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Impact of Risk Stacking on COVID-19-Related Healthcare Utilization: A Real-World Retrospective Cohort Study

Frank R Ernst1, Leah McGrath2, Maya Reimbaeva3

  • 1Pfizer Inc, Cincinnati, OH, USA. Frank.Ernst@Pfizer.com.

Infectious Diseases and Therapy
|December 5, 2025
PubMed

Insights

Younger adults with multiple high-risk (HR) comorbidities face greater COVID-19 healthcare risks than older adults or those with immunocompromising conditions. "Risk stacking" of HR conditions significantly increases the likelihood of severe COVID-19 outcomes.

Area of Science:

  • Public Health
  • Epidemiology
  • Health Services Research

Background:

  • COVID-19 poses significant health risks, particularly for individuals with underlying health conditions.
  • Understanding the cumulative impact of multiple high-risk (HR) conditions, termed 'risk stacking,' is crucial for targeted public health interventions.
  • Previous research has focused on individual HR conditions, but the synergistic effects of multiple comorbidities require further investigation.

Purpose of the Study:

  • To evaluate the impact of 'risk stacking' on COVID-19-related healthcare resource utilization (HCRU) across different age groups and risk categories.
  • To compare HCRU among non-immunocompromised adults (18-49 and 50-64 years) with immunocompromised individuals and those aged 65 years and older.
  • To assess the influence of multimorbidity and specific HR categories on COVID-19 HCRU.

Main Methods:

  • Utilized Optum Clinformatics® data for a large cohort of adults (n=10,631,427).
  • Categorized adults based on CDC-defined HR conditions: HR-Conclusive, HR-Suggestive, Mixed Evidence, and No HR Conditions.
  • Analyzed the association between multimorbidity quantities, HR categories, and COVID-19 HCRU (hospitalizations, ED/UC visits, outpatient visits).

Main Results:

  • The most prevalent conditions included hypertension (47.4%), obesity (31.9%), chronic heart disease (CHD; 28.1%), and diabetes (DBT; 20.3%).
  • COVID-19 HCRU was elevated for combinations like CHD with DBT and CHD with obesity, surpassing that of immunocompromised individuals.
  • Multimorbidity across multiple HR categories significantly increased adjusted risk for COVID-19 HCRU across all age groups.

Conclusions:

  • Younger adults with multiple non-immunocompromising comorbidities exhibited higher COVID-19 HCRU risk than older adults without multimorbidity or those with immunocompromising conditions.
  • 'Risk stacking' of HR comorbidities demonstrably amplifies the risk of severe COVID-19 outcomes and HCRU.
  • Broad vaccination and timely treatment access are essential to mitigate severe COVID-19 impacts in all HR populations, irrespective of age.
Abstract

Keywords:
COVID-19ComorbidityHealthcare resource utilizationMultimorbiditySARS-CoV-2

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