Outcome measures in long COVID clinical trials: a review
9 affiliations
- 1Department of Nephrology and Hypertension, University Medical Center Utrecht
- 2Department of Theoretical Philosophy, University of Groningen
- 3Department of Human Media Interaction, University of Twente
- 4Research Physician
- 5Department of Primary and Community Care, Radboud University Medical Center
- 6Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center
- 7Independent Researcher
- 8Institute for Life Sciences and Chemistry, HU University of Applied Sciences
- 9Department of Respiratory Medicine, Erasmus Medical Center
Abstract
Background: Long COVID is a multisystem disease that affects approximately 10% of people after a SARS-CoV-2 infection. In the absence of curative treatment, high-quality clinical treatment trials are urgently needed for long COVID. There is significant overlap between long COVID and other infection-associated chronic conditions, in particular myalgic encephalomyelitis. As such, trial design for long COVID can benefit from prior experience in this field. In this review we explore outcome measures in long COVID and myalgic encephalomyelitis clinical trials to survey current practices, and provide recommendations for future clinical trials. PubMed and Clinicaltrials.gov were searched for clinical trials on long COVID and myalgic encephalomyelitis that featured a biomedical intervention. 37 myalgic encephalomyelitis and 68 long COVID trials were identified that used 397 outcome measures in total. We then critically assessed the relevance of these outcome measures for patients.
Conclusion: Long COVID trial design could be improved by incorporating outcomes that address important symptom clusters such as post-exertional malaise, dysautonomia and mast cell activation. Clinical assessments, physical tests and biomarkers can supplement patient reported outcome measure data, if safety, feasibility and applicability are carefully considered. Lastly, safety of the intervention is rarely adequately evaluated. We recommend a concerted effort to include patient input at all steps of clinical trial design, execution and evaluation.
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BibTeX
@article{rhijnbrouwer2026outcome,
title = {{Outcome measures in long COVID clinical trials: a review}},
author = {Femke C. C. van Rhijn-Brouwer and Chloé de Canson and Joanneke E. L. VanDerNagel and Xandra Westerhuis and Susanne Y. Young and Sander M. J. van Kuijk and Laura V. de Vries and Jon-Ruben van Rhijn and Merel Hellemons},
journal = {Frontiers in Public Health},
year = {2026},
month = oct,
doi = {10.3389/fpubh.2026.1972605},
url = {https://www.frontiersin.org/articles/10.3389/fpubh.2026.1972605/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Outcome measures in long COVID clinical trials: a review
AU - Femke C. C. van Rhijn-Brouwer
AU - Chloé de Canson
AU - Joanneke E. L. VanDerNagel
AU - Xandra Westerhuis
AU - Susanne Y. Young
AU - Sander M. J. van Kuijk
AU - Laura V. de Vries
AU - Jon-Ruben van Rhijn
AU - Merel Hellemons
PY - 2026
DA - 2026/10/19
JO - Frontiers in Public Health
DO - 10.3389/fpubh.2026.1972605
UR - https://www.frontiersin.org/articles/10.3389/fpubh.2026.1972605/full
AB - Background: Long COVID is a multisystem disease that affects approximately 10% of people after a SARS-CoV-2 infection. In the absence of curative treatment, high-quality clinical treatment trials are urgently needed for long COVID. There is significant overlap between long COVID and other infection-associated chronic conditions, in particular myalgic encephalomyelitis. As such, trial design for long COVID can benefit from prior experience in this field. In this review we explore outcome measures in long COVID and myalgic encephalomyelitis clinical trials to survey current practices, and provide recommendations for future clinical trials. PubMed and Clinicaltrials.gov were searched for clinical trials on long COVID and myalgic encephalomyelitis that featured a biomedical intervention. 37 myalgic encephalomyelitis and 68 long COVID trials were identified that used 397 outcome measures in total. We then critically assessed the relevance of these outcome measures for patients. Conclusion: Long COVID trial design could be improved by incorporating outcomes that address important symptom clusters such as post-exertional malaise, dysautonomia and mast cell activation. Clinical assessments, physical tests and biomarkers can supplement patient reported outcome measure data, if safety, feasibility and applicability are carefully considered. Lastly, safety of the intervention is rarely adequately evaluated. We recommend a concerted effort to include patient input at all steps of clinical trial design, execution and evaluation.
SN - 2296-2565
ER -