{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:04:21Z","timestamp":1771603461980,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Fondazione di Sardegna, Bando Salute Pubblica, Medicina Preventiva e Riabilitativa","award":["PNRR\u2014PE13 INF-ACT"],"award-info":[{"award-number":["PNRR\u2014PE13 INF-ACT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis (CFS\/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS\/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p &lt; 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID.<\/jats:p>","DOI":"10.3390\/jcm14155363","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"5363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"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"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1245-016X","authenticated-orcid":false,"given":"Giulia","family":"Cossu","sequence":"first","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-6577","authenticated-orcid":false,"given":"Goce","family":"Kalcev","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6335-003X","authenticated-orcid":false,"given":"Diego","family":"Primavera","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"given":"Stefano","family":"Lorrai","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5791-1655","authenticated-orcid":false,"given":"Alessandra","family":"Perra","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"given":"Alessia","family":"Galetti","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-9767","authenticated-orcid":false,"given":"Roberto","family":"Demontis","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-0980","authenticated-orcid":false,"given":"Enzo","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy"}]},{"given":"Fabrizio","family":"Bert","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics Sciences, University of Torino, 10124 Torino, Italy"}]},{"given":"Roberta","family":"Montisci","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"given":"Alberto","family":"Maleci","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3437-8664","authenticated-orcid":false,"given":"Pedro Jos\u00e9 Fragoso","family":"Castilla","sequence":"additional","affiliation":[{"name":"PhD Program in Tropical Medicine, Universidad Popular del Cesar, Valledupar 200001, Colombia"},{"name":"Microbiology Program, Universidad Popular del Cesar, Valledupar 200001, Colombia"}]},{"given":"Shellsyn Giraldo","family":"Jaramillo","sequence":"additional","affiliation":[{"name":"Faculty of Health, Universidad Popular del Cesar, Valledupar 200001, Colombia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-6147","authenticated-orcid":false,"given":"Peter K.","family":"Kurotschka","sequence":"additional","affiliation":[{"name":"Department of General Practice, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3139-2786","authenticated-orcid":false,"given":"Nuno Barbosa","family":"Rocha","sequence":"additional","affiliation":[{"name":"Center for Translational Health and Medical Biotechnology Research (TBIO), Health Research Network (RISE-Health), E2S, Polytechnic of Porto, R. Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0706-9687","authenticated-orcid":false,"given":"Mauro Giovanni","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"},{"name":"PhD Program in Tropical Medicine, Universidad Popular del Cesar, Valledupar 200001, Colombia"},{"name":"Department of Nursing, Universidad Popular del Cesar, Valledupar 200001, Colombia"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13863","DOI":"10.1111\/apha.13863","article-title":"Chronic fatigue syndrome: An old public health issue highlighted by the COVID-19 pandemic","volume":"236","author":"Bonk","year":"2022","journal-title":"Acta Physiol."},{"key":"ref_2","unstructured":"Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (2015). 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