Variation in the COVID-19 infection-fatality ratio by age, time, and geography during the pre-vaccine era: a systematic analysis

Background The infection-fatality ratio (IFR) is a metric that quantifies the likelihood of an individual dying once infected with a pathogen. Understanding the determinants of IFR variation for COVID-19, the disease caused by the SARS-CoV-2 virus, has direct implications for mitigation efforts with respect to clinical practice, non-pharmaceutical interventions, and the prioritisation of risk groups for targeted vaccine delivery. The IFR is also a crucial parameter in COVID-19 dynamic transmission models, providing a way to convert a population's mortality rate into an estimate of infections.Methods We estimated age-specific and all-age IFR by matching seroprevalence surveys to total COVID-19 mortality rates in a population. The term total COVID-19 mortality refers to an estimate of the total number of deaths directly attributable to COVID-19. After applying exclusion criteria to 5131 seroprevalence surveys, the IFR analyses were informed by 2073 all-age surveys and 718 age-specific surveys (3012 age-specific observations). When seroprevalence was reported by age group, we split total COVID-19 mortality into corresponding age groups using a Bayesian hierarchical model to characterise the non-linear age pattern of reported deaths for a given location. To remove the impact of vaccines on the estimated IFR age pattern, we excluded age-specific observations of seroprevalence and deaths that occurred after vaccines were introduced in a location. We estimated age-specific IFR with a non-linear meta-regression and used the resulting age pattern to standardise all-age IFR observations to the global age distribution. All IFR observations were adjusted for baseline and waning antibody-test sensitivity. We then modelled age-standardised IFR as a function of time, geography, and an ensemble of 100 of the top-performing covariate sets. The covariates included seven clinical predictors (eg, age-standardised obesity prevalence) and two measures of health system performance. Final estimates for 190 countries and territories, as well as subnational locations in 11 countries and territories, were obtained by predicting age-standardised IFR conditional on covariates and reversing the age standardisation.Findings We report IFR estimates for April 15, 2020, to January 1, 2021, the period before the introduction of vaccines and widespread evolution of variants. We found substantial heterogeneity in the IFR by age, location, and time. Age-specific IFR estimates form a J shape, with the lowest IFR occurring at age 7 years (0-0023%, 95% uncertainty interval [UI] 0-0015-0-0039) and increasing exponentially through ages 30 years (0-0573%, 0-0418-0-0870), 60 years (1-0035%, 0-7002-1-5727), and 90 years (20-3292%, 14-6888-28-9754). The countries with the highest IFR on July 15, 2020, were Portugal (2-085%, 0-946-4-395), Monaco (1-778%, 1-265-2-915), Japan (1-750%, 1-302-2-690), Spain (1-710%, 0-991-2-718), and Greece (1-637%, 1-155-2-678). All-age IFR varied by a factor of more than 30 among 190 countries and territories.After age standardisation, the countries with the highest IFR on July 15, 2020, were Peru (0-911%, 0-636-1-538), Portugal (0-850%, 0-386-1-793), Oman (0-762%, 0-381-1-399), Spain (0-751%, 0-435-1-193), and Mexico (0-717%, 0-426-1-404). Subnational locations with high IFRs also included hotspots in the UK and southern and eastern states of the USA. Sub-Saharan African countries and Asian countries generally had the lowest all-age and age-standardised IFRs. Population age structure accounted for 74% of logit-scale variation in IFRs estimated for 39 in-sample countries on July 15, 2020. A post-hoc analysis showed that high rates of transmission in the care home population might account for higher IFRs in some locations. Among all countries and territories, we found that the median IFR decreased from 0-466% (interquartile range 0-223-0-840) to 0-314% (0-143-0-551) between April 15, 2020, and Jan 1, 2021.Interpretation Estimating the IFR for global populations helps to identify relative vulnerabilities to COVID-19. Information about how IFR varies by age, time, and location informs clinical practice and non-pharmaceutical interventions like physical distancing measures, and underpins vaccine risk stratification. IFR and mortality risk form a J shape with respect to age, which previous research, such as that by Glynn and Moss in 2020, has identified to be a common pattern among infectious diseases. Understanding the experience of a population with COVID-19 mortality requires consideration for local factors; IFRs varied by a factor of more than 30 among 190 countries and territories in this analysis. In particular, the presence of elevated age-standardised IFRs in countries with well resourced health-care systems indicates that factors beyond health-care capacity are important. Potential extenuating circumstances include outbreaks among care home residents, variable burdens of severe cases, and the population prevalence of comorbid conditions that increase the severity of COVID-19 disease. During the pre-vaccine period, the estimated 33% decrease in median IFR over 8 months suggests that treatment for COVID-19 has improved over time. Estimating IFR for the pre-vaccine era provides an important baseline for describing the progression of COVID-19 mortality patterns.Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study

Introduction This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks’ intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. Results There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings

Maltreated children use more grammatical negations

Many studies reveal a strong impact of childhood maltreatment on language development, mainly resulting in shorter utterances, less rich vocabulary, or a delay in grammatical complexity. However, different theories suggest the possibility for resilience – a positive adaptation to an otherwise adverse environment – in children who experienced childhood maltreatment. Here, we investigated different measures for language development in spontaneous speech, examining whether childhood maltreatment leads to a language deficit only or whether it can also result in differences in language use due to a possible adaptation to a toxic environment. We compared spontaneous speech during therapeutic peer-play sessions of 32 maltreated and 32 non-maltreated children from the same preschool and equivalent in gender, age (2 to 5 years), home neighborhood, ethnicity, and family income. Maltreatment status was reported by formal child protection reports, and corroborated by independent social service reports. We investigated general language sophistication (i.e., vocabulary, talkativeness, mean length of utterance), as well as grammatical development (i.e., use of plurals, tense, grammatical negations). We found that maltreated and non-maltreated children showed similar sophistication across all linguistic measures, except for the use of grammatical negations. Maltreated children used twice as many grammatical negations as non-maltreated children. The use of this highly complex grammatical structure shows an advanced linguistic skill, which shows that childhood maltreatment does not necessarily lead to a language deficit. The result might indicate the development of a negativity bias in the structure of spontaneous language due to an adaptation to their experiences

Sedentary behavior among Spanish children and adolescents: findings from the ANIBES study

Background: An increase of sedentary behaviors far from the Mediterranean lifestyle is happening in spite of the impact on health. The aims of this study were to describe sedentary behaviors in children and adolescents. Methods: A representative sample of 424 Spanish children and adolescents (38% females) involved in the ANIBES study was analyzed regarding their sedentary behaviors, together with the availability of televisions, computers, and consoles by means of the HELENA sedentary behavior questionnaire. Results: For the total sample of children, 49.3% during weekdays and 84% during weekends did not meet the recommendation of less than 2 hours of screen viewing per day. The use of TV was higher during weekdays (p < 0.05) and there were significant differences between adolescents and children (16.9 vs. 25.1%, p < 0.05). The use of computer, console games and of internet for non-study reasons was higher during weekends (p < 0.001). Adolescents played more computer games and used more internet for non-study reasons than children during both weekdays and weekends (p < 0.05 and p < 0.001, respectively). The use of internet for academic reasons was lower in children (p < 0.001) than adolescents during weekends; however, no significant differences were found between sexes. In addition, more than 30% of the children and adolescents had at least one electronic device in their bedrooms. Conclusions: Spanish children and adolescents are not meeting the recommendations regarding the maximum of screen viewing (<2 h/day), especially during the weekend, for all of sedentary behaviors. Urgent strategies and intervention studies are needed to reduce sedentary behavior in young people.The ANIBES study was financially supported by a grant from Coca-Cola Iberia through an agreement with the Spanish Nutrition Foundation (FEN). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data; in the writing of the manuscript, and in the decision to publish the results

Depression, psychological distress and Internet use among community-based Australian adolescents: a cross-sectional study

BACKGROUND: There has been rapid increase in time spent using Internet as a platform for entertainment, socialising and information sourcing. This study aimed to evaluate the relationship between duration of time spent using Internet for leisure, depressive symptoms, and psychological distress among Australian adolescents. METHODS: Depressive symptoms were indicated by the youth self-report module from the Diagnostic and Statistical Manual of Mental Disorders Version IV criteria, and psychological distress was measured by Kessler Psychological Distress scale. Internet use was self-reported based on use on an average weekday, and an average weekend day. Multivariate logistic regression models were used to examine the relationship between Internet use and mental health outcomes. Models were adjusted for potential confounders: age; relative level of socio-economic disadvantage, and body mass index. RESULTS: Adolescents were aged 11-17 years (M = 14.5 years, SD = 2.04 years). Greatest time spent using internet (≥7 h a day) was significantly associated with experiencing depressive symptoms among females (OR = 2.09, 95% CI = 1.16, 3.76, p < 0.05), and high/very high levels of psychological distress for male (OR = 2.23, 95% CI = 1.36, 3.65, p < 0.01) and female (OR = 2.38, 95% CI = 1.55, 3.67, p < 0.01) adolescents. CONCLUSIONS: With current initiatives to improve health behaviours among adolescents to improve physical health outcomes such as overweight or obesity, it is imperative that the reciprocal relationship with mental health is known and included in such public health developments. Internet use may interact with mental health and therefore could be a modifiable risk factor to reach and improve mental health outcomes for this age group. Caution is advised in interpretation of findings, with some inconsistencies emerging from this evidence