EVIDENCE from a large national cohort study suggests that individuals with poorer pre-infection mental health and a higher burden of prior COVID symptoms face a greater risk of developing long COVID.
Researchers analyzed data from more than 65,000 U.S. adults with confirmed COVID-19, drawing from health records and survey responses in the All of Us Research Program. Among participants, 40,655 reported at least one post-infection symptom consistent with long COVID, while 24,809 reported none.
The analysis revealed that patients rating their mental health as “good” rather than “excellent” before infection had a significantly higher likelihood of experiencing persistent post-COVID symptoms (adjusted odds ratio [AOR]: 1.14, 99% CI 1.04–1.25). Symptom burden prior to infection also influenced outcomes. Compared with individuals reporting the median of four pre-infection symptoms, those with no symptoms were substantially less likely to develop long COVID (AOR 0.15, 99% CI 0.04–0.61).
Interestingly, no single pre-infection symptom was independently associated with increased risk, and neither self-rated physical ability nor documented clinical impairments predicted outcomes. Instead, cumulative symptom load and self-perceived mental health appeared to drive vulnerability.
The authors emphasize that long COVID reflects a marked departure from baseline functioning and health, even for individuals who had prior symptoms or impairments. These findings highlight the potential value of incorporating functional status assessments into diagnostic frameworks for long COVID. The study also demonstrates the feasibility of using harmonized electronic health record data to evaluate functional health status in large populations, paving the way for refined diagnostic approaches.
With millions of U.S. adults living with long COVID, these results underscore the importance of considering pre-infection health when assessing patient risk and tailoring long-term care strategies.
Reference:
Kehl-Floberg K et al. Long COVID risk by pre-infection symptoms and functional status: A retrospective cohort study of data from the All of Us Research Program. medRxiv. 2025. doi: 10.1101/2025.08.07.25333259
