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Comorbidity Exposure-Window Definitions and Multidimensional Disparities in Long COVID Risk: Evidence from a U.S.
Medrxiv : the Preprint Server for Health Sciences
|July 30, 2026
Summary
Defining comorbidities before SARS-CoV-2 infection, not Long COVID (LC) diagnosis, significantly impacts risk estimates. This methodological choice is crucial for accurate LC epidemiology and identifying high-risk populations.
Area of Science:
- Epidemiology
- Public Health
- Health Informatics
Background:
- Long COVID (LC) affects millions globally, with preexisting comorbidities being a key concern.
- Methodological choices in defining comorbidities (pre-infection vs. pre-LC diagnosis) can bias risk estimates.
- Previous studies often used smaller, geographically limited cohorts, hindering understanding of temporal trends and disparities.
Purpose of the Study:
- To evaluate the impact of different comorbidity exposure-window definitions on Long COVID (LC) risk estimation.
- To analyze temporal trends and disparities in comorbidity-associated LC risk.
- To identify methodological biases in LC epidemiological studies using Electronic Health Records (EHR).
Main Methods:
- Utilized a large-scale dataset from the National COVID Cohort Collaborative (N3C) including 6,130,413 adults with COVID-19 from 2020-2024.
- Employed ensemble cross-fitted double/debiased machine learning to adjust for individual and county-level confounders.
- Compared risk estimations based on comorbidities defined before SARS-CoV-2 infection versus before LC diagnosis.
Main Results:
- Defining comorbidities before SARS-CoV-2 infection resulted in significantly higher adjusted attributable risks (23%-115%) and relative risks (6%-37%) compared to defining them before LC diagnosis.
- Comorbidity-associated risks generally decreased from 2020 to 2024.
- Persistent demographic, socioeconomic, geographic, and multimorbidity disparities in LC risk were observed.
Conclusions:
- Temporal exposure-window specification is a major source of bias in Long COVID (LC) epidemiology.
- Misclassifying preexisting comorbidities can distort disease burden estimates and population-level inference.
- Accurate temporal definitions are essential for identifying high-risk populations and interpreting LC disparities.
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