Identifying direct and indirect effects of SARS-CoV-2 pandemic on mortality in the US

In a recent study posted to the medRxiv* preprint server, researchers differentiated the direct and indirect impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on mortality in the United States (US).

Study: Direct and indirect mortality impacts of the COVID-19 pandemic in the US, March 2020-April 2021. Image Credit: Velimir Zeland/ShutterstockStudy: Direct and indirect mortality impacts of the COVID-19 pandemic in the US, March 2020-April 2021. Image Credit: Velimir Zeland/Shutterstock


The exact impact of the coronavirus disease 2019 (COVID-19) pandemic on several disease conditions is still debated globally as the official death toll rises. To date, more than 77 million confirmed SARS-CoV-2 cases and over 915,000 official deaths have been reported in the US.

Excess mortality investigations are significant for determining the impact of pandemics and other large-scale catastrophes on health. Further, the excess mortality approaches have revealed the underestimations of COVID-19-related deaths in the official statistics associated with the limitations in viral testing during the initial phase of the SARS-CoV-2 pandemic.

The latest analyses have evaluated the death patterns for specific causes of mortality by sociodemographic groups and age and compared the SARS-CoV-2 death toll among countries. However, the contrast between the direct and indirect effects of the COVID-19 pandemic on death is not yet clearly understood.

About the study

In the present study, the researchers utilized the time series strategy to split the direct contribution of COVID-19 on death from the indirect outcomes of the SARS-CoV-2 pandemic interventions and behavioral alterations in the US.

The team evaluated the excess deaths above the seasonal baselines grouped by age, state, week, and causes, including SARS-CoV-2, other respiratory diseases, cancer, diabetes, Alzheimer’s disease, heart disease, cerebrovascular disease, and external causes such as accidents, suicides, and opioids between March 1, 2020, and April 30, 2021. The researchers also compared the excess mortality estimates derived in the study with the serology estimates and explored the variation in SARS-CoV-2 infection fatality rates (IFR) between the US states.


The results show that the study estimates of SARS-CoV-2 excess deaths correlated significantly with the COVID-19 serology data.

While the mortality rates associated with the first wave of the SARS-CoV-2 pandemic in the US concentrated in the Northeastern states, the subsequent second and third waves increased death rates in the Southern and Western states.

During the study period, all-cause deaths, such as those due to SARS-CoV-2, other respiratory diseases, Alzheimer's, diabetes, and external causes, showed an excess of 666,000 deaths, and 90% of them were due to the direct impact of COVID-19. Further, of the 90% of deaths directly impacted by COVID-19, 78% were accounted by the official SARS-CoV-2 statistics.

Except for cancer, all other disease-related deaths increased during the SARS-CoV-2 pandemic. The COVID-19 pandemic had the highest direct effects on mortality from heart disease, diabetes, and Alzheimer's, as well as in people older than 65 years of age.

On the other hand, the main indirect repercussions of the SARS-CoV-2 pandemic were seen in mortality from external causes, and it increased by 45,300 deaths and was statistically associated with the intensity of non-pharmaceutical interventions against SARS-CoV-2. While the excess deaths in this category were most evident in injuries and accidents, assaults and homicides, and drug overdoses, mortality rates from suicide remained unchanged.

The indirect effects of SARS-CoV-2 burdened the younger age groups the most. Further, the excess deaths associated with external causes of the COVID-19 pandemic were concentrated between 15 and 44 years and were significant from May to July 2020.


The study findings show that 90% of the excess mortality due to all-cause of deaths during the study period can be statistically connected to the direct impacts of COVID-19 in America. While the present findings indicate that the direct impacts of the SARS-CoV-2 infection were the most evident in diabetes, Alzheimer’s, heart diseases, and cerebrovascular diseases, the official stats missed this data.

In contrast, the elevations in deaths from younger populations, drug overdoses, assaults, accidents and injuries, and homicides during the SARS-CoV-2 pandemic were due to the indirect effects of the COVID-19 pandemic and statistically associated with the non-pharmaceutical interventions of the disease. In contrast to all other causes of mortality evaluated in the study, deaths from suicides and cancer did not change from the baseline values during the SARS-CoV-2 pandemic.

Overall, the study demonstrates that the direct impact of the SARS-CoV-2 infection was responsible for the majority of the consequences associated with the COVID-19 pandemic in America during the study period. However, the indirect effects of SARS-CoV-2 were more prevalent in younger age groups, during periods of stringent interventions, and in deaths due to external factors.

Future investigations focusing on the driving factors of death among the younger population, specific ethnic groups, and the impact of opioids, chronic diseases, suicides, and violence on pandemics and alterations in behaviors, are recommended soon after the release of the death certificate data to improve the interventions in future pandemics.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.


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