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

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

The downward spiral of mental disorders and educational attainment: a systematic review on early school leaving.

BACKGROUND: Most psychiatric disorders present symptom patterns that cause severe impairment on the emotional, cognitive and social level. Thus, adolescents who suffer from a mental disorder risk finding themselves in a downward spiral caused by the reciprocal association of psychological symptoms and negative school experiences that may culminate in early school leaving. In addition to previous collective work that mainly focused on school refusing behaviour among children and was presented as an expert's opinion, the following systematic review fills the knowledge gap by providing a structured overview of the bidirectional association between mental health and secondary school dropout based on a sound methodology and with a particular focus on mediating factors. METHODS: Four electronic databases were searched from January 1990 until June 2014. Selected references were assessed for study details, main results, mediating factors and methodological limitations. Standardized risk of bias assessment was conducted. RESULTS: Mood and anxiety disorders seemed to have a less consequential direct effect on early school leaving than substance use and disruptive behaviour disorders. The association between externalizing disorders and educational attainment was even stronger when the disorder occurred early in life. On the other hand, internalizing disorders were reported to develop as a consequence of school dropout. Only few studies had addressed gender differences, with discrepant results. Socio-economic background, academic achievement and family support were identified as significant mediating factors of the association between mental disorders and subsequent educational attainment. CONCLUSIONS: Findings suggested a strong association between mental health and education, in both directions. However, most studies focused on mediating factors that could not be targeted by intervention programs

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

Psychosocial risk and protective factors of secondary school dropout in Luxembourg: the protocol of an exploratory case-control study.

BACKGROUND: In Luxembourg, the extensive phenomenon of school dropout is a prime policy concern in the light of individual, social and economic consequences. Although the authorities report an overall decrease of the national dropout rate, the proportion of early school leavers who remain without any specific occupation is still alarming. Therefore, this study intends a shift of focus from system-inherent to individual factors, including mental health and family correlates, to provide a more comprehensive analysis of the dropout phenomenon. METHODS/DESIGN: The objectives of this study are to investigate the type and prevalence of psychiatric disorders among school dropouts and to compare the findings with those by a matched control group of regularly enrolled students. Furthermore, family variables and socioeconomic status will be analysed, as they are factors likely to interfere with both educational attainment and mental health. A trained psychologist will use structured interviews and self-report forms to investigate for mental health issues, information on schooling, socioeconomic situation and family life. Controls will be matched for gender, age, school type and educational grade. DISCUSSION: As school dropouts face a serious risk of long term professional and social marginalization, there is an evident need for action. Identifying psychosocial risk and protective factors of school dropout will deliver solid insight on how to conceive public health strategies for young people who may need a more customized support to carry out their academic potential. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01354236

Life satisfaction two-years after stroke onset: the effects of gender, occupational status, memory function and quality of life among stroke patients (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg

Life satisfaction (LS) of cerebrovascular disease survivors and their family caregivers may relate to socioeconomic factors, impaired functions, health-related quality of life (QoL), but their respective influences remain unclear. This study assessed, two years post-stroke onset, the effects of these factors on patients' LS and family caregivers' LS in Luxembourg. METHODS: All stroke patients admitted to all hospitals in Luxembourg were identified by the 'Inspection Général de la Sécurité Sociale' using the only national system database for care expenditure reimbursement. Their diagnosis was confirmed by medical investigator. The sample included ninety four patients living at home having given consent (mean age 65.5 years) and sixty two main caregivers (mean age 59.3 years). Questionnaires were completed during face-to-face interviews. LS was assessed via European single question (range 1-10), survivors' QoL via Newsqol (11 dimensions), and caregivers' QoL via Whoqol-bref (4 domains) (range 0-100). Data were analysed using multiple regression models. RESULTS: Two years after stroke onset, 44.7% of patients suffered from impaired sensory function, 35.1% from impaired motor function, and 31.9% from impaired memory function. Mean patient' LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among unemployed socioeconomically active patients (-13.1, vs. retired people). Adjusted for sex, occupation, impaired motor and memory functions, LS positively correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers' Whoqol-bref domains. Family caregiver' LS was 7.2 (SD 1.7). It was lower in those with patients suffering from impaired memory function (-12.8) as well as from feelings and emotion issues (slopes 0.22). It was associated with all caregivers' Whoqol-bref domains (physical health, psychological health, environment, and social relationships) (slopes 0.53 to 0.68). CONCLUSIONS: Two-year post-cerebrovascular disease patient' LS was associated with gender, occupation, and impaired memory function. It correlated with feelings, sleep, emotion, cognition, and pain issues. Family caregivers of patients with impaired memory function had lower LS. Family caregiver' LS correlated with dimensions of patients' feelings (less independent, yourself, life changed, depressed, useless, less control because of stroke) and emotion (get more emotional, fear of another stroke or to become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol appeared to be appropriate tools. Our findings may be useful for policy makers in relation to family and medical-social issues of stroke home-based rehabilitation