{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:01:02Z","timestamp":1790780462390,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Post\u2010acute sequelae of <jats:styled-content style=\"fixed-case\">SARS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CoV<\/jats:styled-content>\u20102 (<jats:styled-content style=\"fixed-case\">PASC<\/jats:styled-content> or \u201clong <jats:styled-content style=\"fixed-case\">COVID<\/jats:styled-content>\u201d) and chronic fatigue syndrome\/myalgic encephalitis (<jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content>) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 <jats:styled-content style=\"fixed-case\">PASC<\/jats:styled-content> patients, 11 <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content> patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V\u0307a), lung diffusion capacity (<jats:styled-content style=\"fixed-case\">D<jats:sub>L<\/jats:sub><\/jats:styled-content> ), cardiac output (Q\u0307), skeletal muscle diffusion capacity (<jats:styled-content style=\"fixed-case\">D<jats:sub>M<\/jats:sub><\/jats:styled-content> ), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (V<jats:sub>max<\/jats:sub>) to peak oxygen consumption (V\u0307O<jats:sub>2peak<\/jats:sub>). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V\u0307O<jats:sub>2peak<\/jats:sub>. V\u0307O<jats:sub>2peak<\/jats:sub> was significantly reduced in both <jats:styled-content style=\"fixed-case\">PASC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content> compared to controls. Skeletal muscle <jats:styled-content style=\"fixed-case\">O<jats:sub>2<\/jats:sub><\/jats:styled-content> diffusion (<jats:styled-content style=\"fixed-case\">D<jats:sub>M<\/jats:sub><\/jats:styled-content> ) was the most impaired parameter in both patient groups (<jats:italic>p<\/jats:italic>\u2009=\u20090.01). Correcting <jats:styled-content style=\"fixed-case\">D<jats:sub>M<\/jats:sub><\/jats:styled-content> alone improved V\u0307O<jats:sub>2<\/jats:sub> by 66% in <jats:styled-content style=\"fixed-case\">PASC<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u2009=\u20090.008) and 34.7% in <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u2009=\u20090.06), suggesting a dominant role for peripheral <jats:styled-content style=\"fixed-case\">O<jats:sub>2<\/jats:sub><\/jats:styled-content> extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (<jats:styled-content style=\"fixed-case\">D<jats:sub>M<\/jats:sub><\/jats:styled-content> ) is a shared mechanism of exercise intolerance in <jats:styled-content style=\"fixed-case\">PASC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">ME<\/jats:styled-content> and may represent a therapeutic target. However, our findings are limited by small sample size.<\/jats:p>","DOI":"10.14814\/phy2.70535","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:21:26Z","timestamp":1756833686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long <scp>COVID<\/scp> and chronic fatigue syndrome\/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation"],"prefix":"10.14814","volume":"13","author":[{"given":"Swathi","family":"Jothi","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Insel","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Claessen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Kubba","sequence":"additional","affiliation":[{"name":"Sarver Heart Center, University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin J.","family":"Howden","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Ruiz\u2010Carmona","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Levine","sequence":"additional","affiliation":[{"name":"Honor Health Neurology  Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6861-8304","authenticated-orcid":false,"given":"Franz P.","family":"Rischard","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine University of Arizona  Tucson Arizona USA"},{"name":"Sarver Heart Center, University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201032275\u20103"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10122591"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044432\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010023\u201001662\u20102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101159"},{"key":"e_1_2_10_7_1","volume-title":"Beyond myalgic encephalomyelitis\/chronic fatigue syndrome: Redefining an illness","author":"Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome","year":"2015"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2020\u20100896"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","unstructured":"Davis H. 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