Brand-specific influenza vaccine effectiveness estimates during 2019/20 season in Europe – Results from the DRIVE EU study platform

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) is an IMI funded public–private platform that aims to annually estimate brand-specific influenza vaccine effectiveness (IVE), for public health and regulatory purposes. IVE analyses and reporting are conducted by public partners in the con- sortium. In 2019/20, four primary care-based test-negative design (TND) studies (Austria, England, Italy (n = 2)), eight hospital-based TND studies (Finland, France, Italy, Romania, Spain (n = 4)), and one population- based cohort study (Finland) were conducted. The COVID-19 pandemic affected influenza surveillance in all participating study sites, therefore the study period was truncated on February 29, 2020. Age- stratified (6 m-17y, 18-64y, !65y), confounder-adjusted, site-specific adjusted IVE estimates were calcu- lated and pooled through meta-analysis. Parsimonious confounder-adjustment was performed, adjusting the estimates for age, sex and calendar time. TND studies included 3531 cases (351 vaccinated) and 5546 controls (1415 vaccinated) of all ages. IVE estimates were available for 8/11 brands marketed in Europe in 2019. Most children and adults < 64y were captured in primary care setting and the most frequently observed vaccine brand was Vaxigrip Tetra. The estimate against any influenza for Vaxigrip Tetra in primary care setting was 61% (95%CI 38–77) in children and 32% (95%CI 13–59) in adults up to 64y. Most adults ! 65y were captured in hospital setting and the most frequently observed brand was Fluad, with an estimate of 52% (95%CI 27–68)

Viral suppression and HIV-1 drug resistance 1 year after pragmatic transitioning to dolutegravir first-line therapy in Malawi: a prospective cohort study.

BACKGROUND Many countries are now replacing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) with a regimen containing tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Recognising laboratory limitations, Malawi opted to transition those on NNRTI-based first-line ART to TLD without viral load testing. We aimed to assess viral load and HIV drug resistance during 1 year following transition to TLD without previous viral load testing. METHODS In this prospective cohort study, we monitored 1892 adults transitioning from NNRTI-based first-line ART to the TLD regimen in the Médecins Sans Frontières-supported decentralised HIV programme in Chiradzulu District, Malawi. Eligible adults were enrolled between Jan 17 and May 11, 2019, at Ndunde and Milepa health centres, and between March 8 and May 11, 2019, at the Boma clinic. Viral load at the start of the TLD regimen was assessed retrospectively and measured at month 3, 6, and 12, and additionally at month 18 for those ever viraemic (viral load ≥50 copies per mL). Dolutegravir minimal plasma concentrations (Cmin) were determined for individuals with viraemia. Drug-resistance testing was done at the start of TLD regimen and at viral failure (viral load ≥50 copies per mL, followed by viral load ≥500 copies per mL; resistance defined as Stanford score ≥15). FINDINGS Of 1892 participants who transitioned to the TLD regimen, 101 (5·3%) were viraemic at TLD start. 89 of 101 had drug-resistance testing with 31 participants (34·8%) with Lys65Arg mutation, 48 (53·9%) with Met184Val/Ile, and 42 (40·4%) with lamivudine and tenofovir disoproxil fumerate dual resistance. At month 12 (in the per-protocol population), 1725 (97·9% [95% CI 97·1-98·5]) of 1762 had viral loads of less than 50 copies per mL, including 83 (88·3% [80·0-94·0]) of 94 of those who were viraemic at baseline. At month 18, 35 (97·2% [85·5-99·9]) of 36 who were viraemic at TLD start with lamivudine and tenofovir disoproxil fumarate resistance and 27 (81·8% [64·5-93·0]) of 33 of those viraemic at baseline without resistance had viral load suppression. 14 of 1838 with at least two viral load tests upon transitioning had viral failure (all with at least one dolutegravir Cmin value <640 ng/mL; active threshold), suggesting suboptimal adherence. High baseline viral load was associated with viral failure (adjusted odds ratio [aOR] 14·1 [2·3-87·4] for 1000 to <10 000 copies per mL; aOR 64·4 [19·3-215·4] for ≥10 000 copies per mL). Two people with viral failure had dolutegravir resistance at 6 months (Arg263Lys or Gly118Arg mutation), both were viraemic with lamivudine and tenofovir disoproxil fumarate resistance at baseline. INTERPRETATION High viral load suppression 1 year after introduction of the TLD regimen supports the unconditional transition strategy in Malawi. However, high pre-transition viral load, ongoing adherence challenges, and possibly existing nucleoside reverse transcriptase inhibitor resistance can lead to rapid development of dolutegravir resistance in a few individuals. This finding highlights the importance of viral load monitoring and dolutegravir-resistance surveillance after mass transitioning to the TLD regimen. FUNDING Médecins Sans Frontières. TRANSLATIONS For the French and Portuguese translations of the abstract see Supplementary Materials section

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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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 &lt; 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

Maladies rénales chroniques et dyslipidémies

Bien que les maladies rénales chroniques (MRC) soient associées aux maladies cardiovasculaires (MCV) indépendamment des autres facteurs de risque, la dyslipidémie est un facteur modifiable bien établi des MCV. Des anomalies lipidiques à la fois quantitatives et qualitatives s’aggravent avec le déclin de la filtration glomérulaire. Typique-ment, la MRC est associée avec une élévation des triglycérides et de la lipoprotéine (a) et un abaissement du HDL-C tandis que les changements des taux de cholestérol total et de LDL-C sont moins marqués et que les sous-classes de LDL démontrent une tendance vers un excès de particules LDL petites et denses. Les évidences concernant le bénéfice des statines au niveau CV est clair chez les patients avec MRC aux stades 2 et 3, mais est moins clair chez les patients avec une MRC plus avancée (Stade 4-5) ou en dialyse. Les analyses post-hoc des études d’intervention avec les statines suggèrent aussi que les statines ralentissent la vitesse de dégradation de la fonction rénale et ont un bénéfice sur les protéinuries pathologiques. Ces bénéfices plaident en faveur de l’utilisation des statines chez les patients en stade 2-3 de MRC. En pratique, les patients avec une maladie rénale chronique (MRC) doivent être considérés comme à risque équivalent à ceux qui ont une histoire de maladie coronarienne. Chez les patients avec une maladie rénale chronique stades 2 à 4 (Filtration glomérulaire de 15 à 89 ml/min/1.73 m²), les statines seront d’abord utilisées pour atteindre un taux de LDL-cholestérol 150 mg/dL ou si le taux de non-HDL cholestérol reste > 100 mg/dl. Chez les patients avec insuffisance rénale stade 5 (FG <15 ml/min/1.73 m²) ou en dialyse, les statines doivent être prescrites seulement à faible dose. Les omega 3 (pas les fibrates), peuvent être utilisés en deuxième instance, pour corriger les triglycérides ou le non HDL-

Seasonal influenza vaccine uptake and vaccine refusal among pregnant women in France: results from a national survey

Pregnant women and infants are at high risk for severe influenza and many countries, including France, recommend annual influenza immunization during pregnancy. We aimed to estimate influenza vaccination and refusal rates and assess associated factors among pregnant women during the 2015–16 season in France. We used data from a national representative sample of women who gave birth in March 2016 and were interviewed before hospital discharge (N = 11,752). In the multivariable analysis, robust Poisson regression models were used to study associations with maternal characteristics and prenatal care characteristics. Influenza vaccine coverage among pregnant women was 7.4% (95% confidence interval [CI]: 6.9–7.9). Only 24.9% (95% CI: 24.2–25.7) of women said that they received a care provider proposal for vaccination and 70.4% (95% CI: 68.7–72.0) of these declined it. Vaccine uptake was associated with low parity (prevalence ratio [PR] = 2.1; 95% CI: 1.4–3.2 for parity 0 vs ≥ 3), high educational level (PR = 2.5; 95% CI: 2.0–3.2), healthcare occupation during pregnancy (PR = 1.8; 95% CI: 1.5–2.1) and preexisting conditions at risk for influenza (PR = 1.7; 95% CI: 1.3–2.2). Women were more frequently vaccinated when their main care provider was a general practitioner. Multiparae women and those with medium or low educational level were significantly more likely than others to decline influenza vaccine after a provider proposal. Influenza vaccine coverage is very low in France, mainly because of infrequent care provider proposals and also frequent women’s refusals. Effective interventions should be designed to promote vaccination among medical professionals and reduce vaccine hesitancy among pregnant women

Observations astrométriques de Pluton - Le problème du photocentre

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