Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Stressors at work and elsewhere: a global survival approach

Abstract: The United Nations´ “Agenda 2030” aims, in an integrated manner, to address the entire multitude of major global risks – e.g., to end poverty and hunger, realize the human rights of all, and ensure the lasting protection of the planet and its natural resources. However, recent political changes put this bold initiative at risk. To increase the likelihood  of success, higher education institutions worldwide should teach and train today´s students – tomorrow´s decision makers – to think both critically and ethically, to learn to cope with ethical dilemmas, and to apply systems-thinking approaches to serious and complex societal problems. The Covid-19 pandemic provides just one example of a complex and serious challenge necessitating such approaches. Promoting decent work, full employment and economic growth is one of the other major challenges. And neither of them can be successfully dealt with in a piecemeal manne

Long-term unemployment among women in Sweden

Vulnerability at long-term unemployment is discussed and the results of a study of the effects of job loss and long-term unemployment among Swedish women are presented. Psychological and physiological data for the unemployed were sampled repeatedly over a two year period. Some of the unemployed were subject to an intervention programme aiming at buffering for the possibly negative effects of unemployment. Health data from matched control groups of employed were gathered over the same period. The results indicate a strong negative stress reaction at the job loss period, followed by a gradual adaptation to the conditions of unemployment as measured by biochemical and physiological health indicators. However, a substantial proportion of the unemployed compared to the employed showed a lower degree of psycholigical well-being and more severe depressive reactions. Recommendations are given concerning further research approaches on long-term unemployment. Policy implications to reduce vulnerability at long-term unemployment are discussed.long-term unemployment job loss psychological stress physiological stress

Behavioural and endocrine reactions in boys scoring high on Sennton neurotic scale viewing an exciting and partly violent movie and the importance of social support

Psychoendocrine and behavioural effects elicited by viewing an exciting and partly violent movie were studied in 12-year-old boys (n = 42). The boys were divided into three groups. Group A (n = 13) consisted of boys scoring below the median value on the Sennton neurotic scale for vegetative anxiety symptoms. Group B (n = 13) consisted of boys scoring above the median value on the Sennton neurotic scale. None of these boys had ever visited a psychiatric treatment centre, and they all came from the same school. A third group, Group C (n = 16), consisted of boys who, at least once, had visited an out-patient clinic at a child psychiatric treatment centre for neurotic problems. These boys attended different schools in the hospital catchment area. Group C had the same mean score on the Sennton neurotic scale as did Group B. By having two groups of boys scoring both high on the Sennton neurotic scale, one of which knew the other boys and one that did not, we were able to study possible effects of social support on psychobiologic reactions in neurotic boys. The boys' reactions to the movie were assessed by: (1) self-ratings; (2) direct observations of the boys by a team of trained child psychologists; and (3) by analysis of urinary output of adrenaline, noradrenaline and cortisol. Group B rated their experience the strongest, viewing the movie, while Groups A and C rated themselves as rather unaffected by it. Group C was rated less verbally active, both during the control and the film periods, than were the other two groups. Group A was most motorically active during the film period. There were no significant differences during the control period in endocrine variables. During the film period Group C excerted significantly more noradrenaline than did Group A, and significantly more noradrenaline than did Group B. Intra-group differences in response to the movie were also assessed. Adrenaline excretion increased significantly only in Group C during the movie, compared with the control period. Furthermore, excretion of noradrenaline decreased significantly during the film period in Groups A and B. The A and B groups preferred to review scenes representing danger, while Group C preferred scenes representing security. It is suggested that psychosocial factors, e.g. novelty to the environment and lack of friends, caused the differences between Group C and the other two groups. Group C, which scored the same as Group B on Sennton neurotic scale, did not have access to social support in the form of friends during the movie. They were left alone with their anxiety, with little ability to express it in a group of unknown boys. Group B appeared to have coped in a more 'open way', expressing their emotions during the film period, possibly explaining this group's lower level of physiological arousal. The psychological vulnerability in Group C is further stressed by this group's desire to review scenes depicting security. It suggested that access to social support, here operationally defined as being together with friends, is an important intervening variable in predicting psychobiological effects of viewing exciting and violent motion pictures.