{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:53:22Z","timestamp":1792086802332,"version":"4.4.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430302110003"],"award-info":[{"award-number":["10430302110003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430012010025"],"award-info":[{"award-number":["10430012010025"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430032010010"],"award-info":[{"award-number":["10430032010010"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["11080022420018"],"award-info":[{"award-number":["11080022420018"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>It is important to determine whether the persistent cognitive and fatigue complaints, as part of post-acute sequelae of COVID-19 (PASC), are associated with underlying patterns and specific symptoms clusters. Therefore, the aim of the present study was to investigate symptom clusters and clinical phenotypes in PASC. We included n\u2009=\u2009153 individuals (53 years old, 66% female, 2 years post SARS-CoV-2 infection) categorized into groups with (n\u2009=\u200988) and without (n\u2009=\u200965) PASC, defined by severe fatigue and concentration problems using validated cut-offs. Symptom clusters (i.e., component loadings and component scores) were identified using principal component analyses (PCA, eigenvalue[EV]&gt;1.0), using clinical, somatic, coping and sleep factors, symptom severity, neuropsychological and physical tests (totalling 19 tests and questionnaires). We then used logistic regression techniques on (participant-level) component scores (standardized) to investigate associations with PASC. Finally, K-means clustering methods to identify clinical phenotypes. Analyses were adjusted for age, sex, education, nationality and time since infection. PCA identified 5 components, explaining 70% of the variance. We labelled these components as follows: (1) PEM, ME\/CFS and sleep symptoms, coping factors (EV\u2009=\u20097.0, 36.9% variance), (2) information-processing speed (EV\u2009=\u20092.5, 13.3%), (3) executive functioning (EV\u2009=\u20091.5, 8.0%, (4) physical performance (EV\u2009=\u20091.2, 6.5%), (5) somatic comorbidities and hospital admission (EV\u2009=\u20091.0, 5.5%). Logistic regression showed that only the first component scores (Odds ratio [95% confidence interval] = 97.1 [16.5\u2013570.3], p\u2009&lt;\u20090.001,), and none of the others (all p\u2009&gt;\u20090.05), associated with PASC. Cluster analysis revealed two distinct clinical phenotypes among individuals with severe chronic fatigue: one marked by physical impairment and the other by diminished cognitive performance. Consistent with existing literature, we confirmed that PASC is a heterogeneous syndrome marked by extensive, interrelated symptoms. Notably, we identified specific cognitive and physical clinical phenotypes. These findings are important for future targeted diagnosis and treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0359844","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:39:35Z","timestamp":1792085975000},"page":"e0359844","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Post-acute sequelae of COVID-19 (PASC) are associated with distinct clinical phenotypes two years after SARS-CoV-2 infection: A data-driven approach"],"prefix":"10.1371","volume":"21","author":[{"given":"Sander C. J.","family":"Verfaillie","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Medical Psychology"]},{"name":"GGz inGeest Specialized Mental Health Care","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam UMC Location VUmc","place":["Amsterdam, Netherlands"],"department":["Department of Psychiatry"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Verveen","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Medical Psychology"]},{"name":"Amsterdam Public Health","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Visser","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"],"department":["Department of Radiology & Nuclear Medicine"]},{"name":"University Medical Center Utrecht","place":["Utrecht, Netherlands"],"department":["Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2616-1414","authenticated-orcid":true,"given":"Pythia","family":"Nieuwkerk","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Medical Psychology"]},{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]},{"name":"Amsterdam Public Health","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4560-8410","authenticated-orcid":true,"given":"Brent","family":"Appelman","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Amsterdam UMC Location AMC","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Boellaard","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"],"department":["Department of Radiology & Nuclear Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4272-7315","authenticated-orcid":true,"given":"Caroline M.","family":"van Heugten","sequence":"additional","affiliation":[{"name":"Maastricht University","place":["Maastricht, Netherlands"],"department":["Department of Psychiatry and Neuropsychology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Horn","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Intensive Care"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke E.","family":"Hulst","sequence":"additional","affiliation":[{"name":"Health, Medical and Neuropsychology Unit, Institute of Psychology Leiden University","place":["Leiden, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno D.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]},{"name":"Amsterdam UMC Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Medical Microbiology & Infection Prevention"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-7025","authenticated-orcid":true,"given":"Tanja A.","family":"Kuut","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Medical Psychology"]},{"name":"Amsterdam Public Health","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4029-6577","authenticated-orcid":true,"given":"Tessa van der","family":"Maaden","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Control, National Institute for Public Health and the Environment","place":["Bilthoven, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M. G.","family":"van Os","sequence":"additional","affiliation":[{"name":"Human Resources, University Medical Center","place":["Utrecht, Netherlands"],"department":["Department of Occupational Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2967-0289","authenticated-orcid":true,"given":"Maria","family":"Prins","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Infection and Immunity","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]},{"name":"Amsterdam UMC Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]},{"name":"Public Health Service of Amsterdam","place":["Amsterdam, Netherlands"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M. A.","family":"Visser-Meily","sequence":"additional","affiliation":[{"name":"Physical Therapy Science & Sports, UMC Utrecht Brain Center, University Medical Center Utrecht","place":["Utrecht, Netherlands"],"department":["Department of Rehabilitation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"van Vugt","sequence":"additional","affiliation":[{"name":"Amsterdam UMC Location AMC","place":["Amsterdam, Netherlands"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees C.","family":"van den Wijngaard","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Control, National Institute for Public Health and the Environment","place":["Bilthoven, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart N. 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