Main

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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
GBD 2021 Causes of Death Collaborators*
Summary
Lancet 2024; 403: 2100–32 Background Regular, detailed reporting on population health by underlying cause of death is fundamental for public
Published Online health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide
April 3, 2024 are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important
https://doi.org/10.1016/
following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality
S0140-6736(24)00367-2
rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing
This online publication has been
corrected. The corrected version a nuanced understanding of the effect of these causes on global populations.
first appeared at thelancet.com
on April 19, 2024 Methods The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated
See Comment page 1956 mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories
*Collaborators are listed at the and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data
end of the Article from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among
Correspondence to: others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of
Prof Simon I Hay, Institute for
Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different
Health Metrics and Evaluation,
University of Washington, statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—
Seattle, WA 98195, USA with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study
[email protected] 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,
2100 www.thelancet.com Vol 403 May 18, 2024

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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.
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Introduction a limited subset of the global population. Our analysis

For more than three decades, the Global Burden of provides an opportunity to answer important epidem
Diseases, Injuries, and Risk Factors Study (GBD) has iological questions that have been at the forefront of
been systematically and comprehensively recording and global and public health discourse—eg, which causes
analysing causes of human death stratified by age, sex, have contributed to the largest increase or decrease in
and time across the world.1,2 This information has been life expectancy, which locations are experiencing greater
used to guide policy solutions, reduce modifiable risk concentrations of preventable causes of death, and how
factors, monitor and evaluate national and sub-national has COVID-19 and other pandemic-related mortality
health interventions, and ultimately improve health (OPRM) affected life expectancy and the overall fatal
recommendations at both regional and local levels.1 burden of diseases? Regional variation in many of the
Assessing trends in cause-specific mortality is essential leading causes of death remains evident in these most
to inform health policy that must continuously evolve to recent estimates, representing important opportunities
account for rapid changes to the global health landscape, for creating tailored health policy to improve disparities
such as the COVID-19 pandemic.3 Comprehensive and alleviate concentrations of mortality.
updates to levels and trends in causes of death give GBD 2021 provides an updated, comprehensive set of
insight into emerging global health challenges and can the fatal burden of disease summarised with cause-
facilitate benchmarking in the case of a new pandemic or specific mortality metrics and years-of-life-lost (YLLs)
other events that can lead to a staggering loss of life. metrics for 288 causes by age and sex across
Therefore, documenting novel changes to mortality, such 204 countries and territories from 1990 to 2021, an
as an emerging pandemic, in real time, is important. update from the previously published estimates
Causes of death are not uniformly distributed between covering 1990–2019. In this study, we present mortality
populations; rather, large variability in the leading concentrations and a decomposition analysis of life
causes often reflects important social and geographical expectancy due to different causes of death and illustrate
differences.4 These differences can include access to and the impact of causes of death on global, regional, and
quality of health care, timeliness of health system country-specific life expectancy, as well as highlighting
responsiveness, and exposure to causes that are locations that are most affected by concentrated
endemic to specific geographical locations.4 Mortality geographical mortality burden. As with previous
patterns continually evolve, as some areas become iterations of GBD, this cycle incorporates newly
successful in their reduction efforts, whereas other available data sources and improved methodological
causes persist within specific locations. The past approaches to re-estimate the entire time series,
30 years have seen improvements among many causes providing updated estimates that supersede all previous
of mortality, some of which have considerably narrowed GBD cause-of-death publications. GBD 2021 includes
in geographical range and are now concentrated within an estimation of several different models for disease
smaller areas worldwide. This change enables us to and injury outcomes. This manuscript was produced as
identify the resulting areas of concentrated mortality— part of the GBD Collaborator Network and in accordance
areas where deaths from that cause are occurring within with the GBD Protocol.5
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Research in context
Evidence before this study of mutually exclusive and collectively exhaustive causes of
The Global Burden of Diseases, Injuries, and Risk Factors Study death, this study provides policy makers with information that
(GBD) has provided regular updates on the complex patterns is essential for setting health priorities around the world.
and trends in population health around the world since the first To obtain more comprehensive insights from life expectancy, it
GBD publication in 1993. With each subsequent iteration, there is necessary to break it down into age-specific mortality, which
have been important methodological updates, new datasets is influenced by cause-specific mortality rates. We examined the
included, and an expanded list of causes, risk factors, and effect of COVID-19 and other causes of death on life expectancy
locations for which estimates of the burden of disease are by decomposing death counts into different cause-specific
produced. In 1993, mortality and years of life lost (YLLs) were mortality rates across various dimensions, including country or
reported for 107 categories of diseases that covered all possible territory, region, super-region, and five distinct time periods:
causes of death, for eight regions. In the last GBD cycle—GBD 1990–2000, 2000–2010, 2010–2019, 2019–2021, and
2019—estimates of mortality and YLLs were produced for 1990–2021. We could therefore systematically calibrate the
286 causes of death in 204 countries and territories, including COVID-19 pandemic against other causes of mortality over the
all WHO member states, and for subnational locations in period 1990–2021. Finally, our study identified several causes of
21 countries and territories, for every year from 1990 to 2019. death that exhibited increased geographical concentration over
Although many groups have reported on national-level, cause- time—ie, causes with a disproportionate impact within a specific
specific mortality and other population-health metrics, geographical area compared with the rest of the global
including the WHO World Health Statistics reports, GBD is the observations. This analysis provides policy makers important
most detailed and transparent research effort to date. Further, information on regional variation and inequalities in cause-
estimates of COVID-19-related deaths in 2020 and 2021 have specific mortality. Also new to GBD 2021, we report on
been reported by several sources, including GBD studies that 12 additional causes of death: COVID-19 and other pandemic-
have quantified excess mortality due to the pandemic within a related mortality, pulmonary arterial hypertension, and
subset of GBD locations. However, no previous publications nine cancer types—hepatoblastoma, Burkitt lymphoma, other
have quantified the effect of COVID-19 on life expectancy, while non-Hodgkin lymphoma, eye cancer, retinoblastoma, other eye
considering the full spectrum of disease mortality over the past cancers, soft tissue and other extraosseous sarcomas, malignant
three decades, across all countries and territories. This study neoplasm of bone and articular cartilage, and neuroblastoma
presents, for the first time, 288 causes of death from 1990 to and other peripheral nervous-cell tumours. Granularity of the
2021, complementary to the all-cause mortality findings estimation of deaths in children younger than 5 years was
presented in the GBD 2021 Demographics analysis. Combined, enhanced by the addition of four new age groups: 1–5 months,
these studies provide a comprehensive view of all-cause and 6–11 months, 12–23 months, and 2–4 years.
cause-specific mortality from 1990 to 2021.
Implications of all the available evidence
Added value of this study Our study provides a full analysis of causes of death worldwide
Alongside the all-cause mortality and life-expectancy and across time, alongside the changing patterns in life
assessments in companion publications for GBD 2021, this expectancy precipitated by those causes. Increasing
analysis delineates cause-specific mortality and its effect on life geographical concentration of mortality was observed for many
expectancy. This study includes a comprehensive decomposition causes of death, highlighting disparities between regions and
analysis elucidating the primary cause of death influencing life substantial differences in cause-specific contributions to life
expectancy on a global, regional, and national level. expectancy. On a global scale, this information provides an
Additionally, we present causes of death and YLLs for all opportunity to examine whether reductions in mortality were
countries and territories, providing policy makers with valuable resilient to the onset of a novel pandemic. On a regional level,
insights into variations in cause-specific mortality. This study is the estimates generated by our study provide important detail
also the first of its kind to publish 2021 estimates of COVID-19- on the evolving impact of causes of death among countries,
related deaths and YLLs for 204 countries and territories in the allowing crucial insight into differential success by geography,
context of the global burden of disease. Although other time, and cause. The comprehensive nature of GBD 2021 cause-
publications have estimated deaths due to COVID-19, those of-death estimation provides valuable opportunities to learn
deaths have not previously been compared with deaths from from mortality gains and losses, helping to accelerate progress
other causes. By modelling COVID-19 deaths within a hierarchy in reducing mortality.
Methods birth to 95 years and older; for males, females, and both
Overview sexes combined; in 204 countries and territories grouped
In GBD 2021, we produced estimates for each into 21 regions and seven super-regions; and for every
epidemiological quantity of interest for 288 causes of year from 1990 to 2021. GBD 2021 also includes
death by age-sex-location-year for 25 age groups from subnational analyses for 21 countries and territories

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(appendix 1 section 2.1). An international network of (communicable, maternal, neonatal, and nutritional See Online for appendix 1
collaborators provides, reviews, and analyses the available [CMNN] diseases; non-communicable diseases [NCDs]; For a searchable repository of
data to generate these metrics; GBD 2021 drew on the and injuries) and Level 2 disaggregates those categories cause-specific model details see
https://www.healthdata.org/
expertise of more than 11 000 collaborators from more into 22 clusters of causes, which are further disaggregated
gbd/methods-appendices-2021
than 160 countries and territories. into Level 3 and Level 4 causes. At the most detailed level,
The methods used to generate these estimates closely 288 fatal causes are estimated. For a full list of causes of
followed those for GBD 2019.6 These methods have been death by level, see appendix 1 (table S2). For GBD 2021, we
extensively peer reviewed over previous rounds of the separately report on 12 causes of death for the first time:
GBD study4,6–9 and as part of the peer-review process for COVID-19, OPRM, pulmonary arterial hypertension, and
GBD 2021. Here, we provide an overview of the methods nine cancer types: hepatoblastoma, Burkitt lymphoma,
with an emphasis on the main methodology changes other non-Hodgkin lymphoma, eye cancer, retinoblastoma,
since GBD 2019; a comprehensive description of the other eye cancers, soft tissue and other extraosseous
analytical methods for GBD 2021 is provided in sarcomas, malignant neoplasm of bone and articular
appendix 1. Detailed descriptions of analytical methods cartilage, and neuroblastoma and other peripheral
and models for each cause of death are also available in a nervous cell tumours.
searchable online tool.
The GBD 2021 cause-of-death estimates described here Data sources, processing, and assessing for For the GBD data sources see
include cause-specific mortality and the premature death completeness https://ghdx.healthdata.org/
gbd-2021/sources
metric (YLLs). We calculated YLLs as the number of The GBD 2021 cause-of-death database included data
deaths for each cause-age-sex-location-year multiplied by sources identified in previous rounds of estimation in
the standard life expectancy at each age (appendix 1 addition to 9248 new sources (appendix 1 table S5). We
section 6.3). Standard life expectancy is calculated from included multiple data types to capture the widest array
the lowest age-specific mortality rate between countries.10 of information, including vital registration and verbal
Briefly, we estimated cause-specific death rates for autopsy for all 288 causes as well as survey, census,
209 causes using the Cause of Death Ensemble model surveillance, cancer registry, police records, open-source
(CODEm), and we used alternative strategies to model databases, and minimally invasive tissue sampling. To
causes with little data, substantial changes in reporting standardise these data so that they can be compared by
over the study period, or unusual epidemiology. The cause, age, sex, location, and time, we applied a set of
modelling strategy used for all causes of death can be data processing corrections. First, deaths with insufficient
found in appendix 1 (table S10). CODEm is a modelling age data to estimate the GBD age groups or missing age
tool developed specifically for GBD that assesses the out- and sex data underwent age and sex splitting to assign
of-sample predictive validity of different statistical models GBD age groups as well as sex (appendix 1 section 3.5).
and covariate permutations and then combines the Additionally, garbage codes, which are non-specific,
results from those assessments to produce cause-specific implausible, or intermediate, rather than underlying
estimates of the burden of mortality. Methodological cause of death codes from the International Classification
improvements for cause-of-death estimates in the present of Diseases, were redistributed to appropriate targets to
round of estimation focused on several key areas. First, assign the underlying cause of death.11 We excluded data
cause-of-death data were updated to include age data for sources with more than 50% of all deaths assigned to
the following age groups younger than 5 years: major garbage codes (class 1 or class 2 garbage codes) in
1–5 months, 6–11 months, 12–23 months, and 2–4 years. a given year for a specific location (location-year) to
Second, we implemented enhanced methods to account mitigate the potential for bias from these sources
for stochastic variation in cause-of-death data and improve (appendix 1 section 3.7). For GBD 2021, we established a
the estimation of small cause fractions present in less buffer system so that location-years that were included in
common causes of death. Third, we added 199 new the previous GBD cycle would not be dropped from the
country-years of vital registration cause-of-death data, current cycle as long as less than 55% of all deaths were
5 country-years of surveillance data, 21 country-years of assigned to major garbage codes. This 5% buffer ensured
verbal autopsy data, and 94 country-years of other data greater consistency in data source inclusion from one
types. Lastly, we incorporated COVID-19 and OPRM, cycle to the next.
which includes excess mortality associated with the Assessing data completeness illustrates the coverage
COVID-19 pandemic, excluding deaths from COVID-19, from a data source on overall mortality for the country.
lower respiratory infections, measles, malaria, and Vital registration and verbal autopsy data
pertussis. completeness—a source-specific estimate of the
percentage of total cause-specific deaths that are reported
The GBD disease and injury hierarchy in a given location and year—was assessed by location-
GBD classifies diseases and injuries into a hierarchy with year, and sources with less than 50% completeness were
four levels that include both fatal and non-fatal causes. excluded. We excluded 142 country-years of data because
Level 1 causes include three broad aggregate categories of completeness. As with garbage codes, we used a

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5% buffer so that sources included in the previous GBD The counterfactual estimates the number of deaths if
cycle would not be excluded from the current cycle if infection detection rates were at the highest observed
they had at least 45% completeness, allowing us to retain value for each location-year. Using the ratio of
24 country-years that had previously been dropped. We counterfactual over estimated excess deaths and the ratio
then multiplied the estimated all-cause mortality for of reported COVID-19 deaths over excess deaths, we
each age-sex-location-year by the cause fraction for the calculated the ratio of total COVID-19 deaths over
corresponding age-sex-location-year to adjust all reported COVID-19 deaths and multiplied this figure by
included sources to 100% completeness. Verbal autopsy the number of reported COVID-19 deaths for our final
and vital registration data availability, completeness, and estimates of COVID-19 deaths.12
quality rating for each location-year are available in To account for increases in excess mortality in 2020 and
appendix 1 (section 3), as well as full details on all data 2021 that could not be attributed to particular causes, we
processing corrections. introduced a residual cause, OPRM. We identified four
causes of death—lower respiratory infections, measles,
Improvements in GBD 2021 to cause of death data malaria, and pertussis—as related to the COVID-19
processing and estimation pandemic and having reliable enough estimates to not
Adjustments for stochastic variation contribute to OPRM. Thus, we calculated OPRM as the
In GBD 2021, we made two primary improvements to the difference between excess mortality and the sum of
methods used to reduce stochastic variation, most deaths due to COVID-19 and these four causes.12
affecting causes of death with small sample sizes. First,
we updated the Bayesian algorithm used in the noise Presentation of cause-specific mortality estimates
reduction of these data to improve the preservation of Cause-specific mortality estimates for 2021 are given in
real trends in data with large sample sizes, and imparted death counts and age-standardised rates per
additional information from regional trends for data with 100 000 population, calculated using the GBD standard-
small sample sizes. Second, the non-zero floor, a method population structure.10 For changes over time, we present
that addresses distorted data shapes and nonsensical percentage changes over the period 1990–2021, and
trends caused by small numbers when transformed to annualised rates of change as the difference in the
log space, was updated to be time-invariant and natural log of the values at the start and end of the time
independent of demographic inputs. The full details of interval divided by the number of years in the interval.
these two key improvements, as well as other We computed uncertainty intervals (UIs) for all metrics
improvements that address stochastic variation, can be using the mean estimate across 1000 draws (appendix 1
found in appendix 1 (section 3.14). sections 2–3), and 95% UIs are given as the 2·5th and
97·5th percentiles of that distribution.
COVID-19 and OPRM estimation
We derived COVID-19 and OPRM estimates from an Life-expectancy decomposition
analysis of the overall excess mortality due to the The objective of life-expectancy decomposition is to
COVID-19 pandemic from January 1, 2020, to analyse the difference in life expectancy by age and
December 31, 2021. Full details of the estimation of location, quantifying contributions from specific causes
excess mortality, COVID-19 deaths, and OPRM are (appendix 1 section 7). We examined temporal trends in
provided in appendix 1 (section 5). To estimate excess causes over continuous time periods across different
mortality, we first developed a database of all-cause locations. We aimed to identify the effect of causes
mortality by week and month after accounting for of death on life expectancy by using three main
reporting lags, anomalies such as heat waves, and under- decomposition steps. For this study, we investigated the
registration of deaths. Next, we developed an ensemble top-20 Level 2 and Level 3 GBD causes contributing to
model to predict expected deaths in the absence of the change in life expectancy. The remaining causes were
COVID-19 pandemic for the years 2020 and 2021. In then combined as “other communicable and maternal
location and time combinations with data used for these disorders” or “other NCDs”. The first step involved
models, we estimated excess mortality as observed decomposing the difference in life expectancy by age.
mortality minus expected mortality. To estimate excess We calculated age-specific contributions to understand
mortality for location-years without data, we developed a the variation in life expectancy across different
statistical model to directly predict the excess mortality age groups. In the second step, each age-specific
due to COVID-19, using covariates that pertained to both contribution was further decomposed into cause-age-
the COVID-19 pandemic and background population- specific contributions. This analysis allowed for the
health-related metrics at the population level before identification of the specific causes of death that
SARS-CoV-2 emerged. Uncertainty was propagated contributed to the differences in life expectancy within
through each step of this estimation procedure.12 each age group. Finally, we aggregated the cause-age-
To produce the final estimates of COVID-19 deaths specific contributions across age groups to produce
used in GBD 2021, we used a counterfactual approach. cause-specific contributions to the overall difference

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in life expectancy. This aggregation provided a variation have data that are less centred around the
comprehensive understanding of how different causes mean and indicate a greater likelihood of a concentrated
of death contributed to the observed variations in life cause.
expectancy. By applying this decomposition approach,
we gain insights into the relative effect of different Mortality concentration
causes of death on changes in life expectancy by age and To identify concentrations of mortality—geographical
location. locations or groups of locations with populations that
are disproportionately affected by a particular cause—
Calculation of mortality concentration we first calculated the total number of all-age, both-sex
Concentrated causes in GBD refer to causes that exhibit a deaths in 2021 by cause in each of the 811 subnational
disproportionate impact in a specific geographical subset locations and sorted these locations by number of
of the data compared with the rest of the global deaths in descending order. We then calculated the
observations. In GBD 2021, we used two different methods cumulative percentage of deaths by dividing location-
to identify these concentrated causes: coefficient of specific cumulative deaths by the number of global
variation and mortality concentration. deaths for each cause. When the cumulative percentage
reached or exceeded 90% for a given cause, we divided
Coefficient of variation the population of the geographical subset included in
For each GBD cause, we calculated a coefficient of that cumulative percentage by the total global population
variation using standard statistical methods. This in 2021, using population estimates from the GBD
measure assesses the variability of a population relative population model described in previous publications.10,12
to its mean.13 The observations considered for this This identification of geographical subsets that contain
calculation were national, age-standardised, both-sex at least 90% of deaths from a given cause but represent
mortality rates, using the mean mortality rate between a comparatively small share of the global population
2019 and 2021. Causes with larger coefficients of was used to identify potential inequalities in the
Leading causes 1990 Age-standardised rate Leading causes 2019 Age-standardised rate Leading causes 2021 Age-standardised rate
of deaths per 100000, of deaths per 100000, of deaths per 100000,
1990 2019 2021
1 Ischaemic heart disease 158·9 (147·4 to 165·4) 1 Ischaemic heart disease 110·9 (102·5 to 116·9) 1 Ischaemic heart disease 108·7 (99·8 to 115·6)
2 Stroke 144·3 (134·0 to 152·3) 2 Stroke 89·3 (81·6 to 95·6) 2 COVID-19 94·0 (89·2 to 100·0)
3 COPD 71·9 (64·6 to 77·5) 3 COPD 46·1 (42·0 to 49·8) 3 Stroke 87·4 (79·5 to 94·4)
4 Lower respiratory infections 61·8 (57·0 to 66·8) 4 Lower respiratory infections 34·7 (31·5 to 37·5) 4 COPD 45·2 (40·7 to 49·8)
5 Diarrhoeal diseases 60·6 (46·7 to 79·6) 5 Neonatal disorders 30·7 (26·8 to 35·3) 5 Other pandemic-related death 32·3 (24·8 to 43·3)
6 Neonatal disorders 46·0 (43·5 to 48·9) 6 Alzheimer's and other dementias 25·0 (6·2 to 65·0) 6 Neonatal disorders 29·6 (25·3 to 34·4)
7 Tuberculosis 40·0 (34·1 to 44·6) 7 Lung cancer 23·7 (21·8 to 25·8) 7 Lower respiratory infections 28·7 (26·0 to 31·1)
8 Lung cancer 27·6 (26·1 to 29·0) 8 Diabetes 19·8 (18·5 to 20·8) 8 Alzheimer's and other dementias 25·2 (6·4 to 65·6)
9 Alzheimer's and other dementias 25·1 (6·0 to 66·1) 9 Chronic kidney disease 18·6 (16·9 to 19·8) 9 Lung cancer 23·5 (21·2 to 25·9)
10 Cirrhosis 24·4 (22·3 to 27·5) 10 Diarrhoeal diseases 17·1 (12·4 to 23·2) 10 Diabetes 19·6 (18·2 to 20·8)
11 Stomach cancer 22·0 (20·1 to 24·0) 11 Cirrhosis 17·1 (15·9 to 18·5) 11 Chronic kidney disease 18·5 (16·7 to 19·9)
12 Road injuries 21·8 (20·9 to 22·8) 12 Hypertensive heart disease 16·9 (14·1 to 18·6) 12 Cirrhosis liver 16·6 (15·2 to 18·2)
13 Hypertensive heart disease 20·9 (17·1 to 23·3) 13 Road injuries 15·1 (14·2 to 16·0) 13 Hypertensive heart disease 16·3 (13·7 to 18·1)
14 Diabetes 18·2 (17·0 to 19·1) 14 Tuberculosis 14·9 (13·7 to 16·4) 14 Diarrheal diseases 15·4 (10·9 to 20·9)
15 Colorectal cancer 15·6 (14·5 to 16·3) 15 Colorectal cancer 12·6 (11·6 to 13·4) 15 Road injuries 14·6 (13·6 to 15·6)
16 Congenital defects 15·2 (9·6 to 19·7) 16 Stomach cancer 11·5 (9·9 to 12·9) 16 Tuberculosis 14·0 (12·6 to 15·8)
17 Self-harm 14·9 (12·8 to 15·8) 17 Falls 10·3 (8·8 to 11·2) 17 Colorectal cancer 12·4 (11·2 to 13·4)
18 Chronic kidney disease 14·9 (13·7 to 16·4) 18 HIV/AIDS 9·8 (9·0 to 11·0) 18 Stomach cancer 11·2 (9·6 to 12·6)
19 Malaria 12·5 (6·1 to 26·0) 19 Malaria 9·3 (3·7 to 18·3) 19 Malaria 10·5 (3·9 to 21·4)
20 Measles 11·0 (3·9 to 22·6) 20 Self-harm 9·2 (8·6 to 9·7) 20 Falls 9·9 (8·5 to 10·8)
21 Falls 10·9 (9·8 to 11·8) 21 Congenital defects 8·9 (7·7 to 10·9) 21 Self-harm 9·0 (8·3 to 9·6)
34 HIV/AIDS 5·9 (4·5 to 7·8) 67 Measles 1·4 (0·5 to 3·0) 22 HIV/AIDS 8·7 (8·1 to 9·6)
Non-communicable diseases
Communicable, maternal, neonatal, and nutritional causes
Injuries
Figure 1: Leading Level 3 causes of global deaths and age-standardised death rate per 100 000 population for males and females combined, 1990, 2019, and 2021
Figure shows the 20 leading causes of death in descending order. Causes are connected by lines between time periods; solid lines represent an increase or lateral shift in ranking and dashed lines are
decreases in rank. COPD=chronic obstructive pulmonary disease. Lung cancer=tracheal, bronchus, and lung cancer.

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110·9
109·4
120 108·7
94·0
100 89·3 88·3 87·4
Mortality rate per 100 000 population
80
25·0 24·9 25·2

58·7
60
46·1 45·5 45·2
32·3
40 34·7
30·4 28·7 30·7 30·3 29·6
23·7 23·5 23·5
16·7 19·8 19·7 19·6
20
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Figure 2: Age-standardised mortality rate per 100 000 population for the ten leading Level 3 causes of death globally, 2019–21
Whisker plot in which the y-axis represents the age-standardised mortality rate and the x-axis represents a selected cause-year. Causes are arranged from highest to
lowest age-standardised mortality rate, with each cause assigned a distinct colour for identification. The whiskers represent the 95% uncertainty interval.
COPD=chronic obstructive pulmonary disease. OPRM=other pandemic-related mortality.
incidence of mortality between locations and Role of the funding source

populations. In addition to identifying these The funder of this study had no role in study design, data
concentrations of mortality in 2021, we repeated this collection, data analysis, data interpretation, or the
same analysis for 1990. By comparing the respective writing of the report.
proportions of affected global population in these two
years, we were able to differentiate causes that showed Results
increased, decreased, or unchanged concentrations of Estimates described in the Article are viewable in
See Online for appendix 2 mortality. The causes highlighted in this study were appendix 2. Detailed results for each cause of death in
To view and download those characterised by an age-standardised mortality the analysis are available in downloadable form through
estimates from the GBD Results rate greater than 0·5 per 100 000 population. The the GBD Results tool and via visual exploration through
tool see https://www.vizhub.
purpose of presenting mortality concentrations is to the online tool GBD Compare. Summaries of results for
healthdata.org/gbd-results
illustrate causes that are disproportionately affecting each cause of death included in the analysis are available
To explore estimates of health
burden using GBD Compare see specific populations, when previously that cause affected online.
https://www.vizhub.healthdata. large swaths of the population. Thus, we did not
org/gbd-compare calculate the mortality concentration for causes that are Global causes of death
For summaries of results for endemic to certain regions, as the mortality rate is From 1990 to 2019, the annual rate of change in global
each cause of death see https:// already known to be concentrated among specific parts deaths from all causes ranged from –0·9% (95% UI
www.healthdata.org/research-
analysis/diseases-injuries-risks/
of the global population. We excluded two endemic –2·7 to 0·8) to 2·4% (0·1 to 4·7; appendix 2 figure S1).
factsheets causes, Ebola virus disease and Chagas disease, from The corresponding annual rates of change in the global
this calculation. age-standardised mortality rate ranged from –3·3%
(–5·0 to –1·6) to 0·4% (–1·9 to 2·5). In 2020, however,
GBD research and reporting practices the total number of deaths worldwide increased
This research is compliant with the Guidelines for by 10·8% (6·4 to 15·4) compared with 2019, from
Accurate and Transparent Health Estimates Reporting 57·0 million deaths (54·9 to 59·5) in 2019 to
recommendations (GATHER; appendix 1 table S4).14 63·1 million deaths (60·6 to 65·9) in 2020. This trend
Software packages used in the cause-of-death analysis for persisted in 2021, with an increase of 7·5% (3·1 to 12·4)
GBD 2021 were Python (version 3.10.4), Stata relative to 2020, to 67·9 million (65·0 to 70·8) deaths.
For the statistical code see
http://ghdx.healthdata.org/gbd- (version 13.1), and R (version 4.2.1). Statistical code used The age-standardised mortality rate followed a similar
2021/code for GBD estimation is publicly available online. pattern, increasing by 8·1% (3·9 to 12·4) in 2020 and

Articles
Global Central Europe, High income Latin America North Africa and South Asia Southeast Asia, Sub-Saharan
eastern Europe, and Caribbean Middle East east Asia, and Africa
and central Asia Oceania
2020
1
Cause Ischaemic heart Ischaemic heart Ischaemic heart COVID-19 Ischaemic heart Ischaemic heart Stroke COVID-19
disease disease disease disease disease
Age-standardised rate (per 109·4 215·3 51·4 133.7 205·2 150·3 142·8 158·9
100 000 population) (100·7–116·1) (199·2–225·7) (45·1–54·6) (121·5–145·3) (182·7–225·6) (139·7–162·2) (123·9–159·8) (148·5–170·0)
Number 8 840 000 1 410 000 1 290 000 799 000 760 000 1 960 000 3 460 000 659 000
(8 180 000– (1 310 000– (1 110 000– (725 000– (681 000– (1 820 000– (3 030 000– (615 000–
9 360 000) 1 480 000) 1 390 000) 869 000) 838 000 2 110 000) 3 880 000) 706 000)
2
Cause Stroke Stroke COVID-19 Ischaemic heart COVID-19 Chronic Ischaemic heart Stroke
disease obstructive disease
pulmonary
disease
Age-standardised rate (per 88·3 110·7 41·8 84·3 123·9 104·1 110·8 126·2
100 000 population) (80·2–95·0) (102·7–115·6) (40·8–42·8) (77·2–89·4) (106·8–137·1) (92·3–117·0) (97·3–124·6) (113·4–140·4)
Number 7 140 000 726 000 930 000 496 000 483 000 1 230 000 2 570 000 481 000
(6 500 000– (675 000– (908 000– (454 000– (415 000– (1 090 000– (2 260 000– (432 000–
7 680 000) 758 000) 952 000) 525 000) 537 000) 1 370 000) 2 880 000) 538 000)
3
Cause COVID-19 COVID-19 Stroke Stroke Stroke COVID-19 Chronic Ischaemic heart
obstructive disease
pulmonary disease
100 000 population) (55·8–62·4) (64·1–81·7) (24·7–31·2) (43·4–50·5) (92·0–115·6) (95·0–108·5) (57·4–77·0) (83·1–103·0)
Number 4 800 000 467 000 764 000 278 000 370 000 1 320 000 1 500 000 346 000
(4 560 000– (411 000– (636 000– (255 000– (329 000– (1 230 000– (1 290 000– (309 000–
5 110 000) 523 000) 830 000) 296 000) 414 000) 1 400 000) 1 730 000) 388 000)
4
Cause Chronic Other COVID-19 Alzheimer’s Diabetes mellitus Hypertensive Stroke Tracheal, Lower
obstructive pandemic-related disease and other heart disease bronchus, and respiratory
pulmonary outcomes dementias lung cancer infections
disease
100 000 population) (41·2–49·6) (32·9–51·9) (6·74–65·1) (33·9–38·9) (32·0–46·7) (75·7–90·4) (29·0–41·0) (77·8–98·2)
Number 3 650 000 264 000 774 000 217 000 138 000 1 060 000 938 000 588 000
(3 320 000– (212 000– (198 000– (202 000– (110 000– (969 000– (783 000– (494 000–
3 970 000 333 000) 1 900 000) 231 000) 160 000) 1 150 000) 1 110 000) 686 000)
5
Cause Lower Tracheal, Tracheal, Lower Chronic kidney Diarrhoeal Alzheimer’s Malaria
respiratory bronchus, and bronchus, and respiratory disease diseases disease and other
infections lung cancer lung cancer infections dementias
100 000 population) (27·7–32·9) (24·4–26·5) (23·8–27·0) (29·6–35·1) (33·3–42·4) (32·0–79·4) (6·76–74·8) (22·6–145·0)
Number 2 280 000 168 000 581 000 187 000 142 000 591 000 562 000 713 000
(2 080 000– (161 000– (526 000– (169 000– (125 000– (381 000– (136 000– (251 000–
2 460 000) 174 000) 610 000) 200 000) 159 000) 940 000) 1 490 000) 1 480 000)
6
Cause Neonatal Cirrhosis and Chronic Chronic kidney Other COVID-19 Neonatal Lower respiratory Tuberculosis
disorders other chronic obstructive disease pandemic- disorders infections
liver diseases pulmonary related outcomes
disease
100 000 population) (26·3–35·0) (21·7–23·3) (16·9–20·3) (28·3–33·1) (11·4–52·0) (37·2–51·6) (18·9–23·6) (56·7–77·8)
Number 1 910 000 131 000 490 000 184 000 121 000 672 000 424 000 378 000
(1 650 000– (127 000– (424 000– (169 000– (46 500– (571 000– (378 000– (313 000–
2 200 000) 136 000) 522 000) 197 000) 207 000) 792 000) 469 000) 442 000)
(Table 1 continues on next page)

Articles
(Continued from previous page)
7
Cause Alzheimer’s Alzheimer’s Colon and rectum Chronic Diabetes mellitus Lower respiratory Hypertensive HIV/AIDS
disease and disease and cancer obstructive infections heart disease
other dementias other dementias pulmonary
disease
100 000 population) (6·16–65·0) (4·88–55·3) (13·2–15·6) (22·5–26·5) (26·4–32·3) (35·8–44·7) (14·1–24·8) (59·9–73·2)
Number 1 890 000 136 000 344 000 144 000 113 000 522 000 459 000 539 000
(470 000– (32 100– (300 000– (130 000– (101 000– (465 000– (320 000– (487 000–
4 940 000) 362 000) 367 000) 152 000) 124 000) 582 000) 562 000) 612 000)
8
Cause Tracheal, Lower Chronic kidney Interpersonal Chronic Tuberculosis Stomach cancer Diarrhoeal
bronchus, and respiratory disease violence obstructive diseases
lung cancer infections pulmonary
disease
100 000 population) (21·3–25·8) (18·3–20·8) (12·1–15·3) (22·4–24·8) (23·9–29·7) (30·1–40·1) (14·2–22·0) (36·2–79·4)
Number 1 970 000 96 200 364 000 147 000 92 400 509 000 491 000 452 000
(1 780 000– (91 200– (307 000– (140 000– (82 500– (450 000– (380 000– (324 000–
2 160 000) 101 000) 399 000) 155 000) 102 000) 597 000) 589 000) 588 000)
9
Cause Diabetes Cardiomyopathy Lower respiratory Other COVID-19 Alzheimer’s Diabetes mellitus Road injuries Other COVID-19
mellitus and myocarditis infections pandemic- disease and other pandemic-
related dementias related
outcomes outcomes
100 000 population) (18·4–20·9) (17·9–20·4) (11·8–14·6) (10·3–33·3) (6·30–67·6) (29·8–36·0) (13·9–17·6) (31·3–70·8)
Number 1 630 000 113 000 361 000 125 000 73 600 419 000 380 000 245 000
(1 520 000– (105 000– (306 000– (59 600– (17 900– (378 000– (335 000– (159 000–
1 720 000) 121 000) 390 000) 199 000) 198 000) 457 000) 429 000) 339 000)
10
Cause Chronic kidney Colon and Self-harm Alzheimer’s Lower respiratory Other COVID-19 Chronic kidney Neonatal
disease rectum cancer disease and infections pandemic-related disease disorders
other dementias outcomes
100 000 population) (16·9–19·9) (17·6–19·4) (10·5–11·2) (5·14–53·8) (22·4–28·5) (18·5–39·5) (13·4–17·0) (42·1–59·2)
Number 1 500 000 122 000 149 000 119 000 103 000 370 000 376 000 889 000
(1 360 000– (115 000– (142 000– (29 200– (91 000– (246 000– (333 000– (749 000–
1 610 000) 127 000) 153 000) 308 000) 116 000) 514 000) 420 000) 1 050 000)
2021
1
Cause Ischaemic heart Ischaemic heart Ischaemic heart COVID-19 Ischaemic heart COVID-19 Stroke COVID-19
disease disease disease disease
100 000 population) (99·8–115·6) (196·1–229·1) (44·9–54·2) (182·1–211·4) (179·7–225·9) (150·4–164·4) (123·2–159·7) (250·1–290·7)
Number 8 990 000 1 410 000 1 310 000 1 200 000 769 000 2 060 000 3 550 000 1 150 000
(8 290 000– (1 290 000– (1 120 000– (1 110 000– (679 000– (1 980 000– (3 100 000– (1 060 000–
9 550 000) 1 510 000) 1 400 000) 1 290 000) 863 000) 2 170 000) 4 020 000) 1 240 000)
2
Cause COVID-19 COVID-19 COVID-19 Ischaemic heart COVID-19 Ischaemic heart Ischaemic heart Stroke
disease disease disease
100 000 population) (89·2–100·0) (150·6–186·1) (47·4–48·8) (75·9–90·6) (150·3–191·5) (136·4–161·8) (94·9–124·6) (111·8–138·6)
Number 7 890 000 1 100 000 1 070 000 504 000 698 000 1 990 000 2 660 000 484 000
(7 490 000– (982 000– (1 060 000– (457 000– (608 000– (1 820 000– (2 290 000– (432 000–
8 400 000) 1 210 000) 1 090 000) 545 000) 777 000) 2 160 000) 3 000 000) 544 000)

Articles
3
Cause Stroke Stroke Stroke Stroke Stroke Chronic Chronic Other COVID-19
obstructive obstructive pandemic-
pulmonary pulmonary disease related
disease outcomes
100 000 population) (79·5–94·4) (101·6–116·6) (24·5–30·9) (42·3–50·2) (89·2–114·4) (90·3–114·2) (56·2–77·7) (87·7–159.5)
Number 7 250 000 725 000 771 000 279 000 372 000 1 230 000 1 560 000 584 000
(6 600 000– (671 000– (641 000– (254 000– (325 000– (1 100 000– (1 310 000– (418 000–
7 820 000) 770 000) 838 000) 301 000) 421 000) 1 380 000) 1 820 000) 757 000)
4
Cause Chronic Other COVID-19 Alzheimer’s Other COVID-19 Other COVID-19 Stroke Tracheal, Ischaemic heart
obstructive pandemic-related disease and other pandemic- pandemic- bronchus, and disease
pulmonary outcomes dementias related related outcomes lung cancer
disease outcomes
100 000 population) (40·7–49·8) (34·8–68·7) (6·74–64·8) (22·5–58·4) (34·4–100·6) (74·2–89·6) (28·8–41·1) (83·3–103·5)
Number 3 720 000 321 000 792 000 236 000 265 000 1 070 000 970 000 352 000
(3 360 000– (223 000– (203 000– (135 000– (139 000– (968 000– (800 000– (316 000–
4 090 000) 438 000) 1 940 000) 355 000) 414 000) 1 170 000) 1 150 000) 396 000)
5
Cause Other COVID-19 Tracheal, Tracheal, Diabetes mellitus Hypertensive Other COVID-19 Alzheimer’s Lower
pandemic- bronchus, and bronchus, and heart disease pandemic-related disease and other respiratory
related lung cancer lung cancer outcomes dementias infections
outcomes
100 000 population) (24·8–43·3) (23·7–26·6) (23·8–27·0) (33·2–39·3) (31·3–46·3) (50·4–77·2) (7·41–78·6) (75·3–95·0)
Number 2 690 000 167 000 591 000 221 000 138 000 838 000 608 000 563 000
(2 060 000– (157 000– (537 000– (202 000– (109 000– (674 000– (155 000– (472 000–
3 610 000) 176 000) 620 000) 239 000) 162 000) 1 020 000) 1 670 000) 655 000)
6
Cause Neonatal Cirrhosis and Chronic Chronic kidney Chronic kidney Diarrhoeal COVID-19 Malaria
disorders other chronic obstructive disease disease diseases
liver diseases pulmonary
disease
100 000 population) (25·3–34·4) (21·0–23·5) (16·8–20·2) (27·8–33·5) (32·7–42·8) (30·2–75·7) (16·3–37·2) (23·6–136·7)
Number 1 830 000 131 000 495 000 187 000 145 000 573 000 606 000 704 000
(1 570 000– (123 000– (428 000– (170 000– (126 000– (372 000– (425 000– (265 000–
2 130 000) 138 000) 527 000) 204 000) 164 000) 908 000) 974 000) 1 400 000)
7
Cause Lower Alzheimer’s Colon and rectum Lower Diabetes mellitus Neonatal Lower respiratory Tuberculosis
respiratory disease and cancer respiratory disorders infections
infections other dementias infections
100 000 population) (26·0–31·1) (4·94–55·6) (13·1–15·5) (27·0–33·3) (25·9–32·5) (35·6–50·2) (18·6–23·4) (56·1–76·9)
Number 2 180 000 137 000 348 000 177 000 116 000 636 000 431 000 373 000
(1 980 000– (32 500– (304 000– (157 000– (102 000– (538 000– (384 000– (313 000–
2 360 000) 370 000) 372 000) 194 000) 129 000) 760 000) 482 000) 439 000)
8
Cause Alzheimer’s Cardiomyopathy Chronic kidney Chronic Chronic Lower respiratory Hypertensive HIV/AIDS
disease and and myocarditis disease obstructive obstructive infections heart disease
other dementias pulmonary pulmonary
disease disease
100 000 population) (6·36–65·6) (17·5–20·7) (12·0–15·1) (22·1–26·4) (23·2–29·6) (34·2–44·6) (14·0–24·3) (55·8–68·5)
Number 1 960 000 112 000 368 000 145 000 92 700 516 000 470 000 515 000
(499 000– (103 000– (310 000– (130 000– (82 000– (451 000– (333 000– (467 000–
5 120 000) 122 000) 402 000) 156 000) 104 000) 584 000) 575 000) 583 000)

Articles
9
Cause Tracheal, Colon and Lower respiratory Interpersonal Alzheimer’s Tuberculosis Stomach cancer Diarrhoeal
bronchus, and rectum cancer infections violence disease and other diseases
lung cancer dementias
100 000 population) (21·2–25·9) (17·4–19·6) (10·2–12·7) (21·7–24·8) (6·22–66·8) (29·0–39·1) (14·4–21·8) (33·9–76·7)
Number 2 020 000 122 000 321 000 147 000 73 900 501 000 500 000 434 000
(1 820 000– (115 000– (267 000– (137 000– (18 000– (441 000– (397 000– (310 000–
2 220 000) 129 000) 348 000) 156 000) 198 000) 587 000) 605 000) 570 000)
10
Cause Diabetes Lower Self-harm Alzheimer’s Cirrhosis and Diabetes mellitus Road injuries Neonatal
mellitus respiratory disease and other chronic disorders
infections other dementias liver diseases
100 000 population) (18·2–20·8) (15·4–17·7) (10·4–11·0) (5·18–54·3) (20·2–26·8) (29·5–36·1) (13·6–17·5) (40·3–58·1)
Number 1 660 000 82 800 148 000 121 000 99 600 426 000 379 000 873 000
(1 540 000– (77 800–87 500) (141 000– (30 300– (86 100– (383 000– (331 000– (724 000–
1 760 000) 152 000) 317 000) 116 000) 468 000) 430 000) 1 040 000)
Table 1: Number of deaths and age-standardised mortality rates for ten leading Level 3 causes of death in 2020 and 2021, globally and by super-region, for all ages and males and females
combined
an additional 5·2% (1·0 to 9·7) in 2021. In 2020 and of death due to COVID-19 were highly variable among
2021, deaths from COVID-19 and OPRM changed the GBD super-regions (table 1). In 2021, the rankings from
pattern of mortality for the leading causes of age- highest to lowest were sub-Saharan Africa (271·0 deaths
standardised death (figures 1, 2; table 1). At Level 3 of [250·1–290·7] per 100 000 population); Latin America
the GBD cause-classification hierarchy, the rankings of and the Caribbean (195·4 deaths [182·1–211·4] per
the four causes of death with the highest age- 100 000 population); north Africa and the Middle East
standardised mortality rates were the same in 2019 as (172·4 deaths [150·3–191·5] per 100 000 population);
they were in 1990, with each showing a steady decline central Europe, eastern Europe, and central Asia
in its age-standardised death rate (figure 1). These (168·8 deaths [150·6–186·1] per 100 000 population);
causes were, in descending order, ischaemic heart south Asia (156·5 deaths [150·4–164·4] per
disease, stroke, chronic obstructive pulmonary disease, 100 000 population); high income (48·1 deaths
and lower respiratory infections. In 2021, however, [47·4–48·8] per 100 000 population); and southeast Asia,
COVID-19 replaced stroke as the second leading cause east Asia, and Oceania (23·2 deaths [16·3–37·2] per
of age-standardised death globally (with 94·0 deaths 100 000 population; table 1).
[95% UI 89·2 to 100·0] per 100 000 population), with Deaths from both COVID-19 and OPRM also varied
stroke becoming the third leading cause. Additionally, substantially by age, with older ages being
OPRM—which includes excess mortality associated disproportionately affected (table 2). Individuals aged
with the pandemic, excluding COVID-19, lower 70–74 years had the highest number of deaths from both
respiratory infections, measles, and pertussis causes— COVID-19 and OPRM in 2020 and again in 2021. The
emerged as the fifth leading cause of age-standardised highest percentage of total deaths from COVID-19 was
deaths in 2021; lower respiratory infections decreased found in those aged 40–44 years, whereas the highest
from the fourth to the seventh leading cause. The effect mortality rate occurred in those aged 95 years and older.
of COVID-19 on age-standardised mortality was similar Death rates from OPRM were high among older age
to that of chronic obstructive pulmonary disease in 2020 groups and among the youngest ages, with a rate of
but increased by 60·2% (53·1 to 67·6) in 2021, 141·2 deaths (95% UI 58·0–277·5) per 100 000 population
becoming similar to that of stroke and ischaemic heart for infants aged 0–6 days, and 77·3 deaths (44·0–118·0)
disease (figure 2; table 1). per 100 000 population in infants aged 7–27 days. At a
global scale, COVID-19 deaths and OPRM were slightly
COVID-19 and OPRM higher for males than for females in most age groups
Our estimates show that 4·80 million (95% UI 4·56–5·11) in 2021 (appendix 2 figure S5). Exceptions to this trend
deaths due to COVID-19 occurred globally in 2020, and include those aged 90–94 years and those aged 95 years
7·89 million (7·49–8·40) in 2021. Age-standardised rates and older (appendix 2 figure S5).

Articles
Deaths Deaths per 100 000 population Percentage of total deaths

COVID-19 COVID-19 Other Other COVID-19 COVID-19 Other Other COVID-19 COVID-19 Other Other
2020 2021 COVID-19 COVID-19 2020 2021 COVID-19 COVID-19 2020 2021 COVID-19 COVID-19
pandemic- pandemic- pandemic- pandemic- pandemic- pandemic-
related related related related related related
outcomes outcomes outcomes outcomes outcomes outcomes
2020 2021 2020 2021 2020 2021
Early neonatal 0 1 3518 3462 0·0 <0·1 141·4 141·2 0·0% <0·1% 0·2% 0·2%
Late neonatal 3 5 5069 5641 <0·1 0·1 68·5 77·3 <0·1% <0·1% 1·1% 1·3%
1−5 months 170 287 24269 26 647 0·3 0·5 44·4 49·6 <0·1% <0·1% 3·1% 3·6%
6−11 months 234 394 20 478 30 883 0·4 0·6 31·7 48·9 <0·1% 0·1% 3·5% 5·5%
12–23 months 998 1644 19 042 30 550 0·8 1·3 14·5 23·8 0·2% 0·3% 3·7% 6·2%
2–4 years 8500 14 386 14 730 23 574 2·1 3·6 3·6 5·8 1·2% 2·1% 2·0% 3·4%
5–9 years 7052 11 393 5377 8196 1·0 1·7 0·8 1·2 1·9% 3·2% 1·5% 2·3%
10–14 years 8553 14 405 1588 2715 1·3 2·2 0·2 0·4 2·8% 4·8% 0·5% 0·9%
15–19 years 17 032 26 852 5932 12 576 2·8 4·3 1·0 2·0 3·1% 4·8% 1·1% 2·2%
20–24 years 25 528 40 743 8219 17 453 4·3 6·8 1·4 2·9 3·6% 5·5% 1·2% 2·4%
25–29 years 47 857 78 496 12581 28 816 8·1 13·3 2·1 4·9 5·9% 9·2% 1·6% 3·4%
30–34 years 81 232 137 979 21 625 49 808 13·4 22·8 3·6 8·2 7·9% 12·3% 2·1% 4·5%
35–39 years 112 228 195 380 29 877 69 402 20·5 34·8 5·5 12·4 9·0% 14·1% 2·4% 5·0%
40–44 years 165 337 287 099 44 391 102 041 33·5 57·4 9·0 20·4 10·3% 16·0% 2·8% 5·7%
45–49 years 207 940 355 388 55 989 124 899 44·0 75·1 11·8 26·4 10·1% 15·7% 2·7% 5·5%
50–54 years 253 491 426 785 67 629 147 651 57·7 95·9 15·4 33·2 9·1% 14·0% 2·4% 4·8%
55–59 years 336 162 564 508 90 815 191 441 87·5 142·7 23·6 48·4 9·0% 13·8% 2·4% 4·7%
60–64 years 460 769 774 879 125 433 262 008 146·1 242·1 39·8 81·9 9·8% 15·0% 2·7% 5·1%
65–69 years 564 371 957 557 155 431 321 301 209·4 347·1 57·7 116·5 9·4% 14·5% 2·6% 4·9%
70–74 years 585 549 989 888 156 931 325 295 298·7 480·9 80·1 158·0 8·8% 13·2% 2·4% 4·3%
75–79 years 539 515 861 796 135 849 276 402 417·1 653·4 105·0 209·6 7·9% 11·8% 2·0% 3·8%
80–84 years 551 014 888 813 146 084 277786 638·9 1014·8 169·4 317·2 7·5% 11·3% 2·0% 3·5%
85–89 years 427 770 658 875 106 842 191 824 959·3 1441·1 239·6 419·5 6·9% 10·0% 1·7% 2·9%
90–94 years 280 605 426 185 67 297 114 449 1608·9 2382·3 385·9 639·8 7·5% 10·8% 1·8% 2·9%
≥95 years 120 173 174 390 24 074 42 104 2298·6 3199·6 460·5 772·5 7·8% 10·7% 1·6% 2·6%
Table 2: Number of deaths, age-standardised mortality rates, and percentage of total deaths due to COVID-19 and other pandemic-related mortality by age, globally
Leading causes of global YLLs Decomposition of global life expectancy

The causes of death with the highest age-standardised We found long-standing positive trends in global life
YLL rates show shifting epidemiological trends from expectancy since the early 1990s, with steady increases
CMNN diseases to NCDs at Level 3 of the cause occurring across each decade between 1990 and 2019
hierarchy (appendix 2 figure S2). Globally, the leading (appendix 2 table S4). Altogether, the global increase in life
three causes of age-standardised YLLs in 1990 were all expectancy from 1990 to 2019 totalled 7·8 years (95% UI
CMNN diseases. Ranked in descending order, these 7·1–8·5). In 2019–21, however, we found a global decline
causes were neonatal disorders, lower respiratory in life expectancy of 2·2 years due to deaths from
infections, and diarrhoeal diseases. In 2019, neonatal COVID-19 and OPRM combined. This decrease was partly
disorders remained the leading cause of age- offset by reductions in other diseases, for a net reduction
standardised YLLs, but the second and third leading in global life expectancy of 1·6 years. Despite this notable
causes were replaced by NCDs: ischaemic heart disease reduction, we observed an overall increase in life
(ranked second) and stroke (ranked third). In 2021, expectancy of 6·2 years (5·4–7·0) across the entire study
COVID-19 was the second-leading cause of global age- period. This decomposition analysis provides insights into
standardised YLLs, making the leading two causes the specific causes that influenced changes in life
CMNN diseases (with neonatal disorders ranked first), expectancy over the defined time periods. Among the
with ischaemic heart disease ranked third. Among the various contributing factors to a change in life expectancy,
leading causes of age-standardised YLLs, malaria was the cause with the greatest effect on the increase in life
the only cause to show an increase in age-standardised expectancy worldwide was the reduction in deaths caused
YLL rates between 2019 and 2021 (ranking ninth in 2019 by enteric infections (figure 3). This category includes
and seventh in 2021). diarrhoeal, typhoid, and paratyphoid diseases. A reduction

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Enteric infections, 1·1 years 1990–2000 0·4 0·4 0·3 0·1

2000–10
LRI, 0·9 years 2010–19 0·3 0·3 0·2 0·1
Stroke, 0·8 years 2019–21 0·2 0·3 0·3
Other communicable diseases, 0·6 years 0·2 0·2 0·2 0·1
Ischaemic heart disease, 0·6 years 0·1 0·2 0·2
Neoplasms, 0·6 years 0·1 0·3 0·2
Neonatal disorders, 0·6 years 0·1 0·2 0·2
Tuberculosis, 0·5 years 0·1 0·2 0·1
Other NCDs, 0·5 years 0·2 0·2 0·1 0·1
COPD, 0·5 years 0·1 0·2 0·1
Unintentional injuries*, 0·4 years 0·1 0·1 0·1
Measles, 0·3 years 0·1 0·2 0·1
Digestive diseases, 0·3 years 0·1 0·1 0·1
Nutritional deficiencies, 0·2 years 0·1 0·1
Transport injuries, 0·2 years 0·1 0·1
Suicide and homicide†, 0·2 years 0·1 0·1
Malaria, 0·1 years –0·1 0·1
HIV/AIDS, 0·0 years –0·4 0·2 0·2
Diabetes and CKD, –0·1 years
OPRM, –0·6 years –0·6
COVID-19, –1·6 years –1·6
–2·0 –1·5 –1·0 –0·5 0 0·5 1·0 1·5

Life expectancy gained (years)
Figure 3: Change in life expectancy attributable to leading causes of death for males and females combined, 1990–2000, 2000–10, 2010–19, and 2019–21,
globally
Each row represents the change in global life expectancy from 1990 to 2021 for a given cause. The total change in life expectancy is further broken down by different
colours to represent changes over time periods. A bar to the right of 0 represents an increase in life expectancy due to changes in the given time period, and a bar to
the left of 0 represents a decrease in life expectancy due to a given time period. For readability, labels indicating a change in life expectancy of less than 0·05 years are
not shown. CKD=chronic kidney disease. COPD=chronic obstructive pulmonary disease. LRI=lower respiratory infection. NCD=non-communicable disease.
OPRM=other pandemic-related mortality. *Does not include natural disasters. †Does not include war and terrorism.
in deaths from these diseases is responsible for a progress in each being differentially affected by COVID-19
substantial increase in life expectancy of 1·1 years during (figures 4, 5). Southeast Asia, east Asia, and Oceania
1990–2021, but this increase was most pronounced showed the highest gain, with a net improvement of
between 1990 and 2000 compared with other time periods. 8·3 years (95% UI 6·7–9·9), while also being the least
The second-largest effect on increasing life expectancy is affected by COVID-19, which contributed a loss in life
attributed to the reduction in deaths from lower respiratory expectancy of just 0·4 years. The overall increase in life
infection, contributing 0·9 years of gained life expectancy expectancy in southeast Asia, east Asia, and Oceania can
from 1990 to 2021. Other leading factors include reduced largely be attributed to reduced mortality from chronic
mortality from stroke, CMNN diseases, neonatal deaths, respiratory diseases, contributing to a gain of 1·2 years,
ischaemic heart disease, and neoplasms, each of which whereas reduced mortality from stroke, lower respiratory
increased global life expectancy by 0·6–0·8 years over the infections, and neoplasms were among other causes that
study period. Changing rates of HIV/AIDS and malaria contributed to the 8·3-year (6·7–9·9) increase. The second-
mortality both contributed positively to the overall global largest gain occurred in south Asia, where life expectancy
life expectancy in some years but negatively affected life increased by 7·8 years (6·7–8·9), which can be largely
expectancy in others. Beginning in 2000, reductions in attributed to reduced mortality from enteric infectious
HIV/AIDS-related mortality were evident following diseases, contributing a substantial gain of 3·1 years in life
substantial negative effects in earlier years. Reductions in expectancy. The largest reduction in overall life expectancy
deaths from malaria, however, were less sustained, due to COVID-19 occurred in the super-region of Latin
increasing life expectancy by 0·1 years from 2010 to 2019 America and the Caribbean, which experienced a loss of
but having no effect from 2019 to 2021. Across all causes, 3·6 years. Reductions in deaths due to malaria throughout
the largest effect on the change in global life expectancy sub-Saharan Africa led to an increase in life expectancy of
was from COVID-19, which resulted in a decline of 0·8 years for the super-region.
1·6 years between 2019 and 2021. The differential effect of COVID-19 on reduced life
expectancy was observed across GBD regions (figure 6).
Decomposition of super-region, regional, and country- Although most regions experienced overall improve
level life expectancy ments in life expectancy between 1990 and 2021, a
Each of the seven super-regions experienced an overall reduction occurred in southern sub-Saharan Africa,
increase in life expectancy between 1990 and 2021, despite which faced the greatest impact of HIV and was also

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A COVID-19, 2021
Age-standardised mortality rate

per 100 000
<1·4 151·3 to <181·2
1·4 to <44 181·2 to <209·3
44 to <90·6 209·3 to <248·6
90·6 to <121 248·6 to 295·4
121 to <151·3 >295·4
B OPRM, 2021
Age-standardised mortality rate

per 100 000
<0·2 47·9 to <62·5
0·2 to <1·8 62·5 to <78·2
1·8 to <8·1 78·2 to <97·5
8·1 to <23·8 97·5 to 130·1
23·8 to <47·9 >130·1
Figure 4: Age-standardised mortality rate of COVID-19 and OPRM, 2021

Global choropleth maps of COVID-19 (A) and OPRM (B) for 2021 that show sub-national detail where available. OPRM=other pandemic-related mortality.
COPD HIV/AIDS Natural disasters and conflict OPRM Suicide and homicide*
COVID-19 Ischaemic heart disease and terrorism Other communicable Transport injuries
Diabetes and CKD LRI Neonatal disorders diseases Tuberculosis
Digestive diseases Malaria Neoplasms Other NCDs Unintentional injuries†
Enteric infections Measles Nutritional deficiencies Stroke
Southeast Asia, east Asia, and Oceania, 8·3 years –0·4 1·2 0·4 0·6 1·0 0·6 0·7 0·4 0·8 1·2 0·5 0·6
South Asia, 7·8 years –0·8 –1·9 0·5 3·1 1·0 0·5 0·9 0·4 1·2 0·4 1·4 0·4
Super-region
Sub-Saharan Africa, 7·8 years –1·2 –2·4 1·9 0·5 1·4 0·8 0·9 0·6 0·5 1·5 0·4 1·1
North Africa and Middle East, 5·7 years –0·9 –2·3 0·4 0·6 1·1 0·9 1·1 0·6 1·2 0·9 0·4 0·5
High income, 4·5 years –1·2 1·8 1·2 0·9

Latin America and Caribbean, 2·7 years –0·7 –3·6 0·7 0·8 0·7 0·7 0·4 0·40·4 0·9 0·4
Central europe, Eastern Europe, and central Asia, 2·1 years –0·7 –2·4 1·2 0·5 0·6 1·0 0·4 0·5
–6·0 –4·0 –2·0 0 2·0 4·0 6·0 8·0 10·0 12·0

Change in life expectancy (years)
Figure 5: Change in life expectancy attributable to leading causes of death among super-regions, 1990–2021
Each row represents the change in life expectancy from 1990 to 2021 for a given super-region. A bar to the right of 0 represents an increase in life expectancy due to changes in the given cause, and a
bar to the left of 0 represents a decrease in life expectancy for a given cause. For readability, labels indicating a change in life expectancy of less than 0·3 years are not shown. CKD=chronic kidney
disease. COPD=chronic obstructive pulmonary disease. LRI=lower respiratory infection. NCD=non-communicable disease. OPRM=other pandemic-related mortality. *Does not include natural disasters.
†Does not include war and terrorism.

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East Asia, –0·0 years –0·1

High-income Asia Pacific, –0·1 years –0·1
Australasia, –0·1 years –1·0
Western Europe, –1·0 years –1·4
Southeast Asia, –1·4 years –1·5
Oceania, –1·5 years –1·8
Western sub-Saharan Africa, –1·8 years –1·8
High-income North America, –1·8 years
–1·9
South Asia, –1·9 years
–2·0
Central sub-Saharan Africa, –2·0 years
GBD region
–2·1
Central Asia, –2·1 years
–2·2
Central Europe, –2·2 years
–2·3
North Africa and Middle East, –2·3 years
–2·3
Southern Latin America, –2·3 years
–2·4
Caribbean, –2·4 years
–2·6
Eastern Europe, –2·6 years
Eastern sub-Saharan Africa, –2·7 years –2·7
Southern sub-Saharan Africa, –3·4 years –3·4
Tropical Latin America, –3·4 years –3·4
Central Latin America, –3·5 years –3·5

Andean Latin America, –4·9 years –4·9
–5·0 –4·0 –3·0 –2·0 –1·0 0

Figure 6: Effect of COVID-19 on life expectancy by GBD region, 2019–21

For readability, labels indicating a change in life expectancy of less than 0·05 years are not shown. GBD=Global Burden of Diseases, Injuries, and Risk Factors Study.
heavily affected by COVID-19. The overall decrease in life sub-Saharan Africa had the highest level of recovery to their
expectancy of 4·3 years (95% UI 3·0–5·8) included a life expectancy among the regions, gaining 1·5 years of life
reduction of 2·4 years due to HIV/AIDS and 3·4 years expectancy over the entire study period.
due to COVID-19, which were only partly offset by In 1990, malaria-related deaths had almost no effect on
reductions in mortality due to other causes. Notably, life expectancy in eight of the 21 GBD regions (appendix 2
COVID-19 reduced life expectancy in Andean Latin figure S13). By 2021, however, 90% of malaria deaths across
America by 4·9 years, although the region had an overall all age groups occurred in locations with only 12% of the
gain of 2·6 years (1·0–4·1) between 1990 and 2021. The global population. Efforts to control malaria in various
effect of COVID-19 in eastern sub-Saharan Africa, which regions of sub-Saharan Africa have yielded modest gains in
resulted in a reduction in life expectancy of 2·7 years, life expectancy. Central sub-Saharan Africa gained 0·7 years
was offset by steady improvements across many different in life expectancy between 2000 and 2010, western sub-
causes, which resulted in the highest overall increase in Saharan Africa gained 0·9 years during 2010–19, and
life expectancy among GBD regions (10·7 years eastern sub-Saharan Africa gained 0·7 years in 2000–10.
[9·0–12·2]). Control of enteric infections in this region Despite these advancements, many regions with malaria
contributed to an increase in life expectancy of 1·9 years, transmission experienced a decline in life expectancy
along with reductions in lower respiratory infections and from 2019 to 2021. The most noticeable reductions were in
tuberculosis, each of which contributed to an additional eastern sub-Saharan Africa, with a decrease of 0·2 years,
1·6 years’ increase in life expectancy. Each region in followed by western sub-Saharan Africa, which lost
sub-Saharan Africa experienced reductions in the 0·1 years in life expectancy over the same period.
number of enteric infections, which improved life At the national level, some of the highest gains in life
expectancy in those regions between 0·8 and 2·4 years. expectancy between 1990 and 2021 occurred in the eastern
HIV/AIDS had a substantial negative effect on life- region of sub-Saharan Africa (appendix 2 figure S12). Life
expectancy trends in southern sub-Saharan Africa from expectancy in Ethiopia increased by 18·2 years (95% UI
1990 to 2021 (appendix 2 figure S27). Despite improve 16·3–19·8) as a result of reductions in deaths from many
ments in each of the time periods 2000–2010, 2010–2019, causes, most notably other communicable and maternal
and 2019–2021, this region was unable to recover the disorders (3·2 years), tuberculosis (3·1 years), and enteric
9·0 years lost during 1990–2000. Although we found a net infectious diseases (2·4 year). The largest reduction in life
decline in deaths due to HIV/AIDS between 2000 and 2019, expectancy occurred in Lesotho, at 12·9 years (10·1–15·7),
improvements slowed substantially from 2019 to 2021, largely attributed to increased deaths from HIV/AIDS,
when only 0·2 years in life expectancy were gained as a which resulted in a reduction of 7·3 years (appendix 2
result of reduced HIV/AIDS mortality. Conversely, eastern figures S12, S27, table S4).

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South Asia, 3·1 years 1·4 0·9 0·7 0·1

Western sub-Saharan Africa, 2·4 years 0·5 0·8 1·0 0·2
Central sub-Saharan Africa, 2·0 years 0·1 0·7 1·0 0·1
Eastern sub-Saharan Africa, 1·9 years 0·6 0·6 0·5 0·1
Southeast Asia, 1·6 years 1·0 0·4 0·2
Southern sub-Saharan Africa, 0·8 years 0·3 0·2 0·3 0·1
Central Latin America, 0·8 years 0·6 0·2
Tropical Latin America, 0·8 years 0·5 0·2 0·1
Caribbean, 0·7 years 0·4 0·1 0·2
Andean Latin America, 0·7 years
GBD region
0·4 0·2 0·1

Oceania, 0·6 years 0·3 0·1 0·2
North Africa and Middle East, 0·6 years 0·3 0·2 0·1
Central Asia, 0·4 years 0·2 0·2 0·1
East Asia, 0·2 years 0·2 0·1
Southern Latin America, 0·1 years
Eastern Europe, 0·0 years
Central Europe, 0·0 years
High-income Asia Pacific, 0·0 years
1990–2000
Australasia, 0·0 years 2000–10
Western Europe, –0·0 years 2010–19
High-income North America, –0·0 years 2019–21
–0·5 0 0·5 1·0 1·5 2·0 2·5 3·0 3·5

Figure 7: Effect of enteric infectious diseases on life expectancy by time period and GBD region, 1990–2021
Effect of CMNN diseases on life expectancy and trends impact on life-expectancy trends, particularly in southern
in mortality concentration sub-Saharan Africa, and with 90% of deaths concentrated
Among CMNN causes, several key trends emerged in their in locations containing 46% of the entire population and
effect on global life expectancy and the localisation of 39% of the under-5 population in 2021 (appendix 2
deaths over time. First, the reduction of deaths due to figures S27, S30). However, HIV/AIDS was less
enteric disease had a substantial impact on global life concentrated in 2021 than in 1990. Fourth, efforts to control
expectancy, with notable regional variations (figure 7). As malaria in sub-Saharan Africa resulted in modest gains in
160 countries and territories made progress in reducing life expectancy. Similarly, 90% of malaria-related deaths in
CMNN disease-related mortality, mortality concentration 2021 occurred in locations containing only 12% of the
emerged. Deaths became more concentrated into certain entire population and 20% of the under-5 population,
countries or regions, persisting alongside advancements showing mortality concentration (figure 5; appendix 2
made in other parts of the world. An illustrative example is figures S13, 31). Fifth, reductions in tuberculosis-related
the shift in deaths due to enteric diseases in children deaths had a positive effect on life expectancy across all
younger than 5 years, with 90% of deaths occurring in regions, and changes in mortality rates indicated mortality
locations containing 63% of the population of children concentration, with 90% of deaths occurring in locations
younger than 5 years in 1990, decreasing to locations containing 66% of the entire population in 1990, decreasing
containing 51% of the population by 2021 (appendix 2 to 62% by 2021 (figure 9; appendix 2 figure S14). Lastly,
figure S28). Second, the reduction in the number of lower although measles had a relatively small global effect on life
respiratory infections yielded positive effects on life expectancy, this cause showed high mortality concentration.
expectancy in some regions. Regions such as Andean Latin The disease remained contained globally, with 90% of
America and western and eastern sub-Saharan Africa had deaths concentrated in locations containing only 15% of
gains of 1·6 years in life expectancy due to reduced deaths the entire population and 24% of the under-5 population in
from lower respiratory infections. This progress is further 2021 (figure 3; appendix 2 figure S15).
underscored by the transformation from 90% of deaths Reductions in neonatal deaths contributed to a
from lower respiratory infections in children younger than 0·6-year increase in global life expectancy. Also, 90% of
5 years occurring in locations with 71% of the population neonatal deaths were concentrated in locations
of the under-5 population in 1990 to 90% occurring in containing 71% of the population in 1990, decreasing to
locations with 58% of the under-5 population by 2021, 51% by 2021 (appendix 2 figures S16, S34). Finally,
signalling substantial improvements in some regions and nutritional deficiencies had a relatively small global
increased concentration of this cause in others (figure 8; impact on life expectancy but substantial effects on
appendix 2 figure S29). Third, HIV/AIDS had a substantial specific regions—eastern sub-Saharan Africa, central

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Western sub-Saharan Africa, 1·6 years 0·3 0·6 0·4 0·3
Andean Latin America, 1·6 years 0·8 0·3 0·2 0·2

Eastern sub-Saharan Africa, 1·6 years 0·5 0·6 0·4 0·2
Central Asia, 1·4 years 0·2 0·7 0·3 0·2
Central Sub-Saharan Africa, 1·4 years 0·3 0·6 0·4 0·1
East Asia, 1·1 years 0·5 0·5 0·1
South Asia, 1·0 years 0·3 0·3 0·2 0·2
North Africa and Middle East, 0·9 years 0·4 0·2 0·1 0·1
Southeast Asia, 0·9 years 0·3 0·2 0·2 0·1
Oceania, 0·8 years 0·1 0·1 0·3 0·3
GBD region
High-income Asia Pacific, 0·7 years 0·2 0·1 0·3 0·1

Central Latin America, 0·6 years 0·4 0·2 0·1
Tropical Latin America, 0·6 years 0·4 0·2
Southern sub-Saharan Africa, 0·6 years –0·1 0·4 0·2
Caribbean, 0·5 years 0·2 0·1 0·2
Central Europe, 0·3 years 0·1 0·1 0·1
High-income North America, 0·2 years 0·1 0·1
Western Europe, 0·2 years 0·1 0·1
1990–2000
Australasia, 0·1 years 0·1 0·1 0·1
2000–10
Eastern Europe, 0·1 years –0·1 0·1 0·2 2010–19
Southern Latin America, 0·1 years –0·1 –0·1 0·3 2019–21
–0·2 0 0·2 0·5 0·8 1·0 1·2 1·5 1·8

Figure 8: Effect of lower respiratory infections on life expectancy by time period and GBD region, 1990–2021
Eastern sub-Saharan Africa, 10·7 years –1·3 –2·7 1·9 1·5 1·6 0·9 1·0 0·6 0·8 0·8 1·8 0·50·4 1·6 0·4
East Asia, 9·8 years 1·5 0·4 1·1 0·8 1·0 0·4 1·0 1·4 0·4 0·7
Central sub-Saharan Africa, 8·4 years –1·0 –2·0 2·0 0·4 1·4 1·2 0·60·4 0·5 1·6 0·4 0·4 1·3 0·4
Western sub-Saharan Africa, 7·9 years –1·0 –1·8 2·4 1·6 0·8 1·1 0·6 1·5 0·40·4 0·8
South Asia, 7·8 years –0·8 –1·9 0·5 3·1 1·0 0·5 0·9 0·4 1·2 0·4 1·4 0·4
High-income Asia Pacific, 7·1 years 0·4 0·9 0·7 1·3 0·5 1·8 0·5
Australasia, 6·6 years 2·7 1·3 0·5 0·8 0·4
North Africa and Middle East, 5·7 years –0·9 –2·3 0·4 0·6 1·1 0·9 1·1 0·6 1·2 0·9 0·4 0·5
Southeast Asia, 5·6 years –0·8 –1·4 0·40·4 1·6 0·9 0·6 0·7 0·6 1·0 0·4
Western Europe, 5·5 years –1·0 2·0 1·2 0·5 1·0 0·4
GBD region
Tropical Latin America, 4·3 years –3·4 0·4 0·8 1·2 0·6 1·0 0·4 1·4 0·4
Southern Latin America, 4·1 years –2·3 1·5 0·6 1·0 0·5 1·1 0·5
Central Europe, 4·0 years –0·5 –2·2 1·8 0·50·5 0·5 1·4 0·4
Central Asia, 2·9 years –0·8 –2·1 0·50·4 1·0 1·4 0·8 0·5 0·5
Andean Latin America, 2·6 years –1·8 –4·9 0·7 0·7 0·6 1·6 0·8 0·50·5 0·6 0·7 1·1 0·7
High-income North America, 1·8 years –0·4 –1·8 1·9 1·3
Oceania, 1·7 years –1·4 –1·5 0·6 0·8 0·60·4 0·40·4
Caribbean, 1·7 years –1·0 –2·4 0·7 1·0 0·5 0·5
Central Latin America, 1·3 years –1·0 –3·5 0·4 0·8 0·6 0·60·40·4 0·40·5 0·4
Eastern Europe, 0·6 years –0·8 –2·6 1·0 0·40·6 0·9 0·40·5
Southern sub-Saharan Africa, –4·3 years –1·5 –2·4 –3·4 0·8 0·6 0·4
–10·0 –0·5 0 0·5 10·0 15·0
COPD HIV/AIDS Natural disasters and conflict and terrorism OPRM Suicide and homicide*
COVID-19 Ischaemic heart disease Neonatal disorders Other communicable diseases Transport injuries
Diabetes and CKD LRI Neoplasms Other NCDs Tuberculosis
Digestive diseases Malaria Nutritional deficiencies Stroke Unintentional injuries†
Enteric infections Measles
Figure 9: Change in life expectancy attributable to leading causes of death among GBD regions, 1990–2021
Each row represents the change in life expectancy from 1990 to 2021 for a given GBD region. A bar to the right of 0 represents an increase in life expectancy due to changes in the given cause, and a bar
to the left of 0 represents a decrease in life expectancy for a given cause. For readability, labels indicating a change in life expectancy of less than 0·3 years are not shown. CKD=chronic kidney disease.
COPD=chronic obstructive pulmonary disease. GBD=Global Burden of Diseases, Injuries, and Risk Factors Study. LRI=lower respiratory infection. NCD=non-communicable disease. OPRM=other
pandemic-related mortality. *Does not include war and terrorism. †Does not include natural disasters.

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sub-Saharan Africa, and south Asia saw notable showed little mortality concentration, with 90% of deaths
increases. We found a shift towards mortality occurring in locations containing 88% of the population in
concentration, with 90% of nutritional deficiency-related 2021 (appendix 2 figures S26, S44). Lastly, the overall
deaths in children younger than 5 years concentrated in reduction in mortality rates from self-harm and
locations containing 49% of the population in this age interpersonal violence contributed to a 0·2-year increase in
group by 2021, compared with 59% in 1990 (appendix 2 life expectancy with variable mortality concentration,
figures S18, S35). Overall, CMNN diseases showed a showing concentration in central and tropical Latin
large degree of mortality concentration. America and South Africa, but not exclusively in these
locations (appendix 2 figures S25, S45).
Effect of NCDs on life expectancy and trends in
mortality concentration Discussion
Among NCDs, several findings reflect their effect on Main findings
global life expectancy and death concentration. Reductions The COVID-19 pandemic has emerged as one of the most
in stroke led to a notable gain in life expectancy of defining global health events of recent history. Our latest
0·8 years, but stroke deaths were not concentrated, with comprehensive estimates of cause-specific mortality give
90% occurring in locations containing 84% of the global insight into the global landscape of disease before and
population (appendix 2 figures S23, S36). Similarly, during the first 2 years of the pandemic, revealing the
ischaemic heart disease had a substantial effect on important changes in disease-burden patterns that
improvement to life expectancy, contributing 0·6 years to followed. After more than three decades of consistent
global life expectancy; yet, as with stroke, ischaemic heart improvements in global life expectancy and declining age-
disease showed little mortality concentration, with 90% of standardised death rates, COVID-19 reversed long-
deaths concentrated in locations containing 84% of standing progress and disrupted trends in the
the population in 2021 (appendix 2 figures S17, S37). epidemiological transition. As the second leading cause of
Neoplasms added 0·6 years to life expectancy, with high- age-standardised deaths in 2021, COVID-19 had a
income regions greatly benefiting; as with other NCDs, pronounced influence on the reduction in global life
90% of neoplasms deaths occurred in locations containing expectancy that occurred. The heterogeneous influence of
86% of the population in 2021, indicating a consistent risk the disease across the globe provides important insights
of dying from cancer regardless of geography (appendix 2 for improving future pandemic preparedness and
figures S19, S38). Chronic respiratory diseases contributed ensuring that nations are equitably equipped to respond to
an increase of 0·5 years to life expectancy, with east Asia new outbreaks. Additionally, our analysis of geographical
contributing the most to this increase through substantial and temporal trends in mortality enables us to observe the
improvements in mortality in China. Chronic respiratory changing patterns in causes of death worldwide. Many
diseases also showed little mortality concentration, with causes have exhibited a reduced geographical reach—a
90% of deaths occurring in locations containing 79% of reflection of dedicated and persistent mitigation efforts to
the population (appendix 2 figures S20, S39). Digestive reduce the burden of certain causes, as well as potential
diseases and cirrhosis had a substantial negative effect on changes to risk-factor exposure.15 This study offers an
life expectancy, with little improvement from 2010 to 2019, opportunity to apply the lessons learned from these
and showed little mortality concentration (appendix 2 successes to further reduce deaths from causes that are
figures S21, S40). Diabetes and kidney diseases had a now present within smaller, more concentrated areas
negative effect on life expectancy, resulting in a global loss throughout the world.
of 0·1 years in life expectancy. This cause also had little
mortality concentration, with 90% of deaths occurring in The COVID-19 pandemic
locations representing 89% of the population (appendix 2 The emergence and spread of COVID-19 follows a similar
figures S22, S41). Overall, NCDs largely did not show pattern of regional heterogeneity that is common among
concentration, meaning that we did not observe mortality many leading communicable causes of death, with higher
from these causes moving towards more restricted rates of infection and increased fatalities occurring in
geographical areas (appendix 2 figure S42). lower-resource settings.6,16,17 Although heterogeneity in
COVID-19 outcomes in 2020 and 2021 varied by the
Effect of injuries on life expectancy and trends in income status of a country or territory, outcomes were also
mortality concentration directly related to age, government actions to close borders,
The reduction in transport injuries had a positive effect on and the implementation of transmission-reduction
life expectancy, contributing to a gain of 0·2 years. policies.18 This general pattern did not always hold true at
However, as with NCDs, transport injury-related mortality the national level, however, where estimates from some
was not concentrated, with 90% of deaths concentrated in high-income countries showed a much greater burden
locations containing 88% of the population in 1990, than would have been expected, indicating important
decreasing slightly to 84% of the population by 2021 opportunities for improved pandemic preparedness and
(appendix 2 figures S24, S43). Unintentional injuries also response in these nations.19 The varying effects across

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locations emphasises the complexity of the pandemic. HIV/AIDS and lower respiratory and enteric infections—
Diverse social, economic, and political influences somewhat counterbalanced the decline, the decrease in
contributed to the variations in death rates observed life expectancy was also compounded by increasing rates
between locations. In general, areas with advanced health- of mortality from other causes, such as diabetes and
care systems and robust medical facilities were better able kidney diseases.
to manage abrupt increases in the number of COVID-19 The effect of COVID-19 on life expectancy showed
cases. By contrast, locations with poorer health-care varying degrees of severity, ranging from a large loss of
infrastructure were less equipped to handle the surge in 4·9 years in Andean Latin America to almost no change
infections that occurred,20 although strong health-care in east Asia. From 1990 to 2021, reductions in many of
systems did not singularly influence the outcome of the the leading causes of death resulted in overall life-
pandemic.19 Improving preparedness for future pandemics expectancy increases across most regions, despite heavy
should also include engagement strategies to enhance the setbacks for many because of the COVID-19 pandemic.
trust that individuals place in public health recom We found that despite Andean Latin America having the
mendations.19 Additionally, identifying methods to largest regional reduction in life expectancy due to the
enhance death-reporting systems3 and overcome political pandemic, overall life-expectancy reductions across the
obstacles to ensure accurate reporting will be crucial steps region were tempered by improvements in other causes,
for monitoring COVID-19 and future pandemic with reductions in rates of death from lower respiratory
occurrences.21,22 infections and neonatal disorders responsible for an
Our study shows that COVID-19 was one of the leading increase in life expectancy of 2·6 years overall between
global causes of death during the first 2 years of the 1990 and 2021. The impressive reductions in neonatal
pandemic and provides an opportunity to delineate disorders throughout many countries in Andean Latin
between the disease’s direct and indirect mortality effects America have been attributed to the improvements made
as well as its effect on life expectancy. As previously in implementing effective maternal and neonatal health
predicted,3 COVID-19 shifted baseline patterns of intervention strategies.24
mortality for diseases and injuries that were affected by The reduction in life expectancy in southern sub-
physical-distancing measures and other government- Saharan Africa also exceeded the global average by a
mandated restrictions. Deferred care-seeking during the substantial margin, with a reduction of 3·4 years due to
height of the pandemic also probably contributed to COVID-19. Although life expectancy in the region was
shifts in patterns of mortality for some diseases and substantially affected by the COVID-19 pandemic, the
injuries and might also have contributed to the reduction was also attributable to high mortality rates
emergence of pandemic-related deaths not attributable from HIV/AIDS. Some nations with high pandemic-
directly to COVID-19, lower respiratory infections, related death tolls were among those already burdened
measles, malaria, or pertussis (OPRM). Deferred care- by high rates of other infectious diseases. Several
seeking might also have been a contributing factor in the countries in southern sub-Saharan Africa navigated the
notable divergence in the age distribution in deaths challenges of the pandemic, alongside long histories of
between COVID-19 and OPRM, whereby COVID-19 combatting some of the highest HIV/AIDS prevalence
deaths were substantially higher in older ages, whereas rates in the world.25,26 A subset of countries were faced
the highest rate of OPRM was seen in older ages as well with a triple burden of COVID-19, HIV/AIDS, and
as in children younger than 23 months. Mortality might tuberculosis.27 The combined burden of these causes
have increased in the youngest ages because caregivers across southern sub-Saharan Africa was not offset by
might have hesitated to seek medical care during the sufficient improvements in mortality from other causes,
peak of the virus’s spread. Understanding these leading to an overall reduction in the region’s life
disparities is imperative for shaping future health expectancy of more than 4 years over the entire study
policies and preparedness efforts. period.
Important trends in life expectancy Cause-specific patterns of mortality concentration

Advancements over the past three decades in the Estimates of mortality concentration reflect shifting
prevention and control of infectious diseases have patterns of disease over time, from diseases that have a
contributed to increases in life expectancy in many widespread presence moving to more geographically
locations, increasing the need to support populations reduced subsets of the global population. These changes
living with NCDs.23 The global decline in life expectancy highlight differences between populations and their
that occurred in 2020 and 2021 confounds the longer- progress towards reducing mortality due to diseases and
term trend of increase.10 Our decomposition analysis injuries. These findings also provide an important
suggests that this decline was predominantly a result of opportunity to improve how best public health practices
the pandemic (combined COVID-19 and OPRM), but the are applied to further disease reduction. Broadly,
degree of severity varied greatly by location. Although widespread declines in many communicable diseases
large improvements in many causes—including resulted in mortality from these causes exhibiting more

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concentrated geographical distributions in 2021 relative to A broad and recurring theme from this study is that
patterns seen in 1990. The degree of mortality concentration reductions in enteric infections contributed to improved
estimated by this study for enteric and lower respiratory life expectancies over the past several decades. The
infections, malaria, HIV/AIDS, neonatal disorders, and reductions in childhood mortality associated with
tuberculosis reflects substantial global progress in diarrhoeal diseases that have occurred across many parts
reducing mortality from these causes over the study of Africa35,40–42 can also be partly explained by many
period, underscoring the success of several public health combined local efforts in improved immunisation;43 access
campaigns, global commitments, and improvements in to water, sanitation, and hygiene facilities;12,44
communicable-disease programmes.28–30 Estimates of breastfeeding;45 oral rehydration therapy;46 and zinc
mortality concentration can be used to examine where supplementation,15 alongside global initiatives such as the
disease mitigation strategies have been successful, where Global Action Plan for the Prevention and Control of
they can be further implemented to reduce inequality, and Pneumonia and Diarrhea.47 Given that enteric disease-
where more research might be needed to develop effective related mortality and specifically diarrhoeal disease-related
treatment and intervention strategies. mortality continued to decline during the COVID-19
Notably, our estimates support previous findings31 that pandemic, the post-pandemic period might offer
show deaths from malaria are becoming increasingly opportunities to accelerate progress on prevention and
concentrated and are now particularly concentrated treatment. Diarrhoeal diseases are particularly amenable
within western sub-Saharan Africa, with an additional to public health intervention, and given this cause’s high
corridor running through central Africa and into burden among children, we must continue to direct
Mozambique. Countries in western sub-Saharan Africa resources towards its prevention.47,48 Several locations still
with the highest under-5 death rates from malaria in do not have the necessary financing, governance, and
2021 included Burkina Faso, Sierra Leone, and Niger. political commitment to reduce rates of enteric infections.49
This concentration of malaria mortality reflects both To accelerate progress in reducing enteric disease-related
differential rates of population growth across Africa, as mortality, routine and catch-up immunisation programmes
well as the varying rates of progress in reducing must be strengthened and expanded, including building
transmission, most notably by malaria nets treated with on the global success of the rotavirus roll-out50 and
long-lasting insecticide and in strengthening case countering disruptions in childhood immunisation during
management.32 At a time of growing threats to progress the pandemic.51 Additionally, efforts should focus on
against malaria, including emerging parasite and vector advancing candidate vaccines against enterotoxigenic
resistance and budgetary pressures, but also amid Escherichia coli, norovirus, and shigella.51–55
promising new tools such as second vaccine for malaria, Our study also found that some vaccine-preventable
it is more important than ever that changing patterns of diseases, such as measles, have shown widespread
mortality are quantified and understood.33,34 reductions in mortality rates and were geographically
Enteric infections showed large disease concentration. concen trated. Under-5 deaths from measles were
Under-5 deaths from enteric infections were largely concentrated within western and eastern sub-Saharan
concentrated within sub-Saharan Africa and south Asia. Africa. Although multiple factors contribute to decreases
Countries in sub-Saharan Africa and south Asia with the in infectious disease burden, improvements in measles
highest under-5 death rates from enteric infections in mortality have largely been attributable to the global
2021 included Chad, South Sudan, and the Central African availability of a safe and effective vaccine against measles,
Republic. There are many contributing factors that should producing life-long immunity, with two-dose efficacy
be considered when examining how to reduce enteric exceeding 95%.56 Measles incidence has decreased
infections in the remaining concentrated locations. dramatically where vaccination efforts have been
Alongside the provision of oral rehydration solution and successful, including North America, South America,
rotavirus vaccines, critical public health improvements Europe, and Australia;57–61 although, since 2016, endemic
such as in water, sanitation, and hygiene might have measles transmission has been re-established in ten
contributed to decreases in enteric deaths.35,36 Childhood countries that previously had achieved measles
growth failure, also a leading risk factor for deaths from elimination.61 We found that, as of 2021, measles mortality
lower respiratory infections, malaria, and measles, must was concentrated in countries and regions with
be addressed through interventions to improve women’s insufficient access to the measles vaccine, particularly in
health including anaemia, promotion of early exclusive sub-Saharan Africa. Although valuable insights can be
breastfeeding, and management of acute malnutrition, drawn from countries that have achieved measles control
among others.37,38 Countries with the highest burden of through effective vaccination programmes and
infectious disease mortality in children younger than surveillance systems, interventions still must be tailored
5 years tend to be geographically clustered, suggesting to the affected communities and countries for successful
multisectoral approaches are necessary to continue reductions in mortality.62
reducing mortality in the countries with the highest Some infectious diseases, such as HIV/AIDS, also
rates.39 showed mortality concentration. Deaths from HIV/AIDS

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were largely concentrated within sub-Saharan Africa, most decreased at notably lower levels in 2021 compared with
notably southern sub-Saharan Africa. Countries in sub- in 1990. Examples of this trend include ischaemic heart
Saharan Africa with the highest age-standardised mortality disease, neoplasms, and stroke, all of which largely
rate in 2021 included Lesotho, Eswatini, and Botswana. declined over the study period—although their
Countries in sub-Saharan Africa with the highest under-5 reductions have been widely dispersed and not as
death rates from HIV in 2021 included Lesotho, Equatorial targeted as the CMNN causes. These findings show that
Guinea, and Guinea-Bissau. This concentration highlights NCDs do not appear to be moving towards more
how HIV-control campaigns, preventative measures,63,64 condensed geographical locations over time in the same
improved treatment with the emergence of antiretroviral way that many CMNN diseases are, which could make
therapy,65 access to testing and health care,66 and research interventions and policies more complex to implement.
advancements might have contributed to the reduced Ultimately, the extent of mortality concentration
global mortality of HIV. Despite these successes, reflects both the progress achieved in health-care
substantial barriers remain to reducing HIV mortality, advancements and the shortcomings that persist in their
such as stigma discouraging people from accessing equitable implementation. Disease concentration is
treatment and care,67,68 insufficient health-care evidence that there are effective interventions and
infrastructure, access to testing,70 coverage of antiretroviral
69
policies that have successfully reduced disease burden in
therapy,71 and complications due to co-occurring diseases many locations, but these innovations have not been
such as tuberculosis and HIV.72 Preventative measures are equitably distributed throughout the world or have been
particularly important for the reduction of HIV mortality ineffective at addressing the specific challenges certain
because HIV prevalence is the primary contributor to high populations face. There remains a global need to improve
mortality rates. Although countries can learn from access to new interventions and vaccines, to invest in the
successful HIV campaigns and strategies, global support implementation of validated public health policies, and
is needed to ensure HIV treatment and preventative to strategise with geographical sources of disease in
measures are accessible to all populations at risk.70,73,74 mind. Future efforts should continue the ongoing
In many high-income nations, the overall rate of mitigation of communicable diseases, focusing on
neonatal deaths decreased between 1990 and 2021, locations where these causes have become more
becoming more concentrated over time. Deaths from geographically concentrated, while also initiating efforts
neonatal disorders in 2021 were concentrated within sub- to combat chronic causes within low-resourced settings.
Saharan Africa and south Asia.75 Countries in these Additionally, patterns of high geographical concentration
regions with the highest under-5 death rates from among infectious causes and low geographical
neonatal disorders in 2021 included Mali, South Sudan, concentration among chronic causes reflect the global
and Sierra Leone. However, the disparity in mortality epidemiological transition, wherein mortality rates of
between high-income and low-income countries and infectious deaths declined throughout most years of our
regions highlights inequality in progress. Newborn care study. The increased concentration of a cause of death,
that can reduce mortality includes resuscitation, particularly communicable diseases, illustrates success
prevention of hypothermia and infection, in-facility in mitigation that can be adapted within the countries
delivery, and exclusive breastfeeding.76,77 Neonatal and regions with mortality concentration identified in
mortality might be reduced globally if policy makers our study, with the potential to greatly reduce mortality
examine the strategies that led to successes elsewhere.78 from those causes of death.
Conversely, although the burden of many NCDs has
also been reducing, these causes have typically not Limitations
followed the same pattern of mortality concentration Methodological advancements have enabled GBD 2021
seen in CMNN diseases. These trends emphasise a key to produce cause-specific estimates of mortality more
distinction in the spatial dynamics of NCDs compared easily than in previous iterations; however, as with any
with many communicable diseases. Although non- study of this scope, there are several important limitations
communicable causes might not exhibit the same degree to acknowledge. Cause-specific limitations for every
of concentration as communicable causes, the mortality cause of death in GBD are detailed in appendix 1
burden has changed in distribution, reducing over time (section 3). Here, we describe cross-cutting limitations
in high-income countries and regions, while persisting with applicability across many causes. First, sparsity of
in low-income countries and regions. Age-standardised data or unreliability of data from specific regions, time
mortality rates due to NCDs decreased in most locations periods, or age groups can influence the accuracy of our
within the high-income; Latin America and the estimates, particularly poor data quality and coverage
Caribbean; north Africa and the Middle east; and central from western, eastern, southern, and central sub-
Europe, eastern Europe, and central Asia super-regions Saharan Africa and south Asia. Second, the quality of
between 1990 and 2021. However, NCDs in the south cause-of-death and verbal-autopsy data rely on accurately
Asia; sub-Saharan Africa; and southeast Asia, east Asia, coded death certificates to the international standards set
and Oceania super-regions have either increased or by the International Classification of Diseases and are

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subject to the practice of the doctor completing the death used to calculate COVID-19 have been fully outlined in
certificate, who may or may not have received training to previous publications,12 but it is important to reiterate
facilitate comparability of reporting underlying causes that COVID-19 estimates are limited by data-source
of death. This process is further complicated by availability. The methods to estimate COVID-19-related
comorbidities at the time of death, which might affect deaths were especially limited in certain regions, such as
the accuracy of both vital-registration and verbal-autopsy sub-Saharan Africa, which means our estimates in these
data sources. A key data-processing method for GBD is areas are solely driven by relationships with covariates.
the re-allocation of incorrectly or vaguely assigned Future development of these data sources is crucial
deaths—referred to as garbage codes11—to a more because estimates improve as the quality of the
accurate, plausible underlying cause of death. This step underlying data sources improves. Subsequent GBD
helps to create comparable cause-specific estimates of cycles will provide revised estimates after additional data
mortality by underlying cause. Third, GBD assesses for recent years become available.
quality of cause-of-death data partly by examining levels
of completeness, which indicate the accuracy with which Future directions
the vital registration can capture deaths that occur in a In the next iteration of GBD, we will include over
location-year, irrespective of the percentage of garbage 100 location-years of vital registration and other data
coding. Data completeness depends on the percentage of types that have been reported since GBD 2021 estimates
well-certified data, which is not necessarily indicative of were produced. Additionally, we will continue to expand
low garbage coding. Fourth, some sources of uncertainty, the estimation of causes of death by disaggregating broad
including the covariates used in models, are not captured categories of causes of death into more detailed causes
in our estimation process. Fifth, we used a negative where available. These improvements aim to enhance
binomial modelling approach to improve our estimation precision and timeliness of estimates of COVID-19-
of deaths for some causes with over-dispersed data, but related deaths and other cause of death. We also plan to
do not have a standardised empirical approach for simplify our approach to estimating COVID-19-related
selecting causes to which we apply this method. Sixth, to deaths. In lieu of the residual OPRM category reported in
provide estimates for locations with low levels of GBD 2021, we will use all available location-years of
completeness, as well as to address the lags in data cause-of-death data to attribute mortality to specific
reporting that occur, our estimates for the most recent causes, removing this residual category. We anticipate
years depend more heavily on the modelling process. For that this method will facilitate more timely and actionable
causes where data are limited, providing estimates with insights for public health planning and policy making,
appropriate uncertainty is preferable to providing no especially as we expect to observe more regular and
information. Seventh, in the calculation of life expectancy modellable mortality patterns in the post-pandemic
decomposition, there is instability when the difference in years. Through these advancements, we will improve the
all-cause deaths is too small. In this case, we use the utility and accuracy of the GBD study as a tool for
reduced Das Gupta equation (appendix 1 section 7). effective public strategies.
Additionally, to avoid assigning positive life-expectancy
contributions to COVID-19-related causes, if the signs Conclusion
for the change in life expectancy and all-cause deaths Findings from GBD 2021 provide a comprehensive
were the same, we used the same reduced Das Gupta overview of long-term mortality trends along with
formula, except in the case that the cause in question was important insights into the COVID-19 pandemic years.
COVID-19-related (either COVID-19 or OPRM), when a The COVID-19 pandemic fundamentally changed the
modified version was used. When viewing life expectancy landscape of global health and mortality. As a leading
decomposition, it is important to understand the effects cause of death, COVID-19 reduced life expectancy in
of fatal discontinuity events, such as earthquakes or 2 years nearly as much as reductions in communicable
conflict. If life-expectancy decomposition is calculated for and NCDs have improved it over decades. The changes in
2 consecutive years, we can see the effect of unique, mortality caused by the pandemic were not predictable
stochastic events, but for the longer time periods, the through the standard GBD estimation methods and
interpretation of the effect of these events will be required the development and application of novel
misleading. This method works well with causes that estimation methods as the pandemic emerged in real
have continuous time trends, and not for causes that time. These timely updates on causes of death are
have mortality spikes in select years and locations. This essential for monitoring progress, identifying prevailing
type of event confounds true health trends within a time health concerns, guiding targeted interventions, and
period because the absence or presence of a disaster is optimising resource allocation. GBD 2021 shows that
seen as a change in life expectancy. Finally, this cycle of better life expectancy outcomes might be achieved by
GBD contains additional limitations that pertain to leveraging past successes in mortality reduction. If future
modelling deaths and related mortality from the policy efforts are guided by the successes made in
COVID-19 pandemic. The limitations of the methods countries and regions with effective disease-mitigation

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programmes, such achievements might be replicated in Juan Pablo Arab, Jalal Arabloo, Mosab Arafat, Aleksandr Y Aravkin,
locations where high mortality persists. While COVID-19 Demelash Areda, Abdulfatai Aremu, Olatunde Aremu, Hany Ariffin,
Mesay Arkew, Benedetta Armocida, Michael Benjamin Arndt,
and other health challenges continue, GBD 2021 can offer Johan Ärnlöv, Mahwish Arooj, Anton A Artamonov, Judie Arulappan,
valuable guidance for public health investment and policy Raphael Taiwo Aruleba, Ashokan Arumugam, Malke Asaad,
making. Mohsen Asadi-Lari, Akeza Awealom Asgedom,
Mona Asghariahmadabad, Mohammad Asghari-Jafarabadi,
GBD 2021 Causes of Death Collaborators
Muhammad Ashraf, Armin Aslani, Thomas Astell-Burt,
Mohsen Naghavi*, Kanyin Liane Ong*, Amirali Aali, Hazim S Ababneh,
Mohammad Athar, Seyyed Shamsadin Athari,
Yohannes Habtegiorgis Abate, Cristiana Abbafati,
Bantalem Tilaye Tilaye Atinafu, Habtamu Wondmagegn Atlaw,
Rouzbeh Abbasgholizadeh, Mohammadreza Abbasian,
Prince Atorkey, Maha Moh’d Wahbi Atout, Alok Atreya, Avinash Aujayeb,
Mohsen Abbasi-Kangevari, Hedayat Abbastabar, Samar Abd ElHafeez,
Marcel Ausloos, Abolfazl Avan, Atalel Fentahun Awedew,
Michael Abdelmasseh, Sherief Abd-Elsalam, Ahmed Abdelwahab,
Amlaku Mulat Aweke, Beatriz Paulina Ayala Quintanilla,
Mohammad Abdollahi, Mohammad-Amin Abdollahifar,
Haleh Ayatollahi, Jose L Ayuso-Mateos, Seyed Mohammad Ayyoubzadeh,
Meriem Abdoun, Deldar Morad Abdulah, Auwal Abdullahi,
Sina Azadnajafabad, Rui M S Azevedo, Ahmed Y Azzam, Darshan B B,
Mesfin Abebe, Samrawit Shawel Abebe, Aidin Abedi,
Abraham Samuel Babu, Muhammad Badar, Ashish D Badiye,
Kedir Hussein Abegaz, E S Abhilash, Hassan Abidi, Olumide Abiodun,
Soroush Baghdadi, Nasser Bagheri, Sara Bagherieh, Sulaiman Bah,
Richard Gyan Aboagye, Hassan Abolhassani, Meysam Abolmaali,
Saeed Bahadorikhalili, Najmeh Bahmanziari, Ruhai Bai, Atif Amin Baig,
Mohamed Abouzid, Girma Beressa Aboye, Lucas Guimarães Abreu,
Jennifer L Baker, Abdulaziz T Bako, Ravleen Kaur Bakshi,
Woldu Aberhe Abrha, Dariush Abtahi, Samir Abu Rumeileh,
Senthilkumar Balakrishnan, Madhan Balasubramanian,
Hasan Abualruz, Bilyaminu Abubakar, Eman Abu-Gharbieh,
Ovidiu Constantin Baltatu, Kiran Bam, Maciej Banach,
Niveen ME Abu-Rmeileh, Salahdein Aburuz, Ahmed Abu-Zaid,
Soham Bandyopadhyay, Palash Chandra Banik, Hansi Bansal,
Manfred Mario Kokou Accrombessi, Tadele Girum Adal,
Kannu Bansal, Franca Barbic, Martina Barchitta, Mainak Bardhan,
Abdu A Adamu, Isaac Yeboah Addo, Giovanni Addolorato,
Erfan Bardideh, Suzanne Lyn Barker-Collo, Till Winfried Bärnighausen,
Akindele Olupelumi Adebiyi, Victor Adekanmbi, Abiola Victor Adepoju,
Francesco Barone-Adesi, Hiba Jawdat Barqawi, Lope H Barrero,
Charles Oluwaseun Adetunji, Juliana Bunmi Adetunji,
Amadou Barrow, Sandra Barteit, Lingkan Barua, Zarrin Basharat,
Temitayo Esther Adeyeoluwa, Daniel Adedayo Adeyinka,
Azadeh Bashiri, Afisu Basiru, Pritish Baskaran, Buddha Basnyat,
Olorunsola Israel Adeyomoye, Biruk Adie Adie Admass,
Quique Bassat, João Diogo Basso, Ann V L Basting, Sanjay Basu,
Qorinah Estiningtyas Sakilah Adnani, Saryia Adra,
Kavita Batra, Bernhard T Baune, Mohsen Bayati,
Aanuoluwapo Adeyimika Afolabi, Muhammad Sohail Afzal, Saira Afzal,
Nebiyou Simegnew Bayileyegn, Thomas Beaney, Neeraj Bedi,
Suneth Buddhika Agampodi, Pradyumna Agasthi, Manik Aggarwal,
Massimiliano Beghi, Emad Behboudi, Priyamadhaba Behera,
Shahin Aghamiri, Feleke Doyore Agide, Antonella Agodi,
Amir Hossein Behnoush, Masoud Behzadifar, Maryam Beiranvand,
Anurag Agrawal, Williams Agyemang-Duah, Bright Opoku Ahinkorah,
Diana Fernanda Bejarano Ramirez, Yannick Béjot,
Aqeel Ahmad, Danish Ahmad, Firdos Ahmad, Muayyad M Ahmad,
Sefealem Assefa Belay, Chalie Mulu Belete, Michelle L Bell,
Sajjad Ahmad, Shahzaib Ahmad, Tauseef Ahmad, Keivan Ahmadi,
Muhammad Bashir Bello, Olorunjuwon Omolaja Bello, Luis Belo,
Amir Mahmoud Ahmadzade, Ali Ahmed, Ayman Ahmed,
Apostolos Beloukas, Rose Grace Bender, Isabela M Bensenor,
Haroon Ahmed, Luai A Ahmed, Mehrunnisha Sharif Ahmed,
Azizullah Beran, Zombor Berezvai, Alemshet Yirga Berhie,
Meqdad Saleh Ahmed, Muktar Beshir Ahmed, Syed Anees Ahmed,
Betyna N Berice, Robert S Bernstein, Gregory J Bertolacci,
Marjan Ajami, Budi Aji, Essona Matatom Akara, Hossein Akbarialiabad,
Paulo J G Bettencourt, Kebede A Beyene, Devidas S Bhagat,
Karolina Akinosoglou, Tomi Akinyemiju, Mohammed Ahmed Akkaif,
Akshaya Srikanth Bhagavathula, Neeraj Bhala, Ashish Bhalla,
Samuel Akyirem, Hanadi Al Hamad, Syed Mahfuz Al Hasan,
Dinesh Bhandari, Kayleigh Bhangdia, Nikha Bhardwaj, Pankaj Bhardwaj,
Fares Alahdab, Samer O Alalalmeh, Tariq A Alalwan, Ziyad Al-Aly,
Prarthna V Bhardwaj, Ashish Bhargava, Sonu Bhaskar, Vivek Bhat,
Khurshid Alam, Manjurul Alam, Noore Alam,
Gurjit Kaur Bhatti, Jasvinder Singh Bhatti, Manpreet S Bhatti,
Rasmieh Mustafa Al-amer, Fahad Mashhour Alanezi, Turki M Alanzi,
Rajbir Bhatti, Zulfiqar A Bhutta, Boris Bikbov, Jessica Devin Bishai,
Sayer Al-Azzam, Almaza Albakri, Mohammed Albashtawy,
Catherine Bisignano, Francesca Bisulli, Atanu Biswas, Bijit Biswas,
Mohammad T AlBataineh, Jacqueline Elizabeth Alcalde-Rabanal,
Saeid Bitaraf, Bikes Destaw Bitew, Veera R Bitra, Tone Bjørge,
Khalifah A Aldawsari, Wafa A Aldhaleei, Robert W Aldridge,
Micheal Kofi Boachie, Mary Sefa Boampong, Anca Vasilica Bobirca,
Haileselasie Berhane Alema, Mulubirhan Assefa Alemayohu,
Virginia Bodolica, Aadam Olalekan Bodunrin, Eyob Ketema Bogale,
Sharifullah Alemi, Yihun Mulugeta Alemu, Adel Ali Saeed Al-Gheethi,
Kassawmar Angaw Bogale, Somayeh Bohlouli,
Khalid F Alhabib, Fadwa Alhalaiqa Naji Alhalaiqa,
Obasanjo Afolabi Bolarinwa, Archith Boloor, Milad Bonakdar Hashemi,
Mohammed Khaled Al-Hanawi, Abid Ali, Amjad Ali, Liaqat Ali,
Aime Bonny, Kaustubh Bora, Berrak Bora Basara, Hamed Borhany,
Mohammed Usman Ali, Rafat Ali, Shahid Ali, Syed Shujait Shujait Ali,
Arturo Borzutzky, Souad Bouaoud, Antoine Boustany, Christopher Boxe,
Gianfranco Alicandro, Sheikh Mohammad Alif, Reyhaneh Alikhani,
Edward J Boyko, Oliver J Brady, Dejana Braithwaite, Luisa C Brant,
Yousef Alimohamadi, Ahmednur Adem Aliyi, Mohammad A M Aljasir,
Michael Brauer, Alexandra Brazinova, Javier Brazo-Sayavera,
Syed Mohamed Aljunid, François Alla, Peter Allebeck,
Nicholas J K Breitborde, Susanne Breitner, Hermann Brenner,
Sabah Al-Marwani, Sadeq Ali Ali Al-Maweri, Joseph Uy Almazan,
Andrey Nikolaevich Briko, Nikolay Ivanovich Briko, Gabrielle Britton,
Hesham M Al-Mekhlafi, Louay Almidani, Omar Almidani,
Julie Brown, Traolach Brugha, Norma B Bulamu, Lemma N Bulto,
Mahmoud A Alomari, Basem Al-Omari, Jordi Alonso, Jaber S Alqahtani,
Danilo Buonsenso, Richard A Burns, Reinhard Busse, Yasser Bustanji,
Shehabaldin Alqalyoobi, Ahmed Yaseen Alqutaibi,
Nadeem Shafique Butt, Zahid A Butt,
Salman Khalifah Al-Sabah, Zaid Altaany, Awais Altaf, Jaffar A Al-Tawfiq,
Florentino Luciano Caetano dos Santos, Daniela Calina,
Khalid A Altirkawi, Deborah Oyine Aluh, Nelson Alvis-Guzman,
Luis Alberto Cámera, Luciana Aparecida Campos,
Hassan Alwafi, Yaser Mohammed Al-Worafi, Hany Aly, Safwat Aly,
Ismael R Campos-Nonato, Chao Cao, Yin Cao, Angelo Capodici,
Karem H Alzoubi, Reza Amani, Azmeraw T Amare, Prince M Amegbor,
Rosario Cárdenas, Sinclair Carr, Giulia Carreras, Juan J Carrero,
Edward Kwabena Ameyaw, Tarek Tawfik Amin, Alireza Amindarolzarbi,
Andrea Carugno, Cristina G Carvalheiro, Felix Carvalho,
Sohrab Amiri, Mohammad Hosein Amirzade-Iranaq, Hubert Amu,
Márcia Carvalho, Joao Mauricio Castaldelli-Maia,
Dickson A Amugsi, Ganiyu Adeniyi Amusa, Robert Ancuceanu,
Carlos A Castañeda-Orjuela, Giulio Castelpietra, Ferrán Catalá-López,
Deanna Anderlini, David B Anderson, Pedro Prata Andrade,
Alberico L Catapano, Maria Sofia Cattaruzza, Christopher R Cederroth,
Catalina Liliana Andrei, Tudorel Andrei, Colin Angus, Abhishek Anil,
Luca Cegolon, Francieli Cembranel, Muthia Cenderadewi, Kelly M Cercy,
Sneha Anil, Amir Anoushiravani, Hossein Ansari, Ansariadi Ansariadi,
Ester Cerin, Muge Cevik, Joshua Chadwick, Yaacoub Chahine,
Alireza Ansari-Moghaddam, Catherine M Antony, Ernoiz Antriyandarti,
Chiranjib Chakraborty, Promit Ananyo Chakraborty,
Davood Anvari, Saeid Anvari, Saleha Anwar, Sumadi Lukman Anwar,
Jeffrey Shi Kai Chan, Raymond N C Chan, Rama Mohan Chandika,
Razique Anwer, Anayochukwu Edward Anyasodor, Muhammad Aqeel,

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Gashaw Sisay Chanie, Periklis Charalampous, Vijay Kumar Chattu, Ingeborg Forthun, Daniela Fortuna, Matteo Foschi,
Pankaj Chaturvedi, Victoria Chatzimavridou-Grigoriadou, Kayode Raphael Fowobaje, Kate Louise Francis,
Akhilanand Chaurasia, Angela W Chen, An-Tian Chen, Richard Charles Franklin, Alberto Freitas, Joseph Friedman,
Catherine S Chen, Haowei Chen, Meng Xuan Chen, Simiao Chen, Sara D Friedman, Takeshi Fukumoto, John E Fuller, Blima Fux,
Ching-Yu Cheng, Esther T W Cheng, Nicolas Cherbuin, Peter Andras Gaal, Muktar A Gadanya, Abhay Motiramji Gaidhane,
Wondimye Ashenafi Cheru, Ju-Huei Chien, Odgerel Chimed-Ochir, Santosh Gaihre, Emmanuela Gakidou, Yaseen Galali, Natalie C Galles,
Ritesh Chimoriya, Patrick R Ching, Jesus Lorenzo Chirinos-Caceres, Silvano Gallus, Mandukhai Ganbat, Aravind P Gandhi,
Abdulaal Chitheer, William C S Cho, Bryan Chong, Hitesh Chopra, Balasankar Ganesan, Mohammad Arfat Ganiyani, MA Garcia-Gordillo,
Sonali Gajanan Choudhari, Rajiv Chowdhury, William M Gardner, Jalaj Garg, Naval Garg, Rupesh K Gautam,
Devasahayam J Christopher, Isaac Sunday Chukwu, Eric Chung, Semiu Olatunde Gbadamosi, Tilaye Gebru Gebi, Miglas W Gebregergis,
Erin Chung, Eunice Chung, Sheng-Chia Chung, Mesfin Gebrehiwot, Teferi Gebru Gebremeskel,
Muhammad Chutiyami, Zinhle Cindi, Iolanda Cioffi, Simona Roxana Georgescu, Tamirat Getachew, Peter W Gething,
Mareli M Claassens, Rafael M Claro, Kaleb Coberly, Rebecca M Cogen, Molla Getie, Keyghobad Ghadiri, Sulmaz Ghahramani,
Alyssa Columbus, Haley Comfort, Joao Conde, Samuele Cortese, Khalid Yaser Ghailan, Mohammad-Reza Ghasemi,
Paolo Angelo Cortesi, Vera Marisa Costa, Simona Costanzo, Ghazal Ghasempour Dabaghi, Afsaneh Ghasemzadeh,
Ewerton Cousin, Rosa A S Couto, Richard G Cowden, Ahmad Ghashghaee, Fariba Ghassemi, Ramy Mohamed Ghazy,
Kenneth Michael Cramer, Michael H Criqui, Natália Cruz-Martins, Ajnish Ghimire, Sama Ghoba, Maryam Gholamalizadeh,
Silvia Magali Cuadra-Hernández, Garland T Culbreth, Patricia Cullen, Asadollah Gholamian, Ali Gholamrezanezhad, Nasim Gholizadeh,
Matthew Cunningham, Maria paula Curado, Sriharsha Dadana, Mahsa Ghorbani, Pooyan Ghorbani Vajargah, Aloke Gopal Ghoshal,
Omid Dadras, Siyu Dai, Xiaochen Dai, Zhaoli Dai, Lachlan L Dalli, Paramjit Singh Gill, Tiffany K Gill, Richard F Gillum,
Giovanni Damiani, Jiregna Darega Gela, Jai K Das, Saswati Das, Themba G Ginindza, Alem Girmay, James C Glasbey,
Subasish Das, Ana Maria Dascalu, Nihar Ranjan Dash, Mohsen Dashti, Elena V Gnedovskaya, Laszlo Göbölös, Myron Anthony Godinho,
Anna Dastiridou, Gail Davey, Claudio Alberto Dávila-Cervantes, Amit Goel, Ali Golchin, Mohamad Goldust, Mahaveer Golechha,
Nicole Davis Weaver, Kairat Davletov, Diego De Leo, Katie de Luca, Pouya Goleij, Nelson G M Gomes, Philimon N Gona,
Aklilu Tamire Debele, Shayom Debopadhaya, Louisa Degenhardt, Sameer Vali Gopalani, Giuseppe Gorini, Houman Goudarzi,
Azizallah Dehghan, Lee Deitesfeld, Cristian Del Bo’, Alessandra C Goulart, Bárbara Niegia Garcia Goulart, Anmol Goyal,
Ivan Delgado-Enciso, Berecha Hundessa Demessa, Ayman Grada, Simon Matthew Graham, Michal Grivna,
Andreas K Demetriades, Ke Deng, Xinlei Deng, Edgar Denova-Gutiérrez, Giuseppe Grosso, Shi-Yang Guan, Giovanni Guarducci,
Niloofar Deravi, Nebiyu Dereje, Nikolaos Dervenis, Emina Dervišević, Mohammed Ibrahim Mohialdeen Gubari, Mesay Dechasa Gudeta,
Don C Des Jarlais, Hardik Dineshbhai Desai, Rupak Desai, Avirup Guha, Stefano Guicciardi, Rafael Alves Guimarães,
Vinoth Gnana Chellaiyan Devanbu, Syed Masudur Rahman Dewan, Snigdha Gulati, Damitha Asanga Gunawardane, Sasidhar Gunturu,
Arkadeep Dhali, Kuldeep Dhama, Meghnath Dhimal, Sameer Dhingra, Cui Guo, Anish Kumar Gupta, Bhawna Gupta, Manoj Kumar Gupta,
Vishal R Dhulipala, Diana Dias da Silva, Daniel Diaz, Michael J Diaz, Mohak Gupta, Rajat Das Gupta, Rajeev Gupta, Sapna Gupta,
Adriana Dima, Delaney D Ding, Huanghe Ding, Veer Bala Gupta, Vijai Kumar Gupta, Vivek Kumar Gupta,
Ricardo Jorge Dinis-Oliveira, M Ashworth Dirac, Shirin Djalalinia, Lami Gurmessa, Reyna Alma Gutiérrez, Farrokh Habibzadeh,
Thao Huynh Phuong Do, Camila Bruneli do Prado, Saeid Doaei, Parham Habibzadeh, Rasool Haddadi, Mostafa Hadei, Najah R Hadi,
Masoud Dodangeh, Milad Dodangeh, Sushil Dohare, Nils Haep, Nima Hafezi-Nejad, Alemayehu Hailu, Arvin Haj-Mirzaian,
Klara Georgieva Dokova, Christiane Dolecek, Regina- Esam S Halboub, Brian J Hall, Sebastian Haller, Rabih Halwani,
Mae Villanueva Dominguez, Wanyue Dong, Deepa Dongarwar, Randah R Hamadeh, Sajid Hameed, Samer Hamidi, Erin B Hamilton,
Mario D’Oria, Fariba Dorostkar, E Ray Dorsey, Wendel Mombaque Chieh Han, Qiuxia Han, Asif Hanif, Nasrin Hanifi, Graeme J Hankey,
dos Santos, Rajkumar Doshi, Leila Doshmangir, Robert Kokou Dowou, Fahad Hanna, Md Abdul Hannan, Md Nuruzzaman Haque,
Tim Robert Driscoll, Haneil Larson Dsouza, Viola Dsouza, Mi Du, Harapan Harapan, Arief Hargono, Josep Maria Haro,
John Dube, Bruce B Duncan, Andre Rodrigues Duraes, Ahmed I Hasaballah, Ikramul Hasan, M Tasdik Hasan,
Senbagam Duraisamy, Oyewole Christopher Durojaiye, Laura Dwyer- Hamidreza Hasani, Mohammad Hasanian, Abdiwahab Hashi,
Lindgren, Paulina Agnieszka Dzianach, Arkadiusz Marian Dziedzic, Md Saquib Hasnain, Ikrama Hassan, Soheil Hassanipour,
Abdel Rahman E’mar, Ejemai Eboreime, Alireza Ebrahimi, Hadi Hassankhani, Johannes Haubold, Rasmus J Havmoeller,
Chidiebere Peter Echieh, Hisham Atan Edinur, David Edvardsson, Simon I Hay, Jiawei He, Jeffrey J Hebert, Omar E Hegazi,
Kristina Edvardsson, Defi Efendi, Ferry Efendi, Diyan Ermawan Effendi, Golnaz Heidari, Mohammad Heidari, Mahsa Heidari-Foroozan,
Terje Andreas Eikemo, Ebrahim Eini, Michael Ekholuenetale, Bartosz Helfer, Delia Hendrie, Brenda Yuliana Herrera-Serna,
Temitope Cyrus Ekundayo, Iman El Sayed, Iffat Elbarazi, Claudiu Herteliu, Hamed Hesami, Kamal Hezam, Catherine L Hill,
Teshome Bekele Elema, Noha Mousaad Elemam, Frank J Elgar, Yuta Hiraike, Ramesh Holla, Nobuyuki Horita, Md Mahbub Hossain,
Islam Y Elgendy, Ghada Metwally Tawfik ElGohary, Sahadat Hossain, Mohammad-Salar Hosseini, Hassan Hosseinzadeh,
Hala Rashad Elhabashy, Muhammed Elhadi, Waseem El-Huneidi, Mehdi Hosseinzadeh, Ahmad Hosseinzadeh Adli, Mihaela Hostiuc,
Legesse Tesfaye Elilo, Omar Abdelsadek Abdou Elmeligy, Sorin Hostiuc, Mohamed Hsairi, Vivian Chia-rong Hsieh,
Mohamed A Elmonem, Mohammed Elshaer, Ibrahim Elsohaby, Rebecca L Hsu, Chengxi Hu, Junjie Huang, Michael Hultström,
Theophilus I Emeto, Luchuo Engelbert Bain, Ayesha Humayun, Tsegaye Gebreyes Hundie, Javid Hussain,
Ryenchindorj Erkhembayar, Christopher Imokhuede Esezobor, M Azhar Hussain, Nawfal R Hussein, Foziya Mohammed Hussien,
Babak Eshrati, Sharareh Eskandarieh, Juan Espinosa-Montero, Hong-Han Huynh, Bing-Fang Hwang, Segun Emmanuel Ibitoye,
Habtamu Esubalew, Farshid Etaee, Natalia Fabin, Khalid S Ibrahim, Pulwasha Maria Iftikhar, Desta Ijo, Adalia I Ikiroma,
Adewale Oluwaseun Fadaka, Adeniyi Francis Fagbamigbe, Kevin S Ikuta, Paul Chukwudi Ikwegbue, Olayinka Stephen Ilesanmi,
Ayesha Fahim, Saman Fahimi, Aliasghar Fakhri-Demeshghieh, Irena M Ilic, Milena D Ilic, Mohammad Tarique Imam,
Luca Falzone, Mohammad Fareed, Carla Sofia e Sá Farinha, Mustapha Immurana, Sumant Inamdar, Endang Indriasih,
MoezAlIslam Ezzat Mahmoud Faris, Pawan Sirwan Faris, Andre Faro, Muhammad Iqhrammullah, Arnaud Iradukunda,
Abidemi Omolara Fasanmi, Ali Fatehizadeh, Hamed Fattahi, Kenneth Chukwuemeka Iregbu, Md Rabiul Islam,
Nelsensius Klau Fauk, Pooria Fazeli, Valery L Feigin, Alireza Feizkhah, Sheikh Mohammed Shariful Islam, Farhad Islami, Faisal Ismail,
Ginenus Fekadu, Xiaoru Feng, Seyed-Mohammad Fereshtehnejad, Nahlah Elkudssiah Ismail, Hiroyasu Iso, Gaetano Isola, Masao Iwagami,
Abdullah Hamid Feroze, Daniela Ferrante, Alize J Ferrari, Chidozie C D Iwu, Ihoghosa Osamuyi Iyamu, Mahalaxmi Iyer,
Nuno Ferreira, Getahun Fetensa, Bikila Regassa Feyisa, Irina Filip, Linda Merin J, Jalil Jaafari, Louis Jacob, Kathryn H Jacobsen,
Florian Fischer, Joanne Flavel, David Flood, Bobirca Teodor Florin, Farhad Jadidi-Niaragh, Morteza Jafarinia, Abdollah Jafarzadeh,
Nataliya A Foigt, Morenike Oluwatoyin Folayan, Khushleen Jaggi, Kasra Jahankhani, Nader Jahanmehr,

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Haitham Jahrami, Nityanand Jain, Ammar Abdulrahman Jairoun, Azzam A Maghazachi, Sandeep B Maharaj, Soleiman Mahjoub,
Abhishek Jaiswal, Elham Jamshidi, Mark M Janko, Mansour Adam Mahmoud, Alireza Mahmoudi, Elham Mahmoudi,
Abubakar Ibrahim Jatau, Sabzali Javadov, Tahereh Javaheri, Razzagh Mahmoudi, Azeem Majeed, Irsa Fatima Makhdoom,
Sathish Kumar Jayapal, Shubha Jayaram, Rime Jebai, Sun Ha Jee, Elaheh Malakan Rad, Venkatesh Maled, Reza Malekzadeh,
Jayakumar Jeganathan, Anil K Jha, Ravi Prakash Jha, Heng Jiang, Armaan K Malhotra, Kashish Malhotra, Ahmad Azam Malik,
Yingzhao Jin, Olatunji Johnson, Mohammad Jokar, Jost B Jonas, Iram Malik, Deborah Carvalho Malta, Abdullah A Mamun,
Tamas Joo, Abel Joseph, Nitin Joseph, Charity Ehimwenma Joshua, Pejman Mansouri, Mohammad Ali Mansournia,
Grace Joshy, Jacek Jerzy Jozwiak, Mikk Jürisson, Vaishali K, Lorenzo Giovanni Mantovani, Sajid Maqsood, Bishnu P Marasini,
Billingsley Kaambwa, Ali Kabir, Zubair Kabir, Vidya Kadashetti, Hamid Reza Marateb, Joemer C Maravilla, Agustina M Marconi,
Dler Hussein Kadir, Rizwan Kalani, Laleh R Kalankesh, Parham Mardi, Mirko Marino, Abdoljalal Marjani, Gabriel Martinez,
Leila R Kalankesh, Feroze Kaliyadan, Sanjay Kalra, Vineet Kumar Kamal, Bernardo Alfonso Martinez-Guerra, Ramon Martinez-Piedra,
Sivesh Kathir Kamarajah, Rajesh Kamath, Zahra Kamiab, Daniela Martini, Santi Martini, Francisco Rogerlândio Martins-Melo,
Naser Kamyari, Thanigaivelan Kanagasabai, Tanuj Kanchan, Miquel Martorell, Wolfgang Marx, Sharmeen Maryam,
Himal Kandel, Arun R Kanmanthareddy, Edmund Wedam Kanmiki, Roy Rillera Marzo, Anthony Masaka, Awoke Masrie,
Kehinde Kazeem Kanmodi, Suthanthira Kannan S, Stephanie Mathieson, Alexander G Mathioudakis, Manu Raj Mathur,
Sushil Kumar Kansal, Rami S Kantar, Neeti Kapoor, Jishanth Mattumpuram, Richard Matzopoulos, Richard James Maude,
Mehrdad Karajizadeh, Shama D Karanth, Reema A Karasneh, Andrea Maugeri, Pallab K Maulik, Mahsa Mayeli, Maryam Mazaheri,
Ibraheem M Karaye, André Karch, Asima Karim, Salah Eddin Karimi, Mohsen Mazidi, John J McGrath, Martin McKee,
Arman Karimi Behnagh, Faizan Zaffar Kashoo, Anna Laura W McKowen, Susan A McLaughlin, Steven M McPhail,
Qalandar Hussein Abdulkarim Kasnazani, Hengameh Kasraei, Enkeleint A Mechili, John Robert Carabeo Medina, Rishi P Mediratta,
Nicholas J Kassebaum, Molly B Kassel, Joonas H Kauppila, Navjot Kaur, Jitendra Kumar Meena, Rahul Mehra, Kamran Mehrabani-Zeinabad,
Norito Kawakami, Gbenga A Kayode, Foad Kazemi, Sina Kazemian, Entezar Mehrabi Nasab, Tesfahun Mekene Meto,
Tahseen Haider Kazmi, Getu Mosisa Kebebew, Adera Debella Kebede, Gebrekiros Gebremichael Meles, Max Alberto Mendez Mendez-Lopez,
Fassikaw Kebede, Tibebeselassie S Keflie, Peter Njenga Keiyoro, Walter Mendoza, Ritesh G Menezes, Belayneh Mengist,
Cathleen Keller, Jaimon Terence Kelly, John H Kempen, Jessica A Kerr, Alexios-Fotios A Mentis, Sultan Ayoub Meo, Haftu Asmerom Meresa,
Emmanuelle Kesse-Guyot, Himanshu Khajuria, Atte Meretoja, Tuomo J Meretoja, Abera M Mersha,
Amirmohammad Khalaji, Nauman Khalid, Anees Ahmed Khalil, Bezawit Afework Mesfin, Tomislav Mestrovic,
Alireza Khalilian, Faham Khamesipour, Ajmal Khan, Kukulege Chamila Dinushi Mettananda, Sachith Mettananda,
Asaduzzaman Khan, Gulfaraz Khan, Ikramullah Khan, Imteyaz A Khan, Peter Meylakhs, Adquate Mhlanga, Laurette Mhlanga, Tianyue Mi,
M Nuruzzaman Khan, Maseer Khan, Mohammad Jobair Khan, Tomasz Miazgowski, Georgia Micha, Irmina Maria Michalek,
Moien AB Khan, Zeeshan Ali Khan, Mahammed Ziauddin Khan suheb, Ted R Miller, Edward J Mills, Le Huu Nhat Minh, GK Mini,
Shaghayegh Khanmohammadi, Khaled Khatab, Fatemeh Khatami, Pouya Mir Mohammad Sadeghi, Andreea Mirica, Antonio Mirijello,
Haitham Khatatbeh, Moawiah Mohammad Khatatbeh, Erkin M Mirrakhimov, Mizan Kiros Mirutse, Maryam Mirzaei,
Armin Khavandegar, Hamid Reza Khayat Kashani, Feriha Fatima Khidri, Awoke Misganaw, Ashim Mishra, Sanjeev Misra, Philip B Mitchell,
Elaheh Khodadoust, Mohammad Khorgamphar, Moein Khormali, Prasanna Mithra, Chaitanya Mittal, Mohammadreza Mobayen,
Zahra Khorrami, Ahmad Khosravi, Mohammad Ali Khosravi, Madeline E Moberg, Ashraf Mohamadkhani, Jama Mohamed,
Zemene Demelash Kifle, Grace Kim, Jihee Kim, Kwanghyun Kim, Mouhand F H Mohamed, Nouh Saad Mohamed,
Min Seo Kim, Yun Jin Kim, Ruth W Kimokoti, Kasey E Kinzel, Sakineh Mohammad-Alizadeh-Charandabi, Soheil Mohammadi,
Adnan Kisa, Sezer Kisa, Desmond Klu, Ann Kristin Skrindo Knudsen, Abdollah Mohammadian-Hafshejani, Noushin Mohammadifard,
Jonathan M Kocarnik, Sonali Kochhar, Timea Kocsis, David S Q Koh, Hassen Mohammed, Hussen Mohammed, Mustapha Mohammed,
Ali-Asghar Kolahi, Kairi Kolves, Farzad Kompani, Gerbrand Koren, Salahuddin Mohammed, Shafiu Mohammed, Viswanathan Mohan,
Soewarta Kosen, Karel Kostev, Parvaiz A Koul, Hoda Mojiri-Forushani, Amin Mokari, Ali H Mokdad, Sabrina Molinaro,
Sindhura Lakshmi Koulmane Laxminarayana, Kewal Krishan, Mariam Molokhia, Sara Momtazmanesh, Lorenzo Monasta,
Hare Krishna, Varun Krishna, Vijay Krishnamoorthy, Stefania Mondello, Mohammad Ali Moni, AmirAli Moodi Ghalibaf,
Yuvaraj Krishnamoorthy, Kris J Krohn, Barthelemy Kuate Defo, Maryam Moradi, Yousef Moradi, Maziar Moradi-Lakeh,
Burcu Kucuk Bicer, Md Abdul Kuddus, Mohammed Kuddus, Maliheh Moradzadeh, Paula Moraga, Lidia Morawska,
Ilari Kuitunen, Mukhtar Kulimbet, Vishnutheertha Kulkarni, Rafael Silveira Moreira, Negar Morovatdar, Shane Douglas Morrison,
Akshay Kumar, Ashish Kumar, Harish Kumar, Manasi Kumar, Jakub Morze, Jonathan F Mosser, Rohith Motappa, Vincent Mougin,
Rakesh Kumar, Madhulata Kumari, Fantahun Tarekegn Kumie, Simin Mouodi, Parsa Mousavi, Seyed Ehsan Mousavi,
Satyajit Kundu, Om P Kurmi, Asep Kusnali, Dian Kusuma, Amin Mousavi Khaneghah, Emmanuel A Mpolya, Matías Mrejen,
Alexander Kwarteng, Ilias Kyriopoulos, Hmwe Hmwe Kyu, Sumaira Mubarik, Lorenzo Muccioli, Ulrich Otto Mueller, Faraz Mughal,
Carlo La Vecchia, Ben Lacey, Muhammad Awwal Ladan, Lucie Laflamme, Sumoni Mukherjee, Francesk Mulita, Kavita Munjal,
Abraham K Lagat, Anton C J Lager, Abdelilah Lahmar, Efrén Murillo-Zamora, Fungai Musaigwa, Khaled M Musallam,
Daphne Teck Ching Lai, Dharmesh Kumar Lal, Ratilal Lalloo, Ahmad Mustafa, Ghulam Mustafa, Saravanan Muthupandian,
Tea Lallukka, Hilton Lam, Judit Lám, Kelsey R Landrum, Raman Muthusamy, Muhammad Muzaffar, Woojae Myung,
Francesco Lanfranchi, Justin J Lang, Berthold Langguth, Ahamarshan Jayaraman Nagarajan, Gabriele Nagel, Pirouz Naghavi,
Van Charles Lansingh, Ariane Laplante-Lévesque, Bagher Larijani, Aliya Naheed, Ganesh R Naik, Gurudatta Naik, Firzan Nainu,
Anders O Larsson, Savita Lasrado, Zohra S Lassi, Kamaluddin Latief, Sanjeev Nair, Hastyar Hama Rashid Najmuldeen,
Kaveh Latifinaibin, Paolo Lauriola, Nhi Huu Hanh Le, Thao Thi Thu Le, Noureddin Nakhostin Ansari, Vinay Nangia, Atta Abbas Naqvi,
Trang Diep Thanh Le, Caterina Ledda, Jorge R Ledesma, Munjae Lee, Sreenivas Narasimha Swamy, Aparna Ichalangod Narayana,
Paul H Lee, Seung Won Lee, Shaun Wen Huey Lee, Wei-Chen Lee, Shumaila Nargus, Bruno Ramos Nascimento, Gustavo G Nascimento,
Yo Han Lee, Kate E LeGrand, James Leigh, Elvynna Leong, Samar Nasehi, Abdulqadir J Nashwan, Zuhair S Natto, Javaid Nauman,
Temesgen L Lerango, Ming-Chieh Li, Wei Li, Xiaopan Li, Yichong Li, Muhammad Naveed, Biswa Prakash Nayak, Vinod C Nayak,
Zhihui Li, Virendra S Ligade, Andrew Tiyamike Makhiringa Likaka, Athare Nazri-Panjaki, Rawlance Ndejjo, Sabina Onyinye Nduaguba,
Lee-Ling Lim, Stephen S Lim, Megan Lindstrom, Christine Linehan, Hadush Negash, Ionut Negoi, Ruxandra Irina Negoi,
Chaojie Liu, Gang Liu, Jue Liu, Runben Liu, Shiwei Liu, Xiaofeng Liu, Serban Mircea Negru, Seyed Aria Nejadghaderi, Chakib Nejjari,
Xuefeng Liu, Erand Llanaj, Michael J Loftus, Rubén López-Bueno, Evangelia Nena, Samata Nepal, Marie Ng, Haruna Asura Nggada,
Platon D Lopukhov, Arianna Maever Loreche, Stefan Lorkowski, Georges Nguefack-Tsague, Josephine W Ngunjiri, Anh Hoang Nguyen,
Paulo A Lotufo, Rafael Lozano, Jailos Lubinda, Giancarlo Lucchetti, Dang H Nguyen, Hau Thi Hien Nguyen, Phat Tuan Nguyen,
Alessandra Lugo, Raimundas Lunevicius, Zheng Feei Ma, Van Thanh Nguyen, Robina Khan Niazi, Katie R Nielsen,
Kelsey Lynn Maass, Nikolaos Machairas, Monika Machoy, Yeshambel T Nigatu, Taxiarchis Konstantinos Nikolouzakis,
Farzan Madadizadeh, Christian Madsen, Áurea M Madureira-Carvalho, Ali Nikoobar, Fatemeh Nikoomanesh, Amin Reza Nikpoor,

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Dina Nur Anggraini Ningrum, Chukwudi A Nnaji, Antonio Luiz P Ribeiro, Jennifer Rickard, Hannah R Riva,
Lawrence Achilles Nnyanzi, Efaq Ali Noman, Shuhei Nomura, Hannah Elizabeth Robinson-Oden, Célia Fortuna Rodrigues,
Mamoona Noreen, Nafise Noroozi, Bo Norrving, Jean Jacques Noubiap, Mónica Rodrigues, Leonardo Roever, Emma Lynn Best Rogowski,
Amanda Novotney, Chisom Adaobi Nri-Ezedi, George Ntaios, Peter Rohloff, Debby Syahru Romadlon, Esperanza Romero-Rodríguez,
Mpiko Ntsekhe, Virginia Nuñez-Samudio, Dieta Nurrika, Michele Romoli, Luca Ronfani, Gholamreza Roshandel, Gregory A Roth,
Jerry John Nutor, Bogdan Oancea, Kehinde O Obamiro, Himanshu Sekhar Rout, Nitai Roy, Priyanka Roy, Enrico Rubagotti,
Mary Aigbiremo Oboh, Ismail A Odetokun, Nkechi Martina Odogwu, Guilherme de Andrade Ruela, Susan Fred Rumisha, Tilleye Runghien,
Martin James O’Donnell, Michael Safo Oduro, Godfrey M Rwegerera, Andrzej Rynkiewicz, Chandan S N,
Akinyemi O D Ofakunrin, Abiola Ogunkoya, Aly M A Saad, Zahra Saadatian, Korosh Saber,
Ayodipupo Sikiru Oguntade, In-Hwan Oh, Hassan Okati-Aliabad, Maha Mohamed Saber-Ayad, Morteza SaberiKamarposhti,
Sylvester Reuben Okeke, Akinkunmi Paul Okekunle, Siamak Sabour, Simona Sacco, Perminder S Sachdev, Rajesh Sachdeva,
Osaretin Christabel Okonji, Andrew T Olagunju, Basema Saddik, Adam Saddler, Bashdar Abuzed Sadee, Ehsan Sadeghi,
Muideen Tunbosun Olaiya, Matthew Idowu Olatubi, Erfan Sadeghi, Farideh Sadeghian, Mohammad Reza Saeb, Umar Saeed,
Gláucia Maria Moraes Oliveira, Isaac Iyinoluwa Olufadewa, Fahimeh Safaeinejad, Sher Zaman Safi, Rajesh Sagar,
Bolajoko Olubukunola Olusanya, Jacob Olusegun Olusanya, Amene Saghazadeh, Dominic Sagoe, Fatemeh Saheb Sharif-Askari,
Yinka Doris Oluwafemi, Hany A Omar, Ahmed Omar Bali, Narjes Saheb Sharif-Askari, Amirhossein Sahebkar,
Goran Latif Omer, Maureene Auma Ondayo, Sokking Ong, Soumya Swaroop Sahoo, Umakanta Sahoo, Monalisha Sahu, Zahra Saif,
Obinna E Onwujekwe, Kenneth Ikenna Onyedibe, Michal Ordak, Mirza Rizwan Sajid, Joseph W Sakshaug, Nasir Salam, Payman Salamati,
Orish Ebere Orisakwe, Verner N Orish, Doris V Ortega-Altamirano, Afeez Abolarinwa Salami, Luciane B Salaroli, Mohamed A Saleh,
Alberto Ortiz, Wael M S Osman, Samuel M Ostroff, Sana Salehi, Marwa Rashad Salem, Mohammed Z Y Salem,
Uchechukwu Levi Osuagwu, Adrian Otoiu, Nikita Otstavnov, Sohrab Salimi, Hossein Samadi Kafil, Sara Samadzadeh,
Stanislav S Otstavnov, Amel Ouyahia, Guoqing Ouyang, Saad Samargandy, Yoseph Leonardo Samodra, Abdallah M Samy,
Mayowa O Owolabi, Yaz Ozten, Mahesh Padukudru P A, Juan Sanabria, Francesca Sanna, Damian Francesco Santomauro,
Alicia Padron-Monedero, Jagadish Rao Padubidri, Pramod Kumar Pal, Itamar S Santos, Milena M Santric-Milicevic, Bruno Piassi Sao Jose,
Tamás Palicz, Claudia Palladino, Raffaele Palladino, Made Ary Sarasmita, Sivan Yegnanarayana Iyer Saraswathy,
Raul Felipe Palma-Alvarez, Feng Pan, Hai-Feng Pan, Adrian Pana, Aswini Saravanan, Babak Saravi, Yaser Sarikhani, Tanmay Sarkar,
Paramjot Panda, Songhomitra Panda-Jonas, Rodrigo Sarmiento-Suárez, Gargi Sachin Sarode, Sachin C Sarode,
Seithikurippu R Pandi-Perumal, Helena Ullyartha Pangaribuan, Arash Sarveazad, Brijesh Sathian, Thirunavukkarasu Sathish,
Georgios D Panos, Leonidas D Panos, Ioannis Pantazopoulos, Maheswar Satpathy, Abu Sayeed, Md Abu Sayeed, Mete Saylan,
Anca Mihaela Pantea Stoian, Paraskevi Papadopoulou, Romil R Parikh, Mehdi Sayyah, Nikolaos Scarmeas, Benedikt Michael Schaarschmidt,
Seoyeon Park, Ashwaghosha Parthasarathi, Ava Pashaei, Maja Pasovic, Markus P Schlaich, Winfried Schlee, Maria Inês Schmidt,
Roberto Passera, Deepak Kumar Pasupula, Hemal M Patel, Jay Patel, Ione Jayce Ceola Schneider, Art Schuermans, Austin E Schumacher,
Sangram Kishor Patel, Shankargouda Patil, Dimitrios Patoulias, Aletta Elisabeth Schutte, Michaël Schwarzinger, David C Schwebel,
Venkata Suresh Patthipati, Uttam Paudel, Hamidreza Pazoki Toroudi, Falk Schwendicke, Mario Šekerija, Siddharthan Selvaraj,
Spencer A Pease, Amy E Peden, Paolo Pedersini, Umberto Pensato, Sabyasachi Senapati, Subramanian Senthilkumaran, Sadaf G Sepanlou,
Veincent Christian Filipino Pepito, Emmanuel K Peprah, Prince Peprah, Dragos Serban, Yashendra Sethi, Feng Sha, Maryam Shabany,
João Perdigão, Marcos Pereira, Mario F P Peres, Amir Shafaat, Mahan Shafie, Nilay S Shah, Pritik A Shah,
Arokiasamy Perianayagam, Norberto Perico, Richard G Pestell, Syed Mahboob Shah, Saeed Shahabi, Ataollah Shahbandi, Izza Shahid,
Konrad Pesudovs, Fanny Emily Petermann-Rocha, William A Petri, Samiah Shahid, Wajeehah Shahid, Hamid R Shahsavari,
Hoang Tran Pham, Anil K Philip, Michael R Phillips, Moyad Jamal Shahwan, Ahmed Shaikh, Masood Ali Shaikh,
Daniela Pierannunzio, Manon Pigeolet, David M Pigott, Alireza Shakeri, Ali S Shalash, Sunder Sham,
Thomas Pilgrim, Zahra Zahid Piracha, Michael A Piradov, Muhammad Aaqib Shamim, Mehran Shams-Beyranvand,
Saeed Pirouzpanah, Nishad Plakkal, Evgenii Plotnikov, Vivek Podder, Hina Shamshad, Mohammad Anas Shamsi, Mohd Shanawaz,
Dimitri Poddighe, Suzanne Polinder, Kevan R Polkinghorne, Abhishek Shankar, Sadaf Sharfaei, Amin Sharifan, Javad Sharifi-Rad,
Ramesh Poluru, Ville T Ponkilainen, Fabio Porru, Maarten J Postma, Rajesh Sharma, Saurab Sharma, Ujjawal Sharma, Vishal Sharma,
Govinda Raj Poudel, Akram Pourshams, Naeimeh Pourtaheri, Rajesh P Shastry, Amin Shavandi, Maryam Shayan,
Sergio I Prada, Pranil Man Singh Pradhan, Thejeswar N Prakasham, Amr Mohamed Elsayed Shehabeldine, Aziz Sheikh, Rahim Ali Sheikhi,
Manya Prasad, Akila Prashant, Elton Junio Sady Prates, Jiabin Shen, Adithi Shetty, B Suresh Kumar Shetty,
Daniel Prieto Alhambra, TINA PRISCILLA, Natalie Pritchett, Pavanchand H Shetty, Peilin Shi, Kenji Shibuya, Desalegn Shiferaw,
Bharathi M Purohit, Jagadeesh Puvvula, Nameer Hashim Qasim, Mika Shigematsu, Min-Jeong Shin, Youn Ho Shin, Rahman Shiri,
Ibrahim Qattea, Asma Saleem Qazi, Gangzhen Qian, Suli Qiu, Reza Shirkoohi, Nebiyu Aniley Shitaye, Aminu Shittu, Ivy Shiue,
Maryam Faiz Qureshi, Mehrdad Rabiee Rad, Amir Radfar, K M Shivakumar, Velizar Shivarov, Farhad Shokraneh, Azad Shokri,
Raghu Anekal Radhakrishnan, Venkatraman Radhakrishnan, Sina Shool, Seyed Afshin Shorofi, Sunil Shrestha, Kerem Shuval,
Hadi Raeisi Shahraki, Quinn Rafferty, Alberto Raggi, Emmanuel Edwar Siddig, João Pedro Silva,
Pankaja Raghav Raghav, Nasiru Raheem, Fakher Rahim, Luís Manuel Lopes Rodrigues Silva, Soraia Silva, Colin R Simpson,
Md Jillur Rahim, Vafa Rahimi-Movaghar, Md Mosfequr Rahman, Anjali Singal, Abhinav Singh, Balbir Bagicha Singh, Garima Singh,
Mohammad Hifz Ur Rahman, Mosiur Rahman, Jasbir Singh, Narinder Pal Singh, Paramdeep Singh, Surjit Singh,
Muhammad Aziz Rahman, Amir Masoud Rahmani, Shayan Rahmani, Dhirendra Narain Sinha, Robert Sinto, Md Shahjahan Siraj,
Vahid Rahmanian, Sathish Rajaa, Prashant Rajput, Ivo Rakovac, Sarah Brooke Sirota, Freddy Sitas, Shravan Sivakumar,
Shakthi Kumaran Ramasamy, Sheena Ramazanu, Kritika Rana, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina,
Chhabi Lal Ranabhat, Nemanja Rancic, Amey Rane, Chythra R Rao, David A Sleet, Bogdan Socea, Anton Sokhan, Ranjan Solanki,
Indu Ramachandra Rao, Mithun Rao, Sowmya J Rao, Shipra Solanki, Hamidreza Soleimani, Sameh S M Soliman,
Drona Prakash Rasali, Davide Rasella, Sina Rashedi, Vahid Rashedi, Suhang Song, Yimeng Song, Reed J D Sorensen, Joan B Soriano,
Mohammad-Mahdi Rashidi, Ashkan Rasouli-Saravani, Azad Rasul, Ireneous N Soyiri, Michael Spartalis, Sandra Spearman,
Giridhara Rathnaiah Babu, Santosh Kumar Rauniyar, Ramin Ravangard, Chandrashekhar T Sreeramareddy, Vijay Kumar Srivastava,
Nakul Ravikumar, David Laith Rawaf, Salman Rawaf, Lal Rawal, Jeffrey D Stanaway, Muhammad Haroon Stanikzai, Benjamin A Stark,
Reza Rawassizadeh, Bharat Rawlley, Rabail Zehra Raza, Christian Razo, Joseph R Starnes, Antonina V Starodubova, Caroline Stein, Dan J Stein,
Elrashdy Moustafa Mohamed Redwan, Faizan Ur Rehman, Fridolin Steinbeis, Caitlyn Steiner, Jaimie D Steinmetz,
Lennart Reifels, Robert C Reiner Jr, Giuseppe Remuzzi, Paschalis Steiropoulos, Aleksandar Stevanović, Leo Stockfelt,
Luis Felipe Reyes, Maryam Rezaei, Nazila Rezaei, Negar Rezaei, Mark A Stokes, Stefan Stortecky, Vetriselvan Subramaniyan,
Mohsen Rezaeian, Taeho Gregory Rhee, Mavra A Riaz, Muhammad Suleman, Rizwan Suliankatchi Abdulkader, Abida Sultana,

Articles
Haitong Zhe Sun, Jing Sun, Johan Sundström, David Sunkersing, Elric Zweck, Samer H Zyoud, Eve E Wool†,
Katharina S Sunnerhagen, Chandan Kumar Swain, Lukasz Szarpak, and Christopher J L Murray†.
Mindy D Szeto, Miklós Szócska, Payam Tabaee Damavandi, *Joint first authors.
Rafael Tabarés-Seisdedos, Seyyed Mohammad Tabatabaei, †Joint senior authors
Ozra Tabatabaei Malazy, Seyed-Amir Tabatabaeizadeh, Shima Tabatabai,
Affiliations
Mohammad Tabish, Jyothi Tadkamadla, Santosh Kumar Tadakamadla,
See Online for appendix 3 For list of collaborator affiliations see appendix 3
Yasaman Taheri Abkenar, Moslem Taheri Soodejani, Jabeen Taiba,
Ken Takahashi, Iman M Talaat, Ashis Talukder, Mircea Tampa, Contributors
Jacques Lukenze Tamuzi, Ker-Kan Tan, Sarmila Tandukar, Haosu Tang, Please see appendix 1 section 10 for more detailed information about
Hong K Tang, Ingan Ukur Tarigan, Mengistie Kassahun Tariku, individual author contributions to the research, divided into the
Md Tariqujjaman, Elvis Enowbeyang Tarkang, Razieh Tavakoli Oliaee, following categories: managing the overall research enterprise; writing
Seyed Mohammad Tavangar, Nuno Taveira, Yibekal Manaye Tefera, the first draft of the manuscript; primary responsibility for applying
Mohamad-Hani Temsah, Reem Mohamad Hani Temsah, analytical methods to produce estimates; primary responsibility for
Masayuki Teramoto, Riki Tesler, Enoch Teye-Kwadjo, Rishu Thakur, seeking, cataloguing, extracting, or cleaning data; designing or coding
Pugazhenthan Thangaraju, Kavumpurathu Raman Thankappan, figures and tables; providing data or critical feedback on data sources;
Samar Tharwat, Rasiah Thayakaran, Nihal Thomas, developing methods or computational machinery; providing critical
Nikhil Kenny Thomas, Azalea M Thomson, Amanda G Thrift, feedback on methods or results; drafting the manuscript or revising it
Chern Choong Chern Thum, Lau Caspar Thygesen, Jing Tian, critically for important intellectual content; and managing the
Ales Tichopad, Jansje Henny Vera Ticoalu, Tala Tillawi, estimation or publications process. The lead, corresponding, and senior
Tenaw Yimer Tiruye, Mariya Vladimirovna Titova, Marcello Tonelli, authors had full access to the data in the study and had final
Roman Topor-Madry, Adetunji T Toriola, Anna E Torre, Mathilde Touvier, responsibility for the decision to submit for publication.
Marcos Roberto Tovani-Palone, Jasmine T Tran, Nghia Minh Tran,
Declaration of interests
Domenico Trico, Samuel Joseph Tromans, Thien Tan Tri Tai Truyen,
S Afzal reports support for the present manuscript from King Edward
Aristidis Tsatsakis, Guesh Mebrahtom Tsegay,
Medical University including study material, research articles, valid data
Evangelia Eirini Tsermpini, Munkhtuya Tumurkhuu, Kang Tung,
sources and authentic real time information for this manuscript;
Stefanos Tyrovolas, Sayed Mohammad Nazim Uddin,
payment or honoraria for lectures, presentations, speakers bureaus,
Aniefiok John Udoakang, Arit Udoh, Atta Ullah, Irfan Ullah,
manuscript writing or educational events from King Edward Medical
Saeed Ullah, Sana Ullah, Srikanth Umakanthan,
University and collaborative partners including University of Johns
Chukwuma David Umeokonkwo, Brigid Unim,
Hopkins, University of California, University of Massachusetts,
Bhaskaran Unnikrishnan, Carolyn Anne Unsworth, Era Upadhyay,
KEMCAANA, KEMCA-UK Scientific Conferences and Webinars;
Daniele Urso, Jibrin Sammani Usman, Seyed Mohammad Vahabi,
support for attending meetings and/or travel from King Edward Medical
Asokan Govindaraj Vaithinathan, Rohollah Valizadeh,
University to attend meetings; participation on a Data Safety Monitoring
Sarah M Van de Velde, Jef Van den Eynde, Orsolya Varga, Priya Vart,
Board or Advisory Board with National Bioethics Committee Pakistan,
Shoban Babu Varthya, Tommi Juhani Vasankari, Milena Vasic,
King Edward Medical University Ethical Review Board, as well as Ethical
Siavash Vaziri, Balachandar Vellingiri,
Review Board Fatima Jinnah Medical University and Sir Ganga Ram
Narayanaswamy Venketasubramanian, Nicholas Alexander Verghese,
Hospital; leadership or fiduciary roles in board, society, committee or
Madhur Verma, Massimiliano Veroux, Georgios-Ioannis Verras,
advocacy groups, paid or unpaid with Pakistan Association of Medical
Dominique Vervoort, Jorge Hugo Villafañe, Gabriela Ines Villanueva,
Editors, Fellow of Faculty of Public Health Royal Colleges UK (FFPH),
Manish Vinayak, Francesco S Violante, Maria Viskadourou,
and Society of Prevention, Advocacy And Research, King Edward
Sergey Konstantinovitch Vladimirov, Vasily Vlassov, Bay Vo,
Medical University (SPARK); and other support as Dean of Public
Stein Emil Vollset, Avina Vongpradith, Theo Vos, Isidora S Vujcic,
Health and Preventive Medicine at King Edward Medical University, as
Rade Vukovic, Hatem A Wafa, Yasir Waheed, Richard G Wamai,
the Chief Editor Annals of King Edward Medical University, as the
Cong Wang, Ning Wang, Shu Wang, Song Wang, Yanzhong Wang,
Director of Quality Enhancement Cell King Edward Medical University,
Yuan-Pang Wang, Muhammad Waqas, Paul Ward,
as an international-level Fellow of Faculty of Public Health United
Emebet Gashaw Wassie, Stefanie Watson,
Kingdom, as an Advisory Board Member and Chair Scientific Session
Stephanie Louise Watson Watson, Kosala Gayan Weerakoon,
KEMCA-UK, as a Chairperson of KEMCAANA (the International
Melissa Y Wei, Robert G Weintraub, Daniel J Weiss, Ronny Westerman,
Scientific Conference), as a national-level member on the Research and
Joanna L Whisnant, Taweewat Wiangkham,
Publications Higher Education Commission (HEC Pakistan), as a
Dakshitha Praneeth Wickramasinghe,
member of the Research and Journals Committee (Pakistan) the Medical
Nuwan Darshana Wickramasinghe, Angga Wilandika,
and Dental Council (Pakistan), the National Bioethics Committee
Caroline Wilkerson, Peter Willeit, Shadrach Wilson,
(Pakistan), the Corona Experts Advisory Group (Punjab), the Chair of the
Marcin W Wojewodzic, Demewoz H Woldegebreal, Axel Walter Wolf,
Dengue Experts Advisory Group, and a member of the Punjab Residency
Charles D A Wolfe, Yohannes Addisu Wondimagegene, Yen Jun Wong,
Program Research Committee; all outside the submitted work.
Utoomporn Wongsin, Ai-Min Wu, Chenkai Wu, Felicia Wu,
R Ancuceanu reports consulting fees from Abbvie; payment or honoraria
Xinsheng Wu, Zenghong Wu, Juan Xia, Hong Xiao, Yang Xie,
for lectures, presentations, speakers’ bureaus, manuscript writing or
Suowen Xu, Wang-Dong Xu, Xiaoyue Xu, Yvonne Yiru Xu,
educational events from Abbvie, Sandoz, B. Braun, Laropharm, and
Ali Yadollahpour, Kazumasa Yamagishi, Danting Yang, Lin Yang,
MagnaPharm; all outside the submitted work. J Ärnlöv reports payment
Yuichiro Yano, Yao Yao, Habib Yaribeygi, Pengpeng Ye,
or honoraria for lectures, presentations, speakers’ bureaus, manuscript
Sisay Shewasinad Yehualashet, Metin Yesiltepe, Subah Abderehim Yesuf,
writing or educational events from AstraZeneca and Novartis for lecture
Saber Yezli, Siyan Yi, Amanuel Yigezu, Arzu Yiğit, Vahit Yiğit, Paul Yip,
fees; participation on a Data Safety Monitoring Board or Advisory Board
Malede Berihun Yismaw, Yazachew Yismaw, Dong Keon Yon,
with AstraZeneca, Astella, Boehringer Ingelheim; all outside the
Naohiro Yonemoto, Seok-Jun Yoon, Yuyi You, Mustafa Z Younis,
submitted work. O C Baltatu reports support for the present manuscript
Zabihollah Yousefi, Chuanhua Yu, Yong Yu, Faith H Yuh,
from National Council for Scientific and Technological Development
Siddhesh Zadey, Vesna Zadnik, Nima Zafari, Fathiah Zakham,
(CNPq, 304224/2022-7) and Anima Institute (AI research professor
Nazar Zaki, Sojib Bin Zaman, Nelson Zamora, Ramin Zand,
fellowship); Leadership or fiduciary role in other board, society,
Moein Zangiabadian, Heather J Zar, Iman Zare, Armin Zarrintan,
committee or advocacy group, paid or unpaid, as Founding Member of
Mohammed G M Zeariya, Zahra Zeinali, Haijun Zhang,
the Health and Biotechnology Advisory Board at Technology Park São
Jianrong Zhang, Jingya Zhang, Liqun Zhang, Yunquan Zhang, Zhi-
José dos Campos–Center for Innovation in Health Technologies (CITS),
Jiang Zhang, Hanqing Zhao, Chenwen Zhong, Juexiao Zhou, Bin Zhu,
outside the submitted work. T W Bärnighausen reports grants or
Lei Zhu, Makan Ziafati, Magdalena Zielińska, Osama A Zitoun,
contracts from National Institutes of Health, Alexander von Humboldt
Mohammad Zoladl, Zhiyong Zou, Liesl J Zuhlke, Alimuddin Zumla,
Foundation, German National Research Foundation (DFG), European

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Union, German Ministry of Education and Research, German Ministry submitted work. A Biswas reports consulting fees from INTAS
of the Environment, Wellcome, and KfW, all as payments to their Pharmaceuticals Ltd, India, Lupin Pharmaceuticals, Ltd, India, and
institution; participation on a Data Safety Monitoring Board or Advisory Alkem Laboratories, India as personal payments; payment or honoraria
Board on two Scientific Advisory Boards for NIH-funded research for lectures, presentations, speakers’ bureaus, manuscript writing or
projects in Africa on Climate Change and Health; stock or stock options educational events from Roche Diagnostics, India, as personal
in CHEERS, an SME focusing on approaches to measure climate change payments; all outside the submitted work. E J Boyko reports payment or
and health-related variables in population cohorts; all outside the Honoria for lectures, presentations, speakers bureaus, manuscript
submitted work. S Barteit reports grants from Carl-Zeiss Foundation writing or education events from the Korean Diabetes Association,
and the German research foundation (DFG); stock or stock options in Diabetes Association of the R.O.C (Taiwan), the American Diabetes
CHEERS, a for-profit company focusing on climate change and health Association, and the International Society for the Diabetic Foot; Support
evaluation and response systems; all outside the submitted work. for attending meetings and/or travel from the Korean Diabetes
M Beghi reports consulting fees from Lundbeck and Angelini, all Association; Diabetes Association of the R.O.C (Taiwan), International
outside the submitted work. Y Bejot reports consulting fees from Society for the Diabetic Foot; outside the submitted work. M Carvalho
Medtronic and Novartis; payment or honoraria for lectures, reports other financial or non-financial interests from LAQV/
presentations, speakers bureaus, manuscript writing or educational REQUIMTE, University of Porto (Porto, Portugal) and acknowledges the
events from BMS, Pfizer, Medtronic, Amgen, NovoNordisk, and Servier; support from FCT under the scope of the project UIDP/50006/2020;
support for attending meetings and/or travel from Medtronic; leadership outside the submitted work. E Chung reports support for the present
or fiduciary role in other board, society, committee or advocacy group, manuscript from the National Institute of Health NICHD
unpaid, with the French Neurovascular Society; all outside the submitted T32HD007233. J Conde reports grants or contracts form the European
work. M Bell reports grants or contracts from US EPA, NIH, High Tide Research Council Starting Grant ERC-StG-2019-848325 (funding
Foundation, Health Effects Institute, Yale Women Faculty Forum, 1.5M Euro), outside the submitted work. S Cortese reports grants or
Environmental Defense Fund, Yale Climate Change and Health Center, contracts from National Institute for Health and Care Research (NIHR)
Wellcome Trust Foundation, Robert Wood Johnson Foundation, and the and the European Research Executive Agency; payment or honoraria for
Hutchinson Postdoctoral Fellowship (all paid to their institution); lectures, presentations, speakers bureaus, manuscript writing or
Consulting fees from Clinique; Payment or honoraria for lectures, educational events from the Association of Child and Adolescent Mental
presentations, speakers bureaus, manuscript writing or education events Health, British Association of Psychopharmacology, Medice, and
from Colorado School of Public Health, Duke University, University of Canadian ADHD Resource Alliance; support for attending meetings
Texas, Data4Justice, Korea University, Organization of Teratology and/or travel the Association of Child and Adolescent Mental Health,
Information Specialists, University of Pennsylvania, Boston University, British Association of Psychopharmacology, Medice, and Canadian
IOP Publishing, NIH, Health Canada, PAC-10, UKRI, AXA Research ADHD Resource Alliance; leadership or fiduciary role in other board,
Fund Fellowship, Harvard University and the University of Montana; society, committee or advocacy group, unpaid, with the European ADHD
Support for attending meeting and/or travel from Colorado School of Guidelines Group and the European Network for Hyperkinetic
Public Health, University of Texas, Duke University, Boston University, Disorders; all outside the submitted work. Sa Das reports leadership or
University of Pennsylvania, Harvard University, American Journal of fiduciary role in other board, society, committee or advocacy group,
Public Health, Columbia University and Harvard University; Leadership unpaid, with the Association for Diagnostics and Laboratory Medicine as
or fiduciary role in other board, society, committee or advocacy group, program chair, and the Women in Global Health India Chapter, outside
unpaid with Fifth National Climate Assessment and Lancet Countdown, the submitted work. A Dastiridou reports support for attending
Johns Hopkins Advisory Board, Harvard external advisory committee for meetings and/or travel from THEA and ABBVIE, outside the submitted
training grant, WHO Global Air Pollution and Health Technical work. L Degenhardt reports untied educational grants from Indivior and
Advisory group and the National Academies Panels and Committee; and Seqirus to examine new opioid medications in Australia, outside the
paid with the US EPA Clean Air Scientific Advisory Committee submitted work. A K Demetriades reports leadership or fiduciary role in
(CASAC); outside the submitted work. L Belo reports other financial or other board, society, committee or advocacy group, unpaid, with the AO
non-financial interests with UCIBIO – FFUP through support from FCT Knowledge Forum Degenerative Steering Committee, Global Neuro
in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of Foundation Board, and the European Association of Neurological
UCIBIO and the project LA/P/0140/2020 of i4HB, all outside the Societies Board of Officers, all outside the submitted work. A Faro
submitted work. R S Bernstein reports other financial or non-financial reports support for the present manuscript from National Council for
support as a full-time Medical Consultant employee of the California Scientific and Technological Development, CNPq, Brazil as CNPq
Department of Public Health in the Center for Heal Care Quality; Researcher (scholarship). I Filip reports support for the present
outside the submitted work. P J G Bettencourt reports patents planned, manuscript from Avicenna Medical and Clinical Research Institute.
issued, or pending (WO2020229805A1, BR112021022592A2, D Flood reports grants or contracts from NHLBI (award number
EP3965809A1, OA1202100511, US2023173050A1, EP4265271A2, and K23HL161271), the University of Michigan Claude D. Pepper Older
EP4275700A2); other financial or non-financial interests with the Botnar Americans Independence Center (award number 5P30AG024824), and
Foundation as project reviewer, outside the submitted work. S Bhaskar the University of Michigan Caswell Diabetes Institute Clinical
reports grants or contracts from the Japan Society for the Promotion of Translational Research Scholars Program; consulting fees from the
Science (JSPS), Japanese Ministry of Education, Culture, Sports, Science World Health Organization as payments to their institution; leadership
and Technology (MEXT) and JSPS and the Australian Academy of or fiduciary role in other board, society, committee or advocacy group,
Science; Leadership or fiduciary role in other board, society, committee unpaid, as Staff Physician for Maya Health Alliance, a non-governmental
or advocacy group, paid or unpaid with Rotary District 9675 as the health organization in Guatemala; all outside the submitted work.
district chair, Global Health & Migration Hub Community as Chair and A A Fomenkov reports support for the present manuscript from
Manager (Berlin, Germany), PLOS One, BMC Neurology, Frontiers in Development of effective biotechnologies based on cell cultures, tissues
Neurology, Frontiers in Stroke, Frontiers in Public Health and the BMC and organs of higher plants, microalgae and cyanobacteria. The research
Medical Research Methodology as an Editorial Board Member, and as a carried out within the state assignment of Ministry of Science and
Member of the College of Reviewers (Canadian Institutes of Health Higher Education of the Russian Federation (theme No. 122042600086-
Research, Canada); outside the submitted work. B Bikbov reports grants 7). M Foschi reports consulting fees from Roche and Novartis; support
or contracts from the European Commission and The University of for attending meetings and/or travel from Biogen, Roche, Novartis,
Rome; Support for attending meetings/travel from the European Renal Sanofi, Bristol, and Merck; leadership or fiduciary role in other board,
Association; Leadership or fiduciary role in other board, society, society, committee or advocacy group, unpaid, with MBase Foundation;
committee or advocacy group, unpaid in an advocacy group with the all outside the submitted work. R Franklin reports grants or contracts
International Society of Nephrology and unpaid on the Western Europe from Heatwaves (Queensland Government, Queensland, Australia) and
Regional Board of the International Society of Nephrology; Other Arc Flash (Human Factors, Queensland Government, Queensland,
financial or non-financial support from Scientific-Tools.org; outside the Australia), and Mobile Plant Safety (Agrifutures); Support for attending

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meetings and/or travel from ACTM Tropical Medicine and Travel all outside the submitted work. J H Kempen reports grants or contracts
Medicine Conference 2022 and 2023, and ISTM Travel Medicine from the Massachusetts Eye and Ear Surgery Program and Sight for
Conference in Basel 2023; leadership or fiduciary role in other board, Souls through payments to their institution; leadership or fiduciary role
society, committee or advocacy group, paid or unpaid as the president/ in other board, society, committee or advocacy group, paid or unpaid, as
director of Kidsafe, the director of Auschem, a member of the President of Sight for Souls; stock or stock options with Betaliq and
governance committee of ISASH, the director of Farmsafe, the Vice Tarsier; all outside the submitted work. T Kocsis reports grants or
President of ACTM, and as a PHAA Injury Prevention SIG Convenor; contracts from Novartis Magyarország Ltd through payment for market
outside the submitted work. P S Gill reports support for the present access activities, outside the submitted work. K Krishan reports other
manuscript from the National Institute for Health and Care Research non-financial interests from the UGC Centre of Advanced Study, CAS II,
(NIHR) as Senior Investigator with payments to their institution; the awarded to the Department of Anthropology, Panjab University
views expressed in this publication are those of the author(s) and not (Chandigarh, India); outside the submitted work. B Lacey reports
necessarily those of the NIHR or the UK Department of Health and support for the present manuscript from the UK Biobank, funded
Social Care. A Guha reports grants or contracts from the American largely by the UK Medical Research Council and Wellcome, through
Heart Association and Department of Defense; consulting fees from their employment at the University of Oxford. M Lee reports support for
Pfizer, Novartis, and Myovant; leadership or fiduciary role in other the present manuscript from the Ministry of Education of the Republic
board, society, committee or advocacy group, paid or unpaid, with ZERO of Korea and the National Research Foundation of Korea
Prostate Cancer Health Equity Task Force and Doctopedia as a founding (NRF-2021R1I1A4A01057428) and Bio-convergence Technology
medical partner; all outside the submitted work. C Herteliu reports Education Program through the Korea Institute for Advancement
grants or contracts from the Romanian Ministry of Research Innovation Technology (KIAT) funded by the Ministry of Trade, Industry and Energy
and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021; (No. P0017805). M-C Li reports grants or contracts from The National
grant of the European Commission Horizon 4P-CAN (Personalised Science and Technology Council in Taiwan (NSTC 112-2410-H-003-031;
Cancer Primary Prevention Research through Citizen Participation and leadership or fiduciary role in other board, society, committee or
Digitally Enabled Social Innovation); Project “Societal and Economic advocacy group, paid or unpaid, as the technical editor of the Journal of
Resilience within multi-hazards environment in Romania” funded by the American Heart Association; outside the submitted work. J Liu
European Union – NextgenerationEU and Romanian Government, reports support for the present manuscript from the National Natural
under National Recovery and Resilience Plan for Romania, contract Science Foundation of China (grant number: 72122001; 72211540398).
no.760050/ 23.05.2023, cod PNRR-C9-I8-CF 267/ 29.11.2022, through the S Lorkowski reports grants or contracts from Akcea Therapeutics
Romanian Ministry of Research, Innovation and Digitalization, within Germany through payments to their institution; consulting fees from
Component 9, Investment I8; Project “A better understanding of socio- Danone, Novartis Pharma, Swedish Orphan Biovitrum (SOBI), and
economic systems using quantitative methods from Physics” funded by Upfield; payment or honoraria for lectures, presentations, speakers
European Union–NextgenerationEU and Romanian Government, under bureaus, manuscript writing or educational events from Akcea
National Recovery and Resilience Plan for Romania, contract number Therapeutics Germany, AMARIN Germany, Amedes Holding, AMGEN,
760034/ 23.05.2023, cod PNRR-C9-I8-CF 255/ 29.11.2022, through the Berlin-Chemie, Boehringer Ingelheim Pharma, Daiichi Sankyo
Romanian Ministry of Research, Innovation and Digitalization, within Deutschland, Danone, Hubert Burda Media Holding, Janssen-Cilag,
Component 9, Investment I8; outside the submitted work. M Hultström Lilly Deutschland, Novartis Pharma, Novo Nordisk Pharma, Roche
reports support for the present manuscript from Knut och Alice Pharma, Sanofi-Aventis, and SYNLAB Holding Deutschland & SYNLAB
Wallenberg Foundation and the Swedish Heart-Lung Foundation, all as Akademie; support for attending meetings and/or travel from AMGEN;
payments to their institution; Support for attending meetings and/or participation on a Data Safety Monitoring Board or Advisory Board with
travel from the American Physiological Society and the Swedish Society Akcea Therapeutics Germany, AMGEN, Daiichi Sankyo Deutschland,
for Anaesthesiology and Intensive Care; leadership or fiduciary role in Novartis Pharma, and Sanofi-Aventis; all outside the submitted work.
other board, society, committee or advocacy group, paid or unpaid, with M A Mahmoud reports grant or contract funding from the Deputyship
the American Physiological Society, Water and Electrolyte Section; for Research and Innovation, Ministry of Education in Saudi Arabia
all outside the submitted work. I Ilic and M Ilic report support for the (project number 445-5-748). L G Mantovani reports support for the
present manuscript from Ministry of Science, Technological present manuscript from the Italian Ministry of Health. H R Marateb
Development and Innovation of the Republic of Serbia. S M Islam reports support for the present manuscript from The Beatriu de Pinós
reports support for the present manuscript from NHMRC and Heart post-doctoral programme from the Office of the Secretary of Universities
Foundation, N E Ismail reports leadership or fiduciary role in other and Research from the Ministry of Business and Knowledge of the
board, society, committee or advocacy group, unpaid, as Bursar (Council Government of Catalonia programme: 2020 BP 00261. R Matzopoulos
Member) of the Malaysian Academy of Pharmacy, outside the submitted reports consulting fees from New York University and DG Murray Trust;
work. T Joo reports support for the present manuscript from National Support for attending meetings/travel paid by SA MRC and University
Research, Development, and Innovation Office in Hungary of Cape Town; leadership or fiduciary role in other board, society,
(RRF-2.3.1-21-2022-00006), Data-Driven Health Division of National committee or advocacy group, unpaid, as a Board member of Gun Free
Laboratory for Health Security. G Joshy reports grants or contracts from South Africa; Stock or Stock options with Sanlam; outside the submitted
the Department of Health and Aged Care 2023 (Understanding the fatal work. R J Maude reports support for the present manuscript from
burden of COVID-19 in residential aged care facilities); support for Wellcome Trust [Grant number 220211] as it provides core funding for
attending meetings and/or travel from the Statistical Society of Australia Mahidol Oxford Tropical Medicine Research and contributes to his
Grant 2023 supporting conference registration; participation on a Data salary. A-F A Mentis reports grants or contract funding from ‘MilkSafe:
Safety Monitoring Board with the Australian Mathematical Sciences A novel pipeline to enrich formula milk using omics technologies’,
Institute (AMSI) and the Statistical Society of Australia (SSA) for the a research co financed by the European Regional Development Fund of
project Community-led nutrition and Lifestyle program for weight loss the European Union and Greek national funds through the Operational
and metabolic Health: a randomised Controlled trial (ELCHO), 2022; Program Competitiveness, Entrepreneurship and Innovation, under the
all outside the submitted work. J Jozwiak reports payment or honoraria call RESEARCH - CREATE - INNOVATE (project code: T2EDK-02222),
for lectures, presentations, speakers bureaus, manuscript writing or as well as from ELIDEK (Hellenic Foundation for Research and
educational events from Novartis, Adamed, and Amgen; outside the Innovation, MIMS-860) (both outside of the present manuscript);
submitted work. N Kawakami reports grants or contracts from the payment for expert testimony from serving as external peer-reviewer for
Junpukai Foundation and the Department of Digital Mental Health is an FONDAZIONE CARIPLO, ITALY; participation in a Data Safety
endowment department, supported with an unrestricted grant from Monitoring or Advisory Board as Editorial Board Member for
15 enterprises (https://dmh.m.u-tokyo.ac.jp/c); consulting fees from “Systematic Reviews”, for “Annals of Epidemiology”, and as Associate
Riken Institute, JAXA, Sekisui Chemicals, and SB@WORK; leadership Editor for “Translational Psychiatry”; stock or stock options from a
or fiduciary role in other board, society, committee or advocacy group, family winery; and other financial interests as the current scientific
paid or unpaid, with the Japan Society for Occupational Health; officer for BGI Group; outside the submitted work. S A Meo reports

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support from King Saud University, Riyadh, Saudi Arabia (https://doi.org/10.54499/DL57/2016/CP1376/CT0004).

(RSP-2024 R47). T R Miller reports grants or contracts from AB InBev R F Palma-Alvarez reports payment or honoraria for lectures,
Foundation, National Institute for Mental Health (Santa Clara County, presentations, speakers bureaus, manuscript writing or educational
CA), and Everytown for Gun Safety; payment for expert testimony in the events from Angelini, Lundbeck, Casen Recordati and Takeda; support
states of Michigan, Nevada & New Mexico Mobile County Board of for attending meetings and/or travel from Janssen and Lundbeck; all
Health; outside the submitted work. P B Mitchell reports payment or outside the submitted work. A M Pantea Stoian reports consulting fees
honoraria for lectures, presentations, speakers’ bureaus, manuscript from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk,
writing or educational events, from Janssen (Australia), outside the Novartis, Sandoz, and Sanofi; payment or honoraria for lectures,
submitted work. L Monasta reports support for the present manuscript presentations, speakers bureaus, manuscript writing or educational
from the Ministry of Health (Ricerca Corrente 34/2017) through events from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Novo
payments made to the Institute for Maternal and Child Health IRCCS Nordisk, Novartis, Sandoz, Medochemie, Servier, and Sanofi; support for
Burlo Garofolo. R S Moreira reports grants or contracts from CNPq attending meetings and/or travel from Sanofi, Novo Nordisk, and
Research Productivity Scholarship (National Council for Scientific and Medochemie; Participation on a Data Safety Monitoring Board or
Technological Development) scholarship registration number Advisory Board with Astra Zeneca, Eli Lilly, Novo Nordisk, and Sanofi;
316607/2021-5; outside the submitted work. J Mosser reports support for Leadership or fiduciary role in other board, society, committee or
the present manuscript from the Bill and Melinda Gates Foundation; advocacy group, unpaid, with the Central European Diabetes Association
grants or contractions from Gavi; Support for attending meetings and/or and the Association for Renal-Metabolic & Nutritional Studies (ASRMN);
travel from the Bill and Melinda Gates Foundation; outside the outside the submitted work. R Passera reports Participation on a Data
submitted work. S Nomura reports support for the present manuscript Safety Monitoring Board or Advisory Board with the non-profit clinical
from Ministry of Education, Culture, Sports, Science and Technology of trial “Consolidation with ADCT-402 (loncastuximab tesirine) after
Japan (21H03203) and Precursory Research for Embryonic Science and immunochemotherapy: a phase II study in BTKi-treated/ineligible
Technology from the Japan Science and Technology Agency Relapse/Refractory Mantle Cell Lymphoma (MCL) patients” - sponsor
(JPMJPR22R8). B Norrving reports participation on a Data Safety FIL, Fondazione Italiana Linfomi, Alessandria-I (unpaid role); leadership
Monitoring Board or Advisory Board with Simbec Orion, outside the or fiduciary role in other board, society, committee or advocacy group,
submitted work. A P Okekunle reports support for the present paid or unpaid, Member of the Statistical Committee of the EBMT –
manuscript from the National Research Foundation of Korea funded by European Society for Bone and Marrow Transplantation, Paris-F (unpaid
the Ministry of Science and ICT (2020H1D3A1A04081265). A Ortiz role); outside the submitted work. A E Peden reports support for the
reports grants or contracts from Sanofi as payments to their institution; present manuscript from the [Australian] National Health and Medical
consulting fees, speaker fees or support for travel from, Advicciene, Research Council (Grant Number: APP2009306). V C F Pepito reports
Astellas, Astrazeneca, Amicus, Amgen, Boehringer Ingelheim, grants or contracts from Sanofi Consumer Healthcare and the
Fresenius Medical, Care, GSK, Bayer, Sanofi-Genzyme, Menarini, International Initiative for Impact Evaluation; outside the submitted
Mundipharma, Kyowa Kirin, Lilly, Alexion, Freeline, Idorsia, Chiesi, work. M Pigeolet reports a grant from the Belgian Kids’ Fund for
Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal, Pediatric Research, outside the submitted work. T Pilgrim reports grants
Pharma and is Director of the Catedra, Mundipharma-UAM of diabetic paid to the institution without personal remuneration from Biotronik,
kidney disease, and the Catedra Astrazeneca-UAM of chronic, kidney Edwards Lifesciences, and ATSens; Payment or honoraria for lectures,
disease and electrolytes; Leadership or fiduciary role in other board, presentations, speakers bureaus, manuscript writing or educational
society, committee or advocacy group, paid or unpaid, with the European events from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott,
Renal Association; stock or stock options with Telara Farma; all outside Medtronic, Biosensors, and Highlife; Participation on a Data Safety
the submitted work. P K Pal reports grants or contracts paid to their Monitoring Board or Advisory Board for EMPIRE study sponsored by
institution from the Indian Council of Medical Research (ICMR), the Biosensors; and receipt of equipment (AT-Patches) from ATSens; outside
Department of Science & Technology (DST)-Science and Engineering the submitted work. D Prieto-Alhambra reports support for the present
Research Board, the Department of Biotechnology (DBT), DST-Cognitive manuscript from European Medicines Agency and Innovative Medicines
Science Research Initiative, Wellcome Trust UK-India Alliance DBT, Initiative, through their institution; grants or contracts from Amgen,
PACE scheme of BIRAC, Michael J. Fox Foundation, and SKAN Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma through
(Scientific Knowledge for Ageing and Neurological ailments)-Research their institution; consulting fees from Astra Zeneca and UCB
Trust; Payment and honoraria for lectures, presentations, speakers Biopharma; other financial or non-financial interest in Amgen, Astellas,
bureaus, manuscript writing or educational events as Faculty/Speaker/ Janssen, Synapse Management Partners and UCB Biopharma for
Author from the International Parkinson and Movement Disorder supported training programmes; outside the submitted work. A Radfar
Society, and Movement Disorder Societies of Korea, Taiwan and reports support for the present manuscript from Avicenna Medical and
Bangladesh; support for attending meetings and/or travel from the Clinical Research Institute. A Rane reports stock or stock options as a
National Institute of Mental Health and Neurosciences (NIMHANS), full-time employee at Agios Pharmaceuticals; outside the submitted
International Parkinson and Movement Disorder Society, and Movement work. L F Reyes reports grants or contracts form MSD and Pfizer;
Disorder Societies of Korea, Taiwan and Bangladesh; Leadership or consulting fees from GSK, MSD, and Pfizer; Payment or honoraria for
fiduciary role in other board, society, committee or advocacy group, lectures, presentations, speakers’ bureaus, manuscript writing or
unpaid, as the Past President of Indian Academy of Neurology, Past educational events from GSK and Pfizer; payment for expert testimony
Secretary of Asian and Oceanian subsection of International Parkinson from GSK and MSD; support for attending meetings and/or travel from
and Movement Disorder Society (MDS-AOS), Editor-in-Chief of Annals GSK; outside the submitted work. T G Rhee reports grants or contracts
of Movement Disorders, Chair of the Education Committee of from the NIH (R21AG070666; R21DA057540; R21AG078972;
International Parkinson and Movement Disorder Society (IPMDS), R01MH131528; R01AG080647); outside the submitted work. S Sacco
President of the Parkinson Society of Karnataka, Chair of Infection reports grants or contracts from Novartis and Uriach; consulting fees
Related Movement Disorders Study Group of MDS, Member of Rare from Novartis, Allergan-Abbvie, Teva, Lilly, Lundbeck, Pfizer, Novo
Movement Disorders Study Group of International Parkinson and Nordisk, Abbott, AstraZeneca; Payment or honoraria for lectures,
Movement Disorder Society (IPMDS), Member of Education Committee presentations, speakers bureaus, manuscript writing or educational
of IAPRD, Member of Rating Scales Education and Training Program events from Novartis, Allergan-Abbvie, Teva, Lilly, Lundbeck, Pfizer,
Committee of IPMDS, Member of Neurophysiology Task Force of Novo Nordisk, Abbott, AstraZeneca; support for attending meetings
IPMDS, Member of Movement Disorders in Asia Study Group, Member and/or travel from Lilly, Novartis, Teva, Lundbeck; leadership or fiduciary
of Post-Stroke Movement Disorders, Member of Ataxia Study Group of role in other board, society, committee or advocacy group, paid or
IPMDS, and as a Member of Ataxia Global Initiative; all outside the unpaid, as the President elect of the European Stroke Organization, and
submitted work. C Palladino reports grants or contracts from FCT – the Second vice-president of the European Headache Federation; receipt
Fundação para a Ciência e a Tecnologia, I.P. (national funding), under a of equipment, materials, drugs, medical writing, gifts or other services
contract-programme as defined by DL No. 57/2016 and Law No. 57/2017 from Allergan-Abbvie, Novo Nordisk; all outside the submitted work.
(DL57/2016/CP1376/CT0004). DOI 10.54499/DL57/2016/CP1376/CT0004 P Sachdev reports grants or contracts from national Health and Medical

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Research Council of Australia and the US National Institutes of Health; fiduciary role in other board, society, committee or advocacy group, paid
Payment or honoraria for lectures from Alkem Labs for the Frontiers of or unpaid with the New Zealand Government Data Ethics Advisory
Psychiatry June 2023 Seminar, Mumbai, India; Participation on a Data Group as the Chair; outside the submitted work. D J Stein reports
Safety Monitoring Board or Advisory Board with Biogen Australia and consulting fees from Discovery Vitality, Johnson & Johnson, Kanna,
Roche Australia; leadership or fiduciary role in other board, society, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen, outside
committee or advocacy group, unpaid, with the VASCOG Society and the the submitted work. K Stibrant Sunnerhagen reports Leadership or
World Psychiatric Association; all outside the submitted work. fiduciary role in other board, society, committee or advocacy group, paid
Y L Samodra reports grants or contracts from Taipei Medical University; or unpaid as the head of the scientific committee of the Sweidhs Stroke
leadership or fiduciary role in other board, society, committee or Foundation; outside the submitted work. S Stortecky reports grants or
advocacy group, paid or unpaid, with the Benang Merah Research contracts paid to their institution from Edwards Lifesciences, Medtronic,
Center; all outside the submitted work. J Sanabria reports support for Abbott, and Boston Scientific; consulting fees from Teleflex; Payment or
attending meetings and/or travel from the Department of Surgery, honoraria for lectures, presentations, speakers bureaus, manuscript
Marshall University School of Medicine; three patents pending; writing or educational events from Boston Scientific/BTG; outside the
participation in quality assessment and assurance for surgeries of the submitted work. A G Thrift reports grants or contracts paid to their
Department of Surgery; leadership or fiduciary role in other board, institution from the National Health & Medical Research Council
society, committee or advocacy group, paid or unpaid with SSAT, ASTS, (Australia) (grant numbers 1171966, 1182071), Heart Foundation (Aus)
AHPBA, IHPBA, and AASLD; all outside the submitted work. and the Stroke Foundation (Australia); outside the submitted
N Scarmeas reports grants or contracts with Novo Nordisk as the Local work. J H V Ticoalu reports Leadership or fiduciary role in other board,
PI of recruiting site for multinational, multicenter industry sponsored society, committee or advocacy group, paid or unpaid, with Benang
phase III treatment trial for Alzheimer’s disease with funding paid to Merah Research Center as co-founder, outside the submitted work. M V
the institution; Participation on a Data Safety Monitoring Board or Titova reports support for the present manuscript from the Ministry of
Advisory Board with Albert Einstein College of Medicine (NIH funded Science and Higher Education of the Russian Federation (theme No.
study) as the Chair of Data Safety Monitoring Board; all outside the 122042600086-7). S J Tromans reports grants or contracts from the 2023
submitted work. A E Schutte reports Speaker Honoraria from Servier, Adult Psychiatric Morbidity Survey team, collecting epidemiological data
Novartis, Sanofi, Medtronic, Abbott, Omron, Aktiia; Support for on community-based adults living in England. This is a contracted study
attending meetings and/or travel from Servier, Medtronic, and Abbott; from NHS Digital, via the Department of Health and Social Care;
Participation on a Data Safety Monitoring Board or Advisory Board with outside the submitted work. P Willeit reports consulting fees from
Abbott Pharmaceuticals Advisory Board, Skylabs devices Advisory Board; Novartis; outside the submitted work. M Zielińska reports other
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advocacy group, paid or unpaid, with Co-Chair: National Hypertension work. A Zumla reports grants or contracts from The Pan-African
Taskforce of Australia, Board Member: Hypertension Australia, Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET,
Company Secretary: Australian Cardiovascular Alliance; all outside the CANTAM-3, and EACCR-3) funded by the European and Developing
submitted work. B M Schaarschmidt reports research grants from Else Countries Clinical Trials Partnership, the EU Horizon 2020 Framework
Kröner-Fresenius Foundatuin, DFG, and PharmaCept; Payment or Programme, UK National Institute for Health and Care Research Senior
honoraria for lectures, presentations, speakers bureaus, manuscript Investigator, and Mahathir Science Award and EU-EDCTP Pascoal
writing or educational events from AstraZeneca; support for attending Mocumbi Prize Laureate; Participation on a Data Safety Monitoring
meetings and/or travel from Bayer AG; all outside the submitted work. Board or Advisory Board member of the WHO Mass Gatherings Expert
M Šekerija reports consulting fees from Roche; Payment or Honoraria Group and WHO Health Emergencies Programme in Geneva, a
for lectures, presentations, speakers bureaus, manuscript writing or member of the EU-EDCTP3-Global Health (Brussels) Scientific
educational events from Johnson and Johnson, and Astellas; outside the Committee; all outside the submitted work.
submitted work. A Sharifan reports leadership or fiduciary role in other
Data sharing
board, society, committee or advocacy group, unpaid with Cochrane as a
To download the data used in these analyses, please visit the Global
steering member of the Cochrane Early Career Professionals Network;
health Data Exchange GBD 2021 website (https://ghdx.healthdata.org/
and receipt of thirty days of complimentary access to ScienceDirect,
gbd-2021/sources).
Scopus, Reaxys, and Geofacets after reviewing manuscripts for two
journals published by Elsevier; outside the submitted work. S Sharma Acknowledgments
reports support for the present manuscript from the John J. Bonica Research reported in this publication was supported by the Bill &
Postdoctoral Fellowship from the International Association for the Study Melinda Gates Foundation; Queensland Department of Health,
of Pain (IASP; 2021-2023); Payment or honoraria for lectures, Australia; UK Department of Health and Social Care; the Norwegian
presentations, speakers bureaus, manuscript writing or educational Institute of Public Health; St Jude Children’s Research Hospital; and the
events and a travel grant for delivering a talk on “Technologies for pain New Zealand Ministry of Health. The content is solely the responsibility
education in developing countries” conducted by the Pain Education SIG of the authors and does not necessarily represent the official views of the
of the IASP at the World Pain Congress in Toronto (2022); outside the funders. The Palestinian Central Bureau of Statistics granted the
submitted work. V Sharma reports other financial or non-financial researchers access to relevant data in accordance with license number
support from DFSS (MHA)’s research project (DFSS28(1)2019/EMR/6) SLN2014-3-170, after subjecting data to processing aiming to preserve the
at Institute of Forensic Science & Criminology, Panjab University, confidentiality of individual data in accordance with the General
Chandigarh, India, outside the submitted work. K Shibuya reports Statistics Law–2000. The researchers are solely responsible for the
support for the present manuscript from Tokyo Foundation for Policy conclusions and inferences drawn upon available data. Collection of
Research. V Shivarov reports one patent and one utility model with the these data was made possible by USAID under the terms of cooperative
Bulgarian Patent Office; stock or stock options from ICONplc (RSUs); agreement GPO-A-00-08-000_D3-00. The opinions expressed are those
and other financial interests from an ICONplc salary; all outside the of the authors and do not necessarily reflect the views of USAID or the
submitted work. S Shrestha reports other financial interests from the US Government. Data for this research were provided by MEASURE
Graduate Research Merit Scholarship from the School of Pharmacy at Evaluation, funded by the US Agency for International Development
Monash University Malaysia, outside the submitted work. J P Silva (USAID). Views expressed do not necessarily reflect those of USAID,
reports support for the present manuscript from the Portuguese the US Government, or MEASURE Evaluation. The data reported here
Foundation for Science and Technology through payment of their salary have been supplied by the US Renal Data System (USRDS).
(contract with reference 2021.01789.CEECIND/CP1662/CT0014). The interpretation and reporting of these data are the responsibility of
L M L R Silva reports grants or contracts from CENTRO-04-3559- the authors and in no way should be seen as an official policy or
FSE-000162, Fundo Social Europeu (FSE), outside the submitted work. interpretation of the US Government. This manuscript is based on data
C R Simpson reports grants or contracts from MBIE (NZ), HRC (NZ), collected and shared by the International Vaccine Institute (IVI) from an
Ministry of Health (NZ), MRC (UK), and CSO (UK); Leadership or original study it conducted. This manuscript was not prepared in

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Articles

Global burden of 288 causes of death and life expectancy

2100 www.thelancet.com Vol 403 May 18, 2024

Funding Bill & Melinda Gates Foundation.

Introduction a limited subset of the global population. Our analysis

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25·0 24·9 25·2

es ory ctio 202

zh er's oth diso s, 20

incidence of mortality between locations and Role of the funding source

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Deaths Deaths per 100 000 population Percentage of total deaths

Leading causes of global YLLs Decomposition of global life expectancy

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Enteric infections, 1·1 years 1990–2000 0·4 0·4 0·3 0·1

–2·0 –1·5 –1·0 –0·5 0 0·5 1·0 1·5

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Age-standardised mortality rate

Age-standardised mortality rate

Figure 4: Age-standardised mortality rate of COVID-19 and OPRM, 2021

High income, 4·5 years –1·2 1·8 1·2 0·9

–6·0 –4·0 –2·0 0 2·0 4·0 6·0 8·0 10·0 12·0

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East Asia, –0·0 years –0·1

Southern sub-Saharan Africa, –3·4 years –3·4

Tropical Latin America, –3·4 years –3·4

Central Latin America, –3·5 years –3·5

–5·0 –4·0 –3·0 –2·0 –1·0 0

Figure 6: Effect of COVID-19 on life expectancy by GBD region, 2019–21

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South Asia, 3·1 years 1·4 0·9 0·7 0·1

0·4 0·2 0·1

–0·5 0 0·5 1·0 1·5 2·0 2·5 3·0 3·5

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Western sub-Saharan Africa, 1·6 years 0·3 0·6 0·4 0·3

Andean Latin America, 1·6 years 0·8 0·3 0·2 0·2

High-income Asia Pacific, 0·7 years 0·2 0·1 0·3 0·1

–0·2 0 0·2 0·5 0·8 1·0 1·2 1·5 1·8

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Important trends in life expectancy Cause-specific patterns of mortality concentration

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