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

Abstract

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.

Figure 1.. Flowchart

Figure 2.. Forest Plot of the Association Between Mental Health Disorders and Mortality (Adjusted Odds Ratio)

AD indicates anxiety disorder; AUD, alcohol use disorder; BD, bipolar disorder; MD, mental health disorder; MDD, major depressive disorder; SUD, substance use disorder.

Figure 3.. Forest Plot of the Association Between Severe Mental Health Disorders and Mortality (Adjusted Odds Ratio)

Severe mental health disorders were defined as schizophrenia spectrum disorder and/or bipolar disorder.