Schizophrenia, Bipolar, or Major Depressive Disorder and Postacute Sequelae of COVID-19

Oct 29, 2025JAMA network open

Long-Term COVID-19 Symptoms in People with Schizophrenia, Bipolar Disorder, or Major Depression

AI simplified

Long Covid on OpenScience ↗PubMed ↗DOI ↗

Abstract

Among 1,625,857 patients with COVID-19, 15.9% had a serious mental illness (SMI) and were at increased risk of developing postacute sequelae of SARS-CoV-2 (PASC).

Patients with SMI had adjusted odds of developing PASC at 1.10 times that of those without SMI.
Higher odds of PASC were associated with older age, particularly for those aged 65 years or older (OR, 1.18).
Non-Hispanic Black and Hispanic individuals had increased odds of PASC compared to non-Hispanic White individuals.
A higher chronic disease burden was linked to greater odds of PASC, with those having a Charlson Comorbidity Index score of 4 or more showing an OR of 1.23.
Hospitalization due to initial COVID-19 infection significantly increased the odds of developing PASC, with those requiring ventilation having an OR of 2.17.
Commercial health insurance was associated with lower odds of PASC compared to public insurance (OR, 0.85).

AI simplified

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.