Authors: Bethan Thomas, Rachael Pattinson, Deborah Edwards, Carys Dale, Benjamin Jenkins, Helena Lande, Christine Bundy, Jennifer Davies
Categories: Public Health, COVID-19, Public health, Research Design, Original Research, 1724, 1506
Source: BMJ Open
Defining and measuring long COVID a scoping review
Authors: Bethan Thomas, Rachael Pattinson, Deborah Edwards, Carys Dale, Benjamin Jenkins, Helena Lande, Christine Bundy, Jennifer Davies
Abstract
Objective
Long COVID encompasses a range of symptoms in which fatigue is one of the most prevalent. It is clear from other conditions that the definition and measurement of fatigue can be complex; however, it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.
Design
This is a scoping review that follows the JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.
Data sources
Medline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertations & Theses databases were searched from January 2020 to May 2023.
Eligibility criteria
This review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.
Data extraction and synthesis
Two independent reviewers screened the title, abstract and full text of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.
Results
The search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were 21 self-report measures (eg, Fatigue Assessment Scale) and 5 fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in the force generating capacity of a muscle).
Conclusions
The definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which is problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.
Review registration
The protocol has been registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/HNF8Z).
Introduction
Long COVID is a multisystem condition in which individuals exhibit persistent symptoms lasting over 12 weeks and which emerge during or after a SARS-CoV-2 infection.^1^ Long COVID has emerged as a significant global health concern.^2^ Between 2020 and 2021, over 17 million individuals in the WHO European Region experienced long COVID,^3^ and as of March 2023 an estimated 1.9 million in the UK have reported symptoms.^4^ The condition has profound ramifications, encompassing increased healthcare utilisation^5^ and workforce attrition, with approximately 80 000 individuals withdrawing from employment since the onset of the pandemic.^6^
Fatigue has emerged as a prevalent and debilitating symptom of long COVID, significantly affecting functioning.710 Although the term fatigue is a common parlance, a formal and widely accepted definition is elusive. There is debate around whether fatigue should be considered an experience of symptoms evaluated through self-report^11 12^ or as a performance decline independent of the perception of fatigue.^13^ Performance decline (fatigability) reflects the extent or speed of change relative to a reference value during a specified duration of task performance or measure of mechanical output.^14^ This review adopts fatigue only as a symptom experience measured through self-report, and any other measure is considered fatigability.^15^
Within these models of fatigue, a multidimensional approach is evident. A dimension is a specific aspect along which fatigue can vary. Billones et al^16^ identified eight dimensions of fatigue in their definitions and measures of fatigue used across non-oncological medical conditions (physical, cognitive, mental, motivational, emotional, peripheral, central and psychosocial). These appear to capture elements of perceived fatigue and performance decline, as well as potential physiological processes that can contribute to both.
Current treatment guidelines for long COVID fatigue focus on managing symptoms.^17^ Ongoing research is investigating the underlying mechanisms of long COVID fatigue to address the root cause and enable more targeted interventions.1820 Valid and reliable measures of fatigue and fatigability are critical to the informed design and evaluation of any intervention.^18^ The first step in developing and selecting measurement tools is defining the construct to be measured.^21^ Uncertainty regarding the definition and measures of long COVID fatigue will hamper information synthesis, impede comprehension of the symptom and ultimately halt the development of targeted interventions.
A clear definition of long COVID fatigue is lacking, and it is not clear which dimensions of fatigue, if any, are considered and captured in this condition. This review will identify the definitions of fatigue used in long COVID research and the dimensions of fatigue and fatigability they consider.
Methods
This scoping review followed the JBI methodology^22^ and reports using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (figure 1).^23^ The protocol has been published^24^ and registered on the Open Science Framework.^25^ In this scoping review, a deviation from the protocol occurred as we used the OVID EMCARE database instead of Embase.
Medline (OVID), Scopus, CINAHL (EBSCO), PsycINFO, Web of Science, Epistemonikos, OVID EMCARE, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertations & Theses databases were searched from January 2020 to May 2023. The search strategy identified quantitative and qualitative studies that included (a) any definition of long COVID fatigue and/or (b) an assessment or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue in adults. The full search strategy can be found in online supplemental material 1.
Search results were collated and deduplicated in EndNote V.20 (Clarivate Analytics, Pennsylvania, USA) by BT. The remaining studies were uploaded to Rayyan for screening. Two independent reviewers screened the title, abstract and full text of the selected studies based on the inclusion criteria (as described earlier). One reviewer (BT) screened 100% of the studies, with a second reviewer (DE, BJ, CD, HL) independently screening 25% each of the studies. Any disagreements were resolved through discussion or with a third reviewer (JD, CB, RP).
A custom form was developed for data extraction, which was piloted on a random sample of 10 included studies and modified based on feedback. One reviewer (BT) performed data extraction on 100% of the studies, with a second reviewer (DE, BJ, CD, HL) independently performing a second data extraction on 25% of the studies.
Data are presented in tabular format to present the concepts that are being explored in this review. Tables are used to present the general characteristics of the included studies, the definitions of fatigue, and the measures and assessment tools (including the name of the measure, the construct measured, whether the measure has been validated and how it is scored or quantified). The tables are accompanied by a narrative summary to uncover patterns of definitions and measures, allowing us to derive new insights and understanding from the data.
Patient and public involvement statement
Patient and public involvement (PPI) partners have been involved since the beginning of this PhD project, contributing to discussions based on their experiences of long COVID. It became clear that participants describe their fatigue in different ways and experience a range of symptoms, including physical, social and cognitive fatigue. This led the research team to consider the importance of identifying studies on long COVID that capture these different aspects of fatigue.
The PPI partners have played an active role in developing ideas and methods for a separate empirical study on long COVID fatigue, which has been the primary focus of PPI discussions. However, these conversations also helped shape the concept for this scoping review.
Although the PPI partners were not directly involved in planning or writing this specific manuscript, they have contributed to the overall PhD project, particularly in shaping the long COVID fatigue research, an area of great interest to both patients and the public.
Results
The search retrieved 9389 studies. After deduplication, 4663 studies were selected and their titles and abstracts were screened, of which 96 were eligible for full-text screening (figure 1). Thirty-nine studies were excluded after full-text screening (online supplemental material 2). Fifty-seven studies met the eligibility criteria and were included in the review.
The characteristics of the included studies are summarised in table 1 (further details are provided in online supplemental material 3). All studies were published between 2021 and 2023. Eleven different study designs were used; the most common were cross-sectional study (n=21), randomised controlled trial (n=9) and cohort study (n=9). A total of 9964 participants were included across the studies (mean=175, range=10–1414), and majority of the participants were women (61%). Across the studies, participants included those with a mix of mild and severe acute COVID-19 (n=28),82652 only mild acute COVID-19 (n=11)5363 and severe acute COVID-19 (n=8),6470 while the remaining studies did not provide information.
Studies spanned 22 Italy (n=7),^27 44 54 60 67 71 72^ Spain (n=6),^30 39 43 57 59 65^ UK (n=7),^31 48 53 56 61 73 74^ USA (n=6),^32 35 36 52 75 76^ Germany (n=5),^28 38 50 63 77^ Ireland (n=3),^8 47 62^ the Netherlands (n=3),^51 68 78^ Denmark (n=2),^26 41^ Egypt (n=2),^66 79^ Brazil (n=2),^45 55^ Hungary (n=2),^40 80^ France (n=1),^64^ India (n=2),^37 81^ Canada (n=1),^9^ Poland (n=1),^69^ Iraq (n=1),^70^ Switzerland (n=1),^34^ Chile (n=1),^33^ Austria (n=1),^42^ Israel (n=1),^58^ Turkey (n=1)^29^ and Japan (n=1).^49^
There are multiple definitions for long COVID, and not all studies used one consistently. Fifty-six studies provided a definition for long COVID (see online supplemental material 4), adopting the definition of WHO (n=9), the National Institute for Health and Care Excellence (n=17) or the Centers for Disease Control and Prevention (CDC; n=4). Two studies stated they followed the WHO definition and two studies the CDC definition but presented modified versions. Twenty-two developed their own definition of long COVID.
Definitions of long COVID fatigue
Only 21 of the 57 studies (37%) provided a definition for fatigue (table 2). These definitions have been mapped into categories based on the terms provided within them, following the framework proposed by Billones et al,^16^ which includes physical, cognitive and mental. Due to the use of novel terms in the reviewed definitions, two additional categories have been postexertional symptom exacerbation (PESE) and psychological fatigue. PESE, which encompasses postexertional malaise, is used in four of the included studies to refer to an exacerbation of multiple symptoms due to exertion. Although PESE involves a worsening of multiple symptoms, the worsening of fatigue is typically a core component,^82^ making it essential for understanding the complexity of fatigue in long COVID. From the 19 studies that provided a definition for fatigue, 2 studies included and summarised their participants’ definitions of fatigue rather than developing their own definition of fatigue.
The 20 most common words used in the definitions are presented in figure 2. The top 10 included were fatigue (n=56), physical (n=25), cognitive (n=16), mental (n=14), COVID (n=13), tiredness (n=9), feeling (n=9), exertion (n=8), central (n=7) and exhaustion (n=7).
Measures of long COVID fatigue
Of the 57 included studies, 55 employed at least one measure of fatigue. All these 55 (100%) used a self-report measure (online supplemental material 5), while 4 (7%) studies also used fatigability (non-self-report) measures of physiological processes or task performance (see table 3).
Self-report measures
Across the 55 studies using self-report measures, there were 20 validated measures of fatigue, 2 validated measures of other constructs (long COVID symptoms, depressive symptoms) and 2 non-validated measures developed for the purpose of the study. The most frequently used validated measures were the Chalder Fatigue Questionnaire (CFQ; 14/55 studies), the Fatigue Severity Scale (FSS; 11/55 studies) and the Fatigue Assessment Scale (FAS; 9/55 studies). From the validated measures of fatigue, various types of self-report measures were generic (designed to be used across conditions; 11/20 studies) and disease-specific (developed specifically for use in patients with a certain condition; 9/20), as well as evaluative (designed to measure the severity of symptoms; 20/20) and discriminative (designed to differentiate fatigued from non-fatigued individuals; 2/20). From all of the measures used across the studies, both unidimensional (13/24) and multidimensional (11/24) scales were identified. Unidimensional measures provide a singular score for overall fatigue, whereas multidimensional measures present information on more than one dimension of fatigue, for example, physical, cognitive or mental, allowing for calculation of both subscale and global scores. The self-report measures used by studies and their adherence to the original measures are presented in online supplemental material 5.
Measures of fatigability
Fatigability (non-self-report) measures were used in 5 of 57 studies (see table 3), each aimed at quantifying a change in task performance. None of the five studies quantified if their measure of fatigability was associated with any self-reported measure of fatigue.
Measuring dimensions of long COVID fatigue
Physical fatigue
Physical fatigue was the most assessed dimension in 29 of 57 studies. Nineteen studies used a validated multidimensional measure that provided a subscore for physical fatigue. The most common were the CFQ (14/29 studies) and the Modified Fatigue Impact Scale (MFIS; 4/29 studies). Nine studies used the FAS unidimensional measure, which considers physical fatigue, but only provides a composite score of fatigue. One study used an unvalidated measure in which questions related to physical fatigue were taken from the Checklist of Individual Strength (CIS) fatigue subscale.
Cognitive fatigue
Cognitive fatigue was assessed in 12 of 57 (21%) studies. All used a multidimensional measure that included a cognitive fatigue subscale. The most common measure was the MFIS (4/12 studies).
Mental fatigue
Mental fatigue was assessed separately from cognitive fatigue in 26 of 57 studies without explaining the differences between the two concepts. Sixteen used validated multidimensional measures that included a mental fatigue subscale, the most common of which was the CFQ-11 (14/26 studies). One study used only the last six items of the CFQ-11 measure, which relate to mental fatigue, invalidating the scale. Nine studies used the FAS unidimensional measure, which considers physical fatigue but only provides a composite score of fatigue. One study used an unvalidated measure in which questions related to physical fatigue were taken from the CIS fatigue subscale and replaced the word ‘physical’ in the question with ‘mental’.
Psychosocial fatigue
Psychosocial fatigue was not clearly defined as a construct but was assessed in 5 of 57 studies. All used a multidimensional measure that included a psychosocial fatigue subscale, the most common of which was the MFIS (4/5 studies).
Emotional fatigue
Emotional fatigue was similarly not clearly defined as a construct but was assessed in 2 of 57 studies. Both used the Profile of Fatigue-Related States, which is a validated multidimensional measure that provides an individual subscore of emotional distress.
PESE was assessed in 2 of 57 studies.
Observable measures
Across the five studies that used fatigability (non-self-report) measures, none quantified whether their fatigability measure was associated with any self-reported measure of fatigue.
Discussion
This scoping review sought to summarise the definitions and measures of long COVID fatigue being used by researchers. The definitions and measures of fatigue used in long COVID research were reviewed and most contained methodological problems. There was a lack of consistency in the conceptualisation of fatigue and in the measures used to quantify fatigue in long COVID. This hinders comparisons across studies and impedes progress towards improved treatment and management.^16^
Only 37% of the reviewed studies provided an explicit definition of fatigue. Among the 21 definitions, 19 involved an interplay of multiple categories. This scoping review found that the categories of long COVID fatigue were referenced with little consistency; therefore, it is difficult to make any claims from the literature because it is not known how fatigue is being defined. The lack of precision in defining fatigue categories, as seen in mental and cognitive fatigue, hinders our understanding of the symptoms associated with each category, as well as the ability to measure these constructs.
Although PESE is not one of the categories of fatigue put forward by Billones et al,^16^ our review identified that it is frequently measured in long COVID fatigue research. PESE is not a type of fatigue itself but rather an exacerbation of multiple symptoms due to exertion, with fatigue often being one of the core symptoms.^82^ Given that fatigue is a core component of PESE and long COVID, while PESE is not a type of fatigue in itself, it is often being used as a measure of fatigue in the studies identified in this review. We have included this detail within the manuscript and highlighted that research needs to be careful in using these terms interchangeably.
The categories of fatigue identified through the definitions of fatigue used in long COVID research indicate that there are different dimensions of long COVID fatigue. However, these categories are not well defined across the available studies, and there appears to be an overlap between the identified categories, including the lack of distinction made between mental and cognitive fatigue. Therefore, there is not yet enough information to identify the specific dimensions of long COVID fatigue.
This scoping review also found that some studies defined fatigue only as an experience of symptoms (perceived fatigue only measurable via self-report), while others included elements of both perceived and performance fatigue (fatigue/fatigability) in their definition. Moreover, some studies seemed to contradict themselves within their definition; for example, ‘post-COVID-19 fatigue was defined as the reduction in physical and/or mental performance …. Fatigue is a multidimensional symptom based on subjective perceptions’.^29^, p2 These terms being used interchangeably or together exacerbates the confusion surrounding long COVID.
Almost all studies in this scoping review focused on evaluating fatigue by self-report (89%). There is a core outcome set of recommended long COVID measures that recommends three measures for long COVID FAS, FSS and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).^83^ We found that 15 studies used at least one of these measures. The FSS was appropriately used in 7 of 11 studies; the FAS was used appropriately in seven of nine studies; and the FACIT-F was used appropriately in one of four studies. All three measures recommended from the core outcome set are unidimensional, providing an overall score of fatigue without individual scores for any dimension of fatigue. Within the core outcome set, there is also a Symptom Burden Questionnaire for long COVID, which considers burden of symptoms, including memory, thinking and communication, and have a subscale that accounts for fatigue and the burden of symptoms.
Future studies should use recommended measures to allow comparisons across research. Where researchers want to evaluate multiple dimensions of fatigue, care should be taken when splitting validated unidimensional measures of fatigue into multiple dimensions, as this may invalidate measurement properties. Therefore, until there is a bespoke/consensus on long COVID fatigue measure that encompasses multiple fatigue-specific dimensions, researchers may wish to consider the multidimensional measures of fatigue outlined in this review.
Strengths and limitations
This review searched a number of databases to ensure that all relevant studies were identified. This included specialised databases that could have unique references where the topic of fatigue may be represented. However, this review only included English-language publications in the final analysis, possibly limiting the conclusions as the definitions and measures used in studies in different languages could have been omitted.
Implications for research
There is an urgent need to (a) define and measure long COVID fatigue more consistently and (b) identify the mechanisms involved in the experience of fatigue. Variability in how fatigue is defined and measured within the literature poses a substantial challenge to the synthesis of evidence and hinders our ability to develop effective, evidence-based interventions.
Our review highlights the critical importance of establishing consensus regarding the definition and measurement of long COVID fatigue in research. This consensus is being identified and developed in other clinical conditions, for example, rheumatology.^84^ Future research should explore the concordance between research definitions and patient experiences to enhance intervention relevance and effectiveness in mitigating the impact of long COVID.
Implications for clinical practice
Without a unified understanding of long COVID fatigue, clinicians and policymakers cannot accurately interpret and compare study outcomes. This will hinder the development of effective and cost-effective interventions, which depend on a consistent approach to obtaining evidence.
Conclusion
This review highlights an inconsistency in definitions and measures of fatigue within long COVID research. The definitions for long COVID are inconsistent and at times contradictory, including both symptom experience and performance decline within a description of fatigue. To develop our understanding of long COVID fatigue, definitions of long COVID fatigue need to be clear, with distinct separations made between the self-report experience and the measures of fatigability that researchers decide to use within their research. Measures of fatigue or fatigability need to reflect and be consistent with the definition of fatigue.
Although not all studies used a multidimensional approach to long COVID fatigue, adopting a holistic approach that considers all possible dimensions will facilitate better understanding. This review identified dimensions of fatigue currently considered in long COVID research. If we believe long COVID fatigue has multiple dimensions, future research should map patient experiences onto these dimensions to ensure that the aspects patients report as important are being accurately measured. Research has begun exploring patient perspectives on long COVID symptoms, as demonstrated by the development of the core outcome set for long COVID measures.^83^ This review also identified several qualitative studies that reported patient experiences and their personal definitions of fatigue. However, further research is needed to bridge the gap between the measures identified in this review and the reported patient experiences.
Additionally, studies should examine which fatigue dimensions are most commonly reported in self-report and fatigability measures to understand which aspects of fatigue people with long COVID experience most intensely. This comprehensive mapping can help better align research with patient experiences. Gaining a more comprehensive understanding of these dimensions could ultimately support clinicians in improving patient outcomes and enhancing the quality of life for individuals navigating this condition.