{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:48Z","timestamp":1790618268876,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Although an increasing number of studies have reported 2- and 3-year outcomes of post-acute sequelae of SARS-CoV-2 infection (PASC), the long-term symptom patterns of and their clinical phenotypes beyond four years remains unknown. We aimed to characterize 48-month clinical outcomes and symptom profiles using hierarchical cluster analysis. Methods: We conducted a longitudinal cohort study of 79 patients with persistent PASC enrolled between March 2021 and March 2022. Of these, 77 patients completed the 48-month follow-up. Symptoms were assessed at 11 and 48 months post-infection. Hierarchical cluster analysis using Jaccard distance and Ward\u2019s linkage identified symptom-based phenotypes at 48 months. Cluster membership was subsequently mapped back to 11-month symptom profiles to evaluate longitudinal trajectories. Results: Of the 77 patients completing the 48-month follow-up, symptom profiles at 48 months could be descriptively characterized into four exploratory, symptom-based profiles, which differed from the broader symptom patterns observed at month 11: Cluster 1 (cardiorespiratory and neurosensory symptoms; 16.9%, n = 13), characterized by persistent chest discomfort and palpitations; Cluster 2 (musculoskeletal\/pain-predominant; 33.8%, n = 26), characterized by persistent myalgia and arthralgia. Cluster 3 (neurocognitive and mixed multisystem profile; 23.4%, n = 18), characterized by persistent cognitive impairment and musculoskeletal pain and Cluster 4 (minimal residual symptom burden; 26.0%, n = 20), demonstrating the lowest overall residual symptom burden at 48 months. Conclusions: At 48 months, PASC symptoms showed substantial heterogeneity, with four exploratory symptom-based profiles. In our cohort, over one-quarter of patients had the lowest observed residual symptom burden at 48 months; neurocognitive and musculoskeletal symptoms remained prominent in specific profiles, supporting the need for targeted multidisciplinary post-acute care.<\/jats:p>","DOI":"10.3390\/jcm15197487","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"7487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Four-Year Longitudinal Phenotyping of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Single-Centre Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6330-4011","authenticated-orcid":false,"given":"Anna Ter\u00e9z","family":"S\u00e1rk\u00f6zi","sequence":"first","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Medical Sciences, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2165-4196","authenticated-orcid":false,"given":"Ilona","family":"Tornyi","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Ildik\u00f3","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"National Koranyi Institute of Pulmonology, 1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_2","unstructured":"World Health Organization (2021). 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