Schizophrenia, bipolar, or major depressive disorder and postacute sequelae of COVID-19

View Publication on PubMed

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Published

October 2025

Journal

JAMA Network Open

Abstract

Importance: Given the increased vulnerability to COVID-19 among those with a serious mental illness (SMI), it remains unclear whether these individuals face a higher risk of developing postacute sequelae of SARS-CoV-2 (PASC). Understanding this association could inform secondary prevention efforts.

Objective: To identify the risk of developing PASC in patients with an SMI.

Design, setting, and participants: This longitudinal cohort study used data derived from large-scale electronic health records (EHRs) between March 2020 and April 2023, inclusive of 180-day follow-up. Patients included adults aged 21 years or older with a confirmed COVID-19 infection evidenced by a relevant laboratory result, diagnosis, or prescription order.

Exposures: Evidence of an SMI diagnosis (schizophrenia, bipolar disorder, or recurrent major depressive disorder) recorded before COVID-19 infection.

Main outcomes and measures: Evidence of PASC symptoms within 30 to 180 days' follow-up after COVID-19 infection reported as odds ratios (OR) mutually adjusted for age, sex, race and ethnicity, insurance type, Charlson Comorbidity Index (CCI) score, and COVID-19 severity.

Results: A total of 1,625,857 patients with a COVID-19 infection were included (mean [SD] age, 52 [17] years; 998,237 [61.4%] female, 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 whom 258,523 (15.9%) had an SMI and 403,641 (24.8%) developed PASC. Individuals with an SMI had increased adjusted odds of developing PASC (OR, 1.10; 95% CI, 1.08-1.11; P < .001). Variables associated with greater odds of PASC among the study population included older age compared with age 22 to 34 years (35 to 44 years: OR, 1.04; 95% CI, 1.03-1.06; 45 to 64 years: OR, 1.11; 95% CI, 1.10-1.12; ≥65 years: OR, 1.18; 95% CI, 1.17-1.20), non-Hispanic Black and Hispanic compared with non-Hispanic White race and ethnicity (non-Hispanic Black: OR, 1.08; 95% CI, 1.07-1.10; Hispanic: OR, 1.12; 95% CI, 1.11-1.13), higher chronic disease burden vs no chronic disease (CCI 1 to 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 vs no hospitalization (hospitalized: OR, 1.80; 95% CI, 1.77-1.82; hospitalized with ventilation: OR, 2.17; 95% CI, 2.12-2.22; P < .001). Compared with public insurance, commercial health insurance was associated with lower odds of PASC (OR, 0.85; 95% CI, 0.84-0.86).

Conclusions and relevance: In this cohort study of patients infected with COVID-19, patients with SMI compared with those without SMI were at increased risk of PASC, underscoring the need for coordinated mental health and COVID-19 care strategies.

Authors

Veer Vekaria, Rohith Kumar Thiruvalluru, Zoe Verzani, Sajjad Abedian, Mark Olfson, Braja Gopal Patra, Yunyu Xiao, Katherine S Salamon, Karin Hoth, Frank Blancero, Maxwell M Hornig-Rohan, Teresa Akintonwa, Mahfuza Sabiha, Mark G Weiner, Thomas W Carton, Rainu Kaushal, Jyotishman Pathak, RECOVER PCORnet EHR consortium

Keywords

Humans; COVID-19/complications/epidemiology/psychology; Female; Male; Depressive Disorder, Major/epidemiology/complications; Middle Aged; Adult; Bipolar Disorder/epidemiology/complications; Longitudinal Studies; Schizophrenia/epidemiology/complications; SARS-CoV-2; Aged; Risk Factors; Post-Acute COVID-19 Syndrome; Comorbidity