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Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62354 COVID-19 cases in the USA

Our take —

This large, national, retrospective cohort study demonstrated a significantly higher risk of psychiatric sequelae among COVID-19 survivors, especially anxiety disorders, insomnia, and dementia for those above 65 years old, compared to six control health events. The study also suggested that having a pre-existing psychiatric diagnosis is an independent risk factor for being diagnosed with COVID-19. However, these results should be interpreted with caution given possible selection bias and residual confounding.

Study design

Retrospective Cohort

Study population and setting

This retrospective cohort study assessed whether a diagnosis of COVID-19 was associated with subsequent psychiatric diagnoses, and whether patients with pre-existing psychiatric diagnoses were at higher risk of being diagnosed with COVID-19. The study used the TriNetX Research Network, a network of electronic health records, including 69.8 million patients across 54 health-care organizations in the US. Diagnostic categorizations were determined using ICD-10 codes. Incidence of psychiatric sequelae following COVID-19 diagnosis was compared (after propensity score matching) to six control health events – influenza (n=26,497), another respiratory tract infection (n=44,775), skin infection (n=38,977), cholelithiasis (n=19,733), urolithiasis (n=28,827), and fracture of a large bone (37,841). For all cohorts, the study population included individuals over 10 years of age, diagnosed with the specified health event between January 20 and August 1, 2020. Incident psychiatric illness was considered as the first psychiatric diagnosis over a period of 14 to 90 days after diagnosis with COVID-19 or the control health event. To evaluate whether individuals with psychiatric diagnoses were at increased risk of developing COVID-19 (psychiatric antecedent), incidence of COVID-19 was compared between two propensity score-matched cohorts (n=1,729,837 per cohort). One group included all patients older than 18 years with a recorded psychiatric diagnosis in the previous year (Jan 21, 2019 to Jan 20, 2020) and the other group included patients with no history of psychiatric diagnosis but who did make a health-care visit in the same period.

Summary of Main Findings

Regarding psychiatric sequelae, a diagnosis of COVID-19 was associated with increased incidence of a first psychiatric diagnosis compared with all six control health events (hazard ratios [HR] between 1.58-2.24, all p<0.0001). Among psychiatric diagnoses, anxiety disorders were most common, and patients diagnosed with COVID-19 were more likely to be diagnosed with anxiety disorders than any other cohort (incidence among COVID-19 4.7%, 95% CI: 4.2-5.3%; hazard ratios (HR) 1.59-2.62, all p<0.0001). Insomnia (incidence 1.9%, 95% CI: 1.2-2.2%; HR 1.85-3.29, all p<0.0001) and dementia among patients ≥65 years (incidence 1.6%, 95% CI: 1.2-2.1%; HR 1.89-3.18, all p<0.005) were also associated with COVID-19 diagnosis, compared to all other control conditions. Regarding psychiatric antecedents, having a psychiatric diagnosis in the year before the COVID-19 outbreak was associated with a significantly increased risk of being diagnosed with COVID-19 (RR 1.65, 95% CI 1.59-1.71) compared with a cohort without a psychiatric diagnosis. These trends were robust to all sensitivity analyses.

Study Strengths

This study included a large and representative cohort of patients cared for across 54 U.S. health care centers, increasing the generalizability across the United States. Propensity matching accounted for some potential confounders, and the use of multiple controls and sensitivity analyses increased confidence in the robustness of trends.


As this study used electronic medical record data from early in the COVID-19 pandemic when coding for diagnoses of COVID-19 changed rapidly and reliable testing was not widespread, there is potential for patient selection bias toward those with severe disease and classic presentation. There is potential for diagnostic bias as clinicians may be more likely to diagnose psychiatric illness after a COVID-19 diagnosis than control events due to differences in the nature or extent of assessments. Patients accessing care at out-of-network locations may not be captured in this dataset which may underestimate incidence figures. As the prevalence of undiagnosed patients with COVID-19 has fluctuated with testing capacity throughout the pandemic, and this study is unable to assess undiagnosed patients, outcome generalizability may be temporally limited. This study was not randomized, and residual confounding may exist despite propensity score matching. The authors do not mention missing data, and it is assumed missing data were excluded, which may additionally bias the results.

Value added

To the best of our knowledge, this study is the first to investigate psychiatric sequelae and antecedents of COVID-19 in a large cohort.

This review was posted on: 9 December 2020