Coronavirus disease 2019 (COVID-19) has caused a marked increase in all-cause deaths in the US, mostly among older adults.1 Although the burden of COVID-19 among hospitalized younger adults has been described, fewer data focus on mortality in this demographic, owing to lower case-fatality rates.2
Excess mortality reflects the full burden of the pandemic that may go uncaptured due to uncoded COVID-19 and other pandemic-related deaths. Accordingly, we examined all-cause excess mortality and COVID-19–related mortality during the early pandemic period among adults aged 25 to 44 years. Because unintentional drug overdoses are the usual leading cause of death in this demographic, COVID-19 deaths were compared with unintentional opioid deaths.
To determine excess mortality (the gap between observed and expected deaths), projected monthly expected deaths for 2020 were calculated by applying autoregressive integrated moving averages to US population and mortality counts (2015-2019).3 We examined 2020 population and seasonal autoregressive integrated moving averages for each of the 10 US Department of Health and Human Services (HHS) regions, which comprise the entire US and are the smallest subdivisions for which 2020 age-stratified COVID-19 mortality data are currently available from the National Center for Health Statistics. Population covariates were used to calculate 95% CIs for expected deaths.
Observed all-cause mortality and COVID-19 mortality (coded as either “underlying cause” or “multiple cause” of death) for March 1, 2020, to July 31, 2020, were obtained from provisional National Center for Health Statistics data (released October 28, 2020).4 Unintentional opioid overdose death counts (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes X41-X44, Y11-Y15, and T40.0-6) for the corresponding period of 2018 (the most recently available data) were assembled for each HHS region.3 Incident rates per 100 000 person-months with 95% CIs were calculated for COVID-19 and unintentional opioid deaths using SAS, version 9.4. Statistical significance was defined as a 95% CI that excluded the null value.
This study used publicly available data and was not subject to institutional review approval.
From March 1, 2020, to July 31, 2020, a total of 76 088 all-cause deaths occurred among US adults aged 25 to 44 years, which was 11 899 more than the expected 64 189 deaths (incident rate ratio, 1.19 [95% CI, 1.14-1.23]; Table). Nationally, excess mortality occurred in every month of the study period and overall in every HHS region (Table and eTable in the Supplement). Among adults aged 25 to 44 years, 4535 COVID-19 deaths were recorded, accounting for 38% (95% CI, 32%-48%) of the measured excess mortality.
During surges in HHS Region 2 (New York, New Jersey), the incident rate for all-cause mortality was 2.30 (95% CI, 2.03-2.66) and 80% of deaths were related to COVID-19; during surges in HHS Region 6 (Arkansas, Louisiana, New Mexico, Oklahoma, Texas), the incident rate was 1.46 (95% CI, 1.33-1.63) and 48% were related to COVID-19; and during surges in HHS Region 9 (Arizona, California, Hawaii, Nevada), the incident rate was 1.47 (95% CI, 1.36-1.59) and 40% were attributed to COVID-19.
In contrast, from March through July 2018, a total of 10 347 unintentional opioid deaths occurred among US adults aged 25 to 44 years. Deaths due to COVID-19 exceeded 2018 unintentional opioid deaths during 1 month in 2020 in HHS Region 2 (April), HHS Region 6 (July), and HHS Region 9 (July) and either exceeded (HHS Region 6) or were similar to (HHS Regions 2 and 9) unintentional opioid deaths during the entire study period (Table).
The COVID-19 pandemic was associated with increases in all-cause mortality among US adults aged 25 to 44 years from March through July 2020. In 3 HHS regions, COVID-19 deaths were similar to or exceeded unintentional opioid overdoses that occurred during several corresponding months of 2018.
Only 38% of all-cause excess deaths in adults aged 25 to 44 years recorded during the pandemic were attributed directly to COVID-19. Although the remaining excess deaths are unexplained, inadequate testing in this otherwise healthy demographic likely contributed. These results suggest that COVID-19–related mortality may have been underdetected in this population.
This study has limitations. The provisional data used represent lower-bound estimates due to reporting lags, necessitating future updates. Additionally, although COVID-19 deaths exceeded unintentional opioid deaths in 2018 in some areas, it is possible that simultaneous increases in opioid deaths may have occurred during the pandemic period, making it less clear which of these 2 diseases represents the current leading cause of death among younger adults in areas experiencing COVID-19 surges.
Corresponding Author: Jeremy Samuel Faust, MD, MS, Brigham and Women’s Hospital Department of Emergency Medicine, 10 Vining St, Boston, MA 02115 (email@example.com).
Accepted for Publication: November 18, 2020.
Published Online: December 16, 2020. doi:10.1001/jama.2020.24243
Author Contributions: Dr Faust had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Faust, Lin, Mayes, Gilman, Walensky.
Acquisition, analysis, or interpretation of data: Faust, Krumholz, Du, Lin, Mayes, Walensky.
Drafting of the manuscript: Faust, Mayes, Gilman, Walensky.
Critical revision of the manuscript for important intellectual content: Faust, Krumholz, Du, Lin, Walensky.
Statistical analysis: Faust, Du, Lin, Mayes.
Obtained funding: Walensky.
Administrative, technical, or material support: Mayes, Walensky.
Supervision: Faust, Lin, Gilman.
Conflict of Interest Disclosures: Dr Krumholz reported receiving personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, Siegfried & Jensen Law Firm, Arnold & Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases, Beijing; being a cofounder of HugoHealth, a personal health information platform, and Refactor Health, an enterprise health care artificial intelligence–augmented data management company; receiving contracts from the Centers for Medicare & Medicaid Services, through Yale New Haven Hospital, to develop and maintain measures of hospital performance; and receiving grants from Medtronic, the US Food and Drug Administration, Johnson & Johnson, and Shenzhen Center for Health Information outside the submitted work. Dr Lin reported working under contract with the Centers for Medicare & Medicaid Services to develop quality measures. Dr Walensky reported receiving grants from the Mass General Research Institute as the Steven and Deborah Gorlin MGH Research Scholar during the conduct of the study. No other disclosures were reported.
Additional Contributions: We thank Lauren M. Rossen, PhD, MS (National Center for Health Statistics), for facilitating the public release of National Center for Health Statistics data used for this study and for providing expertise on excess death determination and Michael Colin Tasi, MD, MBA (Harvard Affiliated Emergency Medicine Residency), for assistance in supporting data preparation. Neither individual received compensation for their contributions.