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Cited by 90COVID-19 epidemiological studiesCOVID-19 and healthcare impactsCOVID-19 Clinical Research Studies

Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022

Open access
Lee, Wha-Eum, Woo Park, Sang, Weinberger, Daniel M, Olson, Donald, Simonsen, Lone, Grenfell, Bryan T, Viboud, Cécile·2023·eLife
DOI 10.7554/elife.77562PMC PMC8863161

Published version of a preprint

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Abstract

Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we use time series approaches to separate the direct contribution of SARS-CoV-2 infection on mortality from the indirect consequences of the pandemic in the United States. We estimate excess deaths occurring above a seasonal baseline from March 1, 2020 to January 1, 2022, stratified by week, state, age, and underlying mortality condition (including COVID-19 and respiratory diseases; Alzheimer’s disease; cancer; cerebrovascular diseases; diabetes; heart diseases; and external causes, which include suicides, opioid overdoses, and accidents). Over the study period, we estimate an excess of 1,065,200 (95% Confidence Interval (CI) 909,800–1,218,000) all-cause deaths, of which 80% are reflected in official COVID-19 statistics. State-specific excess death estimates are highly correlated with SARS-CoV-2 serology, lending support to our approach. Mortality from 7 of the 8 studied conditions rose during the pandemic, with the exception of cancer. To separate the direct mortality consequences of SARS-CoV-2 infection from the indirect effects of the pandemic, we fit generalized additive models (GAM) to age- state- and cause-specific weekly excess mortality, using covariates representing direct (COVID-19 intensity) and indirect pandemic effects (hospital intensive care unit (ICU) occupancy and measures of interventions stringency). We find that 84% (95% CI 65–94%) of all-cause excess mortality can be statistically attributed to the direct impact of SARS-CoV-2 infection. We also estimate a large direct contribution of SARS-CoV-2 infection (≥67%) on mortality from diabetes, Alzheimer’s, heart diseases, and in all-cause mortality among individuals over 65 years. In contrast, indirect effects predominate in mortality from external causes and all-cause mortality among individuals under 44 years, with periods of stricter interventions associated with greater rises in mortality. 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 and in mortality from external causes. Further research on the drivers of indirect mortality is warranted as more detailed mortality data from this pandemic becomes available.

AI snapshot

Written from the paper’s full text.

TL;DR

Using US weekly mortality data from March 1, 2020 to April 30, 2021, the authors estimate 666,000 excess all-cause deaths, about 90% of which were directly attributable to SARS-CoV-2 infection. Indirect mortality was concentrated in younger age groups and external causes, especially accidents, drug overdoses, and assaults/homicides, and was statistically linked to stricter non-pharmaceutical interventions.

Key findings

  • There were 666,000 (95% CI 556,000–774,000) excess all-cause deaths; 90% (95% CI 82–99) were directly attributable to COVID-19, and 78% were reflected in official COVID-19 statistics. Excess respiratory deaths were 507,000 (95% CI 487,000–526,000).
  • Mortality rose for 6 of 7 non-respiratory conditions studied; cancer did not increase. Direct COVID-19 contributions were 59% (42–76) for diabetes, 58% (30–86) for Alzheimer’s, and 97% (40–158) for heart disease.
  • External-cause mortality increased by 45,300 (30,800–59,500) excess deaths. Subcategories included accidents/injuries 23,800 (8,400–39,200; 11% increase), drug overdoses 15,300 (7,500–23,100; 15%), and assaults/homicides 5,100 (2,700–7,600; 21%); suicides remained stable.
  • Age patterns differed: ages 85+ had 155,100 (117,300–192,100) excess all-cause deaths, while ages 25–44 had 54,500 (47,500–61,300) and under 25 had 10,200 (6,000–14,300). Official COVID-19 statistics captured 11% (8–19%) of excess deaths under 25 but over 100% in those over 85. The nationwide IFR was 0.61% (0.49–0.73) based on excess respiratory mortality, 0.86% (0.72–0.99) based on all-cause excess mortality, and 5.7% (4.7–6.8) in individuals over 65.

Methods

  • The authors used NCHS weekly mortality counts from August 1, 2014 to April 30, 2021, stratified by state, 6 age groups, and 8 underlying causes; external-cause subcategories were analyzed monthly. They also used CDC seroprevalence surveys, influenza surveillance, and the Oxford COVID-19 containment index.
  • Seasonal regression models were fitted to pre-pandemic weekly mortality rates from August 1, 2014 to March 1, 2020, including harmonic seasonality, time trends, and a weekly influenza proxy; baselines were projected to April 30, 2021, and excess mortality was observed minus predicted mortality, with block bootstraps for 95% prediction intervals.
  • Direct and indirect impacts were assessed via correlation and regression analyses of cause- and age-specific excess mortality against COVID-19 deaths and the containment index, plus serology-based validation and IFR estimation. Cause-specific analyses covered 16 states for respiratory mortality and 33 states for non-respiratory mortality.

Limitations

  • The paper states that mortality counts below 10 were suppressed, restricting age-specific analyses to larger states and preventing assessment of race/ethnicity; official coding practices may have changed across states and time; negative excesses in cancer and cardiovascular/heart disease may reflect ascertainment changes or harvesting; baseline respiratory mortality could be affected by non-influenza pathogens; and the study ends in April 2021, so it does not capture Delta or Omicron and estimates are conservative.
  • The paper also states that its conclusions are based on ecologic analyses that are useful to generate hypotheses but do not prove causality.
  • The provided full text covers March 2020–April 2021, not the January 1, 2022 endpoint in the bibliographic record, and it contains an internal numerical discrepancy for external-cause excess deaths: the abstract/results report 45,300 (30,800–59,500), while the Discussion reports 51,300 (39,700–62,700).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.7554/elife.77562

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Mortality from all disease conditions rose during the pandemic except for cancer.

    “Mortality from all disease conditions rose during the pandemic, except for cancer.”
    Quote in the paperNot a substantial claim
  • Findingown data

    78% of excess all-cause deaths were reflected in official COVID-19 statistics.

    “and 78% were reflected in official COVID-19 statistics.”
    Quote in the paperSubstantial claim
  • Findingown data

    External cause deaths were statistically linked to the intensity of non-pharmaceutical interventions.

    “and were statistically linked to the intensity of non-pharmaceutical interventions.”
    • Also stated in: § Direct and indirect pandemic impacts by cause of death · plain
      “Periods of more stringent interventions were statistically associated with elevated mortality from external causes”
    Quote in the paperSubstantial claim
  • Findingown data

    The rate of death from suicides remained stable during the pandemic.

    “while the rate of death from suicides remained stable.”
    • Also stated in: § Direct and indirect pandemic impacts by cause of death · plain
      “In contrast, mortality from suicides remained within historic baselines throughout the COVID-19 period.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Deaths from external causes increased by 45,300 (95% CI 30,800-59,500).

    “which increased by 45,300 (95% CI 30,800, 59,500)”
    • Also stated in: § Direct and indirect pandemic impacts by cause of death · plain
      “We found a significant rise in deaths from external causes during the pandemic period March 2020–April 2021, corresponding to 45,300 (30,800, 59,500) excess deaths nationally (Figure 2).”
    Quote in the paperSubstantial claim
  • May combine two claims. 44
  • Classified as probably not a substantial claim. 27

  • May combine two claims.

    Findingown data

    The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer's, and heart diseases, and in age groups over 65 years.

    “The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer’s, and heart diseases, and in age groups over 65 years.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Seroprevalence estimates ranged between 4.7% and 28% at the end of April 2021, with a population-weighted national seroprevalence of 22.8%.

    “Seroprevalence estimates ranged between 4.7 and 28% at the end of April 2021, with a population-weighted national seroprevalence of 22.8%.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Individuals 85 years and older had 155,100 (117,300-192,100) excess all-cause deaths, accounting for 23% of excess deaths during the pandemic period.

    “Individuals 85 years and older had 155,100 (117300, 192100) excess all-cause deaths, accounting for 23% of excess deaths during the pandemic period.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The first excess mortality peaks occurred within one week of the first respiratory mortality peak on April 18, 2020, and synchronicity between mortality causes was most evident in New York and New Jersey in the first wave.

    “Across these causes of death, the first excess mortality peaks occurred within one week of the first respiratory mortality peak on April 18, 2020, and synchronicity between mortality causes was most evident in New York and New Jersey in the first wave.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Cancer and suicides remained within baseline levels during the pandemic.

    “In contrast to other causes of deaths studied, cancer and suicides remained within baseline levels during the pandemic.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Individuals 25-44 years accounted for 8.1% of pandemic excess mortality, representing 54,500 (47,500-61,300) excess all-cause deaths.

    “individuals under 25 years and 25–44 years accounted for only 1.5% and 8.1% of pandemic excess mortality, representing 10,200 (6000, 14300) and 54,500 (47500, 61300) excess all-cause deaths.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Children had a low absolute rate of excess mortality during the pandemic, and only 11% was attributable to SARS-CoV-2 infection, while stricter interventions were associated with rising mortality in this age group.

    “And even though children had a low absolute rate of excess mortality during the pandemic, only 11% was attributable to SARS-CoV-2 infection, while stricter interventions were associated with rising mortality in this age group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Individuals under 25 years accounted for 1.5% of pandemic excess mortality, representing 10,200 (6,000-14,300) excess all-cause deaths.

    “individuals under 25 years and 25–44 years accounted for only 1.5% and 8.1% of pandemic excess mortality, representing 10,200 (6000, 14300) and 54,500 (47500, 61300) excess all-cause deaths.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Excess deaths from external causes were concentrated in ages 15-44 years, with a notable elevation in May-July 2020 compared to historic baselines.

    “Excess deaths from external causes were concentrated in ages 15–44 years, with a notable elevation in May-July 2020 compared to historic baselines (Figure S14).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The COVID-19 term measuring the direct impact of viral infection was highest in older age groups and statistically significant in all age groups but those under 25 years.

    “The COVID-19 term measuring the direct impact of viral infection was highest in older age groups and statistically significant in all age groups but those under 25 years.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cancer deaths have remained below historic levels since March 2020, although cumulative weekly departures from baseline were not significantly different from zero.

    “Cancer deaths have remained below historic levels since March 2020, although cumulative weekly departures from baseline were not significantly different from zero (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    The first wave was concentrated in Northeastern states, while Southern and Western states showed larger mortality increases during the second and third waves.

    “The first wave was concentrated in Northeastern states, while the Southern and Western states showed larger mortality increases during the second and third waves.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Overdoses were the first to peak in May 2020, followed by accidents and assaults in July 2020.

    “Overdoses were the first to peak in May 2020, followed by accidents and assaults in July 2020.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Excess deaths from assaults and homicides were 5,100 (2,700-7,600), a 21% increase.

    “and assaults and homicides (5,100 (2,700–7,600), a 21% increase, Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Excess deaths from drug overdoses were 15,300 (7,500-23,100), a 15% increase.

    “drug overdoses (15,300 (7,500–23,100), a 15% increase)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No predictors of cause-specific mortality were identified at the state level, possibly due to lack of power.

    “We did not identify predictors of cause-specific mortality at the state level, possibly due to lack of power (Table S2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The indirect impact of the pandemic measured by the intervention term was highest in youngest age groups, decreased with age, and lost significance in individuals above 65 years.

    “In contrast, the indirect impact of the pandemic measured by the intervention term was highest in youngest age groups, decreased with age, and lost significance in individuals above 65 years.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    National mortality patterns comprised three waves from March 1-June 20, 2020; June 21-September 19, 2020; and September 20, 2020 to April 30, 2021, with varying timing and intensity by state.

    “National mortality patterns comprise three waves from March 1–June 20, 202; June 21–September 19, 2020; and September 20, 2020 to April 30, 2021, with varying timing and intensity by state (Figure 1A and S1–S8).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Excess deaths from accidents and injuries were 23,800 (8,400-39,200), an 11% increase over baseline.

    “The largest excess death tolls observed during this period were from accidents and injuries (23,800 (8,400–39,200), an 11% increase over baseline)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In April 2021, mortality from cancer, Alzheimer and heart diseases was below baseline (negative excess mortality), with a similar phenomenon for all-cause mortality among individuals 75-84 and over 85 years.

    “It is interesting that at this particular point in the pandemic, in April 2021, mortality from cancer, Alzheimer and heart diseases was below baseline (negative excess mortality), with a similar phenomenon observed for all-cause mortality among individuals 75–84 and over 85 yrs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Mortality from all causes and respiratory diseases declined continuously in the first months of 2021 and had just returned to baseline by the end of the study period in April 2021.

    “Accordingly, mortality from all causes and respiratory diseases declined continuously in the first months of 2021 and had just returned to baseline by the end of the study period in April 2021, before the arrival of new SARS-CoV-2 variants such as Delta and Omicron.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The roll-out of a large SARS-CoV-2 vaccination campaign starting in late December 2020 in the US had a major impact on rates of hospitalizations and deaths for COVID-19 in 2021.

  • May combine two claims.

    Findingown data

    The rise in mortality was most pronounced in assaults and homicide (21% over baseline, averaged over the pandemic period), followed by overdoses (15%) and accidents (11%).

    “The rise in mortality was most pronounced in assaults and homicide (21% over baseline, averaged over the pandemic period), followed by overdoses (15%) and accidents (11%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There is a large indirect impact of the pandemic in children and young adults, and on mortality from external causes, particularly from accidents, assaults, and overdoses.

    “There is however a large indirect impact of the pandemic in children and young adults, and on mortality from external causes, particularly from accidents, assaults, and overdoses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Excess mortality approaches have been used for over a century to capture the full scope of large-scale infectious disease events, heatwaves, and earthquakes, by measuring the rise in mortality over a historical baseline.

    “Excess mortality approaches have been used for over a century to capture the full scope of large-scale infectious disease events, heatwaves, and earthquakes, by measuring the rise in mortality over a historical baseline”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Serfling, 1963 source

      Not checked in the free run.

    • cites Weinberger et al., 2020 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Block bootstraps were used to generate 95% prediction intervals and uncertainty intervals on estimates.

    “We used block bootstraps to generate 95% prediction intervals and obtain uncertainty intervals on estimates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The upper bound of the 95% CI for heart diseases was above 100% (158%), suggesting that for every excess death from heart disease estimated by our model, up to 1.58 deaths from heart disease could be directly linked to SARS-CoV-2 infection.

    “The upper bound of the 95% confidence interval for heart diseases was above 100% (158%), suggesting that for every excess death from heart disease estimated by our model, up to 1.58 death from heart disease could be directly linked to SARS-CoV-2 infection.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    More recent analyses have examined excess mortality patterns for specific causes of death by age and socio-demographic groups and have compared the COVID-19 death toll between countries.

    “More recent analyses have examined excess mortality patterns for specific causes of death by age and socio-demographic groups and have compared the COVID-19 death toll between countries”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Banerjee et al., 2020 source

      Not checked in the free run.

    • cites Islam et al., 2021 source

      Not checked in the free run.

    • cites Karlinsky & Kobak, 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In a study of excess mortality in over 100 countries, Karlinsky and Kobak note that the direct mortality consequences of the pandemic typically predominate over the indirect consequences; however, they did not study age patterns.

    “In a study of excess mortality in over 100 countries, Karlinsky and Kobak note that the direct mortality consequences of the pandemic typically predominate over the indirect consequences (Karlinsky & Kobak, 2021); however, they did not study age patterns.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Karlinsky & Kobak, 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A decrease in emergency visits for diabetes, stroke, and myocardial infarctions in all age groups coincided with a rise in mortality for these conditions.

    “Prior studies have shown that a decrease in emergency visits for diabetes, stroke, and myocardial infarctions in all age groups coincided with a rise in mortality for these conditions (Lange, 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lange, 2020 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    There was little reporting delay for the data presented in this study.

    “Even though there was little reporting delay for the data presented in this study, we wanted to ensure comparability with prior work”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The indirect impacts of the pandemic include avoidance of the healthcare system for treatment of acute conditions and for management of underlying chronic conditions, stressed healthcare systems in periods of high COVID-19 incidence, and societal disruptions.

    “The indirect impacts of the pandemic include avoidance of the healthcare system for treatment of acute conditions and for management of underlying chronic conditions, stressed healthcare systems in period of high COVID19 incidence, and societal disruptions”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sharma et al., 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Sensitivity analyses using maximum seroprevalence were run to account for potential waning of natural immunity.

    “We ran sensitivity analyses on the maximum seroprevalence reported during the study period, rather than seroprevalence at the end of the study period, to account for potential waning of natural immunity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The trajectory of mortality in individuals 25-44 years is disjoint from periods of intense COVID-19 circulation and statistically tied to the strength of interventions, supporting a possible detrimental effect of COVID-19 control measures beyond the initial lockdown period in Spring 2020.

    “The trajectory of mortality in this age group is disjoint from the periods of intense COVID-19 circulation and statistically tied to the strength of interventions, supporting a possible detrimental effect of COVID-19 control measures beyond the initial lockdown period in Spring 2020.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Respiratory mortality (aggregated deaths ascribed to COVID-19, influenza, pneumonia, and chronic lower respiratory diseases) was the most specific indicator of excess deaths directly caused by SARS-CoV-2 infection.

    “We used aggregated mortality counts ascribed to COVID-19, influenza, pneumonia, and chronic lower respiratory diseases as an indicator of ‘respiratory mortality’, which was our most specific indicator of excess deaths directly caused by SARS-CoV-2 infection.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The balance between direct and indirect effects is age-dependent and can skew towards indirect effects in the young, even in countries that experienced relatively high infection rates like the US.

    “Our results support that the balance between direct and indirect effects is age-dependent and can skew towards indirect effects in the young, even in countries that experienced relatively high infections rates like the US.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The decrease in New York seroprevalence from August 2020 to April 2021 could be due to declining antibody titers or sampling issues.

    “Seroprevalence for New York state decreased from a peak of 23% in August 2020 to 13% in April 2021 in CDC data (Centers for Disease Control and Prevention, 2021f), which could be due to declining antibody titers (Buss et al., 2021) or sampling issues.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Buss et al., 2021

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Faust et al. reported a decrease in suicide in several countries during March-July 2020, including in the US (10%).

    “Prior work by Faust et al reported a decrease in suicide in several countries during March-July 2020, including in the US (10%) (Faust, Du, et al., 2021); here we show that suicide mortality remained stable throughout the rest of 2020.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Faust, Du, et al., 2021

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The study ends in April 2021 and does not capture a recrudescence of COVID-19-related deaths due to the more transmissible Delta variant, primarily in states with low vaccine coverage, nor does it estimate the impact of the Omicron immune escape variant.

    “Finally, our study ends in April 2021 and does not capture a recrudescence of COVID19-related deaths due to the more transmissible Delta variant, primarily in states with low vaccine coverage, nor do we estimate the impact of the Omicron immune escape variant.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the UK, cancer deaths increased about 10% at the height of the April 2020 lockdown; however, more recent fluctuations in cancer mortality remain unclear.

    “In the UK, cancer deaths increased about 10% at the height of the April 2020 lockdown; however, more recent fluctuations in cancer mortality remain unclear (Lai et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lai et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Italy, the case fatality rate for acute myocardial infarction increased 3-fold during the first wave, while hospitalizations for these conditions decreased by 48%.

    “In Italy, the case fatality rate for acute myocardial infarction increased 3-fold during the first wave, while hospitalizations for these conditions decreased by 48% (Odone et al., 2021), suggesting that at least some of the excess deaths were indirect deaths.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Odone et al., 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a comprehensive analysis of mortality in 21 countries in Europe, New Zealand and Australia, official COVID-19 deaths accounted for an average of 77% (62%−93%) of all-cause excess deaths during the first wave of the pandemic March-May 2020.

    “In a comprehensive analysis of mortality in 21 countries in Europe, New Zealand and Australia, official COVID-19 deaths accounted for an average of 77% (62%−93%) of all-cause excess deaths during the first wave of the pandemic March-May 2020 (Kontis et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kontis et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The age profile of COVID-19 severity risk dictates that older individuals would bear the strongest effects of harvesting, which is consistent with the US data.

    “Further, the age profile of COVID-19 severity risk dictates that older individuals would bear the strongest effects of harvesting, which is consistent with the US data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Several non-mutually exclusive factors could drive New York's high IFR, including a higher proportion of deaths among older individuals, large outbreaks in long-term care facilities, and lack of knowledge on management of severe patients early in the pandemic.

    “Several non-mutually exclusive factors could drive these findings, including a higher proportion of deaths among older individuals (aligned with the demography of New York state), large outbreaks in long-term care facilities, and lack of knowledge on management of severe patients early in the pandemic (Barnett et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Barnett et al., 2020 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A study of all-cause excess mortality in the Netherlands reports a substantially higher IFR (1%).

    “A study of all-cause excess mortality in the Netherlands reports a substantially higher IFR (1%) (Asten et al., 2021); however, all-cause mortality is not specific to COVID-19 (our estimate based on all-cause mortality is higher at 0.86% (0.72 – 0.99)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Asten et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The all-age IFR estimate is consistent with a recent meta-analysis and aligns with an early study from China.

    “Our all-age estimate of 0.61% (0.49 – 0.73) is consistent with a recent meta-analysis (Meyerowitz-Katz & Merone, 2020) and aligns with an early study from China (0.66%; 95% CI: 0.39—1.33%) (Verity et al., 2020).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Meyerowitz-Katz & Merone, 2020

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    • cites Verity et al., 2020 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In a study of over 100 countries, the ratio between excess mortality and official deaths was 1.6 on average, but went as high as 50 (e.g. Nicaragua).

    “In a study of over 100 countries, the ratio between excess mortality and official deaths was 1.6 on average, but went as high as 50 (e.g. Nicaragua) (Karlinsky & Kobak, 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Karlinsky & Kobak, 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Differences in COVID-19 death attribution by state could explain the findings on IFR estimates and serology correlation.

    “Differences in COVID-19 death attribution by state could explain these findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Higher IFRs may be associated with healthcare systems working above capacity, as would have been the case in the first phase of the pandemic in New York.

    “Higher IFRs may be associated with healthcare systems working above capacity, as would have been the case in the first phase of the pandemic in New York.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The disconnect was primarily attributed to under-detection of COVID-19 rather than indirect effects, although indirect effects were not explicitly modeled.

    “The disconnect was primarily attributed to under-detection of COVID-19 rather than indirect effects, although indirect effects were not explicitly modeled.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Karlinsky & Kobak, 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior work has shown important disparities in COVID-19 impact by race/ethnicity and economic status in the US and abroad.

    “Prior work has shown important disparities in COVID-19 impact by race/ethnicity and economic status (Mena et al., 2021; Rossen, 2021) in the US and abroad.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mena et al., 2021 source

      Not checked in the free run.

    • cites Rossen, 2021 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The study ran a sensitivity analysis using the maximum seroprevalence recorded over the study period rather than the seroprevalence at the end of the study period.

    “To address this issue, we ran a sensitivity analysis using the maximum seroprevalence recorded over the study period rather than the seroprevalence at the end of the study period (Figure S9); New York remained an outlier in this analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pandemic excess mortality patterns have been heterogeneous globally.

    “Pandemic excess mortality patterns have been heterogeneous globally (Islam et al., 2021; Karlinsky & Kobak, 2021; Kontis et al., 2020; Nørgaard et al., 2021).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Islam et al., 2021 source

      Not checked in the free run.

    • cites Karlinsky & Kobak, 2021 source

      Not checked in the free run.

    • cites Kontis et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Public health interventions, limited medical care, and behavioral changes could have contributed to the surge in excess deaths unrelated to COVID-19 in young adults, resulting in a notable peak of mortality in summer 2020.

    “Public health interventions, limited medical care, and behavioral changes (e.g., delays in seeking timely medical help due to fear of infection) (Bollmann et al., 2020; Kansagra et al., 2020; Mafham et al., 2020; Woolf et al., 2021) could have contributed to the surge in excess deaths unrelated to COVID-19 in young adults, resulting in a notable peak of mortality in summer 2020.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bollmann et al., 2020 source

      Not checked in the free run.

    • cites Kansagra et al., 2020 source

      Not checked in the free run.

    • cites Mafham et al., 2020 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Official coding practices may have changed between states and through time based on SARS-CoV-2 testing availability, location of death, demographic factors, and comorbidities.

    “Second, official coding practices may have changed between states and through time based on SARS-CoV-2 testing availability, location of death, demographic factors, and comorbidities.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The negative excess mortality is unlikely to be an artifact of reporting lags because a reporting adjustment is built in the model and reporting is 99% complete after 4 months.

    “It is unlikely to be an artifact of reporting lags, as a reporting adjustment is built in the model, and reporting is 99% complete after 4 months.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    As a result, the study's age-specific analyses are restricted to larger states, and the study could not assess the role of race/ethnicity.

    “As a result, our age-specific analyses are restricted to larger states, and we could not assess the role of race/ethnicity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Harvesting could also have affected estimates in the oldest age groups.

    “As discussed earlier, harvesting could also have affected estimates in oldest age groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    In the US, the direct impacts of the pandemic greatly outweigh the indirect consequences in all age data, but the reverse is true in children and young adults.

    “In the US, the direct impacts of the pandemic greatly outweigh the indirect consequences in all age data, but the reverse is true in children and young adults.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In New Zealand, where control of COVID-19 has been remarkable, mortality was slightly but not significantly below baseline.

    “Interestingly, in New Zealand, where control of COVID-19 has been remarkable, mortality was slightly but not significantly below baseline (Kontis et al., 2020).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kontis et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    A lockdown without COVID-19 is neither preventing nor causing an appreciable number of deaths, although effects could be country-dependent.

    “This suggests that a lockdown without COVID-19 is neither preventing nor causing an appreciable number of deaths, although effects could be country-dependent.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The study's conclusions are based on ecologic analyses that are useful to generate hypotheses but do not prove causality.

    “Our conclusions are based on ecologic analyses that are useful to generate hypotheses but do not prove causality.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A similar finding was described in Russian provinces where a lockdown was implemented before the onset of COVID-19.

    “A similar finding was described in Russian provinces where a lockdown was implemented before the onset of COVID-19 (Kobak, 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kobak, 2021 source

      Not checked in the free run.

62 of 62

  • The paper relies on this without support.

    It remains a challenge to separate the direct and indirect impacts of the pandemic.

    “Yet, it remains a challenge to separate the direct and indirect impacts of the pandemic.”

  • The paper relies on this without support.

    There is substantial heterogeneity in the trajectory of the COVID-19 pandemic and public health measures across the US, providing an opportunity to separate the contributions of viral infection on mortality from that of pandemic interventions, in a large country with homogenous death ascertainment.

    “There is substantial heterogeneity in the trajectory of the COVID-19 pandemic and public health measures across the US, providing an opportunity to separate the contributions of viral infection on mortality from that of pandemic interventions, in a large country with homogenous death ascertainment.”

  • The paper relies on this without support.

    The direct impacts of the virus include potential effects on deaths ascribed to chronic conditions; for instance, death in a diabetic patient could have been triggered by SARS-CoV-2 infection and be coded as diabetes.

    “The direct impacts of the virus include potential effects on deaths ascribed to chronic conditions; for instance, death in a diabetic patient could have been triggered by SARS-CoV-2 infection and be coded as diabetes.”

  • The paper relies on this without support.

    As the nucleocapsid is not a component of the vaccines used in the US, the serologic assay captures natural infections.

    “As the nucleocapsid is not a component of the vaccines used in the US, the serologic assay captures natural infections.”

  • The authors state this as an assumption.

    There should be a direct correspondence between rates of infection and death.

    “in a model without intercept since there should be a direct correspondence between rates of infection and death.”

  • The paper relies on this without support.

    Correlation between non-respiratory and respiratory excess mortality signals a direct but undetected effect of COVID-19 on non-respiratory mortality.

    “This would signal a direct but undetected effect of COVID-19 on non-respiratory mortality.”

  • The paper relies on this without support.

    The COVID-19 term in regression measures the direct impact of viral infection; the intervention term measures the indirect impact of the pandemic.

    “The COVID-19 term measuring the direct impact of viral infection was highest in older age groups and statistically significant in all age groups but those under 25 years.”
    “In contrast, the indirect impact of the pandemic measured by the intervention term was highest in youngest age groups, decreased with age, and lost significance in individuals above 65 years.”

  • The paper relies on this without support.

    Many deaths in nursing homes or at-home during March-April 2020 were never tested, and they were recorded as known underlying conditions (i.e. heart disease, Alzheimer’s and diabetes) by default.

    “Many deaths in nursing homes or at-home during March-April 2020 were never tested, and they were recorded as known underlying conditions (i.e. heart disease, Alzheimer’s and diabetes) by default.”

  • The paper relies on this without support.

    Alzheimer patients typically live in nursing homes and may have been at increased risk of untested COVID-19 infection early in the pandemic.

    “In addition, Alzheimer patients typically live in nursing homes and may have been at increased risk of (untested) COVID-19 infection early in the pandemic.”

  • The paper relies on this without support.

    All-cause mortality is not specific to COVID-19.

    “however, all-cause mortality is not specific to COVID-19”

  • The paper relies on this without support.

    The roll-out of a large SARS-CoV-2 vaccination campaign starting in late December 2020 in the US had a major impact on rates of hospitalizations and deaths for COVID-19 in 2021.

    “The roll-out of a large SARS-CoV-2 vaccination campaign starting in late December 2020 in the US has had a major impact on rates of hospitalizations and deaths for COVID-19 in 2021.”
11 of 11

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting estimates of excess deaths from external causes

    Major

    The Results section estimates 45,300 excess deaths from external causes for March 2020-April 2021, but the Discussion gives 51,300 for the same period. Their uncertainty intervals also differ.

1 of 1

Cites

Flagged first, then by citations

1 of the 42 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Viboud C. 2023. DirectIndirectCOVID19MortalityEstimation. Software Heritage. swh:1:rev:f0c23c87a00f589179af5351e89732f51d5a2b19. https://archive.softwareheritage.org/swh:1:dir:1fa09d8b19c99ca1fa8920eacef451bfa76f2e75;origin=https://github.com/viboudc/DirectIndirectCOVID19MortalityEstimation;visit=swh:1:snp:720b8da3a3f85c5faa65b77f8cada7dcce1833d3;anchor=swh:1:rev:f0c23c87a00f589179af5351e89732f51d5a2b19.

Cited by

Sorted by citations

Related

Authors
Lee, W.-E., Woo Park, S., Weinberger, D. M., Olson, D., Simonsen, L., Grenfell, B. T., & Viboud, C.
Affiliations
  • Princeton University (US)
  • Department of Ecology and Evolutionary Biology, Princeton University
  • Yale University (US)
  • New York City Department of Health and Mental Hygiene (US)
  • Roskilde University (DK)
  • Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2023-02-22
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.77562
PMC
PMC8863161
OpenAlex
W4321495929
Semantic Scholar
30692f5859e74f42b1d2ae939438b93d92174f54
Cited by
90
References
42
Citations by year
2026: 15 · 2025: 20 · 2024: 31 · 2023: 20 · 2022: 4
FWCI
18.28
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • medRxiv (acceptedVersion)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • RUCforsk (Roskilde University) (publishedVersion, public-domain)
  • PubMed Central (submittedVersion, public-domain)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Allergy and Infectious Diseases (R01AI137093)
  • Carlsbergfondet
Topics
  • Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
  • Health Sciences › Medicine › Oncology › COVID-19 and healthcare impacts
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
COVID-19 pandemic, excess mortality, pandemic interventions, ICU bed occupancy, COVID-19 serology, age-specific mortality, suicide, opioid overdose, respiratory diseases, Alzheimer's disease, heart disease, diabetes mellitus, older adults, United States, generalized additive models, time series decomposition

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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