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

Abstract

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.

Keywords: COVID-19; epidemiology; health informatics; mental health; public health; statistics & research methods.

Figure 1

Trends in population-adjusted death counts by week of influenza season,^a 2014–2015 through 2019–2020 seasons. ^aFor each influenza season, week 1 begins on approximately 1 October and week 52 ends on approximately 30 September. A total of 312 weeks (52 weeks for six seasons) were included in the analyses. Dividing lines represent the ends of weeks 16 (week prior to pandemic awareness period), 26 (week prior to initial pandemic peak) and 35 (week prior to pandemic post-peak period). Prior season benchmarks are means (deaths summed across seasons, divided by 2, 3 and 5, respectively, for two-season, three-season and five-season benchmarks). Benchmarks for two, three and five seasons, respectively, are indicated by long dashed lines, alternating short and long dashed lines, and dotted lines. ^bExplained deaths include specific causes reported in the mortality files, including heart disease, cancer, chronic lower respiratory disease, cerebrovascular disease, Alzheimer’s disease, diabetes, influenza/pneumonia, other respiratory illness, kidney disease, septicaemia and COVID-19. Diagnosis codes for each category are in online supplemental appendix 1. Unexplained deaths are all-cause deaths with no reported underlying cause or with a not elsewhere classified (NEC) cause (all-cause deaths minus explained deaths). NEC deaths are described in ICD-10 nomenclature as ‘symptoms, signs, and abnormal clinical and laboratory findings NEC’ (ICD-10 range R00–R99), include ‘ill-defined and unknown cause of mortality’ (R99), a code commonly used pending forensic investigation of injurious death. ICD-10, International Classification of Diseases, 10th Revision.