key: cord-0808981-k9daj559
authors: Simonelli, Carla; Paneroni, Mara; Vitacca, Michele; Ambrosino, Nicolino
title: Measures of physical performance in COVID-19 patients: A mapping review
date: 2021-06-24
journal: Pulmonology
DOI: 10.1016/j.pulmoe.2021.06.005
sha: c252c39b620974373904af6c17367971f44a4b9f
doc_id: 808981
cord_uid: k9daj559

BACKGROUND AND OBJECTIVE: There is evidence of short- and long-term impairment of physical performance in patients with COVID-19 infection, but a verification of measures of physical impairment in this condition is lacking. We reviewed the measures used to assess physical performance in these patients. Secondary targets were measures of exercise or daily life activities induced symptoms. METHODS: Medline, CINAHL, and Pedro databases were searched from January 2020 to February 2021 for articles in the English language. Two investigators independently conducted the database search, screened all titles and/or abstracts based on the inclusion criteria and independently scored the studies. The quality of the studies was evaluated by two reviewers according to the NIH quality assessment tool for observational cohort and cross-sectional studies. Discrepancies were resolved through consensus. RESULTS: Out of 156 potentially relevant articles, 31 observational studies (8 cross-sectional), 1 randomized controlled trial, and 1 protocol were included. The quality of most of 31 evaluable studies was judged as low (11 studies) or fair (14 studies). Sample sizes of each study ranged from 14 to 20,889 patients. Among the 28 reported measures, Barthel Index (42.4% of studies), Six-Minute Walking Distance Test (36.4%), Short Physical Performance Battery (21.2%) and 1-Minute Sit-to-Stand (12.1%) were the most used. Fifteen% and 36% of studies reported exercise induced desaturation and dyspnoea when performing the assessments, respectively. Other exercise induced symptoms were fatigue and pain. Studies reported wide ranges of impairment in physical performance as compared to “reference” values (range of mean or median reported values vs “reference values”: 11-77 vs 100 points for Barthel Index; 11-22 vs 22–37 repetitions/min for 1m-STS; 0.5-7.9 vs 11.4 ±1.3 points for SPPB; and 45-223 vs 380-782 meters for 6MWT respectively). CONCLUSION: This review found that a wide variety of functional status tests have been used, making comparisons difficult between studies. These measures show impairment in physical performance in COVID-19 patients. However, the quality of most of the studies was judged as low or fair.

Clinical Presentation of COVID-19 varies widely, ranging from no symptoms or light flu to pneumonia with acute respiratory failure requiring admission to the Intensive Care Unit (ICU) and possible death. [1] [2] [3] In addition to the physiological consequences, a high prevalence of impairment in physical performance is reported in patients recovering from COVID-19. [4] [5] [6] [7] In patients without previous disabilities, maximal voluntary contraction for quadriceps and biceps was found to be 54% and 69% of predicted respectively. 4 In another study, 76% of patients reported at least one symptom, and 23% reported anxiety or depression up to 6 months after acute infection. The most common symptoms were fatigue, muscle weakness, or sleep difficulties. 5 Thus the need for validated measures is of utmost importance, using safe equipment and procedures, 8 to evaluate the short-and long-term consequences of COVID-19. To the best of our knowledge, a review of the measures of physical performance used during the pandemic in COVID-19 patients is lacking. Standardisation of batteries of measures would allow us to make comparisons among studies and different follow-up time-points. Therefore, we reviewed the measures used to assess physical performance in these patients.

Secondary targets of our research were the measures of exercise or activities of daily life (ADL) induced symptoms.

We performed a mapping review, defined as a systematic search of data in a broad field of the knowledge, presented as a visual synthesis (map). 9 This study follows all Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and reports the required information accordingly. 10 

Medline, CINAHL, and Pedro databases were searched from January 2020 to February 2021 for articles in the English language. We also searched the references of retrieved articles for additional studies. Keywords used were COVID AND "physical performance" OR "functional status" OR "disability" OR "impairment" OR "physical function" OR "activities of daily life" OR "muscle function"

OR "exercise tolerance" OR "exercise capacity" OR "exercise-induced desaturation" OR "dyspnoea" OR "rehabilitation".

Inclusion criteria: The search was limited to randomised controlled trials (RCTs), observational (including cross-sectional) studies, and protocols, which used at least one measure of physical performance, either patient reported measures by means of questionnaires, or objectively measured by means of standardised test such as exercise, functional performance or functional capacity. For the purposes of this review, a measure was defined as quantitative data described in the study. As secondary targets we searched also the measures of exercise or ADL induced symptoms.

We included all studies on COVID-19 patients, diagnosed either by positive test using a swab from upper or lower respiratory sources or by clinical or radiological findings. No restrictions were placed on the procedures used to diagnose COVID-19, or on the setting (hospitalization, rehabilitation, follow-up). No restriction was applied regarding age, ethnicity or sex.

Exclusion criteria: Studies not reporting any measure of physical performance (e.g. studies measuring only lung function, blood chemistry, etc.), were excluded. Systematic reviews, case report and case series were also excluded. For quantitative description of measures, we excluded studies with data reported as other than mean (standard deviation: SD) or median [Interquartile range: IQR].

The methodological quality of the studies was evaluated using the National Institute of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. 11, 12 For each study 14 items were defined independently by two authors (CS, MP) according to the absence or presence of risk of bias or undetermined. In addition, reviewers assigned each study an overall subjective rating of quality (low, fair, good). 11, 12 Discrepancies were decided through consensus or with the final judgment of a third author (MV): the percentage of inter-rater agreement was recorded. For each study, we recorded type, country, number of centres involved, setting, sample size, patients' age, measures used, and whether or not exercise-induced desaturation (EID), or exercise or ADL induced symptoms were assessed. The performance of rehabilitation/physiotherapy programs was also recorded, if any. Among symptoms, we included all those symptoms measured during or at the end of exercise tests or physical activity (e.g. at the end of an exercise test, or during ADL). Symptoms measured at rest or not related to physical activity (e.g. ageusia, headache, etc) were not considered in this review. The results of intervention (if any) on these measures were outside the aims of the study.

For each measurement, we recorded results (mean and SD or median and IQR). When available, the time between the disease onset (index event: positive swab, hospitalization or emergency department admission) and the first administration of the measure was recorded. For the four most used measures, we performed a quick literature search for predicted values and we compared them with the mean or median data reported in the included studies. No other quantitative analysis (e.g. of the scores obtained in the measurement scales) was carried out.

We identified 156 potentially relevant articles. Thirty-one observational studies (8 cross-sectional), 1 RCT and 1 study protocol were eligible. (Figure 1) . Table 1 shows the methodological quality of the studies. The inter-rater agreement of item definitions was very good: 94.2%. The overall quality was considered as low for 11 studies, fair for 14, and good for 6 studies. The most frequent motives for bias were the absence of assessor blinding and missing justification of the sample size or power estimation. Table 2 shows the characteristics of the included studies. Most studies were from Europe, six from Asia, 5, 17, 24, 31, 34, 35 and one from the USA. 27 The sample size of each study ranged from 14 to 20,889 participants, the mean or median age ranged from 49 to 72 years and in 13 out of 33 studies (39.4%) a rehabilitation program was performed. Twenty-eight measures were found, mostly administered in hospitalised subjects or during inpatient rehabilitation. Other settings were emergency department (ED), ICU, and follow-up visits. Figure 2 shows the proportion of studies using each measure of physical performance or of exercise or ADL induced symptoms, and the overall sample size of studies using each measure.

The Barthel Index 44 Figure 2 ). The Barthel Index was mainly used in the acute phase, whereas the 6MWT was assessed in interventional and follow-up studies. The SPPB was mainly used in the acute ward. Table 3 

Exercise-induced dyspnoea was assessed in twelve studies. 4, 5, 9, [25] [26] [27] [28] [29] [35] [36] [37] 40, 41 The most commonly used scale to assess dyspnoea in daily life was the modified Medical Research Council (mMRC) scale 54 used in four studies. 5, 28, 32, 35 Two studies in a rehabilitative setting found the most severe score (level 5) in 87.5 and 90.2% of patients. 28,32 One study 5 reported that six months following disease onset, 26% of patients had mMRC levels greater than 1. Only one study 26 used the Barthel Dyspnoea Index 55 in a rehabilitative setting, and reported moderate levels of dyspnoea during ADL. 

Exercise-Induced Desaturation was reported in five studies. 4, 25, 29, 40, 41 It was defined as oxygen saturation (SpO 2 ) < 90% in four studies; 25, 29, 40, 41 in the other study, 4 it was defined as a reduction in SpO 2 by > 3 % points during the exercise tests. In the acute setting, 24 to 50% of patients demonstrated EID. 4, 25 One study 29 in the rehabilitation setting reported EID in 38% of patients assessed.

Thirteen studies 14, 19, 22, 28, [30] [31] [32] [33] [34] [35] [36] [37] [38] included at least one rehabilitative intervention during the timecourse of the study. Four studies 30,31,37,38 described structured multidisciplinary rehabilitation programs, while in five studies 14, 19, 23 ,31,36 the rehabilitation was a short intervention provided to respond to the needs of patients during the first phase of the pandemic. In two studies 28,32 the components were selected according to the patient's level of oxygen saturation.

In this mapping review, we presented the measures of physical performance employed in studies on patients with COVID-19. In addition, we presented also the measures of dyspnoea and other exercise or ADL induced symptoms. In the studies evaluated, mostly of low or fair quality, we found twenty-eight measures, the Barthel Index, 44, 45 6MWT, 46, 53 SPPB 47, 48, 52 and 1m-STS 49-51 being the most commonly used measures. The other tests were reported in a few studies or even in just one.

A wide range of impairment in physical performance (e.g. from 11% to 77% of normal values for Barthel Index) was reported with the use of these tools.

Patients recovering from COVID-19 may show impairment in respiratory function, 57 and the majority of patients hospitalised with COVID-19 report persistent symptoms several months after infection onset. 5, 58 However studies evaluating symptoms may suffer from recall bias and subjective rating of symptoms. Therefore, tools that objectively measure the functional consequences of COVID-19 disease in the short-and long-term are necessary.

In routine clinical practice, the Barthel Index is the most widely used scale to measure patients' motor and functional disabilities in ADL. 45 This index was developed for chronic and long-term hospital patients with neurological diseases to examine their performance before and after treatment and predict the time needed for motor rehabilitation and the degree of nursing aid required. 45 The 6MWT is the gold standard field exercise test and it has been validated for most chronic lung diseases. It is sensitive, reproducible, easy to perform, and does not require any specialized equipment. 46 The SPPB represents the sum of the scores in three component tests of functional relevance, namely standing balance, 4-meter gait speed, and five-repetition sit-to-stand test. 47 The SPPB is the most commonly used performance-based measure for patients with chronic obstructive pulmonary disease (COPD). It is a standardized objective tool, rapid and simple to conduct, and less influenced by cultural and educational background than other self-reported measures. Because lower-limb strength is important for a satisfactory completion of the mobility activities, the SPPB has also been cited as a measure of lower-extremity function. 59 It has also been shown that the SPPB is significantly related to the capacity to perform ADL, such as changing and maintaining body position, carrying, moving, and handling objects, or walking and gait pattern. 47 The 1m-STS requires only a chair and is easy to perform, making it feasible for use in the physician's office. 60 Studies to date have shown that the 1m-STS is well tolerated, sensitive, and reproducible in patients with COPD, 49 cystic fibrosis 61 and interstitial lung diseases. 50 Dyspnoea is a symptom limiting exercise and ADL, therefore we also searched papers reporting this symptom. The severity of dyspnoea cannot be predicted from lung function; therefore, dyspnoea must be assessed specifically. Several instruments are commonly used to measure different domains of dyspnoea such as sensory-perceptual experience, affective distress, symptom impact or burden. 62 We found twelve studies investigating dyspnoea during physical activity with various scales.

Fatigue is an important debilitating symptom affecting all chronic respiratory diseases. It is a leading cause of consultations with major clinical implications. Despite its well-acknowledged negative impact on patient's life, fatigue is still a misunderstood and underdiagnosed symptom in respiratory diseases such as COPD. As a consequence, there is currently no specific intervention to treat all aspects of this symptom which is rather often considered as a secondary outcome in interventions aiming primarily to increase physical fitness and/or health related quality of life. 63 There is lowgrade evidence of positive effect of exercise training on perceived fatigue, at least in patients with COPD. 64 Pain during motion is a debilitating symptom responsible for reduced functional performance. No dedicated scales were used to investigate this symptom, but two studies reported the presence/absence of pain during motion. 20, 27 Exercise induced desaturation is associated with exercise limitation. When evaluating individuals with EID a crucial point is the definition, which varies widely across clinical trials, ranging from SpO 2 ≤ 88% to a decrease in SpO 2 of ≥ 4% with or without a nadir SpO 2 of < 90%. [65] [66] [67] [68] The results of our review confirm that patients with COVID-19 infection of differing severity suffer from a decline in physical performance in the short-4 and long-term. 5 The wide range of results as shown by the SD or IQR reported in the studies and differences in findings across settings indicates differences in case mix and times of evaluation. However, it should be kept in mind that, particularly in the first wave of the pandemic, the allocation of patients might have been influenced by organisational issues, such as bed shortage in ICU or acute wards, over and above the patient's clinical conditions. The different values of physical performance reported with the different measures used confirm that these tools assess somewhat different aspects of physical performance and highlight the need for a more homogeneous set of tools to measure the outcome of these patients.

The quality of most of the studies was judged as fair or low; this result was expected. The sudden pandemic, the need of quick information by the scientific community have led to a high index of publications, 69 which, added to the overwhelming clinical activities of researchers has lead also to a higher level of retractions. 70 This study has limitations. We conducted the search in a limited number of databases, keywords included dyspnoea but no other symptoms potentially relevant in physical performance tests; our search was limited to indexed databases. However, the most important limitation is the ongoing pandemic, which will result in increasing number of studies on the issue addressed in this study.

However, we are confident that our search will contribute to those future studies (like in yellow: at least one reviewer stated that the item could not be determined. 

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The Authors thank Rosemary Allpress for English revision and Laura Comini and Adriana Olivares for technical assistance and editing.