Free: https://www.sciencedirect.com/science/article/pii/S2949834123000211 Brain Behavior and Immunity Integrative Volume 4, December 2023, 100022 What Long COVID investigators can learn from four decades of ME/CFS research☆ Leonard A. Jason a,* , Benjamin H. Natelson b , Hector Bonilla c , Zaki A. Sherif d , Suzanne D. Vernon e , Monica Verduzco Gutierrez f , Lisa O’Brien g , Emily Taylor h , On behalf of the RECOVER consortium, by members of the Diagnostic Testing and Test Algorithms Subcommittee of the Commonalities with Other Post Viral Syndromes Task Force. We appreciate the edits and suggestions from Ben Z. Katz https://doi.org/10.1016/j.bbii.2023.100022Get rights and content Abstract Four decades of research in the field of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have yielded lessons that may be instructive for those devising criteria to better comprehend Post-Acute Sequelae of SARS CoV-2 Infection (PASC) and Long COVID. For instance, substantial effort has been devoted to defining classification systems, operationalizing methods, and developing instruments with adequate reliability and validity in the ME/CFS field. The current article provides guidelines for developing a case definition for Long COVID and discusses the significance of psychometric issues and criterion variance, including how to specify symptoms, develop thresholds, subtypes, and exclusionary conditions. ME/CFS research could enhance our knowledge of Long COVID pathophysiology, early diagnosis, prognosis, and the identification of effective treatments.