The Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial. — CFSMEATLAS
The Use of Heart Rate Variability-Biofeedback (HRV-BF) as an Adjunctive Intervention in Chronic Fatigue Syndrome (CSF/ME) in Long COVID: Results of a Phase II Controlled Feasibility Trial.
Cossu, Giulia, Kalcev, Goce, Primavera, Diego et al. · Journal of clinical medicine · 2025 · DOI
Quick Summary
This study tested whether a technique called heart rate variability biofeedback (HRV-BF)—which uses breathing exercises and computer feedback to help regulate your nervous system—could help people with Long COVID who have severe fatigue. Participants received 10 sessions over 5 weeks, and the results showed that people in the treatment group experienced greater improvement in severe fatigue compared to those receiving usual care. The treatment was well-tolerated with very few people dropping out, suggesting it could be a helpful add-on therapy for ME/CFS.
Why It Matters
Long COVID and ME/CFS remain poorly understood conditions with limited approved treatments, making non-pharmacological, low-risk interventions particularly valuable. This study provides preliminary evidence that HRV-BF may specifically target severe fatigue—the hallmark symptom of ME/CFS—offering patients a potential safe, accessible option to complement standard care. The feasibility findings support advancing to larger trials that could establish HRV-BF as an evidence-based adjunctive therapy.
Observed Findings
Low study drop-out rate of 5.56% with generally high participant satisfaction
Significantly greater improvement in severe fatigue observed in the HRV-BF group compared to treatment-as-usual (H = 4.083, p = 0.043)
Minimal side effects with mean Simulator Sickness Questionnaire score of 24.31 (or 12.82 after outlier exclusion)
When all outcomes assessed collectively, the experimental group showed a significant tendency toward improvement (p < 0.0001)
10 sessions of HRV-BF delivered twice weekly over 5 weeks was completed with high feasibility
Inferred Conclusions
HRV-BF appears feasible and well-tolerated as an adjunctive intervention in Long COVID/ME-CFS populations
HRV-BF shows preliminary efficacy in reducing severe fatigue, the primary symptom of ME/CFS
Phase III trials are warranted to confirm effectiveness and determine optimal implementation protocols
HRV-BF represents a promising non-pharmacological intervention for integrative ME/CFS management
Remaining Questions
Will results replicate in a larger, fully randomized Phase III trial with adequate blinding?
What This Study Does Not Prove
This Phase II study does not establish that HRV-BF is definitively effective; it demonstrates feasibility and preliminary promise requiring confirmation in a larger Phase III trial. The quasi-random assignment (not true randomization) and lack of information about blinding may introduce bias. The study cannot prove causation or explain the mechanisms by which HRV-BF may improve fatigue in ME/CFS populations.
Which ME/CFS patient subgroups benefit most from HRV-BF, and are there predictors of response?
What is the optimal duration and frequency of HRV-BF training, and do benefits persist long-term after treatment ends?
What are the underlying physiological mechanisms by which HRV-BF improves fatigue in ME/CFS—does it involve autonomic nervous system regulation, inflammation, or other pathways?