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Mortality statistics are fundamental to public health decision making. Mortality varies by time and location, and its measurement is affected by well known biases that have been exacerbated during the COVID-19 pandemic. This paper aims to estimate excess mortality from the COVID-19 pandemic in 191 countries and territories, and 252 subnational units for selected countries, from Jan 1, 2020, to Dec 31, 2021.All-cause mortality reports were collected for 74 countries and territories and 266 subnational locations (including 31 locations in low-income and middle-income countries) that had reported either weekly or monthly deaths from all causes during the pandemic in 2020 and 2021, and for up to 11 year previously. In addition, we obtained excess mortality data for 12 states in India. Excess mortality over time was calculated as observed mortality, after excluding data from periods affected by late registration and anomalies such as heat waves, minus expected mortality. Six models were used to estimate expected mortality; final estimates of expected mortality were based on an ensemble of these models. Ensemble weights were based on root mean squared errors derived from an out-of-sample predictive validity test. As mortality records are incomplete worldwide, we built a statistical model that predicted the excess mortality rate for locations and periods where all-cause mortality data were not available. We used least absolute shrinkage and selection operator (LASSO) regression as a variable selection mechanism and selected 15 covariates, including both covariates pertaining to the COVID-19 pandemic, such as seroprevalence, and to background population health metrics, such as the Healthcare Access and Quality Index, with direction of effects on excess mortality concordant with a meta-analysis by the US Centers for Disease Control and Prevention. With the selected best model, we ran a prediction process using 100 draws for each covariate and 100 draws of estimated coefficients and residuals, estimated from the regressions run at the draw level using draw-level input data on both excess mortality and covariates. Mean values and 95% uncertainty intervals were then generated at national, regional, and global levels. Out-of-sample predictive validity testing was done on the basis of our final model specification.Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totalled 5·94 million worldwide, we estimate that 18·2 million (95% uncertainty interval 17·1-19·6) people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120·3 deaths (113·1-129·3) per 100 000 of the population, and excess mortality rate exceeded 300 deaths per 100 000 of the population in 21 countries. The number of excess deaths due to COVID-19 was largest in the regions of south Asia, north Africa and the Middle East, and eastern Europe. At the country level, the highest numbers of cumulative excess deaths due to COVID-19 were estimated in India (4·07 million [3·71-4·36]), the USA (1·13 million [1·08-1·18]), Russia (1·07 million [1·06-1·08]), Mexico (798 000 [741 000-867 000]), Brazil (792 000 [730 000-847 000]), Indonesia (736 000 [594 000-955 000]), and Pakistan (664 000 [498 000-847 000]). Among these countries, the excess mortality rate was highest in Russia (374·6 deaths [369·7-378·4] per 100 000) and Mexico (325·1 [301·6-353·3] per 100 000), and was similar in Brazil (186·9 [172·2-199·8] per 100 000) and the USA (179·3 [170·7-187·5] per 100 000).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.BillMelinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

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 (RWe produced a comprehensive set of global and location-specific estimates of daily and cumulative SARS-CoV-2 infections through Nov 14, 2021, using data largely from Johns Hopkins University (Baltimore, MD, USA) and national databases for reported cases, hospital admissions, and reported deaths, as well as seroprevalence surveys identified through previous reviews, SeroTracker, and governmental organisations. We corrected these data for known biases such as lags in reporting, accounted for under-reporting of deaths by use of a statistical model of the proportion of excess mortality attributable to SARS-CoV-2, and adjusted seroprevalence surveys for waning antibody sensitivity, vaccinations, and reinfection from SARS-CoV-2 escape variants. We then created an empirical database of infection-detection ratios (IDRs), infection-hospitalisation ratios (IHRs), and infection-fatality ratios (IFRs). To estimate a complete time series for each location, we developed statistical models to predict the IDR, IHR, and IFR by location and day, testing a set of predictors justified through published systematic reviews. Next, we combined three series of estimates of daily infections (cases divided by IDR, hospitalisations divided by IHR, and deaths divided by IFR), into a more robust estimate of daily infections. We then used daily infections to estimate cumulative infections and the cumulative proportion of the population with one or more infections, and we then calculated posterior estimates of cumulative IDR, IHR, and IFR using cumulative infections and the corrected data on reported cases, hospitalisations, and deaths. Finally, we converted daily infections into a historical time series of RGlobal daily SARS-CoV-2 infections fluctuated between 3 million and 17 million new infections per day between April, 2020, and October, 2021, peaking in mid-April, 2021, primarily as a result of surges in India. Between the start of the pandemic and Nov 14, 2021, there were an estimated 3·80 billion (95% uncertainty interval 3·44-4·08) total SARS-CoV-2 infections and reinfections combined, and an estimated 3·39 billion (3·08-3·63) individuals, or 43·9% (39·9-46·9) of the global population, had been infected one or more times. 1·34 billion (1·20-1·49) of these infections occurred in south Asia, the highest among the seven super-regions, although the sub-Saharan Africa super-region had the highest infection rate (79·3 per 100 population [69·0-86·4]). The high-income super-region had the fewest infections (239 million [226-252]), and southeast Asia, east Asia, and Oceania had the lowest infection rate (13·0 per 100 population [8·4-17·7]). The cumulative proportion of the population ever infected varied greatly between countries and territories, with rates higher than 70% in 40 countries and lower than 20% in 39 countries. There was no discernible relationship between RCOVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation. Our statistical approach to estimating SARS-CoV-2 infection allows estimates to be updated and disseminated rapidly on the basis of newly available data, which has and will be crucially important for timely COVID-19 research, science, and policy responses.BillMelinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

Background Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020. Methods We conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders. Findings We identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [B] 0·9 [95% uncertainty interval 0·1 to 1·8; p=0·029] for human mobility, 18·1 [7·9 to 28·3; p=0·0005] for daily SARS-CoV-2 infection) and anxiety disorders (0·9 [0·1 to 1·7; p=0·022] and 13·8 [10·7 to 17·0; p

Background National rates of COVID-19 infection and fatality have varied dramatically since the onset of the pandemic. Understanding the conditions associated with this cross-country variation is essential to guiding investment in more effective preparedness and response for future pandemics. Methods Daily SARS-CoV-2 infections and COVID-19 deaths for 177 countries and territories and 181 subnational locations were extracted from the Institute for Health Metrics and Evaluation's modelling database. Cumulative infection rate and infection-fatality ratio (IFR) were estimated and standardised for environmental, demographic, biological, and economic factors. For infections, we included factors associated with environmental seasonality (measured as the relative risk of pneumonia), population density, gross domestic product (GDP) per capita, proportion of the population living below 100 m, and a proxy for previous exposure to other betacoronaviruses. For IFR, factors were age distribution of the population, mean body-mass index (BMI), exposure to air pollution, smoking rates, the proxy for previous exposure to other betacoronaviruses, population density, age-standardised prevalence of chronic obstructive pulmonary disease and cancer, and GDP per capita. These were standardised using indirect age standardisation and multivariate linear models. Standardised national cumulative infection rates and IFRs were tested for associations with 12 pandemic preparedness indices, seven health-care capacity indicators, and ten other demographic, social, and political conditions using linear regression. To investigate pathways by which important factors might affect infections with SARS-CoV-2, we also assessed the relationship between interpersonal and governmental trust and corruption and changes in mobility patterns and COVID-19 vaccination rates. Findings The factors that explained the most variation in cumulative rates of SARS-CoV-2 infection between Jan 1, 2020, and Sept 30, 2021, included the proportion of the population living below 100 m (5·4% [4·0–7·9] of variation), GDP per capita (4·2% [1·8–6·6] of variation), and the proportion of infections attributable to seasonality (2·1% [95% uncertainty interval 1·7–2·7] of variation). Most cross-country variation in cumulative infection rates could not be explained. The factors that explained the most variation in COVID-19 IFR over the same period were the age profile of the country (46·7% [18·4–67·6] of variation), GDP per capita (3·1% [0·3–8·6] of variation), and national mean BMI (1·1% [0·2–2·6] of variation). 44·4% (29·2–61·7) of cross-national variation in IFR could not be explained. Pandemic-preparedness indices, which aim to measure health security capacity, were not meaningfully associated with standardised infection rates or IFRs. Measures of trust in the government and interpersonal trust, as well as less government corruption, had larger, statistically significant associations with lower standardised infection rates. High levels of government and interpersonal trust, as well as less government corruption, were also associated with higher COVID-19 vaccine coverage among middle-income and high-income countries where vaccine availability was more widespread, and lower corruption was associated with greater reductions in mobility. If these modelled associations were to be causal, an increase in trust of governments such that all countries had societies that attained at least the amount of trust in government or interpersonal trust measured in Denmark, which is in the 75th percentile across these spectrums, might have reduced global infections by 12·9% (5·7–17·8) for government trust and 40·3% (24·3–51·4) for interpersonal trust. Similarly, if all countries had a national BMI equal to or less than that of the 25th percentile, our analysis suggests global standardised IFR would be reduced by 11·1%. Interpretation Efforts to improve pandemic preparedness and response for the next pandemic might benefit from greater investment in risk communication and community engagement strategies to boost the confidence that individuals have in public health guidance. Our results suggest that increasing health promotion for key modifiable risks is associated with a reduction of fatalities in such a scenario. Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.