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Multiple long-term conditions (MLTCs) or “multimorbidity”, defined as two or more long-term conditions (LTCs), increase in prevalence and burden with ageing. Living with MLTCs reduces functional capacity and health-related quality of life, increases healthcare utilisation and costs, and increases all-cause mortality [1–3]. Adults living with pre-existing MLTCs are at increased risk of both developing severe coronavirus disease 2019 (COVID-19) after contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [4] and of persistent and more severe sequalae post-COVID-19 [5–7]. Specific underlying LTCs and MLTCs may exacerbate pathological mechanisms or reduce an individuals resilience against organ injury associated with COVID-19 and post-acute sequalae [8]. Long COVID (or “post COVID-19 condition” as defined by the World Health Organization (WHO) [9]) is a multisystemic condition encompassing a wide range of physical and psychosocial consequences with potentially compounding impacts for individuals with pre-existing MLTCs.
Individualised exercise-based (physical) rehabilitation has an established role in the management of a large number of LTCs [10]. In people living with MLTCs, exercise-based interventions have been reported to improve health-related quality of life and physical function, and reduce symptoms of anxiety and depression [11]. In clinical practice, the provision of generally single-condition-focused rehabilitation programmes and the heterogeneity of MLTCs [12] have implications for selection and tailoring of interventions for people with MLTCs. Other rehabilitation strategies include active mind–body movement interventions, e.g. yoga, Tai Chi and dance, where there is a growing body of evidence they improve health and wellbeing outcomes of people living with several specific LTCs [13–18].
In long COVID, multiple single-site, small randomised controlled trials of physical (exercise- and physical activity-based) rehabilitation interventions have demonstrated potential to improve functional exercise capacity and health-related quality of life for some adults with long COVID [19, 20]. Whilst largely positive, meta-analyses to date have been limited by small sample sizes and heterogeneity of both interventions and outcome measures [19–22].
A growing body of evidence has identified distinct symptom groups and phenotypes of long COVID [23]. Some of these phenomena, such as dysautonomia, postural orthostatic tachycardia syndrome (POTS), breathing pattern disorder and post-exertional symptom exacerbation (PESE), may challenge or limit physical rehabilitation similar to myalgic encephalomyelitis/chronic fatigue syndrome. Furthermore, health inequalities are associated with both MLTCs and long COVID, e.g. socioeconomic deprivation is associated with a higher prevalence of MLTCs [12] and incidence of long COVID after SARS-CoV-2-infection [5, 24]. Health and digital literacy, and practical aspects such as transport costs, may affect engagement, uptake and completion of rehabilitation programmes for long COVID. There are therefore likely to be additional rehabilitation needs and challenges for people with both pre-existing MLTCs and long COVID.
Whether physical rehabilitation interventions for long COVID are suitable, accessible, acceptable and effective in improving the health and wellbeing of individuals with pre-existing MLTCs is currently unclear. The presence of MLTCs may influence the selection and tailoring of appropriate rehabilitation interventions, and therefore reporting of pre-existing MLTCs is required for the evaluation of long COVID rehabilitation interventions. However, in available studies the results of rehabilitation interventions for people living with long COVID did not appear to be commonly reported according to individuals with and without pre-existing LTCs, and therefore a systematic review of the impact of pre-existing MLTCs is not currently possible. We therefore need to understand how pre-existing MLTCs are reported in the available evidence describing physical rehabilitation interventions for adults living with long COVID, and where MLTCs are reported, to understand the characteristics of the interventions and outcomes. This scoping review therefore aims to systematically map the extent and nature of reporting of pre-existing MLTCs within the available evidence for physical rehabilitation interventions for adults living with long COVID, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing LTCs and long COVID. Any gaps in the literature will be identified to inform recommendations for reporting of pre-existing MLTCs in long COVID rehabilitation research.
MethodsThe search methods and results are reported in accordance with the latest Joanna Briggs Institute (JBI) guidance for scoping reviews [25] and the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist [26] (see supplementary material).
Protocol and registrationThe protocol was registered on the Open Science Framework [27].
Eligibility criteriaParticipantsEligibility criteria included adults (aged ≥18 years) living with “long COVID” (or “post COVID-19 condition” or “post COVID-19 syndrome”) defined in accordance with the WHO clinical case definition [9]:
“… occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others which generally have an impact on everyday functioning”.
ConceptRehabilitation interventions including a physical activity component defined as repetitive whole-body movement [28] including but not limited to structured exercise (e.g. walking and Tai Chi) were considered for this review. The intervention could be physical only or physical in addition to psychosocial, educational, pharmaceutical and/or other adjunct interventions. The intervention could be supervised (including remote delivery, e.g. via video conferencing) or unsupervised, in any setting (e.g. hospital, community and home-based) and of any duration. Intervention timing is reported according to the length of time post-SARS-CoV-2 infection where available.
ContextNo contextual limitations (e.g. geographical location or care setting) were applied in this review.
Types of evidence sourcesStudy designs that examine interventions or intervention content (e.g. controlled trials, crossover/cluster designs, cohort studies and qualitative studies relating to interventions), systematic literature reviews (e.g. systematic reviews and scoping reviews) and clinical guidelines were included. Case series and case reports were excluded. Relevant opinion-based pieces (e.g. editorials and letters) were used for reference checking only. Clinical guidelines specifically focused on long COVID rehabilitation were included. No other restrictions were placed in terms of study design or the form of article (e.g. quantitative or qualitative, or published or unpublished (where available)). Translation software was used to translate non-English articles to English.
Information sourcesMEDLINE, CINAHL, Scopus, APA PsycInfo, medRxiv (preprint server), OpenGrey and MedNar (grey literature databases) were searched, and manual searching of relevant grey literature (for relevant reports, doctoral theses and clinical guidelines) was conducted. Reference lists of included articles were checked for possible additional articles.
Databases were searched from 1 January 2020 (following identification of the SARS-CoV-2 virus) to 11 July 2023.
Search strategyThe key concepts of long COVID (informed by a relevant recent systematic review [29]) and physical rehabilitation interventions were used to frame the search strategy (see supplementary material).
Following removal of duplicates, screening of titles/abstracts and full-text articles for eligibility was conducted by two independent authors (L. Gardiner and either H.M.L. Young or H. Drover or E. Morgan-Selvaratnam). Screening took place in Covidence (www.covidence.org), a web-based collaboration software platform that streamlines the production of systematic and other literature reviews. Disagreements between reviewers were resolved through discussion (L. Gardiner, H.M.L. Young, H. Drover and E. Morgan-Selvaratnam).
Data extractionData were extracted from articles included in the scoping review by two independent reviewers (L. Gardiner and either H.M.L. Young or H. Drover or E. Morgan-Selvaratnam) using a data extraction tool developed within Covidence (see supplementary material) informed by the research questions, the JBI Manual for Evidence Synthesis [25], the TIDieR (Template for Intervention Description and Replication) checklist [30] and the CERT (Consensus on Exercise Reporting Template) [31].
Country of article origin and associated income classification was reported in accordance with the latest World Bank classification [32].
Where pre-existing LTCs were reported, the tool facilitated the collection of data regarding how pre-existing LTCs are described (number, type, specific named conditions and severity, and weighted measure) and whether individuals with pre-existing LTCs were analysed or considered separately from those without. Further to characteristics of associated long COVID physical rehabilitation interventions (including type of physical activity, timing post-SARS-CoV-2 infection, and mode and setting of intervention delivery and adjunctive interventions), domains of outcome measures reported (e.g. exercise capacity and health-related quality of life) were also extracted. Three reviewers (L. Gardiner, H.M.L. Young and H. Drover) each piloted the data extraction tool on three articles before wider use. Refinements included adding “reporting of severity of pre-existing LTCs” and “number of long COVID participants” (additional to “total number of participants”) to cater for studies that included individuals with acute/post-acute COVID-19 (as well as long COVID). Disagreements between reviewers were resolved through discussion.
Owing to apparent inconsistency in the use of pre-existing LTC-related terminologies and associated definitions, a decision was made to adopt an inclusive approach (i.e. include any terminology that may be considered pre-existing LTCs, such as “comorbidities” and “coexisting disease”). Due to limited ability to discern individuals with two or more pre-existing LTCs (from those with a single LTC), a further decision was made to report on all applicable studies that reported or referred to pre-existing LTCs.
Data analysis and presentationMicrosoft Excel (www.microsoft.com) was used to map the extracted data to highlight the extent and nature of existing evidence and gaps in the literature in accordance with the research question. Extracted data were organised according to associated research questions. Characteristics of eligible articles were summarised using simple descriptive statistics (k=number of articles and n=number of participants). A results-based convergent synthesis design was employed [33] informed by the research questions. Quantitative and qualitative data were analysed separately and presented using tables, figures and narrative summary (organised by research questions). A mixed methods joint display [34] was used to present integrated findings. Data visualisation software Flourish (https://flourish.studio) was used to create figures.
ResultsFollowing removal of duplicates, the search strategy yielded a total of 5326 titles and abstracts. Following screening, 130 full texts were assessed for eligibility, of which 50 eligible articles were identified [35–84] (figure 1 [85]).
FIGURE 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram summarising the identification of articles [85].
Characteristics of articlesA summary of the characteristics of the 50 eligible articles is provided in the supplementary material. All articles were published between 2021 and 2023, and the majority (k=41 (82%)) originated from high-income countries. The number of participants for individual studies ranged from n=5 to n=8724. The eligible articles included eight systematic literature reviews including two protocols, 11 randomised control trials including five protocols, two randomised feasibility studies, seven non-randomised experimental studies including one protocol, 15 cohort studies, two case–control studies, two mixed methods studies, one care pathway development and two consensus statements.
Reporting of pre-existing MLTCsOf the 50 eligible articles, 25 (50%) [36, 37, 39, 42, 43, 45–47, 49, 51, 53–55, 58–60, 62, 70–72, 75, 76, 78, 80, 83] reported or referred to pre-existing LTCs and five (10%) [40, 44, 65, 74, 79] excluded several listed pre-existing LTCs within their eligibility criteria (see supplementary material). One study (4%) [43] reported single pre-existing LTCs but excluded individuals with MLTCs. The majority referred to pre-existing LTCs as “comorbidities” (k=20/25 (80%)). Four protocols [39, 47, 62, 83] referenced their intention to report past medical history, and one consensus statement [45] detailed consideration of pre-existing LTCs as part of comprehensive and holistic assessment for COVID-19 rehabilitation (including long COVID) within service delivery standards (see supplementary material for details).
Of 20 applicable studies [36, 37, 42, 43, 46, 49, 51, 53–55, 58–60, 70–72, 75, 76, 78, 80] (excluding protocols [39, 47, 62, 83] and consensus statement [45]) (figure 2) that reported pre-existing LTCs, four (20%) [51, 53, 58, 78] reported the number of LTCs, enabling the differentiation of individuals with pre-existing MLTCs (figure 3 and table 1). The type or category of LTCs (e.g. respiratory, cardiovascular or metabolic disease) was reported by five out of 20 (25%) studies [51, 54, 59, 60, 72] and specific named LTCs (e.g. COPD, hypertension and diabetes mellitus) by 17 out of 20 (85%) studies [36, 37, 42, 43, 46, 49, 51, 53, 55, 59, 60, 70–72, 75, 76, 80]. The most commonly reported LTCs were diabetes (k=13/20 (65%)), COPD (k=12/20 (60%)) and hypertension (k=12/20 (60%)) (table 1 and figure 4). No articles reported or referred to severity of pre-existing LTCs. One study [76] referenced use of a weighted measure of pre-existing LTCs (Self-Administered Comorbidity Questionnaire (German) [86]) although this was used to report the frequency of specific named LTCs only. Three studies [53, 54, 58] analysed outcomes of individuals with pre-existing LTCs separately to those without. One study [58] reported outcomes of individuals with MLTCs separately to those without.
FIGURE 2
Flow diagram summarising applicable studies according to topic. LTCs: long-term conditions; MLTCs: multiple long-term conditions.
FIGURE 3
Reporting of pre-existing long-term conditions (LTCs): a) reporting or reference to pre-existing LTCs (k=50) and b) characteristics of pre-existing LTCs (k=20 applicable studies).
TABLE 1
Reporting of pre-existing long-term conditions (LTCs) in applicable studies (k=20)
First author, year [ref.]FIGURE 4
Bubble map of reporting of specific named pre-existing long-term conditions (LTCs) (k=20). Bubbles: body system (informed by International Classification of Diseases, 11th Revision). Bubble size: number of studies reporting the named LTC. AF: atrial fibrillation; CAD: coronary artery disease; CVD: cerebrovascular disease; GORD: gastro-oesophageal reflux disease; ID: immunological disorder; ILD: interstitial lung disease; ME: myalgic encephalomyelitis; MS: multiple sclerosis; NMD: neuromuscular disease; PAD: peripheral artery disease.
Characteristics and delivery of physical rehabilitation interventionsA summary of characteristics and delivery of physical rehabilitation interventions in 24 applicable studies (that reported the presence of pre-existing LTCs) [36, 37, 39, 42, 43, 46, 47, 49, 51, 53–55, 58–60, 62, 70–72, 75, 76, 78, 80, 83] (excluding consensus statement [45]) (figure 2) is provided in the supplementary material. The most commonly reported type was combined aerobic and strengthening exercise (k=17 (70.8%)); one study [42] reported the use of active mind–body interventions (QiGong and seated yoga) in addition to functional exercise. Most interventions had a face-to-face supervised component (k=19 (79%)) and were based in an outpatient setting (k=13 (54%)). Four studies [51, 53, 72, 78] reported home-based telerehabilitation interventions (16.7%) and two studies [53, 72] reported unsupervised interventions (8.3%). Most studies reported or referenced tailoring to individuals' needs (k=20 (83%)), three specifically reported tailoring according to pre- or coexisting LTCs [36, 53, 80], but none of the studies provided any description of specific approaches according to LTCs (supplementary material). Physical rehabilitation was delivered with one or more adjunctive interventions in 15 studies (63%); breathing exercises (k=10) and education (k=9) were the most commonly reported types. A summary of timing of intervention delivery post-SARS-CoV-2 infection (reported within nine studies [36, 43, 46, 54, 55, 60, 70,
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