All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020 | Infectious Diseases | JAMA | JAMA Network
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Table.  Excess, Coronavirus Disease 2019 (COVID-19)–Related, and Unintentional Opioid Overdose Deaths
Excess, Coronavirus Disease 2019 (COVID-19)–Related, and Unintentional Opioid Overdose Deaths
1.
Woolf  SH, Chapman  DA, Sabo  RT, Weinberger  DM, Hill  L, Taylor  DDH.  Excess deaths from COVID-19 and other causes, March-July 2020.   JAMA. 2020;324(15):1562-1564. doi:10.1001/jama.2020.19545PubMedGoogle ScholarCrossref
2.
Cunningham  JW, Vaduganathan  M, Claggett  BL,  et al.  Clinical outcomes in young US adults hospitalized with COVID-19.   JAMA Intern Med. Published online September 9, 2020. doi:10.1001/jamainternmed.2020.5313PubMedGoogle Scholar
3.
Underlying cause of death, 1999-2018. Centers for Disease Control and Prevention. Accessed October 28, 2020. https://wonder.cdc.gov/ucd-icd10.html
4.
Monthly provisional counts of deaths by age group and HHS region for select causes of death Centers for Disease Control and Prevention. Accessed October 28, 2020. https://data.cdc.gov/NCHS/Monthly-provisional-counts-of-deaths-by-age-group-/ezfr-g6hf
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    2 Comments for this article
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    Interesting Approach to the COVID issue
    Arsen Melkumian, PhD in Economics | Bridgewater State University
    These data look interesting, however I would like to see more results reported. For instance, how well does the seasonal ARIMA fit the data? What do the monthly data for 2015-2019 look like?
    CONFLICT OF INTEREST: None Reported
    Pandemic COVID-19 and other medical challenges.
    Anatoly Zhirkov, Professor | Saint Petersburg State University
    I read the article with great interest. The authors provide statistics on mortality during the Covid-19 pandemic in the United States. The data are widely discussed from the standpoint of possible causes of death. The authors focus on the role of the COVID-19 pandemic. At the same time, attention is drawn to the fact that the number of deaths from opioid overdose prevails and remains high. Thus, the pandemic is a new problem that does not diminish the importance of opioid addiction. This article clearly demonstrates the need to improve the theory and practice of medicine during an epidemic of disease.
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    December 16, 2020

    All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020

    Author Affiliations
    • 1Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
    • 2Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
    • 3Center for Outcomes Research and Evaluation, Yale School of Medicine, New Haven, Connecticut
    • 4Harvard Affiliated Emergency Medicine Residency, Boston, Massachusetts
    • 5Emergency Medicine Department, Yuma Regional Medical Center, Yuma, Arizona
    • 6Division of Infectious Diseases, Massachusetts General Hospital, Boston
    JAMA. Published online December 16, 2020. doi:10.1001/jama.2020.24243

    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.

    Methods

    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 Classification of Diseases, Version 10 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.

    Results

    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 of 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).

    Discussion

    The COVID-19 pandemic was associated with increases in all-cause mortality among US adults aged 25 to 44 years from March through July of 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.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
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    Article Information

    Corresponding Author: Jeremy Samuel Faust, MD, MS, Brigham and Women’s Hospital Department of Emergency Medicine, 10 Vining St, Boston, MA 02115 (jsfaust@gmail.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 co-founder 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.

    References
    1.
    Woolf  SH, Chapman  DA, Sabo  RT, Weinberger  DM, Hill  L, Taylor  DDH.  Excess deaths from COVID-19 and other causes, March-July 2020.   JAMA. 2020;324(15):1562-1564. doi:10.1001/jama.2020.19545PubMedGoogle ScholarCrossref
    2.
    Cunningham  JW, Vaduganathan  M, Claggett  BL,  et al.  Clinical outcomes in young US adults hospitalized with COVID-19.   JAMA Intern Med. Published online September 9, 2020. doi:10.1001/jamainternmed.2020.5313PubMedGoogle Scholar
    3.
    Underlying cause of death, 1999-2018. Centers for Disease Control and Prevention. Accessed October 28, 2020. https://wonder.cdc.gov/ucd-icd10.html
    4.
    Monthly provisional counts of deaths by age group and HHS region for select causes of death Centers for Disease Control and Prevention. Accessed October 28, 2020. https://data.cdc.gov/NCHS/Monthly-provisional-counts-of-deaths-by-age-group-/ezfr-g6hf
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