Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review

Julian Gutzeit^{1

2}, M Weiß^{3

4}, C Nürnberger⁵, C Lemhöfer⁶, K S Appel^{7

8}, E Pracht⁸, J-P Reese⁵, C Lehmann^{8

9

10}, M C Polidori^{11

12}, G Hein³, J Deckert³

Affiliations

¹ Center of Mental Health, Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany. Gutzeit_j1@ukw.de.
² Department of Psychology III - Psychological Methods, Cognition, and Applied Research, Julius-Maximilians-Universität Würzburg, Röntgenring 11, 97070, Würzburg, Germany. Gutzeit_j1@ukw.de.
³ Center of Mental Health, Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
⁴ Department of Psychology I - Biological Psychology, Clinical Psychology and Psychotherapy, Julius-Maximilians-Universität Würzburg, Marcusstraße 11, 97070, Würzburg, Germany.
⁵ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
⁶ Institute for Physical and Rehabilitative Medicine, University Hospital Jena, Jena, Germany.
⁷ Center for Internal Medicine, Medical Department 2 (Hematology/Oncology and Infectious Diseases), Goethe University Frankfurt, University Hospital, Frankfurt, Germany.
⁸ Faculty of Medicine and University Hospital Cologne, Department I for Internal Medicine, University of Cologne, Cologne, Germany.
⁹ German Center for Infection Research, Partner site Bonn-Cologne, Cologne, Germany.
¹⁰ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
¹¹ Aging Clinical Research, Department II of Internal Medicine, Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Herderstraße 52, 50931, Cologne, Germany.
¹² Cologne Excellence Cluster on Cellular Stress- Responses in Aging- Associated Diseases (CECAD), Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany.

PMID: 39052056
PMCID: PMC11799012
DOI: 10.1007/s00406-024-01868-y

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review

Julian Gutzeit et al. Eur Arch Psychiatry Clin Neurosci. 2025 Feb.

. 2025 Feb;275(1):129-140.

doi: 10.1007/s00406-024-01868-y. Epub 2024 Jul 25.

Authors

Julian Gutzeit^{1

2}, M Weiß^{3

4}, C Nürnberger⁵, C Lemhöfer⁶, K S Appel^{7

8}, E Pracht⁸, J-P Reese⁵, C Lehmann^{8

9

10}, M C Polidori^{11

12}, G Hein³, J Deckert³

Affiliations

¹ Center of Mental Health, Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany. Gutzeit_j1@ukw.de.
² Department of Psychology III - Psychological Methods, Cognition, and Applied Research, Julius-Maximilians-Universität Würzburg, Röntgenring 11, 97070, Würzburg, Germany. Gutzeit_j1@ukw.de.
³ Center of Mental Health, Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
⁴ Department of Psychology I - Biological Psychology, Clinical Psychology and Psychotherapy, Julius-Maximilians-Universität Würzburg, Marcusstraße 11, 97070, Würzburg, Germany.
⁵ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
⁶ Institute for Physical and Rehabilitative Medicine, University Hospital Jena, Jena, Germany.
⁷ Center for Internal Medicine, Medical Department 2 (Hematology/Oncology and Infectious Diseases), Goethe University Frankfurt, University Hospital, Frankfurt, Germany.
⁸ Faculty of Medicine and University Hospital Cologne, Department I for Internal Medicine, University of Cologne, Cologne, Germany.
⁹ German Center for Infection Research, Partner site Bonn-Cologne, Cologne, Germany.
¹⁰ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
¹¹ Aging Clinical Research, Department II of Internal Medicine, Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Herderstraße 52, 50931, Cologne, Germany.
¹² Cologne Excellence Cluster on Cellular Stress- Responses in Aging- Associated Diseases (CECAD), Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany.

PMID: 39052056
PMCID: PMC11799012
DOI: 10.1007/s00406-024-01868-y

Abstract

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.

Keywords: Diagnostic criteria; Fatigue; Long COVID; Neurological complaints; Post-COVID syndrome (PCS); Systematic review.

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Conflict of interest statement

Declarations. Competing interests: JG receives funding from the Nationales Pandemie Kohorten Netz - Therapeutische Interventionsplattform (NAPKON-TIP) network, which is funded by the Federal Ministry of Education and Research. R.P. is supported by grants in the projects COMPASS and NAPKON. The COMPASS and NAPKON projects are part of the German COVID-19 Research Network of University Medicine (“Netzwerk Universitätsmedizin”), funded by the German Federal Ministry of Education and Research (funding reference 01KX2021). MW has nothing to disclose. CN has nothing to disclose. CL (University Hospital Jena) received institutional funding from Federal Joint Committee (G-BA) within the Innovationfond (WATCH, Grant numbers L01NVF22114), Editorial Board Member of ‘Physikalische Medizin, Rehabilitationsmedizin, Kurortmedizin’, Network University Medicine (NUM)/ German Federal Ministry of Education and Research (BMBF) - Speaker Physical and Rehabilitation Group (unpaid), board member of German Society of Physical and Rehabilitation Medicine (Deutsche Gesellschaft für Physikalische und Rehabilitative Medizin e.V. (DGPRM), unpaid). KA has nothing to disclose. EP has nothing to disclose. JPR reports grants from the German Ministry of Research and Education within NUM, CAEHR, RECAP; grants from Bavarian State (ministry for science and the arts, DigiOnko), grants from Federal Joint Committee (G-BA) within the Innovationfond (Peri-OP, StarkeR), grants from the German Center for Lung Research within PASSION, personal fees and fees for EBM Training Lecture from the Landesaerztekammer Hessen. CL (University of Cologne) has nothing to disclose. MPN has nothing to disclose. GH has nothing to disclose; JD is an investigator in the EU-Horizon-funded Predict Study of P1Vital and Co-Applicant with BioVariance in the InDepth Study funded by the Bavarian State Government. All other authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript, except for the Network University Medicine.

Figures

**Fig. 1**
Flow chart of study selection process according to eligibility criteria

**Fig. 2**
Proportions and absolute values (number next to point) of used definitions in each study. Some studies used multiple definitions. WHO = World Health Organization, NICE = National Institute for Health and Care Excellence, CDC = Centers for Disease Control and Prevention, NIH = National Institutes of Health

**Fig. 3**
Proportions and absolute values (number next to point) of studies reporting on each symptom, on quality of life (QOL), and on functional assessments

See this image and copyright information in PMC

References

1. World Health Organization. WHO COVID-19 dashboard. WHO COVID-19 dashboard. Published January 22 (2024) Accessed January 22, 2024. https://data.who.int/dashboards/covid19/cases
1. Phillips N (2021) The coronavirus is here to stay — here’s what that means. Nature 590(7846):382–384. 10.1038/d41586-021-00396-2 - PubMed
1. Nalbandian A, Sehgal K, Gupta A et al (2021) Post-acute COVID-19 syndrome. Nat Med 27(4):601–615. 10.1038/s41591-021-01283-z - PMC - PubMed
1. Lemhöfer C, Appel KS, Häuser W, Hettich N, Kohls M, Polidori MC (2022) Post-COVID: Alles Eine Frage Der Definition? DMW - Dtsch Med Wochenschr 147(21):1391–1397. 10.1055/a-1940-1222 - PubMed
1. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B (2022) Global prevalence of Post-coronavirus Disease 2019 (COVID-19) Condition or Long COVID: a Meta-analysis and systematic review. J Infect Dis 226(9):1593–1607. 10.1093/infdis/jiac136 - PMC - PubMed

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Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review

Affiliations

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

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Medical

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