[Excess of mortality and mortality from COVID-19 and other causes of death in 2020 in Navarra, Spain].

BACKGROUND: In this study, we aimed to present mortality indicators from a database of death causes by age and sex in Navarre (Spain) for 2020: life expectancy at birth, excess mortality, and mortality from COVID-19 and other causes. METHODS: A Poisson regression model, which accounts for temporal trends in the previous years, was used to estimate the expected deaths by sex and age for 2020. RESULTS: Life expectancy at birth in Navarre for 2020 was 80.6 and 85.9 years for men and women, respectively, 1.4 and 1.0 years lower than in 2019. Deaths in people aged <55 years were similar to those expected. The highest adjusted excess mortality rate occurred among men and women aged >85 years, were 61% of excess deaths was concentrated. The estimated number of excess deaths did not exceed the number of reported deaths from COVID-19. In individuals aged >75 years, around 9 out of 10 people died from COVID-19. Coinciding with the COVID-19 pandemic, there was a remarkable decrease in mortality in people affected by diseases where dementia is included. CONCLUSIONS: The first and second waves of the COVID-19 pandemic reduced life expectancy at birth to figures observed ten years ago. The increase in deaths in Navarre for 2020 is largely attributable to COVID-19.

Understanding COVID-19 Vaccine Effectiveness against Death Using a Novel Measure: COVID Excess Mortality Percentage.

COVID-19 vaccines have saved millions of lives; however, understanding the long-term effectiveness of these vaccines is imperative to developing recommendations for booster doses and other precautions. Comparisons of mortality rates between more and less vaccinated groups may be misleading due to selection bias, as these groups may differ in underlying health status. We studied all adult deaths during the period of 1 April 2021-30 June 2022 in Milwaukee County, Wisconsin, linked to vaccination records, and we used mortality from other natural causes to proxy for underlying health. We report relative COVID-19 mortality risk (RMR) for those vaccinated with two and three doses versus the unvaccinated, using a novel outcome measure that controls for selection effects. This measure, COVID Excess Mortality Percentage (CEMP), uses the non-COVID natural mortality rate (Non-COVID-NMR) as a measure of population risk of COVID mortality without vaccination. We validate this measure during the pre-vaccine period (Pearson correlation coefficient = 0.97) and demonstrate that selection effects are large, with non-COVID-NMRs for two-dose vaccinees often less than half those for the unvaccinated, and non-COVID NMRs often still lower for three-dose (booster) recipients. Progressive waning of two-dose effectiveness is observed, with an RMR of 10.6% for two-dose vaccinees aged 60+ versus the unvaccinated during April-June 2021, rising steadily to 36.2% during the Omicron period (January-June, 2022). A booster dose reduced RMR to 9.5% and 10.8% for ages 60+ during the two periods when boosters were available (October-December, 2021; January-June, 2022). Boosters thus provide important additional protection against mortality.

Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017–2019 and 2020

OBJECTIVE To estimate diabetes-related mortality in Mexico in 2020 compared with 2017–2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017–2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017–2019 rates. RESULTS We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017–2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017–2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018–2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.

Excess mortality and the COVID-19 pandemic: causes of death and social inequalities.

BACKGROUND: During the coronavirus diseases 2019 (COVID-19) pandemic, population's mortality has been affected not only by the risk of infection itself, but also through deferred care for other causes and changes in lifestyle. This study aims to investigate excess mortality by cause of death and socio-demographic context during the COVID-19 pandemic in South Korea.  METHODS: Mortality data within the period 2015-2020 were obtained from Statistics Korea, and deaths from COVID-19 were excluded. We estimated 2020 daily excess deaths for all causes, the eight leading causes of death, and according to individual characteristics, using a two-stage interrupted time series design accounting for temporal trends and variations in other risk factors. RESULTS: During the pandemic period (February 18 to December 31, 2020), an estimated 663 (95% empirical confidence interval [eCI]: -2356-3584) excess deaths occurred in South Korea. Mortality related to respiratory diseases decreased by 4371 (3452-5480), whereas deaths due to metabolic diseases and ill-defined causes increased by 808 (456-1080) and 2756 (2021-3378), respectively. The increase in all-cause deaths was prominent in those aged 65-79 years (941, 88-1795), with an elementary school education or below (1757, 371-3030), or who were single (785, 384-1174), while a decrease in deaths was pronounced in those with a college-level or higher educational attainment (1471, 589-2328). CONCLUSION: No evidence of a substantial increase in all-cause mortality was found during the 2020 pandemic period in South Korea, as a result of a large decrease in deaths related to respiratory diseases that offset increased mortality from metabolic disease and diseases of ill-defined cause. The COVID-19 pandemic has disproportionately affected those of lower socioeconomic status and has exacerbated inequalities in mortality.

Understanding COVID-19 Vaccine Effectiveness Against Death Using a Novel Measure: COVID Excess Mortality Percentage (preprint)

COVID-19 vaccines have saved millions of lives and prevented countless adverse patient disease outcomes. Understanding the long-term effectiveness of these vaccines is imperative to developing recommendations for precautions and booster doses. Comparisons between more and less vaccinated groups may be misleading due to selection bias, as these groups may differ in underlying health status and thus risk of adverse COVID-19 outcomes. We study all adult deaths over April 1, 2021-June 30, 2022 in Milwaukee County, Wisconsin, linked to vaccination records, use mortality from other natural causes to proxy for underlying health, and report relative COVID-19 mortality risk (RMR) for vaccinees versus the unvaccinated, using a novel outcome measure that controls for selection effects. This measure, COVID Excess Mortality Percentage (CEMP) uses the non-COVID natural mortality rate (Non-Covid-NMR) as a measure of population risk of COVID mortality without vaccination. We validate this measure during the pre-vaccine period (r = 0.97) and demonstrate that selection effects are large, with Non-Covid-NMRs for two-dose vaccinees less than half those for the unvaccinated, and Non-COVID NMRs still lower for three dose (booster) recipients. Progressive waning of two-dose effectiveness is observed, with relative mortality risk (RMR) for two-dose vaccinees aged 60 + versus the unvaccinated of 11% during April-June 2021, rising steadily to 36% during the Omicron period (January-June, 2022). Notably, a booster dose reduced RMR to 10–11% for ages 60+. Boosters thus provide important additional protection against mortality.

Are COVID-19 age-mortality curves for 2020 flatter in developing countries? Evidence from a cross-sectional observational study of population-level official death counts and excess deaths estimates.

OBJECTIVES: Previous studies have found a pattern of flatter COVID-19 age-mortality curves among low-income and middle-income countries (LMICs) using only official COVID-19 death counts. This study examines this question by comparing the age gradient of COVID-19 mortality in a broad set of countries using both official COVID-19 death counts and excess mortality estimates for 2020. DESIGN: This observational study uses official COVID-19 death counts for 76 countries and excess death estimates for 42 countries. A standardised population analysis was conducted to assess the extent to which variation across countries in the age distribution of COVID-19 deaths was driven by variation in the population age distribution. SETTING AND PRIMARY OUTCOMES: Officially reported COVID-19 deaths and excess deaths for 2020 for all countries where such data were available in the COVerAGE database and the short-term mortality fluctuations harmonised data series, respectively. RESULTS: A higher share of pandemic-related deaths in 2020 occurred at younger ages in middle-income countries compared with high-income countries. People under age 65 years constituted on average (1) 10% of official deaths and 11 % of excess deaths in high-income countries, (2) 34% of official deaths and 33% of excess deaths in upper-middle-income countries, and (3) 54% of official deaths in LMICs. These contrasting profiles are due only in part to differences in population age structure. CONCLUSIONS: These findings are driven by some combination of variation in age patterns of infection rates and infection fatality rates. They indicate that COVID-19 is not just a danger to older people in developing countries, where a large share of victims are people of working age, who are caregivers and breadwinners for their families.

Excess mortality associated with the COVID-19 pandemic (2020-2021) in an urban community of Bangladesh: Evidence from cemetery-based death registration (preprint)

Objectives Unlike high-income countries, the magnitude of COVID-19-related mortality is largely unknown in many low- and middle-income countries. This study aimed to determine the COVID-19-associated excess mortality in an urban setting in Bangladesh using a cemetery-based death registration dataset. Study design Retrospective observational study Methods Data extracted from the death registry books managed by the local municipality. A total of 6,271 deaths (3,790 male and 2,481 female) recorded between January 2015 and December 2021 were analyzed by using the Bayesian structural time series model (BSTS). Results During the pre-COVID-19 period, the average monthly number of deaths was 69, whereas, during the COVID-19 period, this number significantly increased to 92. Overall, according to model-based results, during COVID-19 period, the number of deaths increased on average by 17% (95% CrI: -18%, 57%): males 29% (95 % CrI: -15%, 75%) and 2.9% for females (95% CrI: -61%, 70%). Conclusions This first-of-its-kind study in Bangladesh has revealed the excess mortality due to the COVID-19 pandemic (2020-2021) in an urban community. It appears that cemetery-based death registration could help track various crises (e.g., COVID-19), especially when collecting data on the ground is challenging for resource-limited countries.

Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017-2019 and 2020.

OBJECTIVE: To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS: This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS: Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.

Socio-demographic inequalities and excess non-COVID-19 mortality during the COVID-19 pandemic: a data-driven analysis of 1 069 174 death certificates in Mexico.

BACKGROUND: In 2020, Mexico experienced one of the highest rates of excess mortality globally. However, the extent of non-COVID deaths on excess mortality, its regional distribution and the association between socio-demographic inequalities have not been characterized. METHODS: We conducted a retrospective municipal and individual-level study using 1 069 174 death certificates to analyse COVID-19 and non-COVID-19 deaths classified by ICD-10 codes. Excess mortality was estimated as the increase in cause-specific mortality in 2020 compared with the average of 2015-2019, disaggregated by primary cause of death, death setting (in-hospital and out-of-hospital) and geographical location. Correlates of individual and municipal non-COVID-19 mortality were assessed using mixed effects logistic regression and negative binomial regression models, respectively. RESULTS: We identified a 51% higher mortality rate (276.11 deaths per 100 000 inhabitants) compared with the 2015-2019 average period, largely attributable to COVID-19. Non-COVID-19 causes comprised one-fifth of excess deaths, with acute myocardial infarction and type 2 diabetes as the two leading non-COVID-19 causes of excess mortality. COVID-19 deaths occurred primarily in-hospital, whereas excess non-COVID-19 deaths occurred in out-of-hospital settings. Municipal-level predictors of non-COVID-19 excess mortality included levels of social security coverage, higher rates of COVID-19 hospitalization and social marginalization. At the individual level, lower educational attainment, blue-collar employment and lack of medical care assistance prior to death were associated with non-COVID-19 deaths. CONCLUSION: Non-COVID-19 causes of death, largely chronic cardiometabolic conditions, comprised up to one-fifth of excess deaths in Mexico during 2020. Non-COVID-19 excess deaths occurred disproportionately out-of-hospital and were associated with both individual- and municipal-level socio-demographic inequalities.

Leading causes of excess mortality in Mexico during the COVID-19 pandemic 2020-2021: A death certificates study in a middle-income country.

Background: The death toll after SARS-CoV-2 emergence includes deaths directly or indirectly associated with COVID-19. Mexico reported 325,415 excess deaths, 34.4% of them not directly related to COVID-19 in 2020. In this work, we aimed to analyse temporal changes in the distribution of the leading causes of mortality produced by COVID-19 pandemic in Mexico to understand excess mortality not directly related to the virus infection. Methods: We did a longitudinal retrospective study of the leading causes of mortality and their variation with respect to cause-specific expected deaths in Mexico from January 2020 through December 2021 using death certificate information. We fitted a Poisson regression model to predict cause-specific mortality during the pandemic period, based on the 2015-2019 registered mortality. We estimated excess deaths as a weekly difference between expected and observed deaths and added up for the entire period. We expressed all-cause and cause-specific excess mortality as a percentage change with respect to predicted deaths by our model. Findings: COVID-19 was the leading cause of death in 2020-2021 (439,582 deaths). All-cause total excess mortality was 600,590 deaths (38⋅2% [95% CI: 36·0 to 40·4] over expected). The largest increases in cause-specific mortality, occurred in diabetes (36·8% over expected), respiratory infections (33·3%), ischaemic heart diseases (32·5%) and hypertensive diseases (25·0%). The cause-groups that experienced significant decreases with respect to the expected pre-pandemic mortality were infectious and parasitic diseases (-20·8%), skin diseases (-17·5%), non-traffic related accidents (-16·7%) and malignant neoplasm (-5·3%). Interpretation: Mortality from COVID-19 became the first cause of death in 2020-2021, the increase in other causes of death may be explained by changes in the health service utilization patterns caused by hospital conversion or fear of the population using them. Cause-misclassification cannot be ruled out. Funding: This study was funded by Conacyt.

Sociodemographic inequalities and excess non-COVID-19 mortality during the COVID-19 pandemic: A data-driven analysis of 1,069,174 death certificates in Mexico (preprint)

BACKGROUND: In 2020, Mexico experienced one of the highest rates of excess mortality globally. However, the extent to which non-COVID deaths contributed to excess mortality, its regional characterization, and the association between municipal- and individual-level sociodemographic inequality has not been characterized. METHODS: We conducted a retrospective municipal an individual-level study using death certificate data in Mexico from 2016-2020. We analyzed mortality related to COVID-19 and to non-COVID-19 causes using ICD-10 codes to identify cause-specific mortality. Excess mortality was estimated as the increase in deaths in 2020 compared to the average of 2016-2019, disaggregated by primary cause of death, death setting (in-hospital and out-of-hospital) and geographical location. We evaluated correlates of non-COVID-19 mortality at the individual level using mixed effects logistic regression and correlates of non-COVID-19 excess mortality in 2020 at the municipal level using negative binomial regression. RESULTS: We identified 1,069,174 deaths in 2020 (833.5 per 100,000 inhabitants), which was 49% higher compared to the 2016-2019 average (557.38 per 100,000 inhabitants). Overall excess mortality (276.11 deaths per 100,000 inhabitants) was attributable in 76.1% to COVID-19; however, non-COVID-19 causes comprised one-fifth of excess deaths. COVID-19 deaths occurred primarily in-hospital, while excess non-COVID-19 deaths decreased in this setting and increased out-of-hospital. Excess non-COVID-19 mortality displayed geographical heterogeneity linked to sociodemographic inequalities with clustering in states in southern Mexico. Municipal-level predictors of non-COVID-19 excess mortality included levels of social security coverage, higher rates of COVID-19 hospitalization, and social marginalization. At the individual level, lower educational attainment, blue collar workers, and lack of medical care assistance were associated with non-COVID-19 mortality during 2020. CONCLUSION: Non-COVID-19 causes of death, largely chronic cardiometabolic conditions, comprised up to one-fifth of excess deaths in Mexico during 2020. Non-COVID-19 excess deaths occurred disproportionately out-of-hospital and were associated with both individual- and municipal-level sociodemographic inequalities. These findings should prompt an urgent call to action to improve healthcare coverage and access to reduce health and sociodemographic inequalities in Mexico to reduce preventable mortality in situations which increase the stress of healthcare systems, including the ongoing COVID-19 pandemic.

The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries.

BACKGROUND: Critical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. METHODS: Data comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. RESULTS: This study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89-0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27-1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25). Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

COVID-19 age-mortality curves for 2020 are flatter in developing countries using both official death counts and excess deaths

Using official COVID-19 death counts for 64 countries and excess death estimates for 41 countries, this paper finds a higher share of pandemic-related deaths in 2020 were at younger ages in middle-income countries compared to high-income countries. People under age 65 constituted on average (1) 11 percent of both official deaths and excess deaths in high-income countries, (2) 40 percent of official deaths and 37 percent of excess deaths in upper-middle-income countries, and (3) 54 percent of official deaths in lower-middle-income countries. These contrasting profiles are due only in part to differences in population age structure. Both COVID-19 and excess death age-mortality curves are flatter in countries with lower incomes. This is a result of some combination of variation in age patterns of infection rates and infection fatality rates. In countries with very low death rates, excess mortality is substantially negative at older ages, suggesting that pandemic-related precautions have lowered non-COVID-19 deaths. Additionally, the United States has a younger distribution of deaths than countries with similar levels of income.

Excess Mortality Versus COVID-19 Death Rates: A Spatial Analysis of Socioeconomic Disparities and Political Allegiance Across U.S. States.

Excess mortality is a more robust measure than the counts of COVID-19 deaths typically used in epidemiological and spatial studies. Measurement issues around excess mortality, considering data quality and comparability both internationally and within the U.S., are surveyed. This paper is the first state-level spatial analysis of cumulative excess mortality for the U.S. in the first full year of the pandemic. There is strong evidence that, given appropriate controls, states with higher Democrat vote shares experienced lower excess mortality (consistent with county-level studies of COVID-19 deaths). Important demographic and socio-economic controls from a broad set tested were racial composition, age structure, population density, poverty, income, temperature, and timing of arrival of the pandemic. Interaction effects suggest the Democrat vote share effect of reducing mortality was even greater in states where the pandemic arrived early. Omitting political allegiance leads to a significant underestimation of the mortality disparities for minority populations.

POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USING PRE-PANDEMIC RISK OF MORTALITY IN INDIVIDUALS WITH CHRONIC KIDNEY DISEASE

Introduction: Chronic Kidney Disease (CKD) is a global burden on public health, both as a risk factor for mortality, and as the end syndrome of underlying diseases. CKD is a common comorbidity associated with increased risk of severe coronavirus infection and poor clinical outcomes. The pandemic has had both direct (through infection) and indirect impact. The direct impact on individuals with CKD and other underlying conditions is related to baseline risk, influenced by age, multimorbidity and other socio-demographic factors. However, previous studies of COVID-19 in CKD have been small scale (12-1099 cases), mostly focused on end-stage CKD, and ignored major comorbidities. Thus, using large-scale, population-based electronic health records, in people with incident CKD we aimed to (a) identify the most common comorbidities;(b) estimate 1-year (pre-pandemic) risk of mortality and (c) predict excess deaths related to COVID-19 over 1-year of pandemic based on pre-pandemic risk of mortality at different population infection rates and relative risks. Methods: We used linked primary and secondary care records (Clinical Practice Research Datalink GOLD data) from England;of 3,862,012 individuals aged ≥ 30 registered with a GP practice between 1997 and 2017. Incident CKD was identified based on diagnosis codes and eGFR levels;classified mutually exclusively into five CKD Stages. The underlying conditions were obtained using validated phenotyping algorithms in CALIBER and the most prevalent ones were identified. The 1-year mortality were estimated using Kaplan–Meier survival analysis;stratified by key demographic factors and number of comorbidities. Using these pre-pandemic risk estimates and our recently published Lancet model, we calculated excess COVID-19 related deaths at different population infection rates and relative risks. For validation, we identified the number of people who died with both CKD and positive COVID-19 test result during 1-year of pandemic using the contemporary NHSD TRE data of England (NHS Digital Trusted Research Environment, n=54 million). Results: We identified 294,381 individuals with incident CKD (mean age 72.5 years;female: 59%). Multimorbidity was common among CKD patients especially the presence of hypertension (61.4%) and CVD complications (35.6%) (Fig 1 ). The proportion of CKD patients having at least one underlying condition increases significantly either by age or CKD stage whilst age was the main confounder within each CKD stage. Age, Stage of CKD and underlying conditions combined to influence pre-pandemic risk (Fig 2 ). At an IR of 10%, we predicted 31003 and 46505 excess deaths at RR of 2 and 3 respectively (Table 1 ) which is close to actual observed mortality (47214) from the NHSD TREin England. [Formula presented] [Formula presented] [Formula presented] Conclusions: Individuals with CKD have high risk of pre-pandemic mortality particularly those with comorbidities. The data on multimorbidity, CKD stage and age together could help prioritise patients for vaccination, post-COVID policy, and designing stratified pathways for CKD patients. We illustrate that the direct burden of pandemic could be predicted using pre-pandemic large scale EHR data. Conflict of interest Potential conflict of interest: This study was funded by AstraZeneca and Health Data Research UK. AB has received research grants from AstraZeneca. JBM and TM are employed full-time by AstraZeneca UK Ltd, a biopharmaceutical company who develops, manufactures and markets medicines in the cardiovascular, renal and metabolic disease area.

Diabetes-related excess mortality in Mexico: a comparative analysis of national death registries between 2017-2019 and 2020 (preprint)

BACKGROUND: Excess all-cause mortality rates in Mexico in 2020 during the COVID-19 pandemic were among the highest globally. Recent reports suggest that diabetes-related deaths were also higher, but the contribution of diabetes as a cause of excess mortality in Mexico during 2020 compared to prior years has not yet been characterized. METHODS: We conducted a retrospective, state-level study using national death registries from Mexican adults [≥]20 years for the 2017-2020 period. Diabetes-related deaths were classified using ICD-10 codes that listed diabetes as the primary cause of death, excluding certificates which listed COVID-19 as a cause of death. Excess mortality was estimated as the increase in diabetes-related mortality in 2020 compared to average rates in 2017-2019. Analyses were stratified by diabetes type, diabetes-related complication, and in-hospital vs. out-of-hospital death. We evaluated the geographic distribution of diabetes-related excess mortality and its socio-demographic and epidemiologic correlates using spatial analyses and negative binomial regression models. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177/100,000 inhabitants), 41.6% higher than the average for 2017-2019, with the excess occurring after the onset of the COVID-19 pandemic. In-hospital diabetes-related deaths decreased by 17.8% in 2020 compared to 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes and type 1 diabetes (129.7 and 4.0/100,000 population). Diabetes-related emergencies as contributing causes of death also increased in 2020 compared to 2017-2019 for hyperglycemic hyperosmolar state (128%), and ketoacidosis (116%). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, higher rates of COVID-19 hospitalization, and higher prevalence of HbA1c [≥]7.5%. INTERPRETATION: Diabetes-related mortality increased among Mexican adults by 41.6% in 2020 after the onset of the pandemic compared to 2017-2019, largely attributable to type 2 diabetes. Excess diabetes-related deaths occurred disproportionately out-of-hospital, clustered in southern Mexico, and were associated with higher state-level marginalization, rates of COVID-19 hospitalizations, and higher prevalence of suboptimal glycemic control. Urgent policies to mitigate mortality due to diabetes in Mexico are needed, particularly given the ongoing challenges in caring for people with diabetes posed by the COVID-19 pandemic.

Unexplained mortality during the US COVID-19 pandemic: retrospective analysis of death certificate data and critical assessment of excess death calculations.

OBJECTIVES: Cause-of-death discrepancies are common in respiratory illness-related mortality. A standard epidemiological metric, excess all-cause death, is unaffected by these discrepancies but provides no actionable policy information when increased all-cause mortality is unexplained by reported specific causes. To assess the contribution of unexplained mortality to the excess death metric, we parsed excess deaths in the COVID-19 pandemic into changes in explained versus unexplained (unreported or unspecified) causes. DESIGN: Retrospective repeated cross-sectional analysis, US death certificate data for six influenza seasons beginning October 2014, comparing population-adjusted historical benchmarks from the previous two, three and five seasons with 2019-2020. SETTING: 48 of 50 states with complete data. PARTICIPANTS: 16.3 million deaths in 312 weeks, reported in categories-all causes, top eight natural causes and respiratory causes including COVID-19. OUTCOME MEASURES: Change in population-adjusted counts of deaths from seasonal benchmarks to 2019-2020, from all causes (ie, total excess deaths) and from explained versus unexplained causes, reported for the season overall and for time periods defined a priori: pandemic awareness (19 January through 28 March); initial pandemic peak (29 March through 30 May) and pandemic post-peak (31 May through 26 September). RESULTS: Depending on seasonal benchmark, 287 957-306 267 excess deaths occurred through September 2020: 179 903 (58.7%-62.5%) attributed to COVID-19; 44 022-49 311 (15.2%-16.1%) to other reported causes; 64 032-77 054 (22.2%-25.2%) unexplained (unspecified or unreported cause). Unexplained deaths constituted 65.2%-72.5% of excess deaths from 19 January to 28 March and 14.1%-16.1% from 29 March through 30 May. CONCLUSIONS: Unexplained mortality contributed substantially to US pandemic period excess deaths. Onset of unexplained mortality in February 2020 coincided with previously reported increases in psychotropic use, suggesting possible psychiatric or injurious causes. Because underlying causes of unexplained deaths may vary by group or region, results suggest excess death calculations provide limited actionable information, supporting previous calls for improved cause-of-death data to support evidence-based policy.

Leading Causes of Excess Mortality in Mexico During the COVID-19 Pandemic 2020 – February 2021: A Death Certificates Study in a Lower-Middle-Income Country (preprint)

Background: The death toll after SARS-CoV-2 emergence includes deaths directly or indirectly associated with COVID-19. For Mexico, a 28% excess mortality not directly related to the virus infection has been estimated. We aimed to analyze temporal and percentage changes in the distribution of the leading causes of mortality during the COVID-19 pandemic in Mexico.Methods: We did a retrospective longitudinal study of the leading causes of mortality and their variation with respect to expected deaths in Mexico from 2020 until 27 February 2021 using death certificates information. A Poisson regression model was fitted, to predict the expected, cause specific, mortality during the study period, based on the 2015-2019 registered mortality. Excess deaths were estimated as the weekly difference between expected and observed death. Findings: All-cause excess mortality was 46×5% (CI 95%: 45×2-47×8) over expected mortality. Deaths directly attributed to COVID-19 accounted for 69×6%. Leading causes of excess mortality were: Respiratory infections (59×5%), diabetes (48×0%), ischemic heart diseases (37×8%), hypertensive diseases (30×4%), motor vehicle road injuries (29×6%), and other endocrine, metabolic, hematological, and immunological diseases (28×2%). Causes that decreased with respect to expected mortality were: Other accidents (-29×1%), infectious and parasitic diseases (-23×4%), injuries of undetermined intent (-23×2%), other tumors (-22×5%), and skin diseases (-20×4%).Interpretation: Mortality from COVID-19 became the second cause of death in 2020, after cardiovascular diseases. Respiratory infections, diabetes and cardiovascular increased dramatically with respect to 2019, this could be a consequence of lack of access, but also certification errors.Funding Information: This study did not receive any funds.Declaration of Interests: We declare no competing interests.

Sensitivity of excess mortality due to the COVID-19 pandemic to the choice of the mortality index, method, reference period, and the time unit of the death series (preprint)

Estimating excess mortality is challenging. The metric depends on the expected mortality level, which can differ based on given choices, such as the method and the time series length used to estimate the baseline. However, these choices are often arbitrary, and are not subject to any sensitivity analysis. We bring to light the importance of carefully choosing the inputs and methods used to estimate excess mortality. Drawing on data from 26 countries, we investigate how sensitive excess mortality is to the choice of the mortality index, the number of years included in the reference period, the method, and the time unit of the death series. We employ two mortality indices, three reference periods, two data time units, and four methods for estimating the baseline. We show that excess mortality estimates can vary substantially when these factors are changed, and that the largest variations stem from the choice of the mortality index and the method. We also find that the magnitude of the variation in excess mortality can change markedly within countries, resulting in different cross-country rankings. We conclude that the inputs and method used to estimate excess mortality should be chosen carefully based on the specific research question.