Understanding Post-Exertional Malaise: A Scoping Review and Perspectives from Patients and Clinicians Restricted; Files Only

Abstract

Background and Objectives: Post-exertional malaise (PEM) is a defining feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is increasingly recognized in Long COVID, yet remains inconsistently defined and assessed. This study examined how PEM is conceptualized and measured, identified gaps in current approaches, and generated patient-centered insights to inform improved evaluation and care. 

Methods: A mixed-methods design was used. A scoping review following PRISMA-ScR guidelines identified 110 eligible studies from 2,021 records across five databases. Data were extracted on study characteristics, PEM measures, and key findings. PEM-specific items and findings were categorized using the International Classification of Functioning, Disability and Health (ICF) framework. Additional analyses examined triggers, temporal features, and thematic patterns. A qualitative component included semi-structured interviews with three clinicians and four patients with Long COVID, analyzed using thematic content analysis.

Results: Substantial heterogeneity in PEM assessment was identified. The DePaul Symptom Questionnaire (DSQ) and its variants were most commonly used (53%), though non-validated measures were also frequent (22%). PEM items were overwhelmingly linked to ICF body functions (99%), particularly cardiovascular/immune/respiratory (76%), mental (60%), and neuromusculoskeletal (58%) domains, with limited representation of activities and participation (14%). Physical triggers were most common (71%), followed by effort/exertion (60%) and cognitive triggers (35%); emotional triggers were rarely assessed (3%). Symptom frequency was the most measured temporal feature (56%), whereas role limitation was rarely captured (1%). Thematic analysis showed that symptom outcomes (58%) and functional impairments (35%) predominated, with frequent multisystem involvement (37%).

Qualitative findings highlighted cognitive dysfunction, PEM, autonomic symptoms, and fatigue as central features of Long COVID. Participants described significant participation limitations despite mild-to-moderate symptom severity. Barriers to care included delayed diagnosis, misdiagnosis, and limited access to knowledgeable providers. Pacing and breathing-based strategies were commonly reported as helpful.

Conclusion: PEM is a multidimensional, multisystem phenomenon that is inadequately captured by current assessment approaches. Existing measures emphasize symptoms while underrepresenting triggers, temporal dynamics, and functional impact. Improved, standardized, and patient-centered tools are needed to enhance diagnosis, guide management, and better reflect the lived experience of PEM in ME/CFS and Long COVID.

Table of Contents

INTRODUCTION 1

METHODS 5

RESULTS 14

DISCUSSION 27

FIGURES AND TABLES 37

SUPPLEMENTAL MATERIAL 58

BIBLIOGRAPHY 59

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.A.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Rehabilitation and Therapy
Keyword	myalgic encephalomyelitis SARS-CoV-2 Scoping Review clinical assessment qualitative interviews chronic fatigue syndrome Post-exertional malaise outcome measurement PEM ME/CFS CFS Long COVID
Committee Chair / Thesis Advisor	Krishnan, Shilpa, Emory University
Committee Members	Cole, Megan, Emory University Wiley, Zanthia, Emory University

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