Hospitalization Associated With Comorbid Psychiatric and Substance Use Disorders Among Adults With COVID-19 Treated in US Emergency Departments From April 2020 to August 2021

Lyna Z Schieber; Christopher Dunphy; Richard A Schieber; Barbara Lopes-Cardozo; Ramal Moonesinghe; Gery P Guy, Jr

doi:10.1001/jamapsychiatry.2022.5047

. 2023 Feb 15;80(4):331–341. doi: 10.1001/jamapsychiatry.2022.5047

Hospitalization Associated With Comorbid Psychiatric and Substance Use Disorders Among Adults With COVID-19 Treated in US Emergency Departments From April 2020 to August 2021

Lyna Z Schieber ^1,^✉, Christopher Dunphy ², Richard A Schieber ³, Barbara Lopes-Cardozo ⁴, Ramal Moonesinghe ⁵, Gery P Guy Jr ¹

¹Division of Overdose Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia

²Division of Injury Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia

³Office of Director, Center for Surveillance, Epidemiology, and Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia

⁴Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia

⁵Office of Genomics and Precision Public Health, Centers for Disease Control and Prevention, Atlanta, Georgia

Accepted for Publication: November 28, 2022.

Published Online: February 15, 2023. doi:10.1001/jamapsychiatry.2022.5047

^✉

Corresponding Author: Lyna Z. Schieber, MD, DPhil, Division of Overdose Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, 4770 Buford Hwy, Mailstop S106-8, Atlanta, GA 30341 (chn6@cdc.gov).

Author Contributions: Drs L. Schieber and Dunphy 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: All authors.

Acquisition, analysis, or interpretation of data: L. Schieber, Dunphy, R. Schieber, Moonesinghe, Guy.

Drafting of the manuscript: L. Schieber, Dunphy, R. Schieber, Lopes-Cardozo.

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

Statistical analysis: L. Schieber, Dunphy, Moonesinghe.

Administrative, technical, or material support: Dunphy, R. Schieber, Lopes-Cardozo, Guy.

Supervision: Guy.

Conflict of Interest Disclosures: None reported.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention or Agency for Toxic Substances and Disease Registry. We verify that all information and materials in the manuscript are original.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We thank Ning Rosenthal, MD, PhD, MPH, from Premier for advice on study design and Sachin Agnihotri, MS; Indira Srinivasan, MS; David Nitschke, BS; and Kimberly Riggle, BBA, for facilitating access to these data. None of these individuals received compensation beyond their regular salaries for their work on this study.

^✉

Corresponding author.

PMCID: PMC9932946 PMID: 36790774

Key Points

Question

Do comorbid psychiatric and substance use disorders in adults with COVID-19 affect their probability of hospitalization?

Findings

In this cross-sectional analysis of more than 1.2 million emergency department patients with COVID-19, patients with both psychiatric disorder and substance use disorder had a greater probability of hospitalization, compared with those with psychiatric disorder alone, substance use disorder alone, or neither disorder. Substance use disorders appear to have a greater association than psychiatric disorders with the probability of hospitalization.

Meaning

Among emergency department patients with COVID-19, ascertainment of both psychiatric and substance use disorders is important to accurately determine the likelihood of hospitalization.

This cross-sectional study examines hospital discharge data for adults with a COVID-19 diagnosis to assess the association of comorbid psychiatric and substance use disorders with hospitalization among emergency department patients with COVID-19.

Abstract

Importance

During the COVID-19 pandemic, US emergency department (ED) visits for psychiatric disorders (PDs) and drug overdoses increased. Psychiatric disorders and substance use disorders (SUDs) independently increased the risk of COVID-19 hospitalization, yet their effect together is unknown.

Objective

To assess how comorbid PD and SUD are associated with the probability of hospitalization among ED patients with COVID-19.

Design, Setting, and Participants

This retrospective cross-sectional study analyzed discharge data for adults (age ≥18 years) with a COVID-19 diagnosis treated in 970 EDs and inpatient hospitals in the United States from April 2020 to August 2021.

Exposures

Any past diagnosis of (1) SUD from opioids, stimulants, alcohol, cannabis, cocaine, sedatives, or other substances and/or (2) PD, including attention-deficit/hyperactivity disorder (ADHD), anxiety, bipolar disorder, major depression, other mood disorder, posttraumatic stress disorder (PTSD), or schizophrenia.

Main Outcomes and Measures

The main outcome was any hospitalization. Differences in probability of hospitalization were calculated to assess its association with both PD and SUD compared with PD alone, SUD alone, or neither condition.

Results

Of 1 274 219 ED patients with COVID-19 (mean [SD] age, 54.6 [19.1] years; 667 638 women [52.4%]), 18.6% had a PD (mean age, 59.0 years; 37.7% men), 4.6% had a SUD (mean age, 50.1 years; 61.7% men), and 2.3% had both (mean age, 50.4 years; 53.1% men). The most common PDs were anxiety (12.9%), major depression (9.8%), poly (≥2) PDs (6.4%), and schizophrenia (1.4%). The most common SUDs involved alcohol (2.1%), cannabis (1.3%), opioids (1.0%), and poly (≥2) SUDs (0.9%). Prevalence of SUD among patients with PTSD, schizophrenia, other mood disorder, or ADHD each exceeded 21%. Based on significant specific PD-SUD pairs (Q < .05), probability of hospitalization of those with both PD and SUD was higher than those with (1) neither condition by a weighted mean of 20 percentage points (range, 6 to 36; IQR, 16 to 25); (2) PD alone by 12 percentage points (range, −4 to 31; IQR, 8 to 16); and (3) SUD alone by 4 percentage points (range, −7 to 15; IQR, −2 to 7). Associations varied by types of PD and SUD. Substance use disorder was a stronger predictor of hospitalization than PD.

Conclusions and Relevance

This study found that patients with both PD and SUD had a greater probability of hospitalization, compared with those with either disorder alone or neither disorder. Substance use disorders appear to have a greater association than PDs with the probability of hospitalization. Overlooking possible coexisting PD and SUD in ED patients with COVID-19 can underestimate the likelihood of hospitalization. Screening and assessment of both conditions are needed.

Introduction

The COVID-19 pandemic in the United States has been associated with increased prevalence of emergency department (ED) visits for psychiatric disorders (PDs) and substance use disorders (SUDs).^1,2,3,4,5 About 6% of patients with COVID-19 developed a new psychiatric disorder during the first few months of the pandemic.⁶ New diagnoses of anxiety and major depression increased by 25% worldwide in the first year of the pandemic.² Conversely, those with preexisting psychiatric disorders are at greater risk of acquiring COVID-19 than the general population.^7,8 Residents of the United States with a recent diagnosis of depression or schizophrenia had a 7-fold increased likelihood of acquiring a COVID-19 infection.⁷ Hospitalization for treatment of COVID-19 occurred more than twice as often among patients with vs those without a preexisting PD.⁹

Substance use disorder may also change the risk of acquiring COVID-19 and consequent hospitalization.^{9,10,11,12,13,14,15} People with SUD and an underlying medical condition are more likely to acquire COVID-19^12,13,15 and develop greater severity.¹³ Patients with COVID-19 and opioid use disorder had up to 4 times the odds of hospitalization as those without it.¹³

These separate effects of SUD and PD on hospitalization for COVID-19 were previously studied without consideration of any possible joint effect, so they might be estimated erroneously.^6,9,11,13,16 Therefore, we assessed the association of comorbid PD and SUD with the probability of hospitalization among ED patients with COVID-19.

Methods

Data Source and Study Population

We used the Premier PINC AI Healthcare Data Special Release COVID-19 (PHD-SR COVID-19) edition (release date, September 14, 2021). This 48-state, all-payer longitudinal electronic health record database includes about one-fourth of all ED visits and inpatient admissions in the United States. It contains discharge information from inpatient, outpatient, and ED visits, including 75.3 million patients from 970 hospitals.^{17,18,19,20,21}

We restricted our study to records from medical facilities that contributed both ED and inpatient encounter data. All adult ED patients were classified either as ED only if not subsequently hospitalized or as hospitalized patients if admitted through the ED. Patients were included if they (1) were 18 years or older; (2) had an ED visit for acute illness; (3) were admitted through the ED within 24 hours; (4) had a principal or secondary discharge diagnosis code of U07.1 (COVID-19, virus identified) using the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)²²; and (5) were admitted between January 1, 2020, and August 31, 2021, and discharged or died between April 1, 2020, and August 31, 2021. Discharge codes rather than admission codes were used to avoid misclassification from unsubstantiated “rule-out” diagnoses. Case ascertainment of the U07.1 diagnostic code from this database used alone had 98.0% sensitivity, 99.1% specificity, 91.5% positive predictive value, and 99.8% negative predictive value of COVID-19 disease compared with polymerase chain reaction test result.²³ The PHD-SR COVID-19 has been widely used in clinical and scientific health research related to COVID-19.^{18,19,20,21,23,24,25,26,27}

This study was approved by the Centers for Disease Control and Prevention and deemed exempt from institutional review board review per 45 CFR §46.101(b)(4) and exempt from patient informed consent per 45 CFR §164.506(d)(2)(ii)(B) because the disclosed data had already been deidentified. This report followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.²⁸

Exposures, Outcomes, and Covariates

The primary exposure variables, SUD and PD, were determined from the principal or secondary discharge ICD-10-CM diagnostic codes recorded at a past outpatient or ED visit, inpatient stay, or first encounter for COVID-19. Substance use disorder diagnoses included those involving alcohol, cocaine, cannabis, opioids, sedatives (eg, benzodiazepines), other stimulants (eg, amphetamine), or other substances (eg, lysergic acid diethylamide, or LSD).²⁹ Psychiatric disorder diagnoses included attention-deficit/hyperactivity disorder (ADHD), anxiety, bipolar disorder, major depression, other mood disorder, posttraumatic stress disorder (PTSD), and schizophrenia (eTable 1 in Supplement 1). Nicotine dependence was included as a comorbid covariate rather than a primary exposure variable because (1) its very high prevalence relative to any other SUD would likely risk dwarfing the effect of any other SUD and (2) the clinical and public health screening and treatment for nicotine dependence for an outpatient differs from other SUDs. Because SUD and PD were not consistently diagnosed or recorded at each visit, each record was traced backward to the maximum extent possible (January 2019) and traced forward to the patient’s first COVID-19 visit to determine whether a SUD or PD diagnosis had ever been documented.^30,31

The main outcome measure was any hospitalization, determined solely from hospital billing codes. These included inpatient encounter, inpatient indicator, ED admission, and ED billing charge for any stay less than 24 hours.²¹ Hospitalization was used as a surrogate measure of disease severity because it is historically reserved for inpatients with higher-acuity or more severe or complex illness. Independent variables included patient age, race and ethnicity, sex, primary insurance type, and US Census region of hospital; pandemic wave (first, second, third, or fourth); plus history of pertinent comorbidities previously associated with increased COVID-19 severity, including cancer, chronic kidney disease, chronic obstructive pulmonary disease, heart failure, cardiac dysrhythmia, obesity, nicotine dependency, and type 2 diabetes.³² These were identified from principal or secondary discharge diagnostic ICD-10 codes using backward and forward record reviews of all patient encounters from January 2019 through the initial COVID-19 visit using the Healthcare Cost and Utilization Project Elixhauser Comorbidity Software via R package icd.^29,33

Statistical Analysis

All statistical analyses were performed using SAS version 9.4 (SAS Institute), Stata version 14.1 (StataCorp), and R version 4.02 (R Foundation for Statistical Computing). Significance of distribution of categorical data was determined using Pearson χ² testing. Two-sample comparisons of continuous variables were evaluated using a t test or Wilcoxon rank sum test, as appropriate. Statistical significance was set at P < .05.

Predicted Probability of Hospitalization

Probabilities of hospitalization and their 95% CI were estimated from 9 separate logistic regression models that included sets of variables for SUDs, PDs, and their interactions. Further description of the logit models and their estimates are provided in the eMethods and eTable 5 in Supplement 1.

Difference in Probability of Hospitalization

To assess the association of PD and SUD with probability of hospitalization, we first classified patients into 4 groups according to the presence (+) or absence (−) of their PD and SUD diagnoses, namely, both PD and SUD (PD+ SUD+) present; PD only present (PD+ SUD−); SUD only present (PD− SUD+); and neither PD nor SUD present (PD− SUD−). We then calculated the difference in probability of hospitalization among patients having both PD and SUD (PD+ SUD+), compared with the probability of each of the other 3 comparison groups (Figure 1). Difference in probability of hospitalization is a measure of association that estimates the probability of (1) having PD and SUD among patients in whom neither SUD nor PD is known; (2) having a SUD among patients in whom only a PD is known; and (3) having a PD among patients in whom only a SUD is known. Two-sided P values were corrected for false discovery rate using the Benjamini-Hochberg method to account for type I error due to multiple comparisons using estimated Q values, ie, the P values adjusted for false discovery rate.³⁴ The mean difference in probability of hospitalization for each of 3 comparisons was calculated using the inverse of the standard error of each significant pair of “any SUD-specific PD” and “any PD-specific PD” as the weight to give more weight to estimates with larger sample sizes.

Figure 1. — Patients were classified into 4 groups for comparison by the presence (+) or absence (−) of a diagnosis for psychiatric disorder (PD) and substance use disorder (SUD), namely both PD and SUD (PD+ SUD+), PD only (PD+ SUD−), SUD only (PD− SUD+), and no PD or SUD (PD− SUD−).

Results

Hospital inclusion criteria were met by 873 (90.0%) of 970 possible hospitals. Patient inclusion criteria were met by 1 274 219 ED adults (mean [SD] age, 54.6 [19.1] years; 667 638 women [52.4%]), of whom 567 766 (44.6%) were hospitalized directly from an ED (Table). COVID-19 was the primary discharge diagnosis in 79.3% of all patients with COVID-19, including 89.4% of those discharged from an ED and 66.8% of those hospitalized. Compared with those not admitted, hospitalized patients were more likely male (52.4% vs 43.7%), older (mean age, 63.6 vs 47.4 years), insured by Medicare (53.2% vs 21.4%), living in urban areas (88.3% vs 83.8%), or from the Northeast census region (18.1% vs 9.4%). About three-fourths of those hospitalized with COVID-19 had a chronic disease, compared with about one-third of patients with COVID-19 discharged from an ED (76.6% vs 35.6%). Those hospitalized were more likely than those discharged from the ED to have a PD (26.5% vs 12.2%), a SUD (6.1% vs 3.4%), or both PD and SUD (3.1% vs 1.6%) (Table).

Table. Characteristics, Clinical Outcomes, Substance Use Disorders, Psychiatric Disorders, and Comorbidities Among Adult Emergency Department and Hospitalized Patients With Confirmed COVID-19, United States, April 2020–August 2021^a.

Characteristic	No. (%)			Hospitalized, unadjusted, % (row)
Characteristic	Overall sample	ED only	Hospitalized^b	Hospitalized, unadjusted, % (row)
Total	1 274 219 (100.0)	706 453 (100.0)	567 766 (100.0)	44.6
Discharge diagnosis COVID-19
Primary	1 010 483 (79.3)	631 217 (89.4)	379 266 (66.8)	37.5
Secondary	263 736 (20.7)	75 236 (10.6)	188 500 (33.2)	71.5
Age, mean (SD), y	54.6 (19.1)	47.4 (17.9)	63.6 (16.7)	NA
Age group, y
18-39	324 001 (25.4)	267 964 (37.9)	56 037 (9.9)	17.3
40-54	295 164 (23.2)	191 999 (27.2)	103 165 (18.2)	35.0
55-64	228 654 (17.9)	112 797 (16.0)	115 857 (20.4)	50.7
65-74	201 369 (15.8)	74 939 (16.6)	126 430 (22.3)	62.8
≥75	225 031 (17.7)	58 754 (8.3)	166 277 (29.3)	73.9
Sex
Female	667 638 (52.4)	397 448 (56.3)	270 190 (47.6)	40.5
Male	606 581 (47.6)	309 005 (43.7)	297 576 (52.4)	49.1
Race and ethnicity
Asian	28 255 (2.2)	14 063 (2.0)	14 192 (2.5)	50.2
Hispanic	258 637 (20.3)	159 970 (22.6)	98 667 (17.3)	38.1
Non-Hispanic Black	249 413 (19.6)	146 345 (20.7)	103 068 (18.2)	41.3
Non-Hispanic White	640 251 (50.3)	331 006 (46.8)	309 245 (54.5)	48.3
Other^c	68 765 (5.4)	38 388 (5.4)	30 377 (5.4)	44.2
Unknown^d	28 898 (2.3)	16 681 (2.4)	12 217 (2.2)	42.3
Primary insurance
Medicaid	223 518 (17.5)	150 800 (21.4)	72 781 (12.8)	32.5
Medicare	452 982 (35.6)	150 865 (21.4)	302 117 (53.2)	66.7
Other^e	171 167 (13.4)	122 572 (17.4)	48 595 (8.6)	28.4
Private insurance	426 552 (33.5)	282 216 (40.0)	144 336 (25.4)	33.8
Hospital US Census region^f
Midwest	258 634 (20.3)	143 715 (20.3)	114 919 (20.2)	44.4
Northeast	169 510 (13.3)	66 639 (9.4)	102 871 (18.1)	60.7
South	653 773 (51.3)	384 267 (54.4)	269 506 (47.5)	41.2
West	192 302 (15.1)	111 832 (15.8)	80 470 (14.2)	41.8
Population served
Rural	180 900 (14.2)	114 403 (16.2)	66 497 (11.7)	36.8
Urban	1 093 319 (85.8)	592 050 (83.8)	501 269 (88.3)	45.8
No. of hospital beds
<100	128 863 (10.1)	95 792 (13.6)	33 071 (5.8)	25.7
100-299	465 075 (36.5)	269 501 (38.2)	195 574 (34.5)	42.1
300-499	349 741 (27.5)	180 389 (25.5)	169 352 (29.8)	48.4
≥500	330 540 (25.9)	160 771 (22.8)	169 769 (29.9)	51.4
PD
ADHD	6756 (0.5)	4108 (0.6)	2648 (0.5)	39.2
Anxiety	164 624 (12.9)	62 891 (8.9)	101 733 (17.9)	61.8
Bipolar disorder	401 (0.03)	224 (0.03)	177 (0.03)	44.1
Major depression	125 417 (9.8)	42 311 (6.0)	83 106 (14.6)	66.3
Other mood disorder	6408 (0.5)	1773 (0.3)	4635 (0.8)	72.3
PTSD	10 206 (0.8)	4746 (0.7)	5460 (1.0)	53.5
Schizophrenia	17 871 (1.4)	5782 (0.8)	12 089 (2.1)	67.6
≥1 PD above (any PD)	237 186 (18.6)	86 472 (12.2)	150 714 (26.5)	63.5
≥2 PD above (poly PD)	81 577 (6.4)	29 547 (4.2)	52 044 (9.2)	63.8
No PD	1 037 033 (81.4)	619 981 (87.4)	417 052 (73.5)	40.2
SUD by substance
Alcohol	26 847 (2.1)	9678 (1.4)	17 169 (3.0)	64.0
Other stimulants	8094 (0.6)	3893 (0.6)	4201 (0.7)	51.9
Cannabis	16 469 (1.3)	8820 (1.3)	7649 (1.4)	46.4
Cocaine	6715 (0.5)	2932 (0.4)	3783 (0.7)	56.3
Opioids	12 985 (1.0)	3899 (0.6)	9096 (1.6)	70.1
Other psychoactive substances	7165 (0.6)	3615 (0.5)	3550 (0.6)	49.5
Sedatives	2417 (0.2)	740 (0.1)	1677 (0.3)	69.4
≥1 SUD above (any SUD)	58 876 (4.6)	24 200 (3.4)	34 676 (6.1)	58.9
≥2 SUD above (poly SUD)	11 725 (0.9)	4811 (0.7)	6917 (1.2)	59.0
No SUD	1 215 343 (95.4)	682 253 (96.6)	533 090 (93.9)	43.9
Combinations of PD and SUD
Any PD with any SUD (both PD and SUD)	29 215 (2.3)	11 555 (1.6)	17 660 (3.1)	60.4
Any PD with no SUD (PD only)	207 971 (16.3)	74 917 (10.6)	133 054 (23.4)	64.0
No PD with any SUD (SUD only)	29 661 (2.3)	12 645 (1.8)	17 016 (3.0)	57.4
No PD and no SUD (no PD or SUD)	1 007 372 (79.1)	607 336 (86.0)	400 036 (70.5)	39.7
Comorbidities
Cancer	57 573 (4.5)	14 060 (2.0)	43 521 (7.7)	75.6
Cardiac dysrhythmia	157 453 (12.4)	32 355 (4.6)	125 098 (22.0)	75.9
CKD	151 548 (11.9)	27 125 (3.8)	124 475 (21.9)	82.1
COPD	124 373 (9.8)	29 570 (4.2)	94 825 (16.7)	76.2
Heart failure	131 044 (10.3)	24 124 (3.4)	106 944 (18.8)	81.6
Nicotine dependency	135 193 (10.6)	79 043 (11.2)	56 176 (9.9)	41.6
Obesity	257 037 (20.2)	72546 (10.3)	184 636 (32.5)	71.8
Type 2 diabetes	345 740 (27.1)	108 526 (15.4)	237 315 (41.8)	68.6
≥1 Comorbidities above	686 426 (53.9)	251 613 (35.6)	434 813 (76.6)	63.3
None of the comorbidities above	587 793 (46.1)	454 840 (64.4)	132 953 (23.4)	22.6
Wave
1 (April 2020-May 2020)	106 103 (8.3)	37 535 (5.3)	68 650 (12.1)	64.6
2 (June 2020-August 2020)	194 807 (15.3)	113 694 (16.1)	81 113 (14.3)	41.6
3 (September 2020-June 2021)	868 350 (68.2)	475 966 (67.4)	392 384 (69.1)	45.2
4 (July 2021-August 2021)	104 959 (8.2)	79 258 (11.2)	25 701 (4.5)	24.5

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Abbreviations: ADHD, attention-deficit/hyperactivity disorder; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; ED, emergency department; NA, not applicable; PD, psychiatric disorder; PTSD, posttraumatic stress disorder; SUD, substance use disorder.

^{^a}

Patients with COVID-19 were those who had inpatient and/or ED visits with a discharge diagnosis of U07.1 if admitted from January 1, 2020, through August 31, 2021, and discharged or died from April 1, 2020, through August 31, 2021. Data were obtained from Premier PINC AI Healthcare Data Special Release COVID-19 edition (release date, September 14, 2021).

^{^b}

Indicates P < .001 for distributions by demographics at a 2-tailed Pearson χ² test compared with their counterpart in the same group.

^{^c}

Refers to non-Hispanic American Indian and Alaska Native, Native Hawaiian and Other Pacific Islander, and some other race.

^{^d}

Race and ethnicity both unknown.

^{^e}

Charity, indigent, self-pay, workers’ compensation, direct employer contract, other government payers, or other.

^{^f}

Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.

Comorbid Psychiatric and Substance Use Disorders

Among all ED patients with COVID-19, 237 186 (18.6%) had any PD (mean age, 59.0 years; 37.7% men); 81 577 (6.4%) had 2 or more (poly) PD (mean age, 58.1 years; 33.4% men); 58 876 (4.6%) had any SUD (mean age, 50.1 years; 61.7% men); 11 725 (0.9%) had 2 or more (poly) SUD (mean age, 46.0 years; 65.9% men); 29 215 (2.3%) had both PD and SUD (mean age, 50.4 years; 53.1% men) (Table and eTables 2 and 3 in Supplement 1). The proportions of Black COVID-19 ED patients with any PD, with any SUD, and with both PD and SUD were 1.3 times (15.7% vs 12.0%), 2.0 times (24.3% vs 12.0%), and 1.7 times (20.3% vs 12.0%) their representation in the 2020 adult US population, respectively (eTables 2 and 3 in Supplement 1).³⁵ The most common PD groups were any PD (18.6%), anxiety (12.9%), major depression (9.8%), poly PD (6.4%), and schizophrenia (1.4%). The most common SUD involved any SUD (4.6%), alcohol (2.1%), cannabis (1.3%), opioids (1.0%), and poly SUD (0.9%) (Table). Because only 0.03% of the sample had bipolar disorder, this disorder was excluded from subsequent analyses.

Of 237 186 COVID-19 ED patients with any PD, about 1 in 8 (12.3%) also had any SUD (Figure 2A). Those with PTSD, schizophrenia, other mood disorder, or ADHD each had any SUD exceeding 21%. The leading SUDs among those with any PD involved alcohol, cannabis, poly SUD, or opioids. Conversely, of 58 876 COVID-19 ED patients with a SUD, about half (49.6%) also had a PD, most commonly anxiety, poly PD, major depression, or schizophrenia (Figure 2B). Patients with SUD involving sedatives (n = 2417) and opioids (n = 12 985) each had a notable prevalence of comorbidity with any PD, 81.2% and 63.2%, respectively.

Probability of Hospitalization

The values for probabilities of hospitalization obtained by modeling the 4 groups of 72 PD-SUD pairs are shown in Figure 3 and eTable 4 in Supplement 1. Overall, the probability of hospitalization for patients with both PD and SUD (PD+ SUD+) was highest among the 4 groups, with a mean probability of 61% (median, 62%; range, 44%-77%; IQR, 56%-66%), followed by SUD only (PD− SUD+) with a mean probability of 59% (median, 62%; range, 45%-72%; IQR, 53%-65%), and PD only (PD+ SUD−) with a mean probability of 51% (median, 53%; range, 40%-59%; IQR, 48%-55%). Those with neither disorder (PD− SUD−) had the lowest mean probability of 41% (median, 41%; range, 41%-43%; IQR, 41%-41%).

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD− SUD−

The probability of hospitalization of patients with both PD and SUD (PD+ SUD+) was significantly higher than that for patients with neither condition known to be present (PD− SUD−) for 69 (95.8%) of 72 pairs (Q < .05), with 3 pairs (4.2%) having no significant difference in probability. For these 69 pairs, probability of hospitalization was increased by a weighted mean of 20 percentage points (median, 21; range, 6-36; IQR, 16-25). The highest increases in probability of hospitalization were associated with having both PD and SUD among patients with neither disorder known occurred with these PD-SUD pairs: schizophrenia and sedative use disorder (36%, 95% CI, 28%-43%; Q < .001), ADHD and polysubstance use disorder (34%, 95% CI, 30%-38%; Q < .001), ADHD and opioid use disorder (32%, 95% CI, 25%-38%; Q < .001), and schizophrenia and opioid use disorder (30%, 95% CI, 25%-35%; Q < .001) (Figure 4 and eTable 4 in Supplement 1).

Figure 4. — The sample generated 72 PD-SUD pairs, which was stratified by 4 groups according to the presence (+) or absence (−) of their PD and SUD diagnoses, namely, both PD and SUD present (PD+ SUD+); PD only present (PD+ SUD−); SUD only present (PD− SUD+); and neither PD nor SUD present (PD− SUD−). The change in probability of hospitalization was the difference between the probability for both PD and SUD (PD+ SUD+) and probability for each of the 3 other comparison groups with estimated 95% CI for each of the 72 PD-SUD pairs. The change in probability of hospitalization associated with having both PD and SUD among patients in whom neither SUD nor PD is known equals probability of PD+ SUD+ minus probability of PD− SUD−. Similarly, the change in probability associated with having a SUD among patients in whom only a PD is known equals the probability of PD+ SUD+ minus the probability of PD+ SUD−. The change in probability of hospitalization associated with having a PD among patients in whom only a SUD is known equals the probability of PD+ SUD+ minus the probability of PD− SUD+. Error bars indicate 95% CIs; ADHD indicates attention-deficit/hyperactivity disorder; poly, ≥2 disorders; PTSD, posttraumatic stress disorder; UD, use disorder. Data were calculated from Premier PINC AI Healthcare Data Special Release COVID-19 edition (release date, September 14, 2021).

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD+ SUD−

Compared with patients with only PD known to be present (PD+ SUD−), the probability of hospitalization of those with both PD and SUD (PD+ SUD+) was significantly higher in 56 (77.8%) of 72 pairs and lower in 3 pairs (4.2%; Q < .05), with 13 pairs (18.1%) having no difference. For these 59 significant pairs, the probability was increased by a weighted mean of 12 percentage points (median, 12; range, −4 to 31; IQR, 8 to 16). The largest increases in probability of hospitalization were associated with polysubstance use disorder among patients with either ADHD (31%; 95% CI, 26%-35%; Q < .001) or PTSD (31%; 95% CI, 27%-35%; Q < .001) and opioid use disorder among those with ADHD (28%; 95% CI, 22%-35%; Q < .001) (Figure 4 and eTable 4 in Supplement 1).

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD− SUD+

Compared with patients with only SUD known to be present (PD− SUD+), the probability of hospitalization for those with both PD and SUD (PD+ SUD+) was significantly higher in 21 (29.2%) of 72 pairs and lower in 11 pairs (15.3%; Q < .05); 40 pairs (55.6%) had no significant difference. Of these 32 significant pairs, probability was larger by a weighted mean of 4 percentage points (median, 6; range, −7 to 15; IQR, −2 to 7). The greatest increases in probability of hospitalization were associated with schizophrenia among patients with either sedative use disorder (15%; 95% CI, 8%-22%; Q < .001) or cannabis use disorder (14%; 95% CI, 9%-18%; Q < .001) and other mood disorder among patients with cocaine use disorder (15%; 95% CI, 6%-25%; Q = .002) (Figure 4 and eTable 4 in Supplement 1).

Discussion

These results suggest that the probability of hospitalization for COVID-19 ED patients with a known PD but unrecognized SUD may be underestimated by as much as 31 percentage points (mean, 12), depending on the specific type of SUD. By comparison, the probability of hospitalization for COVID-19 ED patients with a known SUD but unrecognized PD may be underestimated by as much as 15 percentage points (mean, 4), depending on the specific type of PD. If both conditions are unknown, the probability may be underestimated by as much as 36 percentage points (mean, 20). Substance use disorder appeared to have a stronger association with the probability of hospitalization than PD.

Knowing both disorders is critically important. In the 2020 National Survey on Drug Use and Health, 6.7% of US adults self-reported they had a mental illness coexisting with a SUD in the past year.³⁶ We found that 2.3% of all COVID-19 ED patients had coexisting PD and SUD, but among those with any of 4 specific psychiatric diagnoses, the prevalence of coexistence exceeded 21% in each. Coexistence can adversely affect functional impairment, treatment outcomes, morbidity and mortality, treatment costs, and risk of homelessness, incarceration, or suicide.^37,38,39 However, stigma among medical professionals and society reduces the likelihood of SUD disclosure by patients, and fewer medical encounters likely occur because such patients may be hesitant to seek medical care and have barriers to access.^40,41,42 A high index of clinical suspicion of SUD is routinely needed at each encounter. Careful history-taking and substance use screening using standard instruments are helpful in this regard.

The mechanism of action of SUD and PD on COVID-19 severity is unclear. Both PD and SUD have been independently associated with physical comorbidities that increase the risk of acquiring COVID-19 and subsequent hospitalization.^6,15,40 Separately, PD, SUD, and COVID-19 have been found among people with environmental risks or low socioeconomic status, including persons experiencing homelessness and those with poor medical care.^20,40,41 One common pathogenesis pathway proposed is the development of an inflammatory response among those with PD, SUD, or COVID-19.^{43,44,45,46,47} Substance use can influence the pulmonary, cardiac, metabolic, and immune systems; each such system is also targeted by the SARS-CoV-2 virus.⁴¹ Opioid use can dampen the immune response,⁴⁸ initiate or worsen acute respiratory distress syndrome, or depress respiratory drive.^49,50 Of note, the strongest difference in probability of hospitalization we observed occurred among patients with coexisting schizophrenia and opioid use disorder, compared with those without them. These 2 conditions share a common mechanism involving the kappa opioid receptor pathway, which is reversable by opioid antagonists.^45,46,47 The opioid receptor pathway is also required to control respiratory syncytial virus replication, thereby controlling its disease severity.⁵¹ Such observations only suggest but do not indicate a specific mechanism of action here and merit further investigation.

The increase in drug overdose deaths during the COVID-19 pandemic indicates the importance of assessing the possible presence of SUD in ED COVID-19 patients with a known PD.^52,53,54 For hospitalized patients with PD in whom a SUD was present but overlooked, drug withdrawal and worsening COVID-19 severity may occur, complicating their infectious disease.^55,56 Resource shortages for hospitalized patients may occur if patients are more severely ill and likely have a longer length of stay. During the pandemic, shortages occurred widely in hospital bedspace, nursing staff, and personal protective equipment.⁵⁷ Even if acute hospitalization is not needed, medical care, mental health care, and public health prevention of increasing SUD is needed. Patients with coexisting PD and SUD should receive long-term, evidence-based prevention, treatment, and response strategies, particularly in high-risk communities.^41,58 These include risk communication, screening and assessment, public education, implementing harm reduction interventions, and promoting linkage to medications and care for SUD or PD. Integrated service of SUD and PD care delivery by community-based care professionals and social services groups have been shown to have greater benefit than sequential or parallel services for each.⁵⁹ This may require structural improvements in trust-building, enhancing partnerships, reducing clinician stigmatization, and overcoming operational barriers, with additional resources needed for harm-reduction organizations, PD and SUD treatment centers, and recovery support services to help patients with PD and/or SUD avoid severe outcomes related to COVID-19.^60,61

Limitations

Several limitations should be considered. This study, though relatively robust with its large national sample, was not designed to be a probability sample.^10,11,15 Both SUD and PD may have been underdiagnosed and/or underreported because of social desirability bias or undercoding.^30,31,62 About one-third of patients with COVID-19 had COVID-19 listed as a secondary discharge diagnosis, which may have spuriously inflated the percent hospitalization from COVID-19. Misclassification may have occurred either by including a SUD diagnosis when it was an inactive condition or by excluding it when its degree of activity could not be determined. Asymptomatic patients with COVID-19 were not identified or purposely included, nor were those with known COVID-19 who were treated in a non-ED setting or an out-of-network ED. Drug use in the US adult population indicated here is not as inclusive or accurate as population-based surveys, as indicated above.³⁶ Moreover, our study included only those with COVID-19 who sought emergency care in 48 states. Hospitalization may have been postponed or hindered if a shortage of available hospital beds occurred.⁵⁷ COVID-19 vaccination may have lessened disease severity in some, but accurate determination of vaccination was not possible because the Premier database only collects vaccination information from its network of hospital-based outpatient clinics and hospitals, not from pharmacies or local health departments.⁶³ Also, COVID-19 vaccination was not available to the public for the first 8 months of this study.

Conclusions

In this cross-sectional study, patients with both PD and SUD had a greater probability of hospitalization, compared with those with either disorder alone or neither disorder. Substance use disorders appear to have a greater association than PDs with the probability of hospitalization. Overlooking possible coexisting PD and SUD in ED patients with COVID-19 can underestimate the likelihood of hospitalization. Screening and assessment of both conditions are needed because the likelihood of both being present is particularly high.

Supplement 1.

eMethods. Predicted probability of hospitalization

eTable 1. Substance use disorders, psychiatric disorders, and associated ICD-10-CM codes

eTable 2. Characteristics of adult emergency department and hospitalized patients with confirmed COVID-19 by substance use disorders, United States, April 2020–August 2021

eTable 3. Characteristics of adult emergency department and hospitalized patients with confirmed COVID-19 by substance use and psychiatric disorders, United States, April 2020–August 2021

eTable 4. Predicted probability of hospitalization and difference in probability of hospitalization for each psychiatric disorder (PD)-substance use disorder (SUD) pair by patient’s presence (+) or absence (-) of a PD and SUD diagnosis

eTable 5. Coefficient estimates and p value from logit models

Click here for additional data file.^{(327.6KB, pdf)}

Supplement 2.

Data sharing statement

Click here for additional data file.^{(15.2KB, pdf)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eMethods. Predicted probability of hospitalization

eTable 1. Substance use disorders, psychiatric disorders, and associated ICD-10-CM codes

eTable 2. Characteristics of adult emergency department and hospitalized patients with confirmed COVID-19 by substance use disorders, United States, April 2020–August 2021

eTable 3. Characteristics of adult emergency department and hospitalized patients with confirmed COVID-19 by substance use and psychiatric disorders, United States, April 2020–August 2021

eTable 5. Coefficient estimates and p value from logit models

Click here for additional data file.^{(327.6KB, pdf)}

Supplement 2.

Data sharing statement

Click here for additional data file.^{(15.2KB, pdf)}

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PERMALINK

Hospitalization Associated With Comorbid Psychiatric and Substance Use Disorders Among Adults With COVID-19 Treated in US Emergency Departments From April 2020 to August 2021

Lyna Z Schieber, MD, DPhil

Christopher Dunphy, PhD

Richard A Schieber, MD, MPH

Barbara Lopes-Cardozo, MD, MPH

Ramal Moonesinghe, PhD

Gery P Guy Jr, PhD, MPH

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Exposures

Main Outcomes and Measures

Results

Conclusions and Relevance

Introduction

Methods

Data Source and Study Population

Exposures, Outcomes, and Covariates

Statistical Analysis

Predicted Probability of Hospitalization

Difference in Probability of Hospitalization

Figure 1. Groups and Comparisons for Difference in Probability of Hospitalization.

Results

Table. Characteristics, Clinical Outcomes, Substance Use Disorders, Psychiatric Disorders, and Comorbidities Among Adult Emergency Department and Hospitalized Patients With Confirmed COVID-19, United States, April 2020–August 2021a.

Comorbid Psychiatric and Substance Use Disorders

Figure 2. Comorbid Psychiatric Disorder (PD) and Substance Use Disorder (SUD).

Probability of Hospitalization

Figure 3. Probability of Hospitalization by Presence (+) or Absence (−) of a Psychiatric Disorder (PD) and Substance Use Disorder (SUD) Diagnosis.

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD− SUD−

Figure 4. Difference in Probability of Hospitalization for Each Psychiatric Disorder (PD)–Substance Use Disorder (SUD) Pair.

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD+ SUD−

Difference in Probability of Hospitalization for Patients With PD+ SUD+ vs Those With PD− SUD+

Discussion

Limitations

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases

Table. Characteristics, Clinical Outcomes, Substance Use Disorders, Psychiatric Disorders, and Comorbidities Among Adult Emergency Department and Hospitalized Patients With Confirmed COVID-19, United States, April 2020–August 2021^a.