Meta-Analysis

. 2025 May 7;16(1):4249.

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^#¹, Ash Routen^#¹, Clare Gillies^{1

2}, Sian A Jenkins³, Abdullah Almaqhawi⁴, Daniel Ayoubkhani^{2

5}, Amitava Banerjee^{6

7}, Chris Brightling⁸, Melanie Calvert^{9

10

11}, Shabana Cassambai¹, Winifred Ekezie¹², Mark P Funnell¹, Anneka Welford¹, Arron Peace¹, Rachael A Evans^{8

13}, Shavez Jeffers¹, Andrew P Kingsnorth¹⁴, Manish Pareek^{8

15}, Samuel Seidu¹, Thomas J Wilkinson¹, Andrew Willis¹⁶, Roz Shafran¹⁷, Terence Stephenson¹⁷, Jonathan Sterne¹⁸, Helen Ward¹⁹, Tom Ward⁸, Kamlesh Khunti²⁰

Affiliations

¹ Diabetes Research Centre, University of Leicester, Leicester, UK.
² Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK.
³ School of Psychology and Vision Sciences, University of Leicester, Leicester, UK.
⁴ Department of Family and Community Medicine, College of Medicine, King Faisal University, Al Hofuf, Saudi Arabia.
⁵ Office for National Statistics, Government Buildings, Newport, UK.
⁶ Faculty of Population Health Sciences, Institute of Health Informatics, University College London, London, UK.
⁷ Department of Population Science and Experimental Medicine, University College London, London, UK.
⁸ Department of Respiratory Sciences, University of Leicester, Leicester, UK.
⁹ Department of Applied Health Sciences, University of Birmingham, Birmingham, UK.
¹⁰ NIHR Birmingham Biomedical Research Centre and NIHR Applied Research Collaboration West Midlands, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
¹¹ Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK.
¹² School of Social Sciences and Humanities, Aston University, Birmingham, UK.
¹³ NIHR Leicester Biomedical Research Centre, Respiratory Department, University Hospitals of Leicester NHS Trust, Leicester, UK.
¹⁴ School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.
¹⁵ Development Centre for Population Health, University of Leicester, Leicester, UK.
¹⁶ School of Public Health, University College Cork, Cork, Ireland.
¹⁷ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹⁸ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁹ Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
²⁰ Diabetes Research Centre, University of Leicester, Leicester, UK. kk22@leicester.ac.uk.

^# Contributed equally.

PMID: 40335476
PMCID: PMC12059169
DOI: 10.1038/s41467-025-59012-w

Meta-Analysis

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

Lauren L O'Mahoney et al. Nat Commun. 2025.

. 2025 May 7;16(1):4249.

doi: 10.1038/s41467-025-59012-w.

Authors

Affiliations

¹ Diabetes Research Centre, University of Leicester, Leicester, UK.
² Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK.
³ School of Psychology and Vision Sciences, University of Leicester, Leicester, UK.
⁴ Department of Family and Community Medicine, College of Medicine, King Faisal University, Al Hofuf, Saudi Arabia.
⁵ Office for National Statistics, Government Buildings, Newport, UK.
⁶ Faculty of Population Health Sciences, Institute of Health Informatics, University College London, London, UK.
⁷ Department of Population Science and Experimental Medicine, University College London, London, UK.
⁸ Department of Respiratory Sciences, University of Leicester, Leicester, UK.
⁹ Department of Applied Health Sciences, University of Birmingham, Birmingham, UK.
¹⁰ NIHR Birmingham Biomedical Research Centre and NIHR Applied Research Collaboration West Midlands, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
¹¹ Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient Reported Outcomes Research, University of Birmingham, Birmingham, UK.
¹² School of Social Sciences and Humanities, Aston University, Birmingham, UK.
¹³ NIHR Leicester Biomedical Research Centre, Respiratory Department, University Hospitals of Leicester NHS Trust, Leicester, UK.
¹⁴ School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.
¹⁵ Development Centre for Population Health, University of Leicester, Leicester, UK.
¹⁶ School of Public Health, University College Cork, Cork, Ireland.
¹⁷ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹⁸ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁹ Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
²⁰ Diabetes Research Centre, University of Leicester, Leicester, UK. kk22@leicester.ac.uk.

^# Contributed equally.

PMID: 40335476
PMCID: PMC12059169
DOI: 10.1038/s41467-025-59012-w

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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Conflict of interest statement

Competing interests: A.B. is PI of the NIHR-funded STIMULATE-ICP study (COV-LT2-0043) and has also received other research funding from Astra Zeneca, NIHR, BMA, UKRI and EU. M.C. is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research and is a National Institute for Health Research (NIHR) Senior Investigator. MC receives funding from the National Institute for Health Research (NIHR), UK Research and Innovation (UKRI), NIHR Birmingham Biomedical Research Centre, the NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, UK SPINE, European Regional Development Fund – Demand Hub and Health Data Research UK at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, Janssen, GSK and Gilead. She is the senior author of the Symptom Burden Questionnaire™ for Long COVID. M.C. has received personal fees from Aparito Ltd, CIS Oncology, Takeda, Merck, Daiichi Sankyo, Glaukos, GSK and the Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work. In addition, a family member owns shares in GSK. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health (R.S. and T.S.). T.S. is Chair of the Health Research Authority for England and recused himself from all Research Ethics Applications. H.W. is an NIHR Senior Investigator Award and acknowledges support from the NIHR Imperial Biomedical Research Centre, Health Data Research UK, NIHR Applied Research Collaborative North West London, and the Wellcome Trust. K.K. is Chair of the Ethnicity Subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and Member of SAGE and also Chair of the National Long Covid Research Working Group which informs the Chief Medical Officer. K.K. has acted as a consultant, speaker or received grants for investigator-initiated studies for Astra Zeneca, Sanofi-Aventis, Pfizer and Roche. The remaining authors declare no competing interests.

Figures

**Fig. 1. PRISMA flow diagram.**
This diagram shows the systematic process we followed to include papers captured by our search, 48,104 records were screened and 50 studies included in the final review.

**Fig. 2. Forest plot of pooled relative risks for each symptom in all populations combined.**
The figure illustrates pooled relative risks and associated 95% confidence intervals for each symptom using random effects models. All tests were 2-sided and no adjustment was made for multiple comparisons. Heterogeneity was assessed using Higgins I² statistic (I² between 75% and 100% indicates considerable between study heterogeneity).

See this image and copyright information in PMC

References

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1. O’Mahoney, L. L. et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis. eClinicalMedicine55, 101762 (2023). - PMC - PubMed
1. Natarajan, A. et al. A systematic review and meta-analysis of long COVID symptoms. Syst. Rev.12, 88 (2023). - PMC - PubMed
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The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous