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Association Between Mental Health Disorders and Mortality Among Patients With COVID-19 in 7 CountriesA Systematic Review and Meta-analysis

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is there a significant association between mental health disorders and COVID-19–related mortality?

Findings  In this systematic review and meta-analysis of 16 observational studies in 7 countries with 19 086 patients, mental health disorders were associated with increased COVID-19 mortality according to both pooled crude and adjusted odds ratios. Patients with severe mental health disorders had the highest odds ratios.

Meaning  These findings suggest that patients with COVID-19 and mental health disorders should be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.


Importance  Heterogeneous evidence exists for the association between COVID-19 and the clinical outcomes of patients with mental health disorders. It remains unknown whether patients with COVID-19 and mental health disorders are at increased risk of mortality and should thus be targeted as a high-risk population for severe forms of COVID-19.

Objective  To determine whether patients with mental health disorders were at increased risk of COVID-19 mortality compared with patients without mental health disorders.

Data Sources  For this systematic review and meta-analysis, MEDLINE, Web of Science, and Google Scholar were searched from inception to February 12, 2021. Bibliographies were also searched, and the corresponding authors were directly contacted. The search paradigm was based on the following combination: (mental, major[MeSH terms]) AND (COVID-19 mortality[MeSH terms]). To ensure exhaustivity, the term mental was replaced by psychiatric, schizophrenia, psychotic, bipolar disorder, mood disorders, major depressive disorder, anxiety disorder, personality disorder, eating disorder, alcohol abuse, alcohol misuse, substance abuse, and substance misuse.

Study Selection  Eligible studies were population-based cohort studies of all patients with identified COVID-19 exploring the association between mental health disorders and mortality.

Data Extraction and Synthesis  Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. This systematic review is registered with PROSPERO.

Main Outcomes and Measures  Pooled crude and adjusted odds ratios (ORs) for the association of mental health disorders with mortality were calculated using a 3-level random-effects (study/country) approach with a hierarchical structure to assess effect size dependency.

Results  In total, 16 population-based cohort studies (data from medico-administrative health or electronic/medical records databases) across 7 countries (1 from Denmark, 2 from France, 1 from Israel, 3 from South Korea, 1 from Spain, 1 from the UK, and 7 from the US) and 19 086 patients with mental health disorders were included. The studies covered December 2019 to July 2020, were of good quality, and no publication bias was identified. COVID-19 mortality was associated with an increased risk among patients with mental health disorders compared with patients without mental health disorders according to both pooled crude OR (1.75 [95% CI, 1.40-2.20]; P <.05) and adjusted OR (1.38 [95% CI, 1.15-1.65]; P <.05). The patients with severe mental health disorders had the highest ORs for risk of mortality (crude OR: 2.26 [95% CI, 1.18-4.31]; adjusted OR: 1.67 [95% CI, 1.02-2.73]).

Conclusions and Relevance  In this systematic review and meta-analysis of 16 observational studies in 7 countries, mental health disorders were associated with increased COVID-19–related mortality. Thus, patients with mental health disorders should have been targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies. Future studies should more accurately evaluate the risk for patients with each mental health disorder. However, the highest risk seemed to be found in studies including individuals with schizophrenia and/or bipolar disorders.

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Article Information

Corresponding Author: Guillaume Fond, MD, PhD, APHM FondaMental Academic Advanced Center of Expertise, Aix-Marseille University, CEReSS-Health Service Research and Quality of Life Center France, Marseille, France (

Accepted for Publication: June 27, 2021.

Published Online: July 27, 2021. doi:10.1001/jamapsychiatry.2021.2274

Author Contributions: Dr Boyer had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Fond, Etchecopar-Etchart, Lancon, Auquier, Llorca, Boyer.

Acquisition, analysis, or interpretation of data: Fond, Nemani, Etchecopar-Etchart, Loundou, Goff, Lee, Baumstarck, Llorca, Yon, Boyer.

Drafting of the manuscript: Fond, Loundou, Boyer.

Critical revision of the manuscript for important intellectual content: Fond, Nemani, Etchecopar-Etchart, Goff, Lee, Lancon, Auquier, Baumstarck, Llorca, Yon, Boyer.

Statistical analysis: Fond, Etchecopar-Etchart, Loundou, Lee, Boyer.

Administrative, technical, or material support: Llorca.

Supervision: Fond, Auquier, Llorca, Yon, Boyer.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We acknowledge the authors of the included studies, Mohamed Boucekine, PhD (Aix-Marseille University, CEReSS, Marseille, France), for his advice and help (no compensation was received), the patients included in this meta-analysis, and the health care workers who dealt with the first wave of the COVID-19 pandemic.

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