Evidence map›Paper›PMID 42879454›Full record

ArticlePloS one2026

Post-acute sequelae of COVID-19 (PASC) are associated with distinct clinical phenotypes two years after SARS-CoV-2 infection: A data-driven approach.

Sander C J Verfaillie, Anouk Verveen, Denise Visser, Pythia Nieuwkerk, Brent Appelman, Ronald Boellaard, Caroline M van Heugten, Janneke Horn, Hanneke E Hulst, Menno D de Jong and 11 more

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Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

21 authors.

Sander C J VerfaillieDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Anouk VerveenDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Denise VisserDepartment of Radiology & Nuclear Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Pythia NieuwkerkDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.ORCID https://orcid.org/0000-0002-2616-1414
Brent AppelmanCenter for Experimental and Molecular Medicine, Amsterdam UMC Location AMC, Amsterdam, Netherlands.ORCID https://orcid.org/0000-0002-4560-8410
Ronald BoellaardDepartment of Radiology & Nuclear Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Caroline M van HeugtenDepartment of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands.ORCID https://orcid.org/0000-0003-4272-7315
Janneke HornDepartment of Intensive Care, Amsterdam UMC Location AMC, Amsterdam, Netherlands.
Hanneke E HulstHealth, Medical and Neuropsychology Unit, Institute of Psychology Leiden University, Leiden, Netherlands.
Menno D de JongDepartment of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.
Tanja A KuutDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.ORCID https://orcid.org/0000-0003-1081-7025
Tessa van der MaadenCenter for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.ORCID https://orcid.org/0000-0002-4029-6577
Yvonne M G van OsDepartment of Occupational Health, Human Resources, University Medical Center, Utrecht, Netherlands.
Maria PrinsDepartment of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.ORCID https://orcid.org/0000-0003-2967-0289
Johanna M A Visser-MeilyDepartment of Rehabilitation, Physical Therapy Science & Sports, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
Michele van VugtDepartment of Internal Medicine, Amsterdam UMC Location AMC, Amsterdam, Netherlands.
Cees C van den WijngaardCenter for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands.
Bart N M van BerckelDepartment of Radiology & Nuclear Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Jos A BoschDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Nelleke TolboomDepartment of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, Netherlands.
Hans KnoopDepartment of Medical Psychology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 = 153 individuals (53 years old, 66% female, 2 years post SARS-CoV-2 infection) categorized into groups with (n = 88) and without (n = 65) 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]>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 = 7.0, 36.9% variance), (2) information-processing speed (EV = 2.5, 13.3%), (3) executive functioning (EV = 1.5, 8.0%, (4) physical performance (EV = 1.2, 6.5%), (5) somatic comorbidities and hospital admission (EV = 1.0, 5.5%). Logistic regression showed that only the first component scores (Odds ratio [95% confidence interval] = 97.1 [16.5-570.3], p < 0.001,), and none of the others (all p > 0.05), 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.

Indexed as

COVID-19FatigueCluster AnalysisClustering AlgorithmsFemaleHumansMaleMiddle AgedNeuropsychological TestsPhenotypePost-Acute COVID-19 SyndromePrincipal Component AnalysisSARS-CoV-2Symptom Burden

Identifiers

PMID42879454
PMCPMC13671525

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.