Schizophrenia, bipolar, or major depressive disorder and postacute sequelae of COVID-19
Vekaria, V; Thiruvalluru, RK; Verzani, Z; et al., JAMA Network Open
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
Short Summary
In this RECOVER study, researchers wanted to find out if adults with a serious mental illness (SMI)—like major depression, schizophrenia, or bipolar disorder—were more likely to develop Long COVID. To do this, researchers looked at the electronic health records (EHRs) of more than 1.6 million adults across the US. They found that adults with an SMI had a higher chance of developing Long COVID than adults without an SMI. This may be because SMIs can cause stress and problems with a person’s immune system, which could make them more likely to develop long-lasting symptoms after having COVID-19. Among adults with an SMI, higher rates of Long COVID were seen in older people, non-Hispanic Black and Hispanic people, people with public health insurance, people with other long-term illnesses like heart disease or diabetes, and people who were hospitalized after they got COVID-19 for the first time. This study is important because it shows that healthcare teams should look at SMIs in addition to other risk factors to help prevent and treat Long COVID.