Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liège University Hospital (CHU) of Liège in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naïve (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN- on peripheral blood lymphocytes using the QuantiFERON Human IFN- SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naïve HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses

Stress disrupts the intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by probiotic treatment

International audienceBackground: Despite evidence of intestinal epithelial barrier impairment and visceral hypersensitivity in IBS patients and IBS-like models, structural and physical changes in the mucus layer in this condition remain poorly understood. Aim: Using a water avoidance stress (WAS) model, we aimed at evaluating in ileum and colon whether (i) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans and related mucus physical properties, (ii)L. farcimin- is treatment prevented these alterations. Methods: Wistar rats received orally L. farciminis (an adhesion marker) or vehicle for 14 days. At day 10, they were submitted either to sham or 4-day WAS. Intestinal paracellular permeability and visceral sensi- tivity were measured in vivo . The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ . The mucin O-glycosylation profile was obtained by mass spectrom- etry. Surface imaging of intestinal mucus was performed at nanoscale by Atomic Force Microscopy. Results: WAS induced gut hyperpermeability and vis- ceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expressio

Les Géants entre mythe et littérature

On pensait avoir tout dit sur le géant, figure figée dans un double stéréotype de violence archaïque ou de bonté débordante, et n'ayant plus guère sa place dans la littérature, si ce n'est dans celle destinée aux enfants. Or ce colloque a permis de découvrir que le géant, présent dans presque tous les récits d'origine où il est tantôt grand ancêtre protecteur, tantôt monstre sauvage tout droit sorti du chaos, continuait à hanter les oeuvres les plus contemporaines. Les articles qui constituent ce volume explorent, à travers les siècles et les oeuvres littéraires, les nombreux enjeux esthétiques, scientifiques ou philosophique de la figure gigantale et nous invitent à découvrir l'étonnante richesse et complexité de ce " personnage-métaphore". La rencontre des spécialistes de domaines et d'époques très différents a ainsi mis en lumière combien le géant est profondément inscrit, non seulement dans l'imaginaire de l'Occident, mais encore dans sa conscience littéraire et artistique

Littéraire. Pour Alain Viala (tome 2)

Comment rendre hommage à Alain Viala, à la fécondité de ses travaux, à l’inventivité de son œuvre sans le transformer en académicien empaillé ? Puisqu’un de ses buts est de décloisonner les genres et d’éviter les prêts-à-penser, on pouvait tout risquer. Des contributeurs enthousiastes ont donné à leur hommage des formes choisies, entre le poème, le témoignage affectueux et la réflexion érudite s’inscrivant dans le prolongement des concepts qu’il a imposés en histoire, sociologie et théorie de la littérature. L’ensemble est ponctué de quelques textes d’Alain Viala, qui dessinent un parcours, menant des postures d’écrivains qui font la dynamique centrale du champ littéraire jusqu’aux bizarreries qui occupent les marges de ce champ. Ce trajet suit le fil des opérations critiques qui ont marqué de manière décisive la pratique des études littéraires : historiciser la littérature, mettre à jour les mécanismes de la valeur, exhiber les tensions et leur fécondité, traverser les frontières, s’engager… Le trajet d’une révolution qui refuse (l’histoire littéraire des grands hommes), revendique (une méthode), désordonne et brouille pour créer du nouveau.Ouvrage publié avec le concours du centre de recherche Textes et Cultures – Université d’Artois (EA 4028), du centre de recherche FIRL (EA174) – Université Sorbonne Nouvelle – Paris 3, de The Faculty of Medieval and Modern Languages – Universitéd’Oxford, de l’Université d’Artois et d’Arras Université

Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study

International audienceA comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs ( p = 0.07). The proportion of HCWs with a viral load > 5.0 log 10 cp/mL (Ct value  37). More than 90% of cultivable virus had a viral load > 4.5 log 10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work

Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study

Introduction The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated.Methods and analysis We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions.Ethics and dissemination Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.Trial registration number NCT04341142

The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS0000479