Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries

Kim López-Güell¹, Martí Català¹, Daniel Dedman², Talita Duarte-Salles³, Raivo Kolde⁴, Raúl López-Blasco⁵, Álvaro Martínez⁶, Gregoire Mercier⁷, Alicia Abellan⁸, Johnmary T Arinze⁹, Theresa Burkard¹, Edward Burn¹, Zara Cuccu², Antonella Delmestri¹, Dominique Delseny¹⁰, Sara Khalid¹, Chungsoo Kim¹¹, Ji-Woo Kim¹², Kristin Kostka¹³, Cora Loste¹⁴, Miguel A Mayer¹⁵, Jaime Meléndez-Cardiel⁵, Núria Mercadé-Besora¹⁶, Mees Mosseveld⁹, Akihito Nishimura¹⁷, Hedvig Me Nordeng¹⁸, Jessie O Oyinlola², Roger Paredes¹⁹, Laura Pérez-Crespo⁸, Marta Pineda-Moncusí¹, Juan Manuel Ramírez-Anguita¹⁵, Nhung T H Trinh²⁰, Anneli Uusküla²¹, Bernardo Valdivieso²², Daniel Prieto-Alhambra²³, Junqing Xie¹, Lourdes Mateu²⁴, Annika M Jödicke¹

Affiliations

¹ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
² CPRD, Medicines and Healthcare products Regulatory Agency, London, UK.
³ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴ Institute of Computer Science, University of Tartu, Tartu, Estonia.
⁵ Biocomputing Unit, Aragon Health Sciences Institute (IACS), Zaragoza, Spain.
⁶ The Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell, 106 Torre A 7a planta, Valencia 46026, Spain.
⁷ Public Health Department, University Hospital of Montpellier, Montpellier 34295, France; IDESP, Université de Montpellier, INSERM, Montpellier 34000, France.
⁸ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
⁹ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁰ Public Health Department, University Hospital of Montpellier, Montpellier 34295, France.
¹¹ Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
¹² Big Data Department, Health Insurance Review and Assessment Service, Wonju, Republic of Korea.
¹³ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; The OHDSI Center at the Roux Institute, Northeastern University, Portland, ME, USA.
¹⁴ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; REICOP (Red de Investigación Covid Persistente), Madrid, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain.
¹⁵ Parc de Salut Mar, Hospital del Mar Medical Research Institute, Barcelona, Spain.
¹⁶ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
¹⁷ Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁸ Department of Pharmacy, Pharmacoepidemiology and Drug Safety Research Group, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
¹⁹ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain; Department of Pathology, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH; Universitat Autònoma de Barcelona, Catalonia, Spain; CIBER Infectious Diseases (CIBERINFEC), Institute of Health Carlos III (ISCIII), Madrid, Spain; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, Catalonia, Spain.
²⁰ Department of Pharmacy, Pharmacoepidemiology and Drug Safety Research Group, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
²¹ Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
²² The Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell, 106 Torre A 7a planta, Valencia 46026, Spain; The University and Polytechnic La Fe Hospital of Valencia, Avenida Fernando Abril Martorell, 106 Torre H 1a planta, Valencia 46026, Spain.
²³ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: daniel.prietoalhambra@ndorms.ox.ac.uk.
²⁴ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; REICOP (Red de Investigación Covid Persistente), Madrid, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain; Universitat Autònoma de Barcelona, Catalonia, Spain.

PMID: 40517846
DOI: 10.1016/j.jclinepi.2025.111867

Free article

Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries

Kim López-Güell et al. J Clin Epidemiol. 2025 Sep.

Free article

. 2025 Sep:185:111867.

doi: 10.1016/j.jclinepi.2025.111867. Epub 2025 Jun 13.

Authors

Affiliations

¹ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
² CPRD, Medicines and Healthcare products Regulatory Agency, London, UK.
³ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴ Institute of Computer Science, University of Tartu, Tartu, Estonia.
⁵ Biocomputing Unit, Aragon Health Sciences Institute (IACS), Zaragoza, Spain.
⁶ The Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell, 106 Torre A 7a planta, Valencia 46026, Spain.
⁷ Public Health Department, University Hospital of Montpellier, Montpellier 34295, France; IDESP, Université de Montpellier, INSERM, Montpellier 34000, France.
⁸ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
⁹ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁰ Public Health Department, University Hospital of Montpellier, Montpellier 34295, France.
¹¹ Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
¹² Big Data Department, Health Insurance Review and Assessment Service, Wonju, Republic of Korea.
¹³ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; The OHDSI Center at the Roux Institute, Northeastern University, Portland, ME, USA.
¹⁴ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; REICOP (Red de Investigación Covid Persistente), Madrid, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain.
¹⁵ Parc de Salut Mar, Hospital del Mar Medical Research Institute, Barcelona, Spain.
¹⁶ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
¹⁷ Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁸ Department of Pharmacy, Pharmacoepidemiology and Drug Safety Research Group, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
¹⁹ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain; Department of Pathology, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH; Universitat Autònoma de Barcelona, Catalonia, Spain; CIBER Infectious Diseases (CIBERINFEC), Institute of Health Carlos III (ISCIII), Madrid, Spain; IrsiCaixa AIDS Research Institute, Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, Catalonia, Spain.
²⁰ Department of Pharmacy, Pharmacoepidemiology and Drug Safety Research Group, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
²¹ Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia.
²² The Health Research Institute Hospital La Fe, Avenida Fernando Abril Martorell, 106 Torre A 7a planta, Valencia 46026, Spain; The University and Polytechnic La Fe Hospital of Valencia, Avenida Fernando Abril Martorell, 106 Torre H 1a planta, Valencia 46026, Spain.
²³ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: daniel.prietoalhambra@ndorms.ox.ac.uk.
²⁴ Department of Infectious Diseases & irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; University of Vic- Central University of Catalonia (UVic-UCC), Vic, Spain; REICOP (Red de Investigación Covid Persistente), Madrid, Spain; Fundació Lluita Contra les Infeccions, Badalona, Catalonia, Spain; Universitat Autònoma de Barcelona, Catalonia, Spain.

PMID: 40517846
DOI: 10.1016/j.jclinepi.2025.111867

Abstract

Objective: Prior evidence has suggested the multisystem symptomatic manifestations of post-acute COVID-19 condition (PCC). Here we conducted a network cluster analysis of 24 World Health Organization-proposed symptoms to identify potential latent subclasses of PCC.

Study design and setting: Individuals with a positive test of or diagnosed with SARS-CoV-2 after September 2020 and with at least 1 symptom within ≥90 to 365 days following infection were included. Subanalyses were conducted among people with ≥3 different symptoms. Summary characteristics were provided for each cluster. All analyses were conducted separately in 9 databases from 7 countries, including data from primary care, hospitals, national health claims and national health registries, allowing to compare clusters across the different healthcare settings.

Results: This study included 787,078 persons with PCC. Single-symptom clusters were common across all databases, particularly for joint pain, anxiety, depression and allergy. Complex clusters included anxiety-depression and abdominal-gastrointestinal symptoms.

Conclusion: Substantial heterogeneity within and between PCC clusters was seen across health-care settings. Current definitions of PCC should be critically reviewed to reflect this variety in clinical presentation.

Keywords: Clustering; Latent class analysis; Long COVID; Post-acute COVID-19 condition; Real-world data.

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Conflict of interest statement

Declaration of competing interest D.P.A.’s department has received grant/s from Amgen, Chiesi–Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programs organized by D.P.A.'s department. R.P. reports serving on advisory boards for Gilead Sciences, Inc, Pfizer, Inc, Roche Therapeutics, MSD, GSK, ViiV Healthcare, Eli Lilly and Company, PharmaMar, and Atea Pharmaceuticals, Inc; and receiving research grants paid to his institution from MSD, ViiV Healthcare, Gilead Sciences, and PharmaMar. L.M. reports receiving grants from Grifols; receiving honoraria as a speaker from AstraZeneca, Gilead Sciences, GSK, and Pfizer; and participation in advisory boards for Gilead Sciences and Merck. M.M. works for a research group that in the past 3 years received unconditional research grants from Chiesi, UCB, Amgen, Johnson & Johnson, Innovative Medicines Initiative and the European Medicines Agency. D.Ded., Z.C. and J.O. are employees of the Medicines and Healthcare Products Regulatory Agency, which provides the CPRD research service. K.K. is a consortial author in the US National Institutes of Health National COVID Cohort Collaborative (funding expired in 2022 with no renewal or active impact on any current work). There are no competing interests for any other author.

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Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries

Affiliations

Clusters of post-acute COVID-19 symptoms: a latent class analysis across 9 databases and 7 countries

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous