It is uncertain if those with a serious mental illness (SMI) are more likely to have postacute sequelae of SARS-CoV-2 (PASC), given their greater susceptibility to COVID-19. Secondary prevention initiatives might benefit from an understanding of this connection. Thus, this study determined the risk that individuals with an SMI will acquire PASC.
Data from extensive electronic health records (EHRs) between March 2020 and April 2023, including a 180-day follow-up, were used in this longitudinal cohort research. Adults aged 21 years or older who had a proven COVID-19 infection—as shown by a relevant lab test, diagnosis, or prescription order—were considered patients. Evidence of a diagnosis of schizophrenia, bipolar illness, or recurrent major depressive disorder prior to COVID-19 infection was also included.
Evidence of PASC symptoms within 30 to 180 days of follow-up following COVID-19 infection was considered the primary outcome. It was reported as odds ratios (OR) that were mutually adjusted for race, age, sex, ethnicity, insurance type, COVID-19 severity, and Charlson Comorbidity Index (CCI) score.
- A total of 1,625,857 COVID-19–infected patients were included (mean [SD] age, 52 [17] years; 998,237 [61.4%] females; 204,237 [12.6%] non-Hispanic Black; 219,220 [13.5%] Hispanic; 833,411 [51.3%] non-Hispanic White; and 1,228,664 [75.6%] urban patients).
- Of these, 258,523 (15.9%) had an SMI and 403,641 (24.8%) developed PASC. The adjusted odds of developing PASC were higher in those with an SMI (OR, 1.10; 95% CI, 1.08–1.11; P < .001).
- Older age (compared to age 22–34 years), non-Hispanic Black and Hispanic ethnicity (compared to non-Hispanic White) (OR, 1.08; 95% CI, 1.07–1.10; OR, 1.12; 95% CI, 1.11–1.13), higher chronic disease burden (CCI 1–3: OR, 1.13; 95% CI, 1.12–1.14; CCI ≥4: OR, 1.23; 95% CI, 1.22–1.25), and hospitalization with initial COVID-19 infection were also associated with increased PASC risk.
- Commercial health insurance was linked to decreased odds of PASC when compared to public insurance (OR, 0.85; 95% CI, 0.84–0.86). Overall, the necessity for coordinated mental health and COVID-19 care approaches is highlighted by the fact that patients with SMI were more likely to develop PASC than those without SMI.
Source: Vekaria, V., Thiruvalluru, R. K., Verzani, Z., Abedian, S., Olfson, M., Patra, B. G., Xiao, Y., Salamon, K. S., Hoth, K., Blancero, F., Hornig-Rohan, M. M., Akintonwa, T., Sabiha, M., Weiner, M. G., Carton, T. W., Kaushal, R., Pathak, J., & RECOVER PCORnet EHR Consortium. (2025). Schizophrenia, bipolar, or major depressive disorder and postacute sequelae of COVID-19. JAMA Network Open, 8(10), e2540242. https://doi.org/10.1001/jamanetworkopen.2025.40242
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