Abstract
Background
The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic ...pathogens (such
as Enterococcus
) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking.
Methods
We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90.
Results
From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2
(
SAPS 2) at admission was 33 24; 50 and a Sequential Organ Failure Assessment score (SOFA score) at 6 4; 8. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of
Enterococcus
spp.,
Staphylococcus aureus
and
Candida
spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in
Enterococcus
spp
.
,
S. aureus
and
Candida
spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death.
Conclusion
We found that elevated oropharyngeal/intestinal
Enterococcus
spp.
S. aureus
and
Candida
spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients.
Purpose
Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months ...after the resolution of acute COVID-19.
Methods
We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge.
Results
We observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory CD4
+
and effector CD8
+
T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation.
Conclusion
The lack of restoration of gene expression to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures.
Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new ...preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.
L’argumentation est au cœur des préoccupations de ceux qui ont pour vocation de « manipuler » la langue, que ce soit pour transmettre des informations et des savoirs, pour agir sur autrui et ...communiquer ou pour étudier la langue dans ses dimensions interlocutive, dialogique et pragmatique. À la croisée de différentes disciplines scientifiques ayant la langue comme composante transversale – l’analyse de discours, la linguistique textuelle, la didactique des langues, la communication, la pragmatique – l’argumentation est également soumise à une évolution exponentielle des outils et techniques de diffusion et de traitement des données qui rapprochent les locuteurs dans le temps et l’espace. Ce contexte de mondialisation et d’évolution technologique influe considérablement sur la forme, le contenu, la structure, l’impact et l’enjeu des discours argumentatifs. Cet ouvrage collectif réunit les contributions de chercheurs en linguistique, analyse de discours et didactique du français sur objectif spécifique et universitaire autour de la notion de manipulation, au sens premier et au sens dérivé du terme, que l’argumentation peut produire sur le langage. Il propose un double regard franco-espagnol en croisant les articles de collègues français et espagnols afin d’enrichir l’analyse de cette notion très actuelle.
L’influence grandissante du monde économique sur l’école occidentale a favorisé la création d’une multitude d’indicateurs et d’évaluations censés rendre compte de l’efficacité des systèmes éducatifs. ...Les résultats des épreuves internationales comme PISA ainsi que les classements internationaux qu’ils entraînent influencent les politiques éducatives et les pratiques enseignantes. En français, discipline scolaire particulièrement sensible politiquement, les pratiques d’évaluation sommative prennent ainsi souvent le pas sur les évaluations formatives, davantage centrées sur les apprentissages des élèves et sur les indices de leur progression. Les contributeurs de cet ouvrage mettent en tension ces différents volets de l’évaluation en français, étudiant à travers les tâches langagières spécifiques à cette discipline la façon dont les enseignants et les institutions interprètent leur mandat d’évaluation. Deux ensembles de travaux structurent cet ouvrage : ceux portant sur les pratiques d’évaluation en classe et ceux qui abordent les tests d’évaluation certificative, dans une perspective nationale ou internationale.
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