Characterising long term Covid-19: a living systematic review
Authors: Michelen Melina , Cheng Vincent , Manoharan Lakshmi , Elkheir Natalie , Dagens Drew , Hastie Claire , O’Hara Margaret , Suett Jake C. , Dahmash Dania T. , Bugaeva Polina , Rigby Ishmeala , Munblit Daniel , Harriss Eli , Burls Amanda , Foote Carol , Scott Janet T. , Carson Gail , Olliaro Piero , Sigfrid Louise , Stavropoulou Charitini 
Published: December 2020

Background

While it is now apparent clinical sequelae (often called 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 inform clinical management, rehabilitation, and interventional studies to improve long term outcomes.

Methods

A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research Database on Covid-19, LitCOVID, and Google Scholar were searched up to 17th March 2021. Published studies including at least 100 people with confirmed or clinically suspected Covid-19 at 12 weeks or more post-onset were included. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence with 95% confidence intervals (CIs).

Results

Thirty-nine studies were included: 32 cohort, six cross-sectional, and one case-control. Most showed high or moderate risk of bias. None were set in low-income countries, limited studies included children. Studies reported on 10,951 people (48% female) in 12 countries. Most followed-up post hospital discharge (78%, 8520/10951). The longest mean follow-up was 221.7 (SD: 10.9) days post Covid-19 onset. An extensive range of symptoms with wide prevalence was reported, most commonly weakness (41%; 95% CI 25% to 59%), 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%). Other frequent symptoms included musculoskeletal, neurological, and psychological. 37% (95% CI 18% to 60%) of people reported reduced quality of life.

Conclusion

Long Covid is a complex condition with heterogeneous symptoms. The nature of the studies precludes a precise case definition or evaluation of risk factors. 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.

Systematic review registration

The protocol was prospectively registered on the PROSPERO database (CRD42020211131).

Section 1: What is already known?

A significant number of people continue to describe ongoing symptoms long after the acute phase of Covid-19, often referred to as Long Covid.

Long Covid is a heterogeneous condition with an uncertain prevalence, for which there is currently no precise case definition.

Section 2: What are the new findings?

This ‘living’ systematic review provides a comprehensive summary of peer-reviewed published evidence on persistent symptoms of Covid-19 and will be regularly updated as new evidence emerges.

The breadth of reported symptoms suggests a complex, heterogeneous condition affecting both those who were hospitalised and those managed in the community.

Our review identifies weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% confidence interval 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%) as the most common symptoms.

Section 3: What do the new findings imply?

The current evidence base of the clinical spectrum of Long Covid is limited, based on heterogenous data, and vulnerable to biases, hence caution should be used when interpreting or generalising the results.

Our review identifies areas where further Long Covid research is critically needed to help characterise Long Covid in different populations and define its aetiology, risk factors, and biomarkers, as well as the impact on variants of concern and vaccination on long term outcomes.