Cossu, Giulia, Kalcev, Goce, Primavera, Diego et al. · Journal of clinical medicine · 2025 · DOI
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.
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.
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.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Cossu, Giulia, Kalcev, Goce, Primavera, Diego, Lorrai, Stefano, Perra, Alessandra, Galetti, Alessia, et al. (2025). 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.. Journal of clinical medicine. https://doi.org/10.3390/jcm14155363
BibTeX
@article{mecfsatlas-cossu-2025-use-heart,
author = {Cossu, Giulia and Kalcev, Goce and Primavera, Diego and Lorrai, Stefano and Perra, Alessandra and Galetti, Alessia and Demontis, Roberto and Tramontano, Enzo and Bert, Fabrizio and Montisci, Roberta and Maleci, Alberto and Castilla, Pedro José Fragoso and Jaramillo, Shellsyn Giraldo and Kurotschka, Peter K and Rocha, Nuno Barbosa and Carta, Mauro Giovanni},
title = {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.},
journal = {Journal of clinical medicine},
year = {2025},
doi = {10.3390/jcm14155363},
note = {PubMed: 40806985},
url = {https://www.mecfsatlas.com/evidence/cossu-2025-use-heart},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/cossu-2025-use-heart
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