{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:14:13Z","timestamp":1787062453058,"version":"build-2736575974"},"reference-count":167,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and\/or complications from COVID-19. The risk factors and clinical manifestations are many and various. Advanced age, sex\/gender, and pre-existing conditions certainly influence the pathogenesis and course of this syndrome. However, the absence of precise diagnostic and prognostic biomarkers may further complicate the clinical management of patients. This review aimed to summarize recent evidence on the factors influencing PCS, possible biomarkers, and therapeutic approaches. Older patients recovered approximately one month earlier than younger patients, with higher rates of symptoms. Fatigue during the acute phase of COVID-19 appears to be an important risk factor for symptom persistence. Female sex, older age, and active smoking are associated with a higher risk of developing PCS. The incidence of cognitive decline and the risk of death are higher in PCS patients than in controls. Complementary and alternative medicine appears to be associated with improvement in symptoms, particularly fatigue. The heterogeneous nature of post-COVID symptoms and the complexity of patients with PCS, who are often polytreated due to concomitant clinical conditions, suggest a holistic and integrated approach to provide useful guidance for the treatment and overall management of long COVID.<\/jats:p>","DOI":"10.3390\/jpm13020334","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:12:26Z","timestamp":1676437946000},"page":"334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Long COVID: Clinical Framing, Biomarkers, and Therapeutic Approaches"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-2739","authenticated-orcid":false,"given":"Valeria","family":"Conti","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology and Pharmacogenetics Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi, D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-889X","authenticated-orcid":false,"given":"Graziamaria","family":"Corbi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-8278","authenticated-orcid":false,"given":"Francesco","family":"Sabbatino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"De Pascale","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology and Pharmacogenetics Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi, D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-7841","authenticated-orcid":false,"given":"Carmine","family":"Sellitto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology and Pharmacogenetics Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi, D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-8704","authenticated-orcid":false,"given":"Berenice","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology and Pharmacogenetics Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi, D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Bertini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology and Pharmacogenetics Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi, D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8172-6134","authenticated-orcid":false,"given":"Matteo","family":"De Simone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-1452","authenticated-orcid":false,"given":"Luigi","family":"Liguori","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-0064","authenticated-orcid":false,"given":"Maddalena","family":"De Bernardo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-4357","authenticated-orcid":false,"given":"Angela","family":"Tesse","sequence":"additional","affiliation":[{"name":"CNRS, INSERM, L\u2019institut du Thorax, Universit\u00e9 de Nantes, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2366-6556","authenticated-orcid":false,"given":"Nicola","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8109-0655","authenticated-orcid":false,"given":"Pasquale","family":"Pagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9118","authenticated-orcid":false,"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. 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