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Substance-specific Mortality Risk Stratification Among Adults With Substance Use Disorders During Acute Respiratory
Journal of Addiction Medicine
|July 3, 2026
Summary
Individuals with pre-existing substance use disorders (SUDs), especially alcohol use disorder (AUD) and opioid use disorder (OUD), face significantly higher 30-day mortality after SARS-CoV-2 infection. SUDs indicate heightened vulnerability beyond measured comorbidities.
Area of Science:
- Public Health
- Epidemiology
- Infectious Diseases
Background:
- Substance use disorders (SUDs) are prevalent and associated with various health complications.
- The impact of pre-existing SUDs on mortality risk during acute SARS-CoV-2 infection requires detailed quantification.
- Understanding comorbidity burden's role in SUD-associated mortality is crucial for risk stratification.
Purpose of the Study:
- To quantify 30-day all-cause mortality in adults with SUDs and SARS-CoV-2 infection.
- To compare mortality risks across different SUD subtypes.
- To assess the influence of comorbidity burden on observed mortality differences.
Main Methods:
- Retrospective cohort study of over 3.4 million adults with confirmed SARS-CoV-2 infection (March 2020-June 2023).
- Utilized data from 63 US healthcare organizations in the National COVID Cohort Collaborative (N3C).
- Multivariable logistic regression analyzed 30-day mortality, adjusting for demographics and comorbidities; sensitivity analyses included the Elixhauser Comorbidity Index.
Main Results:
- 11.8% of infected adults had a pre-existing SUD; 0.43% died within 30 days.
- SUDs were associated with more than doubled adjusted odds of 30-day mortality (aOR 2.38).
- Alcohol use disorder (AUD) and opioid use disorder (OUD) showed the highest mortality risks (aORs 2.63 and 2.53, respectively).
Conclusions:
- Pre-existing SUDs, particularly AUD and OUD, identify a high-risk population for 30-day mortality post-COVID-19 diagnosis.
- SUDs act as a marker of heightened vulnerability, with unmeasured factors contributing to excess risk beyond comorbidities.
- SUD status, especially AUD and OUD, should be integrated into risk stratification for respiratory infections in clinical care and pandemic planning.
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