Treatable traits for long COVID

Abstract

Long COVID, or post‐acute COVID‐19 sequelae, is experienced by an estimated one in eight adults following acute COVID‐19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one‐size‐fits‐all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. ‘Treatable Traits’ is a personalized medicine approach, purpose‐built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high‐quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.

Treatable traits models of care

“…Advantages of this label free approach are that the diagnosis does not need to be clearly established to commence the patient on the best treatments, as this is guided by the individuals' identified traits 1,20 . It also means that this approach is adaptable to different health care settings, 17,34 and as we have seen, to other patient populations with respiratory disease 2,3,5,35,36 …”

“…As long COVID (post‐acute COVID‐19 sequelae) is a chronic and complex condition that affects multiple organ systems it lends itself well to a treatable traits approach. In this Respirology treatable traits review series, Lewthwaite et al propose a treatable traits model for the management of long COVID 5 . Following a systematic umbrella review of the literature, the authors propose eight prevalent long COVID clusters, rather than the typical three domains of pulmonary, extra‐pulmonary and behavioural/lifestyle/risk‐factors.…”

“…1,20 It also means that this approach is adaptable to different health care settings, 17,34 and as we have seen, to other patient populations with respiratory disease. 2,3,5,35,36 The first RCT of a comprehensive treatable traits model of care was in a tertiary care population of adults with severe asthma. 26 Traits were identified using a multidimensional assessment, a multidisciplinary care plan targeting the traits was developed and implemented using a shared decision approach (described later).…”

“…In this Respirology treatable traits review series, Lewthwaite et al propose a treatable traits model for the management of long COVID. 5 Following a systematic umbrella review of the literature, the authors propose eight prevalent long COVID clusters, rather than the typical three domains of pulmonary, extra-pulmonary and behavioural/lifestyle/risk-factors.…”

“…Treatable traits is an approach to personalized management of patients with respiratory diseases. Originally proposed for the management of asthma and chronic obstructive pulmonary disease (COPD), 1 the approach has since been recommended in other areas of respiratory and now immunology including bronchiectasis, 2 interstitial lung disease, 3,4 long COVID, 5 systemic sclerosis 6 among other conditions 7 . Since the first publication using the term ‘treatable traits’ in 2016, 1 there has been a rapid increase in new publications of this approach.…”