{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:09:50Z","timestamp":1783948190113,"version":"3.55.0"},"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with Long COVID (LC) often experience neuropsychiatric symptoms such as depression, anxiety, and chronic fatigue syndrome (CFS), collectively referred to as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance significantly contribute to the physio-affective phenome associated with LC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cohort of 90 individuals, categorized into those with and without LC, we evaluated, 3-6 months following acute SARS-CoV-2 infection, the correlations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA), and Fibro-Fatigue (FF) Rating Scale scores, and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), S100B and neuron-specific enolase (NSE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HAMD, HAMA, FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B are all higher in people with LC compared to those without LC. The HAMD\/HAMA\/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) \u2013 oxygen saturation (SpO2) (PBT\/SpO2 index) during the acute infectious phase. A combination of biomarkers explained a large part of the variance in CFS and affective scores (33.6%-42.0%), with GAL-GALR1 signaling, PGE2, and CRP being the top 3 most important biomarkers. The inclusion of the PBT\/SpO2 index increased the prediction (55.3%-67.1%). The PBT\/SpO2 index predicted the increases in GAL-GALR1 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results indicate that the CFS and affective symptoms that are linked to LC are the consequence of metabolic aberrations, activated immune-inflammatory pathways, and the severity of inflammation during the acute phase of SARS-CoV-2 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0316373","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T13:25:41Z","timestamp":1741267541000},"page":"e0316373","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID"],"prefix":"10.1371","volume":"20","author":[{"given":"Wasim Talib Mahdi","family":"Al Masoodi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami Waheed","family":"Radhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habiba Khdair","family":"Abdalsada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-5196","authenticated-orcid":true,"given":"Hussein Kadhem","family":"Al-Hakeim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"issue":"1","key":"pone.0316373.ref001","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/papt.12498","article-title":"Cognitive behavioural therapy for psychosis: the end of the line or time for a new approach?","volume":"97","author":"K Newman\u2010Taylor","year":"2024","journal-title":"Psychol Psychother"},{"issue":"1","key":"pone.0316373.ref002","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12888-023-05481-6","article-title":"The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis","volume":"24","author":"N 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