Illustration depicting the long-term impact of COVID-19 on healthIntroduction

The COVID-19 pandemic has had a profound impact on global health, affecting millions worldwide. While the acute phase of the disease has been extensively studied, the long-term health consequences, known as post-acute sequelae of COVID-19 (PASC) or Long COVID, are still being unraveled. A recent comprehensive study published in Nature Medicine by the researchers from the VA St. Louis Health Care System and Scripps Research investigates the three-year outcomes of PASC, providing critical insights into the enduring health impacts of COVID-19.

Study Design and Cohorts

Researchers Miao Cai, Yan Xie, Eric J. Topol, and Ziyad Al-Aly analyzed data from the US Department of Veterans Affairs (VA), encompassing 135,161 individuals who survived the first 30 days of COVID-19 and a control group of 5,206,835 individuals with no evidence of SARS-CoV-2 infection. This large-scale longitudinal study followed these cohorts for three years, offering a robust analysis of the long-term risks and burdens associated with COVID-19.

Key Findings

Mortality Risks

  • Among non-hospitalized individuals, the increased risk of death dissipated after the first year post-infection.
  • Hospitalized individuals exhibited a persistently elevated risk of death even in the third year, with an incidence rate ratio (IRR) of 1.29, corresponding to an excess burden of 8.16 deaths per 1000 persons.

Disability-Adjusted Life Years (DALYs)

  • Non-hospitalized individuals experienced a decline in PASC risk over the three years but still contributed 9.6 DALYs per 1000 persons in the third year.
  • Hospitalized individuals faced a substantial residual risk of PASC in the third year, leading to 90.0 DALYs per 1000 persons.

Organ System Impact

  • Non-hospitalized individuals showed increased risks for neurologic, pulmonary, and gastrointestinal disorders in the third year.
  • Hospitalized individuals exhibited significant long-term risks across multiple organ systems, including cardiovascular, mental, neurologic, and pulmonary disorders.

Cumulative Burden

  • The three-year cumulative burden of sequelae was markedly higher in hospitalized individuals, with 2391.7 sequelae per 1000 persons, compared to 378.7 per 1000 persons in non-hospitalized individuals.
  • The top five organ systems contributing to DALYs in hospitalized patients were cardiovascular, mental, neurologic, coagulation and hematologic, and kidney disorders.


This study highlights the enduring health impacts of COVID-19, particularly among those who were hospitalized during the acute phase of the disease. The findings underscore the importance of long-term monitoring and care for COVID-19 survivors, especially those with severe initial infections.

The persistent elevated risk of death and significant health burden among hospitalized individuals necessitate targeted interventions to mitigate long-term consequences. Strategies should include increasing vaccine uptake to prevent severe disease, early recognition and management of PASC, and comprehensive follow-up care.


The three-year follow-up study provides critical insights into the long-term health effects of COVID-19, revealing persistent risks and substantial health burdens, particularly among those who were hospitalized. These findings emphasize the need for ongoing research, surveillance, and healthcare strategies to address the chronic impacts of COVID-19 and support affected individuals in their recovery journey.

For more detailed information, you can access the full article here.

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