Christianismes du Sud à l’épreuve de l’Europe

Parler de « christianismes du Sud », c’est prendre acte du déplacement de centre de gravité du christianisme vers l’Afrique, l’Asie, l’Amérique latine ; un mouvement qui bouscule les problématiques du religieux de l’aire européenne (désenchantement, sécularisation). Dans cette globalisation polycentrique à laquelle participent les « christianités » orientales, asiatiques, sud-américaines, les christianismes africains occupent, une place singulière et exemplaire, par leur souffrance historique, leur démographie exponentielle, mais aussi par leur théologie messianique de la mission « en retour ». L’Europe découvre le phénomène des « Eglises africaines » par la circulation migratoire des chrétiens d’Afrique, l’écho bruyant des églises de banlieues, les croisades de pasteurs prophètes, ou le relais de prêtres « noirs » dans les paroisses. Ce numéro ouvre une fenêtre sur ces « Eglises Indépendantes » inscrites dans des réseaux transnationaux. La diversité des entrées (études de communautés, parcours prophétiques, histoires d’Eglises) illustre l’hétérogénéité et la scissiparité de ces groupes religieux. Le croisement des regards du dedans et du dehors invite à relativiser tout essentialisme des identités en présence, et le suivi de générations conduit de la niche communautaire, en lien ombilical avec les Eglises mères, au prosélytisme d’assemblées ouvertes sur la société globale. Il y a là tout un chantier de recherche : la globalisation indigène des christianismes africains interpellent les compromis de l’inculturation ou les promesses d’un œcuménisme interculturel ; les ambivalences de l’identité chrétienne africaine conjuguent les catégories d’ethnie, de race, et de nations bibliques, jusqu’à faire perdre son latin au message chrétien ; enfin, les réactions aux discriminations religieuses et les demandes de « reconnaissance » introduisent à une confrontation inédite avec les règles de l’espace public ou le régime de droit de la « société des individus »

Quantitative CT Extent of Lung Damage in COVID-19 Pneumonia Is an Independent Risk Factor for Inpatient Mortality in a Population of Cancer Patients: A Prospective Study

International audienceBackground: CT lung extent has emerged as a potential risk factor of COVID-19 pneumonia severity with mainly semiquantitative assessment, and outcome was not assessed in the specific oncology setting. The main goal was to evaluate the prognostic role of quantitative assessment of the extent of lung damage for early mortality of patients with COVID-19 pneumonia in cancer patients. Methods: We prospectively included consecutive cancer patients with recent onset of COVID-19 pneumonia assessed by chest CT between March 15, 2020, and April 20, 2020, and followed until May 1, 2020. Demographic, clinical, laboratory test data and imaging findings were recorded. Quantitative chest CT assessment of COVID-19 pneumonia was based on the density distribution of lung lesions using a freely available software recently released (Myrian XP-Lung). The association between extent of lung damage and overall survival was studied by univariate and multivariate Cox analysis. The Uno C-index was used to assess the discriminatory value of the quantitative CT extent of lung damage. Results: Seventy cancer patients with chest CT evidence of COVID-19 were included. After a median follow-up of 25 days, 17 patients (24%) had died. The median quantitative chest CT extent of COVID-19 was 20% (IQR = 14–35, range = 3–59) for non-survivors vs. 10% (IQR = 6–15, range = 2–55) for survivors (p = 0.002). The extent of COVID-19 pneumonia was correlated with inpatient management (p = 0.003) and oxygen therapy requirements (p < 0.001). Independent factors associated with death were performance status (PS) ≥2 (HR = 3.9, 95% CI = [1.1–13.8] p = 0.04) and extent of COVID-19 pneumonia ≥30% (HR = 12.0, 95% CI = [2.2–64.4] p = 0.004). No differences were found regarding the histology of cancer, cancer stage, metastases sites, or type of oncologic treatment between the survivor and non-survivor groups. The cross-validated Uno C-index of the model including PS and extent of COVID-19 pneumonia was 0.83, 95% CI = [0.73–0.93]. Conclusions: The quantitative chest CT extent of COVID-19 pneumonia was a strong independent prognostic factor of early inpatient mortality in a population of cancer patients

A single droplet digital PCR for ESR1 activating mutations detection in plasma

International audienceActivating mutations in the estrogen receptor 1 (ESR1) gene confer resistance to aromatase inhibitors (AI), and may be targeted by selective estrogen receptor downregulators. We designed a multiplex droplet digital PCR (ddPCR), which combines a drop-off assay, targeting the clustered hotspot mutations found in exon 8, with an unconventional assay interrogating the E380Q mutation in exon 5. We assessed its sensitivity in vitro using synthetic oligonucleotides, harboring E380Q, L536R, Y537C, Y537N, Y537S, or D538G mutations. Further validation was performed on plasma samples from a prospective study and compared with next generation sequencing (NGS) data. The multiplex ESR1-ddPCR showed a high sensitivity with a limit of detection ranging from 0.07 to 0.19% in mutant allele frequency. The screening of plasma samples from patients with AI-resistant metastatic breast cancer identified ESR1 mutations in 29% of them, all mutations being confirmed by NGS. In addition, this test identifies patients harboring polyclonal alterations. Furthermore, the monitoring of circulating tumor DNA using this technique during treatment follow-up predicts the clinical benefit of palbociclib–fulvestrant. The multiplex ESR1-ddPCR detects, in a single reaction, the most frequent ESR1 activating mutations with good sensitivity. This method allows real-time liquid biopsy for ESR1 mutation monitoring in large cohorts of patients

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

BACKGROUND: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). METHODS: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. RESULTS: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (&gt; 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. CONCLUSIONS: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients

COVID-19 in breast cancer patients: A cohort at the Institut Curie hospitals in the Paris area

International audienceBackground: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old