Association of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection | Infectious Diseases | JAMA Network Open | JAMA Network
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Figure 1.  Kaplan-Meier Survival Curves for Hospitalized Patients With Coronavirus Disease 2019, With or Without a Psychiatric Diagnosis
Kaplan-Meier Survival Curves for Hospitalized Patients With Coronavirus Disease 2019, With or Without a Psychiatric Diagnosis
Figure 2.  Multivariable Cox Hazard Regression Assessing Risk of Death for Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) and Psychiatric Diagnosis
Multivariable Cox Hazard Regression Assessing Risk of Death for Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) and Psychiatric Diagnosis

CHF indicates congestive heart failure; COPD, chronic obstructive pulmonary disease; DMC, diabetes with complications; HR, hazard ratio; PI, Pacific Islander.

aPsychiatric diagnosis included International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F01 to 99 (mental and behavioral health), specific codes G30 to 32 (Alzheimer disease), and codes X60 to 63 (self-injury).

bThe numbers in each categorical variable correspond with the number of deaths in the numerator and the number of inpatients hospitalized with COVID-19 with that categorical variable in the denominator.

cThe HR for age is presented as an increase of risk with every 5-year increase in age.

dHospitals A, B, C, and D represent community hospitals affiliated with the health system, and Hospital E represents an academic medical center within the health system. None of the hospitals were rehabilitation hospitals. Although there are psychiatric units associated with the academic medical center and 2 of the community hospitals, the patients who were hospitalized for COVID-19 were hospitalized in the general hospitals for hospital-based care or intensive care.

1.
Weye  N, Momen  NC, Christensen  MK,  et al.  Association of specific mental disorders with premature mortality in the Danish population using alternative measurement methods.   JAMA Netw Open. 2020;3(6):e206646. doi:10.1001/jamanetworkopen.2020.6646PubMedGoogle Scholar
2.
Druss  BG, Bradford  WD, Rosenheck  RA, Radford  MJ, Krumholz  HM.  Quality of medical care and excess mortality in older patients with mental disorders.   Arch Gen Psychiatry. 2001;58(6):565-572. doi:10.1001/archpsyc.58.6.565PubMedGoogle ScholarCrossref
3.
Davydow  DS, Ribe  AR, Pedersen  HS, Vestergaard  M, Fenger-Grøn  M.  The association of unipolar depression with thirty-day mortality after hospitalization for infection: a population-based cohort study in Denmark.   J Psychosom Res. 2016;89:32-38. doi:10.1016/j.jpsychores.2016.08.006PubMedGoogle ScholarCrossref
4.
Kilbourne  AM, Morden  NE, Austin  K,  et al.  Excess heart-disease-related mortality in a national study of patients with mental disorders: identifying modifiable risk factors.   Gen Hosp Psychiatry. 2009;31(6):555-563. doi:10.1016/j.genhosppsych.2009.07.008PubMedGoogle ScholarCrossref
5.
Kales  HC, Valenstein  M, Kim  HM,  et al.  Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications.   Am J Psychiatry. 2007;164(10):1568-1576. doi:10.1176/appi.ajp.2007.06101710PubMedGoogle ScholarCrossref
6.
Miller  AH, Maletic  V, Raison  CL.  Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.   Biol Psychiatry. 2009;65(9):732-741. doi:10.1016/j.biopsych.2008.11.029PubMedGoogle ScholarCrossref
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    Research Letter
    Psychiatry
    September 30, 2020

    Association of a Prior Psychiatric Diagnosis With Mortality Among Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) Infection

    Author Affiliations
    • 1Yale University School of Medicine, Department of Psychiatry, New Haven, Connecticut
    • 2Yale University School of Public Health, New Haven, Connecticut
    JAMA Netw Open. 2020;3(9):e2023282. doi:10.1001/jamanetworkopen.2020.23282
    Introduction

    Psychiatric disorders are associated with shortened life expectancy (ie, shortened by as much as 10 years).1 There is a concern that psychiatric comorbidity might increase Coronavirus Disease 2019 (COVID-19)–related mortality, as suggested by prior preliminary studies of cardiac and infectious disease outcomes.2,3 A large population study in Demark suggested that an a priori diagnosis of depression was associated with a higher 30-day mortality for those hospitalized for an infection.3 Here, we evaluate the association between having any prior psychiatric diagnosis and COVID-19–related mortality of hospitalized patients with COVID-19.

    Methods

    This cohort study was conducted at Yale New Haven Health System, a 5-hospital system in the Northeast of the United States. Data were obtained from Epic Systems and included all encounters of hospitalized COVID-19–positive patients between February 15 and April 25, 2020, and followed up to May 27, 2020, for mortality. Descriptive statistics were used to characterize these patients with or without any prior psychiatric diagnoses. Kaplan-Meier analysis was conducted to compare the survival rates using the log-rank test. Univariate Cox proportional hazards regression was used to assess the association of pretreatment risk factors (including age, sex, race/ethnicity, medical comorbidities, and hospital location) with mortality. A multivariable Cox regression analysis was performed to confirm the association of psychiatric comorbidities with mortality after controlling for other risk factors. All analyses were conducted using SAS, version 9.4 (SAS Institute Inc), testing for a 2-sided significance level of .05. The study was approved for exemption by the institutional review board of Yale New Haven Health System, and a waiver of consent was granted. The study used deidentified data and was considered a medical record–only review by the institutional review board. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

    Results

    A total of 1685 patients were hospitalized with COVID-19 during the study period (mean [SD] age, 65.2 [18.4] years; 887 [52.6%] were male). Of the 1685 patients, 473 (28%) received psychiatric diagnoses prior to hospitalization. Patients with psychiatric diagnoses were significantly older and more likely to be female, white, and non-Hispanic and have medical comorbidities (malignant cancer, cerebrovascular disease, congestive heart failure, diabetes, kidney disease, liver disease, myocardial infarction, and/or HIV). Overall, 318 patients (18.9%) died. Patients with a psychiatric diagnosis had a higher mortality rate compared with those with no psychiatric diagnosis (Figure 1), with 35.7% vs 14.7% of 2-week mortality and 40.9% vs 22.2% of 3-week mortality rate (P < .001) (and with 44.8% vs 31. 5% of 4-week mortality rate). The median follow-up time was 8 days (interquartile range, 4-16 days). In the unadjusted model, the risk for COVID-19–related hospital death was greater for those with any psychiatric diagnosis (hazard ratio, 2.3; 95% CI, 1.8-2.9; P < .001). After controlling for demographic characteristics, other medical comorbidities, and hospital location, the risk of death remained significantly greater among patients with a psychiatric disorder (hazard ratio, 1.5; 95% CI, 1.1-1.9; P = .003) (Figure 2).

    Discussion

    This is the first study, to our knowledge, that characterizes the association of psychiatric diagnosis with COVID-19–related mortality. The primary finding is that patients with a prior psychiatric diagnosis while hospitalized for COVID-19 had a higher mortality rate compared those without a psychiatric condition. The finding is similar to previous findings: individuals with concurrent psychiatric and medical diagnoses had poorer outcomes and higher mortality.4,5

    It is unclear why psychiatric illness predisposes to COVID-19–related mortality. Psychiatric symptoms may arise as a marker of systemic pathophysiologic processes, such as inflammation, that may, in turn, predispose to mortality. Similarly, psychiatric disorders may augment systemic inflammation and compromise the function of the immune system, while psychotropic medications may also be associated with to mortality risk.6

    The limitations to the study include the fact that those individuals not hospitalized for COVID-19 or who died outside the hospital were not used in the analysis. In addition, diagnosis codes were used to assess for any psychiatric diagnosis, without accounting for the status of psychiatric treatment (patient with active, in-remission, or recovered psychiatric disorder). The data also do not include COVID-19 treatment information.

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    Article Information

    Accepted for Publication: August 27, 2020.

    Published: September 30, 2020. doi:10.1001/jamanetworkopen.2020.23282

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Li L et al. JAMA Network Open.

    Corresponding Author: Luming Li, MD, Yale University School of Medicine, Department of Psychiatry, 184 Liberty St, New Haven, CT 06511 (luming.li@yale.edu).

    Author Contributions: Dr L. Li and Mr F. Li had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: L. Li, Fortunati, Krystal.

    Acquisition, analysis, or interpretation of data: L. Li, F. Li.

    Drafting of the manuscript: L. Li, F. Li.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: F. Li, Krystal.

    Obtained funding: Krystal.

    Administrative, technical, or material support: L. Li, Fortunati.

    Supervision: Krystal.

    Conflict of Interest Disclosures: Dr L. Li reported grants from a Health and Aging Policy Fellowship during the conduct of the study. Dr Krystal reported receiving royalties from Janssen Pharmaceuticals, stock from Biohaven Pharmaceuticals, stock options from Blackthorn Pharmaceuticals, stock from Spring Health, stock options from Terran Biosciences, personal fees and provision of drugs for research from Novartis, provision of drugs for research from AstraZeneca, personal fees from Sunovion, Takeda, Cerevel, Biogen, EpiVario, Heptares, Otsuka, Taisho, BioXcel, and Psychogenics, stock from Sage, and personal fees from Cadent Pharmaceuticals outside the submitted work and is the editor of Biological Psychiatry and a member of the Society of Biological Psychiatry. No other disclosures were reported.

    Additional Contributions: The authors would like to acknowledge Mr Todd Barnes of Yale New Haven Hospital for help reviewing the results of the study. No compensation was received for his role.

    References
    1.
    Weye  N, Momen  NC, Christensen  MK,  et al.  Association of specific mental disorders with premature mortality in the Danish population using alternative measurement methods.   JAMA Netw Open. 2020;3(6):e206646. doi:10.1001/jamanetworkopen.2020.6646PubMedGoogle Scholar
    2.
    Druss  BG, Bradford  WD, Rosenheck  RA, Radford  MJ, Krumholz  HM.  Quality of medical care and excess mortality in older patients with mental disorders.   Arch Gen Psychiatry. 2001;58(6):565-572. doi:10.1001/archpsyc.58.6.565PubMedGoogle ScholarCrossref
    3.
    Davydow  DS, Ribe  AR, Pedersen  HS, Vestergaard  M, Fenger-Grøn  M.  The association of unipolar depression with thirty-day mortality after hospitalization for infection: a population-based cohort study in Denmark.   J Psychosom Res. 2016;89:32-38. doi:10.1016/j.jpsychores.2016.08.006PubMedGoogle ScholarCrossref
    4.
    Kilbourne  AM, Morden  NE, Austin  K,  et al.  Excess heart-disease-related mortality in a national study of patients with mental disorders: identifying modifiable risk factors.   Gen Hosp Psychiatry. 2009;31(6):555-563. doi:10.1016/j.genhosppsych.2009.07.008PubMedGoogle ScholarCrossref
    5.
    Kales  HC, Valenstein  M, Kim  HM,  et al.  Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications.   Am J Psychiatry. 2007;164(10):1568-1576. doi:10.1176/appi.ajp.2007.06101710PubMedGoogle ScholarCrossref
    6.
    Miller  AH, Maletic  V, Raison  CL.  Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.   Biol Psychiatry. 2009;65(9):732-741. doi:10.1016/j.biopsych.2008.11.029PubMedGoogle ScholarCrossref
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