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The coronavirus disease-2019 (COVID-19) pandemic has imposed unforeseen and unprecedented constraints on emergency departments (EDs). In this study, we detail the organizational and managerial tools recently implemented among 5 academic EDs in a French region particularly affected by COVID-19 and analyze how EDs responded to the COVID-19-related disease burden during different phases of the epidemic. Initially, they focused on the early detection of suspected cases by identifying 3 predominant COVID-19 syndromes. During this diagnostic process, patients were placed in respiratory isolation (facial mask before triage) and droplet isolation (ED rooms). A 3-level strategy for triage, clinical pathways in the EDs, and the organization of hospital spaces was based on the real-time polymerase chain reaction (RT-PCR) COVID-19 positivity rate, with ED strategies adapted to the exigencies of each level. This crisis demonstrated hospitals' adaptability and capacity to mobilize in the face of new risks, with hospitals and EDs coordinating their management to reallocate resources, optimize interoperability, and rethink patient pathways. This report on their processes may assist hospitals and EDs in areas currently spared by the new variants., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)