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Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and DeathA Systematic Review and Meta-analysis

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

Question  Are preexisting mood disorders associated with higher risk of COVID-19 infection, hospitalization, severe complications, and death?

Findings  In this systematic review and meta-analysis of more than 91 million people, individuals with preexisting mood disorders, compared with those without mood disorders, had significantly higher pooled odds ratios for COVID-19 hospitalization and death. There were no associations between preexisting mood disorders and risk of COVID-19 infection or severe events.

Meaning  These results suggest that individuals with mood disorders should be categorized as an at-risk group for COVID-19 hospitalization and death, providing basis for vaccine prioritization.


Importance  Preexisting noncommunicable diseases (eg, diabetes) increase the risk of COVID-19 infection, hospitalization, and death. Mood disorders are associated with impaired immune function and social determinants that increase the risk of COVID-19. Determining whether preexisting mood disorders represent a risk of COVID-19 would inform public health priorities.

Objective  To assess whether preexisting mood disorders are associated with a higher risk of COVID-19 susceptibility, hospitalization, severe complications, and death.

Data Sources  Systematic searches were conducted for studies reporting data on COVID-19 outcomes in populations with and without mood disorders on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, LitCovid, and select reference lists. The search timeline was from database inception to February 1, 2021.

Study Selection  Primary research articles that reported quantitative COVID-19 outcome data in persons with mood disorders vs persons without mood disorders of any age, sex, and nationality were selected. Of 1950 articles identified through this search strategy, 21 studies were included in the analysis.

Data Extraction and Synthesis  The modified Newcastle-Ottawa Scale was used to assess methodological quality and risk of bias of component studies. Reported adjusted odds ratios (ORs) were pooled with unadjusted ORs calculated from summary data to generate 4 random-effects summary ORs, each corresponding to a primary outcome.

Main Outcomes and Measures  The 4 a priori primary outcomes were COVID-19 susceptibility, COVID-19 hospitalization, COVID-19 severe events, and COVID-19 death. The hypothesis was formulated before study search. Outcome measures between individuals with and without mood disorders were compared.

Results  This review included 21 studies that involved more than 91 million individuals. Significantly higher odds of COVID-19 hospitalization (OR, 1.31; 95% CI, 1.12-1.53; P = .001; n = 26 554 397) and death (OR, 1.51; 95% CI, 1.34-1.69; P < .001; n = 25 808 660) were found in persons with preexisting mood disorders compared with those without mood disorders. There was no association between mood disorders and COVID-19 susceptibility (OR, 1.27; 95% CI, 0.73-2.19; n = 65 514 469) or severe events (OR, 0.94; 95% CI, 0.87-1.03; n = 83 240). Visual inspection of the composite funnel plot for asymmetry indicated the presence of publication bias; however, the Egger regression intercept test result was not statistically significant.

Conclusions and Relevance  The results of this systematic review and meta-analysis examining the association between preexisting mood disorders and COVID-19 outcomes suggest that individuals with preexisting mood disorders are at higher risk of COVID-19 hospitalization and death and should be categorized as an at-risk group on the basis of a preexisting condition.

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Article Information

Accepted for Publication: May 25, 2021.

Published Online: July 28, 2021. doi:10.1001/jamapsychiatry.2021.1818

Corresponding Author: Roger S. McIntyre, MD, University Health Network, 399 Bathurst St, MP 9-325, Toronto, ON M5T 2S8, Canada (

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

Concept and design: Ceban, Lee, Xiong, Gill, Mansur, Rosenblat, Ho, McIntyre.

Acquisition, analysis, or interpretation of data: Ceban, Nogo, Carvalho, Lee, Nasri, Lui, Subramaniapillai, Liu, Joseph, Teopiz, Cao, Lin, Rosenblat, McIntyre.

Drafting of the manuscript: Ceban, Nogo, Carvalho, Lui, Liu, Teopiz, McIntyre.

Critical revision of the manuscript for important intellectual content: Ceban, Nogo, Carvalho, Lee, Nasri, Xiong, Subramaniapillai, Gill, Joseph, Cao, Mansur, Lin, Rosenblat, Ho, McIntyre.

Statistical analysis: Ceban, Carvalho.

Administrative, technical, or material support: Nogo, Carvalho, Nasri, Xiong, Lui, Subramaniapillai, Gill, Liu, Joseph, Rosenblat.

Supervision: Nogo, Lee, Mansur, Lin, Rosenblat, Ho, McIntyre.

Conflict of Interest Disclosures: Ms Lee reported receiving personal fees from Braxia Scientific Corp outside the submitted work. Ms Lui is a contractor to Braxia Scientific Corp. Ms Teopiz reported receiving personal fees from Braxia Scientific Corp outside the submitted work. Dr Rosenblat is the medical director of Braxia Health (formally known as the Canadian Rapid Treatment Center of Excellence and is a fully owned subsidiary of Braxia Scientific Corp), which provides ketamine and esketamine treatment for depression, and has received research grant support from the American Psychiatric Association, American Society of Psychopharmacology, Canadian Cancer Society, Canadian Psychiatric Association, Joseph M. West Family Memorial Fund, Timeposters Fellowship, University Health Network Centre for Mental Health, and University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck, and Sunovion. Dr McIntyre reported receiving grant support from Canadian Institutes of Health Research, Global Alliance for Chronic Diseases, and Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. Dr McIntyre is a chief executive officer of Braxia Scientific Corp.

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