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Characterising long COVID: a living systematic review
  1. Melina Michelen1,2,
  2. Lakshmi Manoharan2,
  3. Natalie Elkheir3,
  4. Vincent Cheng4,
  5. Andrew Dagens2,
  6. Claire Hastie5,
  7. Margaret O'Hara5,
  8. Jake Suett6,
  9. Dania Dahmash2,
  10. Polina Bugaeva7,
  11. Ishmeala Rigby2,
  12. Daniel Munblit8,9,10,
  13. Eli Harriss11,
  14. Amanda Burls1,
  15. Carole Foote12,
  16. Janet Scott13,
  17. Gail Carson2,
  18. Piero Olliaro2,
  19. Louise Sigfrid2,
  20. Charitini Stavropoulou1
  1. 1School of Health Sciences, City University of London, London, UK
  2. 2ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
  3. 3Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
  4. 4Bristol Medical School, University of Bristol, Bristol, UK
  5. 5Long Covid Support, Birmingham, UK
  6. 6Anaesthetic Department, Queen Elizabeth Hospital, Kings Lynn, UK
  7. 7Julius-Maximilians-Universität Würzburg, Würzburg, Bayern, Germany
  8. 8Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
  9. 9Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK
  10. 10Research and Clinical Center for Neuropsychiatry, Moscow, Russia
  11. 11Bodleian Health Care Libraries, University of Oxford, Oxford, UK
  12. 12Freelance, Soquel, California, USA
  13. 13MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Charitini Stavropoulou; C.Stavropoulou{at}city.ac.uk

Abstract

Background While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.

Methods A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.

Results A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case–control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.

Conclusion Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.

PROSPERO registration number CRD42020211131.

  • COVID-19
  • public health
  • systematic review

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

http://dx.doi.org/10.1136/bmjgh-2021-005427

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • LS and CS are joint senior authors.

    • Handling editor Seye Abimbola

    • LM, NE, VC and AD contributed equally.

    • Contributors MM, CS, VC and LS developed the concept of the study and led on the development of the protocol in collaboration with EH and members of the Long Covid Support Group (CH, MO, JSuett). MM, CS and LS led on the drafting of the manuscript with contributions from all coauthors. EH, VC and MM performed the online searches. MM, CS, NE and LM screened the articles for inclusion. MM, CS and PB extracted data from the included articles. DD, IR and CS critically appraised the studies. VC led on the meta-analysis and presentation of the figures, in collaboration with MM, DD, VC, NE, LM, CH, MO, JScott, DD, PB, IR, DM, AJEB, CF, GC, PO, CS and LS, who helped inform the analysis, interpretation of the results and formulation of recommendations. All coauthors reviewed and approved the manuscript.

    • Funding This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z), the Bill & Melinda Gates Foundation (OPP1209135) and the EU FP7 project PREPARE (602525).

    • Competing interests JSuett declares he is an individual living with long-term symptoms of probably COVID-19. All other authors declare no other relationships or activities that could appear to have influenced the submitted work.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.