(1) Background: Our study investigated whether monocyte distribution width (MDW) could be used in emergency department (ED) settings as a predictor of prolonged length of stay (LOS) for patients with COVID-19. (2) Methods: A retrospective cohort study was conducted; patients presenting to the ED of an academic hospital with confirmed COVID-19 were enrolled. Multivariable logistic regression models were used to obtain the odds ratios (ORs) for predictors of an LOS of >14 days. A validation study for the association between MDW and cycle of threshold (Ct) value was performed. (3) Results: Fever >38◦ C (OR: 2.82, 95% CI, 1.13–7.02, p = 0.0259), tachypnea (OR: 4.76, 95% CI, 1.67–13.55, p = 0.0034), and MDW ≥ 21 (OR: 5.67, 95% CI, 1.19–27.10, p = 0.0269) were robust significant predictors of an LOS of >14 days. We developed a new scoring system in which patients were assigned 1 point for fever > 38◦ C, 2 points for tachypnea > 20 breath/min, and 3 points for MDW ≥ 21. The optimal cutoff was a score of ≥2. MDW was negatively associated with Ct value (β: −0.32 per day, standard error = 0.12, p = 0.0099). (4) Conclusions: Elevated MDW was associated with a prolonged LOS.
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