSaint-EtienneFrance Laboratoire Interuniversitaire de Biologie de la Motricité Universitéde LyonUniversitéJean MonnetSaint-EtienneFrance Department of Anesthesiology and Critical Care University-Hospital of Saint-EtienneSaint-EtienneFrance

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for *** this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive *** show that nAb titers correlated strongly with disease severity and with anti-spike IgG ***,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low *** found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other ***,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against ***,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization ***,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

关键词： Antibody Pathogenesis Humoral response COVID-19 SARS-CoV-2v

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Factors associated with mobile phone ownership and potential use for rabies vaccination campaigns in southern Malawi

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Infectious Diseases of Poverty 2020年第3期9卷 136-137页

作者： Orla Marron Gareth thomas Jordana LBurdon Bailey Dagmar Mayer paul OGrossman Frederic Lohr Andy DGibson Luke Gamble Patrick Chikungwa Julius Chulu Ian GHandel Barend Mde C Bronsvoort Richard JMellanby Stella Mazeri 不详 The Royal(Dick)School of Veterinary Studies Division of Veterinary Clinical StudiesThe University of EdinburghHospital for Small AnimalsEaster Bush Veterinary CentreRoslinMidlothianUK

Background:Rabies is a fatal but preventable viral disease,which causes an estimated 59000 human deaths globally every *** vast majority of human rabies cases are attributable to bites from infected domestic dogs and consequently control of rabies in the dog population through mass vaccination campaigns is considered the most effective method of eliminating the *** the WHO target of 70%vaccination coverage has proven challenging in low-resource settings such as Sub Saharan Africa,and lack of public awareness about rabies vaccination campaigns is a major barrier to their *** this study we surveyed communities in three districts in Southern Malawi to assess the extent of and socio-economic factors associated with mobile phone ownership and explore the attitudes of communities towards the use of short message service(SMS)to inform them of upcoming rabies vaccination ***:This study was carried out between 1 October–3 December 2018 during the post-vaccination assessment of the annual dog rabies campaign in Blantyre,Zomba and Chiradzulu districts,Malawi.1882 questionnaires were administered to households in 90 vaccination *** surveys gathered data on mobile phone ownership and use,and barriers to mobile phone access.A multivariable regression model was used to understand factors related to mobile phone ***:Most survey respondents owned or had use of a mobile phone,however there was evidence of an inequality of access,with higher education level,living in Blantyre district and being male positively associated with mobile phone *** principal barrier to mobile phone ownership was the cost of the phone *** feature phones were most common and few owned *** was commonly used and the main reason for not using SMS was *** to receiving SMS reminders about future rabies vaccination campaigns were ***:The study showed a majority of those surveyed have the use of

关键词： Rabies Mass vaccination mHealth Short message service

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The hemodynamic management of elderly patients with sepsis

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Journal of Geriatric Cardiology 2007年第2期4卷 120-126页

作者： paul E. Marik Joseph Varon Division of Pulmonary and Critical Care Medicine Thomas Jefferson University Philadelphia PA The University of Texas Health Science Center at Houston Houston Texas USA

Sepsis is among the most common reason for admission to intensive care units throughout the world. In the US and most Western nations sepsis is largely a disease of the elderly. Management of elderly patients with severe sepsis is challenging. Early recognition of this syndrome, together with the early administration of appropriate antibiotics and cautious fluid resuscitation is the cornerstone of therapy. Echocardiography together with non-invasive or invasive hemodynamic monitoring is recommended in patients who have responded poorly to fluids or have significant underlying cardiac disease. This paper reviews the hemodynamic changes that characterize sepsis, particularly as they apply to elderly patients and provides recommendations for the management of these patients.

关键词： sepsis elderly septic shock fluids norepinephrine activated protein C corticosteroids ventricular function vasopressin echocardiography cardiac output

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Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

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Cellular & Molecular Immunology 2010年第3期7卷 211-220页

作者： paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom thomas N Wight Benaroya Research Institute SeattleWAUSA

Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and *** hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC *** primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA ***,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA *** effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th *** data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell *** also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen *** data point to a pivotal role for HA in DC–T cell interactions at the IS.

关键词： dendritic cell hyaluronan immune synapse pericellular matrix Th1

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Attributable cost of a nosocomial infection in the intensive care unit: A prospective cohort study

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World Journal of Critical Care Medicine 2017年第1期6卷 79-84页

作者： Binila Chacko Kurien thomas Thambu David Hema paul Lakshmanan Jeyaseelan John Victor Peter Medical ICU Division of Critical Care Christian Medical College Department of Medicine Pondicherry Institute of Medical Sciences Department of Medicine Ⅱ Christian Medical College Hospital Infection Control Committee Christian Medical College Department of Biostatistics Christian Medical College

AIM To study the impact of hospital-acquired infections(HAIs) on cost and outcome from intensive care units(ICU) in India. METHODS Adult patients(> 18 years) admitted over 1-year, to a 24-bed medical critical care unit in India, were enrolled prospectively. Treatment cost and outcome data were collected. This cost data was merged with HAI data collected prospectively by the Hospital Infection Control Committee. Only infections occurring during ICU stay were included. The impact of HAI on treatment cost and mortality was assessed. RESULTS The mean(± SD) age of the cohort(n = 499) was42.3 ± 16.5 years. Acute physiology and chronic health evaluation-Ⅱ score was 13.9(95%CI: 13.3-14.5); 86% were ventilated. ICU and hospital length of stay were 7.8 ± 5.5 and 13.9 ± 10 d respectively. Hospital mortality was 27.9%. During ICU stay, 76(15.3%) patients developed an infection(ventilator-associated pneumonia 50; bloodstream infection 35; urinary tract infections 3), translating to 19.7 infections/1000 ICU days. When compared with those who did not develop an infection, an infection occurring during ICU stay was associated with significantly higher treatment cost [median(inter-quartile range, IQR) INR 92893(USD 1523)(IQR 57168-140286) vs INR 180469(USD 2958)(IQR 140030-237525); P < 0.001 and longer duration of ICU(6.7 ± 4.5 d vs 13.4 ± 7.0 d; P < 0.01) and hospital stay(12.4 ± 8.2 d vs 21.8 ± 13.9 d; P < 0.001)]. However ICU acquired infections did not impact hospital mortality(31.6% vs 27.2%; P = 0.49).CONCLUSION An infection acquired during ICU stay was associated with doubling of treatment cost and prolonged hospitalization but did not significantly increase mortality.

关键词： Attributable cost Nosocomial infection Length of stay Mortality Intensive care

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A segmented conical electric lens for optimization of the beam spot of the low-energy muon facility at PSI: a Geant4 simulation analysis

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Nuclear Science and Techniques 2017年第3期28卷 13-22页

作者： Ran Xiao Elvezio Morenzoni Zaher Salman Bang-Jiao Ye thomas Prokscha State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026 China Department of Modern Physics University of Science and Technology of China Hefei 230026 China Laboratory for Muon Spin Spectroscopy Paul Scherrer Institut (PSI) 5232 Villigen Switzerland

The low-energy muon facility at PSI provides nearly fully polarized positive muons with tunable energies in the ke V range to carry out muon spin rotation(LE-μSR)experiments with nanometer depth resolution on thin films,heterostructures, and near-surface regions. The low-energy muon beam is focused and transported to the sample by electrostatic lenses. In order to achieve a minimum beam spot size at the sample position and to enable the steering of the beam in the horizontal and vertical direction, a special electrostatic device has been implemented close to the sample position. It consists of a cylinder at ground potential followed by four conically shaped electrodes,which can be operated at different electric potential. In LE-μSR experiments, an electric field at the sample along the beam direction can be applied to accelerate/decelerate muons to different energies(0.5–30 keV). Additionally, a horizontal or vertical magnetic field can be superimposed for transverse or longitudinal field μSR experiments. The focusing properties of the conical lens in the presence of these additional electric and magnetic fields have been investigated and optimized by Geant4 simulations. Some experimental tests were also performed and show that the simulation well describes the experimental setup.

关键词： Muon beam Muon spin rotation Low-energy muon Beam size Geant4

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Comparative Proteomics Analysis of Exhaled Breath Condensate in Lung Cancer Patients

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Journal of Cancer Therapy 2011年第1期2卷 1-8页

作者： Zujian Cheng Craig R. Lewis paul S. thomas Mark J. Raftery 不详

The prognosis for patients with non-small cell lung cancer (NSCLC) remains poor in spite of better treatments. This relates mainly to the fact that the majority of patients present with advanced disease. There is a need to identify tools which can improve screening for lung cancer in the at risk patient population. The aim of this study was to compare the breath proteomic profile of NSCLC patients with healthy control subjects to explore the potential of new biomarkers of lung cancer. Comparative proteomic analysis of exhaled breath condensate (EBC) between 14 patients with NSCLC and 13 healthy control subjects were carried out using LTQ FT Ultra mass spectrometry and database searching to determine any unique proteins. In total, 29 unique proteins were identified using multiple protein identification algorithms. A comparison of lung cancer, smoker, and ex-smoker proteomes showed that 18 proteins were shared among the three groups. While one unique protein was found in smokers and lung cancer patients, four proteins were unique to ex-smokers. This data set provides a foundation for evaluation of these proteins from EBC as potential biomarkers for non-invasive lung cancer diagnosis.

关键词： Lung Cancer Exhaled Breath Condensate Mass Spectrometry Proteomics

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Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer

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Journal of Cancer Therapy 2012年第4期3卷 460-466页

作者： Enoch Chan Thevaki Sivagnanam Qi Zhang Craig R. Lewis paul S. thomas Department of Respiratory Medicine Prince of Wales Hospital Randwick Australia Inflammation and Infection Research Centre and Prince of Wales Clinical School Faculty of Medicine University of New South Wales Sydney Australia

Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.

关键词： Exhaled Breath Condensate Lung Cancer Ascorbic Acid Oxidation Tumour Necrosis Factor Alpha

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Comparison of Humoral Immune Responses Elicited by DNA and Protein Vaccines Based on Merozoite Surface Protein-1 from Plasmodium yoelii,a Rodent Malaria Parasite

Comparison of Humoral Immune Responses Elicited by DNA and P...

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作者： paul A．Calvo thomas M．Daly Carole A．Long Department of Microbiology and Immunology Allegheny University of the Health SciencesPhiladelphiaPA 19129USA

Immunization with DNA vaccines encoding relevant Ags can induce not only cell-mediated immune response but also humoral immune responses against pathogenic microorganisms in several animal models. Our previous results demonstrated that,when the C terminus (PyC2) of Plasmodium yoelii merozoite surface protein-1 (MSP-1).a leading vaccine candidate against erythrocytic stages of malaria, was expressed as a fusion protein (GST-PyC2) with glutathione S-transferase (GST), it elicited Ab-mediated protective immune responses in BALB/c mice. In our present study, we wished to examine

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Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in type 2 diabetes mellitus patients presenting to a functional medicine clinic

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Journal of Biomedical Science and Engineering 2013年第5期6卷 12-15页

作者： paul A. Oakley Stephanie J. Chaney Michael A. Persinger thomas A. Chaney Behavioral Neuroscience Program Laurentian University Sudbury Canada Private Practice Annapolis USA Private Practice Newmarket Canada

This study explores the relationship of 25-hydroxylvitamin D blood levels in 106 randomly selected patient files with diagnosed type 2 Diabetes Mellitus (t2DM) who enrolled in a functional medicine diabetes reversal program from a chiropractic clinic located in Annapolis, Maryland, USA. Using a conservative recommendation for normal serum 25-hydroxyvitamin D concentration of 32 ng/ml, insufficiency level of 20 - 30 ng/ml, and deficiency level < 20 ng/ml, 21% (22/106) of our population were normal, 39% (41/106) were insufficient, and alarmingly, 35% (37/106) were outright deficient. Clinically, 74% (78/ 106) of our entire sample had significantly low vitamin D levels. Ou et al. (2011) determined the optimal concentration of serum 25OHD to be 40 ng/ml in order to optimize insulin sensitivity. In our sample 100/ 106 (94%) had vitamin D levels at or below this optimal cut-off level. BMI was negatively correlated with vitamin D;that is, the greater the BMI of the patient the less their vitamin D level. Both obesity and hypovitaminosis D are each mutually exclusive predictors for t2DM. Obesity and vitamin D deficiency may work synergistically to propel an individual into the diseased state of t2DM. As this study demonstrates that the majority of people with t2DM suffer from inadequate amounts of vitamin D, vitamin D testing should be routine for all people at risk for t2DM, prediabetics and those currently suffering with t2DM in order to elevate levels sufficiently to improve insulin sensitivity and improve long-term outcomes.

关键词： Diabetes Mellitus BMI Vitamin D Deficiency Insufficiency Functional Medicine

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