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

The state of health in Indonesia's provinces, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Analysing trends and levels of the burden of disease at the national level can mask inequalities in health-related progress in lower administrative units such as provinces and districts. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to analyse health patterns in Indonesia at the provincial level between 1990 and 2019. Long-term analyses of disease burden provide insights on Indonesia's advance to universal health coverage and its ability to meet the United Nations Sustainable Development Goals by 2030. Methods We analysed GBD 2019 estimated cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy at birth, healthy life expectancy, and risk factors for 286 causes of death, 369 causes of non-fatal health loss, and 87 risk factors by year, age, and sex for Indonesia and its 34 provinces from 1990 to 2019. To generate estimates for Indonesia at the national level, we used 138 location-years of data to estimate Indonesia-specific demographic indicators, 317 location-years of data for Indonesia-specific causes of death, 689 location-years of data for Indonesia-specific non-fatal outcomes, 250 location-years of data for Indonesia-specific risk factors, and 1641 location-years of data for Indonesia-specific covariates. For subnational estimates, we used the following source counts: 138 location-years of data to estimate Indonesia-specific demographic indicators; 5848 location-years of data for Indonesia-specific causes of death; 1534 location-years of data for Indonesia-specific non-fatal outcomes; 650 location-years of data for Indonesia-specific risk factors; and 16 016 location-years of data for Indonesia-specific covariates. We generated our GBD 2019 estimates for Indonesia by including 1 915 207 total source metadata rows, and we used 821 total citations. Findings Life expectancy for males across Indonesia increased from 62·5 years (95% uncertainty interval 61·3–63·7) to 69·4 years (67·2–71·6) between 1990 and 2019, a positive change of 6·9 years. For females during the same period, life expectancy increased from 65·7 years (64·5–66·8) to 73·5 years (71·6–75·6), an increase of 7·8 years. There were large disparities in health outcomes among provinces. In 2019, Bali had the highest life expectancy at birth for males (74·4 years, 70·90–77·9) and North Kalimantan had the highest life expectancy at birth for females (77·7 years, 74·7–81·2), whereas Papua had the lowest life expectancy at birth for males (64·5 years, 60·9–68·2) and North Maluku had the lowest life expectancy at birth for females (64·0 years, 60·7–67·3). The difference in life expectancy for males between the highest-ranked and lowest-ranked provinces was 9·9 years and the difference in life expectacy for females between the highest-ranked and lowest-ranked provinces was 13·7 years. Age-standardised death, YLL, and YLD rates also varied widely among the provinces in 2019. High systolic blood pressure, tobacco, dietary risks, high fasting plasma glucose, and high BMI were the five leading risks contributing to health loss measured as DALYs in 2019. Interpretation Our findings highlight that Indonesia faces a double burden of communicable and non-communicable diseases that varies across provinces. From 1990 to 2019, Indonesia witnessed a decline in the infectious disease burden, although communicable diseases such as tuberculosis, diarrhoeal diseases, and lower respiratory infections have remained a main source of DALYs in Indonesia. During that same period, however, all-ages death and disability rates from non-communicable diseases and exposure to their risk factors accounted for larger shares of health loss. The differences in health outcomes between the highest-performing and lowest-performing provinces have also widened since 1990. Our findings support a comprehensive process to revisit current health policies, examine the root causes of variation in the burden of disease among provinces, and strengthen programmes and policies aimed at reducing disparities across the country. Funding The Bill & Melinda Gates Foundation and the Government of Indonesia. Translation For the Bahasa Indonesia translation of the abstract see Supplementary Materials section

Estimating global, regional, and national daily and cumulative infections with SARS-CoV-2 through Nov 14, 2021: a statistical analysis

Timely, accurate, and comprehensive estimates of SARS-CoV-2 daily infection rates, cumulative infections, the proportion of the population that has been infected at least once, and the effective reproductive number (Reffective) are essential for understanding the determinants of past infection, current transmission patterns, and a population’s susceptibility to future infection with the same variant. Although several studies have estimated cumulative SARS-CoV-2 infections in select locations at specific points in time, all of these analyses have relied on biased data inputs that were not adequately corrected for. In this study, we aimed to provide a novel approach to estimating past SARS-CoV-2 daily infections, cumulative infections, and the proportion of the population infected, for 190 countries and territories from the start of the pandemic to Nov 14, 2021. This approach combines data from reported cases, reported deaths, excess deaths attributable to COVID-19, hospitalisations, and seroprevalence surveys to produce more robust estimates that minimise constituent biases

Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020???21

The full impact of the pandemic has been much greater than what is indicated by reported deaths due to COVID-19 alone. Strengthening death registration systems around the world, long understood to be crucial to global public health strategy, is necessary for improved monitoring of this pandemic and future pandemics. In addition, further research is warranted to help distinguish the proportion of excess mortality that was directly caused by SARS-CoV-2 infection and the changes in causes of death as an indirect consequence of the pandemic