{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:54:03Z","timestamp":1790776443686,"version":"4.1.0"},"posted":{"date-parts":[[2022,2,15]]},"group-title":"Epidemiology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we used time series approaches to separate the direct contribution of SARS-CoV-2 infections on mortality from the indirect consequences of pandemic interventions and behavior changes in the United States. We estimated deaths occurring in excess of seasonal baselines stratified by state, age, week and cause (all causes, COVID-19 and respiratory diseases, Alzheimer\u2019s disease, cancer, cerebrovascular disease, diabetes, heart disease, and external causes, including suicides, opioids, accidents) from March 1, 2020 to April 30, 2021. Our estimates of COVID-19 excess deaths were highly correlated with SARS-CoV-2 serology, lending support to our approach. Over the study period, we estimate an excess of 666,000 (95% Confidence Interval (CI) 556000, 774000) all-cause deaths, of which 90% could be attributed to the direct impact of SARS-CoV-2 infection, and 78% were reflected in official COVID-19 statistics. Mortality from all disease conditions rose during the pandemic, except for cancer. The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer\u2019s, and heart diseases, and in age groups over 65 years. In contrast, the largest indirect consequences of the pandemic were seen in deaths from external causes, which increased by 45,300 (95% CI 30,800, 59,500) and were statistically linked to the intensity of non-pharmaceutical interventions. Within this category, increases were most pronounced in mortality from accidents and injuries, drug overdoses, and assaults and homicides, while the rate of death from suicides remained stable. Younger age groups suffered the brunt of these indirect effects. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups, in periods of stricter interventions, and in mortality from external causes. Further research on the drivers of indirect mortality is warranted to optimize interventions in future pandemics.<\/jats:p>","DOI":"10.1101\/2022.02.10.22270721","type":"posted-content","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T05:30:14Z","timestamp":1644903014000},"source":"Crossref","is-referenced-by-count":13,"title":["Direct and indirect mortality impacts of the COVID-19 pandemic in the US, March 2020-April 2021"],"prefix":"10.64898","author":[{"given":"Wha-Eum","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Woo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Weinberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1535-8526","authenticated-orcid":false,"given":"Lone","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3227-5909","authenticated-orcid":false,"given":"Bryan T.","family":"Grenfell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-4711","authenticated-orcid":false,"given":"C\u00e9cile","family":"Viboud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2022021602100444000_2022.02.10.22270721v1.1","doi-asserted-by":"crossref","unstructured":"Asten, L. van , Harmsen, C. 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Excess Deaths during Influenza and Coronavirus Disease and Infection-Fatality Rate for Severe Acute Respiratory Syndrome Coronavirus 2, the Netherlands\u2014Volume 27, Number 2\u2014February 2021\u2014Emerging Infectious Diseases journal\u2014CDC. https:\/\/doi.org\/10.3201\/eid2702.202999","DOI":"10.3201\/eid2702.202999"},{"issue":"10238","key":"2022021602100444000_2022.02.10.22270721v1.2","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(20)30854-0","article-title":"Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: A population-based cohort study","volume":"395","year":"2020","journal-title":"The Lancet"},{"key":"2022021602100444000_2022.02.10.22270721v1.3","doi-asserted-by":"crossref","unstructured":"Barnett, M. L. , Hu, L. , Martin, T. , & Grabowski, D. (2020). Mortality, Admissions, and Patient Census at SNFs in 3 US Cities During the COVID-19 Pandemic. 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