Characterising long COVID: a living systematic review

Melina Michelen, Lakshmi Manoharan, Natalie Elkheir, Vincent Cheng, Andrew Dagens, Claire Hastie, Margaret O'Hara, Jake Suett, Dania Dahmash, Polina Bugaeva, Ishmeala Rigby, Daniel Munblit, Eli Harriss, Amanda Burls, Carole Foote, Janet Scott, Gail Carson, Piero Olliaro, Louise Sigfrid, Charitini Stavropoulou, Melina Michelen, Lakshmi Manoharan, Natalie Elkheir, Vincent Cheng, Andrew Dagens, Claire Hastie, Margaret O'Hara, Jake Suett, Dania Dahmash, Polina Bugaeva, Ishmeala Rigby, Daniel Munblit, Eli Harriss, Amanda Burls, Carole Foote, Janet Scott, Gail Carson, Piero Olliaro, Louise Sigfrid, Charitini Stavropoulou

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.

Keywords: COVID-19; public health; systematic review.

Conflict of interest statement

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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Map of study distribution.
Figure 2
Figure 2
Long COVID signs and symptoms.
Figure 3
Figure 3
Signs and symptoms in all studies. RoB, risk of bias.
Figure 4
Figure 4
Sign and symptoms in hospitalised and non-hospitalised cohorts. Note: The data on sign and symptoms from studies with data on hospitalised or non-hospitalised cohorts, it does not include studies that included mixed cohorts without subcategorisation. PTSD, post-traumatic stress disorder.

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