The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies

Lauren L. O’Mahoney; Ash Routen; Clare Gillies; Sian A. Jenkins; Abdullah Almaqhawi; Daniel Ayoubkhani; Amitava Banerjee; Chris Brightling; Melanie Calvert; Shabana Cassambai; Winifred Ekezie; Mark P. Funnell; Anneka Welford; Arron Peace; Rachael A. Evans; Shavez Jeffers; Andrew P. Kingsnorth; Manish Pareek; Samuel Seidu; Thomas J. Wilkinson; Andrew Willis; Roz Shafran; Terence Stephenson; Jonathan Sterne; Helen Ward; Tom Ward; Kamlesh Khunti

doi:10.1038/s41467-025-59012-w

The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies

Lauren L. O’Mahoney
, Ash Routen
, Clare Gillies
, Sian A. Jenkins
, Abdullah Almaqhawi
, Daniel Ayoubkhani
, Amitava Banerjee
, Chris Brightling
, Melanie Calvert
, Shabana Cassambai
, Winifred Ekezie
, Mark P. Funnell
, Anneka Welford
, Arron Peace
, Rachael A. Evans
, Shavez Jeffers
, Andrew P. Kingsnorth
, Manish Pareek
, Samuel Seidu
, Thomas J. Wilkinson

Andrew Willis, Roz Shafran, Terence Stephenson, Jonathan Sterne, Helen Ward, Tom Ward, Kamlesh Khunti^*

^*Corresponding author for this work

University of Leicester, Diabetes Research Centre, Leicester, UK, ROR: https://ror.org/04h699437, GRID: grid.9918.9, ISNI: 0000 0004 1936 8411
University of Leicester, Leicester Real World Evidence Unit, Diabetes Research Centre, Leicester, UK, ROR: https://ror.org/04h699437, GRID: grid.9918.9, ISNI: 0000 0004 1936 8411
University of Leicester, School of Psychology and Vision Sciences, Leicester, UK, ROR: https://ror.org/04h699437, GRID: grid.9918.9, ISNI: 0000 0004 1936 8411
King Faisal University, Department of Family and Community Medicine, College of Medicine, Al Hofuf, Saudi Arabia, ROR: https://ror.org/00dn43547, GRID: grid.412140.2, ISNI: 0000 0004 1755 9687
Government Buildings, Office for National Statistics, Newport, UK, ROR: https://ror.org/021fhft25, GRID: grid.426100.1, ISNI: 0000 0001 2157 6840
University College London, Department of Population Science and Experimental Medicine, London, UK, ROR: https://ror.org/02jx3x895, GRID: grid.83440.3b, ISNI: 0000 0001 2190 1201
University of Leicester, Department of Respiratory Sciences, Leicester, UK, ROR: https://ror.org/04h699437, GRID: grid.9918.9, ISNI: 0000 0004 1936 8411
University of Birmingham, Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient Reported Outcomes Research, Birmingham, UK, ROR: https://ror.org/03angcq70, GRID: grid.6572.6, ISNI: 0000 0004 1936 7486
University Hospitals of Leicester NHS Trust, NIHR Leicester Biomedical Research Centre, Respiratory Department, Leicester, UK, ROR: https://ror.org/02fha3693, GRID: grid.269014.8, ISNI: 0000 0001 0435 9078
Loughborough University, School of Sport, Exercise and Health Sciences, Loughborough, UK, ROR: https://ror.org/04vg4w365, GRID: grid.6571.5, ISNI: 0000 0004 1936 8542
University of Leicester, Development Centre for Population Health, Leicester, UK, ROR: https://ror.org/04h699437, GRID: grid.9918.9, ISNI: 0000 0004 1936 8411
University College Cork, School of Public Health, Cork, Ireland, ROR: https://ror.org/03265fv13, GRID: grid.7872.a, ISNI: 0000 0001 2331 8773
University College London, Great Ormond Street Institute of Child Health, London, UK, ROR: https://ror.org/02jx3x895, GRID: grid.83440.3b, ISNI: 0000 0001 2190 1201
University of Bristol, Population Health Sciences, Bristol Medical School, Bristol, UK, ROR: https://ror.org/0524sp257, GRID: grid.5337.2, ISNI: 0000 0004 1936 7603
Imperial College London, Faculty of Medicine, School of Public Health, London, UK, ROR: https://ror.org/041kmwe10, GRID: grid.7445.2, ISNI: 0000 0001 2113 8111

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Abstract

The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.

Original language	English
Article number	4249
Number of pages	8
Journal	Nature Communications
Volume	16
DOIs	https://doi.org/10.1038/s41467-025-59012-w
Publication status	Published - 7 May 2025

Bibliographical note

Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Data Access Statement

The dataset generated during and analysed during the current study are available in the Figshare repository (https://doi.org/10.6084/m9.figshare.28695185.v1).

Funding

This work is funded by National Institute for Health and Care Research Applied Research Collaboration East Midlands NIHR ARC East Midlands). K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC). S.J. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM). We would also like to thank academic librarian Keith Nockels for his assistance with the searches. This review was part funded by PHOSP-COVID. PHOSP-COVID is jointly funded by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19 (grant references: MR/V027859/1 and COV0319). The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.

Keywords

COVID-19/epidemiology
Humans
Post-Acute COVID-19 Syndrome/epidemiology
Risk Factors
SARS-CoV-2/pathogenicity

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10.1038/s41467-025-59012-wLicence: CC BY 4.0

The risk of Long Covid symptoms
Copyright © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
Final published version, 834 KBLicence: CC BY 4.0

Cite this

O’Mahoney, L. L., Routen, A., Gillies, C., Jenkins, S. A., Almaqhawi, A., Ayoubkhani, D., Banerjee, A., Brightling, C., Calvert, M., Cassambai, S., Ekezie, W., Funnell, M. P., Welford, A., Peace, A., Evans, R. A., Jeffers, S., Kingsnorth, A. P., Pareek, M., Seidu, S., ... Khunti, K. (2025). The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies. Nature Communications, 16, Article 4249. https://doi.org/10.1038/s41467-025-59012-w

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abstract = "The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95\% CI 2.66, 6.99), loss of taste (RR 3.71; 95\% CI 2.22, 7.26), poor concentration (RR 2.68; 95\% CI 1.66, 4.33), impaired memory (RR 2.53; 95\% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95\% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.",

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O’Mahoney, LL, Routen, A, Gillies, C, Jenkins, SA, Almaqhawi, A, Ayoubkhani, D, Banerjee, A, Brightling, C, Calvert, M, Cassambai, S, Ekezie, W, Funnell, MP, Welford, A, Peace, A, Evans, RA, Jeffers, S, Kingsnorth, AP, Pareek, M, Seidu, S, Wilkinson, TJ, Willis, A, Shafran, R, Stephenson, T, Sterne, J, Ward, H, Ward, T & Khunti, K 2025, 'The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies', Nature Communications, vol. 16, 4249. https://doi.org/10.1038/s41467-025-59012-w

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The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies

Abstract

Bibliographical note

Data Access Statement

Funding

Keywords

Access to Document

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