French Institute of Health and Medical Research
Recent publications
Innate lymphoid cells (ILCs) - which include cytotoxic Natural Killer (NK) cells and helper-type ILC - are important regulators of tissue immune homeostasis, with possible roles in tumor surveillance. We analyzed ILC and their functionality in human lymph nodes (LN). In LN, NK cells and ILC3 were the prominent subpopulations. Among the ILC3s, we identified a CD56+/ILC3 subset with a phenotype close to ILC3 but also expressing cytotoxicity genes shared with NK. In tumor-draining LNs (TD-LNs) and tumor samples from breast cancer (BC) patients, NK cells were prominent, and proportions of ILC3 subsets were low. In tumors and TD-LN, NK cells display reduced levels of NCR (Natural cytotoxicity receptors), despite high transcript levels and included a small subset CD127- CD56- NK cells with reduced function. Activated by cytokines CD56+/ILC3 cells from donor and patients LN acquired cytotoxic capacity and produced IFNg. In TD-LN, all cytokine activated ILC populations produced TNFα in response to BC cell line. Analyses of cytotoxic and helper ILC indicate a switch toward NK cells in TD-LN. The local tumor microenvironment inhibited NK cell functions through downregulation of NCR, but cytokine stimulation restored their functionality.
The past decades witnessed the clinical employment of targeted therapies including but not limited to tyrosine kinase inhibitors (TKIs) that restrain a broad variety of pro-tumorigenic signals. TKIs can be categorized into (i) agents that directly target cancer cells, (ii) normalize angiogenesis or (iii) affect cells of the hematologic lineage. However, a clear distinction of TKIs based on this definition is limited by the fact that many TKIs designed to inhibit cancer cells have also effects on immune cells that are being discovered. Additionally, TKIs originally designed to target hematological cancers exhibit bioactivities on healthy cells of the same hematological lineage. TKIs have been described to improve immune recognition and cancer immunosurveillance, providing the scientific basis to combine TKIs with immunotherapy. Indeed, combination of TKIs with immunotherapy showed synergistic effects in preclinical models and clinical trials and some combinations of TKIs normalizing angiogenesis with immune checkpoint blocking antibodies have already been approved by the FDA for cancer therapy. However, the identification of appropriate drug combinations as well as optimal dosing and scheduling needs to be improved in order to obtain tangible progress in cancer care. This Trial Watch summarizes active clinical trials combining TKIs with various immunotherapeutic strategies to treat cancer patients.
Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota's composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota's metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.
Background The causes of an early onset of puberty are still not clearly defined and may vary from subject to subject. In girls, even if 90% of early puberty is idiopathic, magnetic resonance imaging (MRI) of the brain is performed to exclude secondary causes of precocious puberty, in particular pathological lesions as hypothalamic tumours (hamartoma). In some cases, other intracranial lesions are considered as incidental findings. Aim of the study is evaluating the prevalence of abnormal intracranial lesions detected by brain magnetic resonance imaging MRI with particular focus on the prevalence of pineal gland cysts in the diagnostic work-up of girls with central precocious puberty (CPP) as onset before 8 years and central early puberty (CEP) as onset before 10 years. Material and methods MRI data of girls referred from January 2010 to December 2015 to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development were collected. Results We collected 123 MRI data of girls referred to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development in the study period. Out of them, 25 (20.3%) had cerebral abnormalities and 15 (12.2%) had pineal gland cysts. No significant differences were noted in auxological, ultrasound and hormonal parameters at diagnosis among girls with or without pineal cysts. Patients have been observed for at least three years after the discontinuation of therapy. None of our patients had an unfavorable evolution. Conclusions Although pineal cysts seem to be not involved in the onset of puberty, the relevance of the finding remains controversial. Our study wants to provide further insight into the incidence of pineal cysts in pubertal advances. Of note, pineal cysts are often asymptomatic and do not evolve over time.
Background Trials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy. Methods We used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation. Results We analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects ( P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, − 14%; 95% confidence interval, − 27% to − 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, − 5% to 21% in patients at intermediate-low risk). Conclusions We have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.
Background Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences. Main text A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended. Conclusion Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Background: Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are the two main RRT modalities in patients with severe acute kidney injury (AKI). Meta-analyses conducted more than 10 years ago did not show survival difference between these two modalities. As the quality of RRT delivery has improved since then, we aimed to reassess whether the choice of IHD or CRRT as first modality affects survival of patients with severe AKI. Methods: This is a secondary analysis of two multicenter randomized controlled trials (AKIKI and IDEAL-ICU) that compared an early RRT initiation strategy with a delayed one. We included patients allocated to the early strategy in order to emulate a trial where patients would have been randomized to receive either IHD or CRRT within twelve hours after the documentation of severe AKI. We determined each patient's modality group as the first RRT modality they received. The primary outcome was 60-day overall survival. We used two propensity score methods to balance the differences in baseline characteristics between groups and the primary analysis relied on inverse probability of treatment weighting. Results: A total of 543 patients were included. Continuous RRT was the first modality in 269 patients and IHD in 274. Patients receiving CRRT had higher cardiovascular and total-SOFA scores. Inverse probability weighting allowed to adequately balance groups on all predefined confounders. The weighted Kaplan-Meier death rate at day 60 was 54·4% in the CRRT group and 46·5% in the IHD group (weighted HR 1·26, 95% CI 1·01-1·60). In a complementary analysis of less severely ill patients (SOFA score: 3-10), receiving IHD was associated with better day 60 survival compared to CRRT (weighted HR 1.82, 95% CI 1·01-3·28; p < 0.01). We found no evidence of a survival difference between the two RRT modalities in more severe patients. Conclusion: Compared to IHD, CRRT as first modality seemed to convey no benefit in terms of survival or of kidney recovery and might even have been associated with less favorable outcome in patients with lesser severity of disease. A prospective randomized non-inferiority trial should be implemented to solve the persistent conundrum of the optimal RRT technique.
Background The clinical use of calcitonin gene-related peptide receptor (CGRP-R) antagonists and monoclonal antibodies against CGRP and CGRP-R has offered new treatment possibilities for migraine patients. CGRP activates both the CGRP-R and structurally related amylin 1 receptor (AMY1-R). The relative effect of erenumab and the small-molecule CGRP-R antagonist, rimegepant, towards the CGRP-R and AMY-R needs to be further characterized. Methods The effect of CGRP and two CGRP-R antagonists were examined in Xenopus laevis oocytes expressing human CGRP-R, human AMY1-R and their subunits. Results CGRP administered to receptor expressing oocytes induced a concentration-dependent increase in current with the order of potency CGRP-R> > AMY1-R > calcitonin receptor (CTR). There was no effect on single components of the CGRP-R; calcitonin receptor-like receptor and receptor activity-modifying protein 1. Amylin was only effective on AMY1-R and CTR. Inhibition potencies (pIC50 values) for erenumab on CGRP induced currents were 10.86 and 9.35 for CGRP-R and AMY1-R, respectively. Rimegepant inhibited CGRP induced currents with pIC50 values of 11.30 and 9.91 for CGRP-R and AMY1-R, respectively. Conclusion Our results demonstrate that erenumab and rimegepant are potent antagonists of CGRP-R and AMY1-R with 32- and 25-times preference for the CGRP-R over the AMY1-R, respectively. It is discussed if this difference in affinity between the two receptors is the likely reason why constipation is a common and serious adverse effect during CGRP-R antagonism but less so with CGRP binding antibodies.
Persistent organic pollutants (POPs) accumulate in the organisms due to their hydrophobicity and resistance to xenobiotic metabolism. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of most representative POPs. Its pathophysiological effects have been extensively studied on many types of tissues but not on muscles. In this study, female C57BL/6J mouse model was used to analyze the long-term effects of maternal exposure to TCDD during gestation and lactation on the skeletal muscles (soleus, plantaris, and gastrocnemius) of the progeny during adulthood. The effects of re-exposure to TCDD in mice exposed during their development were also characterized. Female C57BL/6J mice were maternally exposed to TCDD or its vehicle (n-nonane in corn oil) and then re-exposed to TCDD or its vehicle at 9 weeks of age. The metabolites in the skeletal muscles were analyzed by gas chromatography–quadrupole time of flight-mass spectrometry (GC–qTOF-MS). Univariate analysis showed significant effects in certain metabolites in the skeletal muscle. It also showed that TCDD exerts a more significant impact on exposure to TCDD at 9 weeks of age than during maternal exposure for the soleus. On the other hand, TCDD exerts a more significant impact on mice maternally exposed to TCDD than at 9 weeks of age for the gastrocnemius. Multivariate analysis showed clear discrimination between the TCDD-exposed mice and the control. This study demonstrates the effects of TCDD observed following maternal exposure; some of them can be reinforced or attenuated by a re-exposure at the adult age, suggesting that the POP which mainly acts through the activation of the AhR leads to metabolic adaptation in the skeletal muscles. The period of exposure was a key factor in our study with TCDD playing a crucial role during the maternal period, as compared to when they were exposed at 9 weeks of age. It was inferred that disruption in amino acid metabolism might lead to a loss in muscle mass which may result in muscular atrophy. Our results also show that the metabolite profiles after perinatal exposure are different in different types of muscles even though they are all classified as skeletal muscles. Therefore, TCDD may affect the organism (specifically different skeletal muscles) in a non-homogenous manner.
Background Given slowing secular declines and persistent racial disparities, stillbirth remains a major health burden in the US. We investigate changes in stillbirth rates overall and for Black and White women, and determine how maternal age, delivery year (period), and birth year (cohort) have shaped trends. Methods We designed a sequential time-series analysis utilising the 1980 to 2020 US vital records data of live births and stillbirths at ≥24 weeks gestation. Stillbirth rates overall and among Black and White women were examined. We undertook an age-period-cohort analysis to evaluate temporal changes in stillbirth trends. Findings Of 157,192,032 live births and 710,832 stillbirths between 1980 and 2020, stillbirth rates per 1000 births declined from 10.6 (95% confidence interval [CI] 10.5, 10.7) in 1980 to 5.8 (95% CI 5.7, 5.8) in 2020. Stillbirth rates declined from 9.2 to 5.0 per 1000 births among White women (rate ratio [RR] 0.54, 95% CI 0.53, 0.55), and from 17.4 to 10.1 per 1000 births among Black women (RR 0.57, 95% CI 0.55, 0.59). Black women experienced persistent two-fold higher rates compared to White women (2.01, 95% CI 1.97, 2.05 in 2020). Stillbirth rates declined until 2005, increased from 2005 to the mid-2010s and plateaued thereafter. Strong cohort effects contributed to declining rates in earlier cohorts (1930–1955) and increasing rates among women born after 1980. Interpretation Age, period, and birth cohorts greatly influenced US stillbirth rates over the last forty years. The decline in stillbirth rate was evident between 1980 and 2005, however subsequent declines have been minimal, reflecting no further gains for cohorts of women born in 1955–1980 and stagnation of period effects starting in 2005. A significant racial disparity persisted with a two-fold excess in stillbirth rates for Black compared to White women, underscoring the need for targeted health and social policies to address disparities. Funding None.
Intellectual disability with or without manifestations of autism and/or epilepsy affects 1–2% of the population, and it is estimated that more than 30–50% of these cases have a single genetic cause. More than 1000 genes and recurrent chromosomal abnormalities are involved in these genetic forms of neurodevelopmental disorders, which often remain insufficiently described in terms of clinical spectrum, associated medical problems, etc., due to their rarity and the often-limited number of patients’ phenotypes reported. GenIDA is an international online participatory database that aims to better characterise the clinical manifestations and natural histories of these rare diseases. Clinical information is reported by parents of affected individuals using a structured questionnaire exploring physical parameters, cognitive and behavioural aspects, the presence or absence of neurological disorders or problems affecting major physiological functions, as well as autonomy and quality of life. This strengthens the implication in research of the concerned families. GenIDA aims to construct international cohorts of significant size of individuals affected by a given condition. As of July 2022, GenIDA counts some 1545 documented patient records from over 60 nationalities and collaborates with clinicians and researchers around the world who have access to the anonymized data collected to generate new, medically meaningful information to improve patient care. We present the GenIDA database here, together with an overview of the possibilities it offers to affected individuals, their families, and professionals in charge of the management of genetic forms of neurodevelopmental disorders. Finally, case studies of cohorts will illustrate the usefulness of GenIDA.
The aims of this study were to develop topical liposomal hydrogels based on thermal waters (TWs) acquired in the region of Biskra (Northeast Algeria) and also to investigate their rheological properties. Liposomes containing two highly mineralized thermal waters, Baraka (BTW) and Salhine (STW), were prepared by probe sonication using phosphatidylcholine (PC) and cholesterol (Chol), plain or mixed with phosphatidylglycerol (PG). Based on their lipid composition, obtained liposomes presented vesicle sizes of 60 nm, a low polydispersity index, and various negative zeta potentials. It was noted that with increasing counterions charge in TWs the zeta potential of liposomes decreased toward neutral values. Carbopol (1%, w/w) hydrogels prepared with BTW, STW, and also demineralized water (placebo hydrogel) showed a non-Newtonian behaviour, pseudoplastic fluid adjusted to Carreau model. The composition of thermal waters influenced highly the rheological properties of Carbopol hydrogels. Liposomal hydrogels were prepared by dispersing liposomes in hydrogels formulated with the same encapsulated thermal water. Regardless of composition or lipid concentration of added liposomes, the viscosity and viscoelastic parameters of Carbopol hydrogels changed negligibly. Indeed, liposome composition and lipid concentration seemed to have no effect on the rheological properties of Carbopol hydrogel in the presence of an important charge of cations. Hence, hydrogels and liposomal hydrogels based on thermal waters had suitable rheological properties for topical application and delivery of minerals in the skin.
In 1964, a group of clinicians and scientists established The European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) to promote knowledge on diagnosis and management of poisonings. The association holds annual scientific congresses and has been in collaboration with a variety of international organizations. The EAPCCT aims to encourage research on toxicities and management of poisoned patients and facilitate/enhance communications among members, sister scientific societies and the European countries’ governments and authorities with respect to clinical toxicology. Members of the association are from 51 countries. The official journal of the EAPCCT is Clinical Toxicology.
Introduction Improved knowledge of prediabetic subjects’ profile and their risk of developing type 2 diabetes mellitus (T2DM) would enhance secondary prevention. The primary objective is to describe factors associated with incident T2DM in subjects with pre-diabetes diagnosed in primary care. Methods and analysis The study is based on Reunion Island, a French overseas region that experiences a particularly high disease burden of T2DM. This is an observational, non-randomised prospective cohort study conducted in primary care in which private general practitioner (GP) investigators recruit participants with pre-diabetes from their practices regardless of the initial motive for consultation. Pre-diabetes is defined by WHO criteria, that is, fasting plasma glucose between 1.10 g/L and 1.25 g/L and/or plasma glucose 2 hours after ingestion of 75 g of glucose (2-hour post load plasma glucose) between 1.40 g/L and 1.99 g/L. The design is based on an annual follow-up by the GP (according to French National Health Authority recommendations) with collection of clinical and laboratory data and specific lifestyle questionnaires answered by telephone at three time points: inclusion, and at 2-year and 5-year follow-up visits. Follow-up clinical and laboratory data are collected by the investigating GP as part of the study, and study-specific laboratory collections (serum, DNA and urine) will be obtained 2 and 5 years after inclusion. The primary outcome is transition to T2DM. Ethics and dissemination This protocol has been approved by the research ethics committee of Saint Etienne (CPP Saint Etienne reference number: 2019–03). Enrolment began in August 2019. Results will be disseminated in at least three papers published in peer-reviewed medical journals, one oral communication and a large-scale communication to the local population and healthcare policymakers. Trial registration number NCT04463160 and ID-RCB 2018-A03106-49.
Background. Vitamin D is involved in muscle health and function. This relationship may start from the earliest stages of life during pregnancy when fetal vitamin D relies on maternal vitamin D stores and sun exposure. Our objective was to determine whether there was an effect of the month of birth (MoB) on muscle mass and strength in older adults. Methods. Data from 7598 community-dwelling women aged ≥ 70 years from the French multicentric EPIDOS cohort were used in this analysis. The quadricipital strength was defined as the mean value of 3 consecutive tests of the maximal isometric voluntary contraction strength of the dominant lower limb. The muscle mass was defined as the total appendicular skeletal muscle mass measured using dual energy X-ray absorptiometry scanner. The MoB was used as a periodic function in regressions models adjusted for potential confounders including age, year of birth, latitude of recruitment center, season of testing, body mass index, number of comorbidities, IADL score, regular physical activity, sun exposure at midday, dietary protein intake, dietary vitamin D intake, use vitamin D supplements, history and current use of corticosteroids. Results. A total of 7133 older women had a measure of muscle strength (mean age, 80.5 ± 3.8 years; mean strength, 162.3 ± 52.1 N). Data on total ASM were available from 1321 women recruited in Toulouse, France (mean, 14.86 ± 2.04 kg). Both the sine and cosine functions of MoB were associated with the mean quadricipital strength (respectively β = −2.1, p = 0.045 and β = −0.5, p = 0.025). The sine function of MoB was associated with total ASM (β = −0.2, p = 0.013), but not the cosine function (β = 0.1, p = 0.092). Both the highest value of average quadricipital strength (mean, 163.4 ± 20.2 N) and the highest value of total ASM (15.24 ± 1.27 kg) were found among participants born in August. Conclusions. Summer-early fall months of birth were associated with higher muscle mass and strength in community-dwelling older women.
Cellular inhibitor of apoptosis-1 (cIAP1) is a signaling regulator with oncogenic properties. It is involved in the regulation of signaling pathways controlling inflammation, cell survival, proliferation, differentiation and motility. It is recruited into membrane-receptor-associated signaling complexes thanks to the molecular adaptor TRAF2. However, the cIAP1/TRAF2 complex exists, independently of receptor engagement, in several subcellular compartments. The present work strengthens the importance of TRAF2 in the oncogenic properties of cIAP1. cIAPs-deficient mouse embryonic fibroblasts (MEFs) were transformed using the HRas-V12 oncogene. Re-expression of cIAP1 enhanced tumor growth in a nude mice xenograft model, and promoted lung tumor nodes formation. Deletion or mutation of the TRAF2-binding site completely abolished the oncogenic properties of cIAP1. Further, cIAP1 mediated the clustering of TRAF2, which was sufficient to stimulate tumor growth. Our TRAF2 interactome analysis showed that cIAP1 was critical for TRAF2 to bind to its protein partners. Thus, cIAP1 and TRAF2 would be two essential subunits of a signaling complex promoting a pro-tumoral signal. cIAP1/TRAF2 promoted the activation of the canonical NF-κB and ERK1/2 signaling pathways. NF-κB-dependent production of IL-6 triggered the activation of the JAK/STAT3 axis in an autocrine manner. Inhibition or downregulation of STAT3 specifically compromised the growth of cIAP1-restored MEFs but not that of MEFs expressing a cIAP1-mutant and treating mice with the STAT3 inhibitor niclosamide completely abrogated cIAP1/TRAF2-mediated tumor growth. Altogether, we demonstrate that cIAP1/TRAF2 binding is essential to promote tumor growth via the activation of the JAK/STAT3 signaling pathway.
Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial cell (EC)-based 3D spheroids to better represent in vivo conditions. When co-cultured in 3D conditions, ECs and OCCs formed organized tumor angiospheres with a core of ECs surrounded by proliferating OCCs. We established that Akt and Notch3/Jagged1 pathways played a role in angiosphere formation and peritoneum invasion. In patients’ ascites we found angiosphere-like structures and demonstrated in patients’ specimens that tumoral EC displayed Akt activation, which supports the importance of Akt activation in ECs in OC. Additionally, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3/Jagged1 in OCC–EC crosstalk relating to OCC proliferation and during peritoneal invasion. Our results support the use of multicellular spheroids to better model tumoral and stromal interaction. Such models could help decipher the complex pathways playing critical roles in metastasis spread and predict tumor response to chemotherapy or anti-angiogenic treatment.
This cohort study uses COVID-19 Pediatric Observatory study data to analyze the vaccination status of parents with young children hospitalized for SARS-CoV-2 variants Delta and Omicron.
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Cécilia Chassin
  • ATIP-Avenir Group
Luc G. Legres
  • Laboratoire UMR_S 976
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