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Background: Smoking, alcohol use, and non-prescription drug use are associated with worsened COVID-19 outcomes in hospitalized patients. Whether there is an association between substance use and outcomes in patients with COVID-19 who visited the Emergency Department (ED) but did not require hospitalization has not been well established. We investigated whether smoking, alcohol, and non-prescription drug use were associated with worsened COVID-19 outcomes among such patients presenting to the ED., Methods: We conducted a secondary analysis of a clinical trial which sought to determine the effect of early convalescent plasma administration in patients presenting to the ED within 7 days of onset of mild COVID-19 symptoms. The study recruited 511 participants who were aged 50 years or older or had one or more risk factors for severe COVID-19. The primary outcome was disease progression within 15 days after randomization, which was defined as a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included: no hospitalization within 30 days post-randomization, symptom worsening on the 5-category COVID-19 outpatient ordinal scale within 15 days post-randomization, and all-cause mortality. Substance use was categorized into either use or never use based on participant self-report. Logistic regression models were used to determine the association between substance use and outcomes., Results: The mean age of the 511 patients enrolled was 52 years and the majority were females (274, 54%). Approximately 213 (42%) were non-Hispanic Whites, 156 (30%) Hispanics, 100 (20%) non-Hispanic Blacks, 18 (4%) non-Hispanic Asian, 8 (1%) American Indian Alaskan, and 16 (3%) unknown race. Tobacco 152 (30%) was the most common substance use reported. Alcohol use 36 (7%) and non-prescription drug use 33 (6%) were less common. Tobacco use and non-prescription drug use were associated with an increased risk for meeting the primary outcome ((tobacco: adjusted odds ratio [aOR] =2.08; 95% confidence interval [CI]: 1.37-3.15) and (drug: aOR =2.41; 95%CI: 1.17-5.00)) and increased risk for symptom worsening on the 5-category COVID-19 outpatient scale ((tobacco: aOR = 1.62; 95%CI: 1.09-2.42) and (drug: aOR = 2.32 95% CI: 1.10-4.87)) compared to non-use after adjusting for age, sex, plasma administration, and comorbidity., Conclusion: Tobacco and non-prescription drug use but not alcohol use were associated with worsened COVID-19 outcomes in patients who did not require hospitalization on their initial presentation. Future studies should determine the quantity, duration, and type of drug/tobacco use that may worsen COVID-19., Competing Interests: Declaration of Competing Interest Authors have no declaration., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest JA, DA, SA, ASD, JR, REL, LN, NP, LAS, RDH, SK report no conflicts of interest. RBL has received funding personally from Philips Healthcare and Butterfly Network, Inc. for consulting. AJW reports grant money from the Agency for Healthcare Research and Quality to conduct research conceived and written by Anthony J Weekes MD MSc from Carolinas Medical Center at Atrium Health. AJW reports grant money to Atrium Health to conduct research conceived and sponsored by Scanwell Health, Inc. REL is a member of the medical advisory board of EchoNous. AL is a consultant for EchoNous. MD has received funding personally from National Institutes of Health to conduct research conceived and written by Marina Del Rios, MD, MS from University of Illinois at Chicago. MD is a paid member of the Medscape Steering Committee Elevating Health Equity. MG reported grant funding from the Centers for Disease Control and Prevention, Society for Academic Emergency Medicine, Emergency Medicine Foundation, and the Council of Residency Directors in Emergency Medicine.