Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Huez-Alpe d’Huez (Isère). Brandes-en-Oisans

1) La campagne de fouille 2006 Depuis quelques années, la recherche s’était centrée sur la compréhension des aménagements hydrauliques et sur le fonctionnement des installations liées à l’utilisation de l’eau (meules de broyage du minerai actionnées par l’énergie hydraulique, bassins de lavage, etc.). La campagne 2006 avait deux objectifs principaux : retrouver un four d’essai du minerai et démarrer un nouveau programme de recherche pluriannuel sur l’organisation spatiale du village en commen..

Huez-L'Alpe d'Huez – Brandes-en-Oisans

Identifiant de l'opération archéologique : 229413 Date de l'opération : 2007 (FP) Installations artisanales Le site de Brandes fait l’objet d’une fouille archéologique depuis 1977. Les uns après les autres, les différents ensembles qui constituent cette petite agglomération sont étudiés afin de préciser, au fil des campagnes de terrain et d’études en laboratoire, le portrait de cette microsociété particulière : une population de mineurs, vivant en famille à plus de 1 800 m d’altitude, au XIII..

Huez-Alpe d'Huez (Isère). Brandes-en-Oisans

Le site de Brandes fait l’objet d’une fouille archéologique depuis 1977. Les uns après les autres, les différents ensembles qui constituent cette petite agglomération sont étudiés (église, cimetière, fortification, habitations, chantiers miniers, ateliers de minéralurgie, aménagements hydrauliques) afin de préciser, au fil des campagnes de terrain et d’études en laboratoire, le portrait de cette microsociété particulière : une population de mineurs, vivant en famille à plus de 1 800 m d’altit..

A national study of kidney graft tumor treatments: Toward ablative therapy

International audienceBACKGROUND:Results of the conservative treatment of renal cell carcinomas arising in functional renal transplants are unknown compared to transplant nephrectomy. Only small series or case reports have been reported.METHODS:Data were collected from 32 transplantation centers nationwide on cases of de novo tumors in functional renal transplants presumed to be malignant between January 1988 and December 2013.RESULTS:Among 116 de novo transplant tumors, 62 were treated conservatively including: 48 by partial nephrectomy (PN) and 14 by thermal ablation (TA). These patients were compared to 30 other patients who were treated by transplant nephrectomy. The median age of the transplanted kidneys at the time of diagnosis was 43.5 years old as calculated from the donor's age. Tumors treated by transplant nephrectomy presented more often with symptoms (pain, fever, impaired condition, hematuria) than tumors treated conservatively (P = .019). After PN, final histology showed 27 (47.5%) papillary carcinomas, 19 (32.2%) clear cell carcinomas, 1 mixed carcinoma, and 2 oncocytomas. The median tumor size treated by PN was 24 mm with no difference in comparison to the TA group. Nine patients treated by PN had postoperative complications (21%), including 4 requiring operative intervention (Clavien IIIb). None of the patients treated by TA had complications. Specific survival was 100% at the time of last follow-up (median time after treatment 37 months) for patients treated by PN or TA.CONCLUSION:PN proved to be efficient in the treatment of small tumors of transplanted kidneys with good long-term functional and oncologic outcomes, including avoiding return to dialysis. TA seems to be an alternative therapy with good results in selected patients

National prospective study on the use of local haemostatic agents during partial nephrectomy

International audienceOBJECTIVE:To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs).PATIENTS AND METHODS:Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010. In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case-report form: five different sheets were included for preoperative, perioperative, postoperative and follow-up data respectively. Information related to haemostasis was analysed.RESULTS:The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19-15) cm. An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024). In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%). One or more additional haemostatic action(s) was needed in 12.3% of the cases. When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713).CONCLUSION:HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron-sparing surgery is still to be evaluated