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; (2) PD alone by 12 percentage points; 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.