Resistance Exercise Therapy for Long COVID: a Randomized, Controlled Trial

Resistance Exercise Therapy for Long COVID: a Randomized, Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Resistance Exercise Therapy for Long COVID: a Randomized, Controlled Trial Colin Berry, Gemma McKinley, Hannah Bayes, David Anderson, Chim Lang, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6269439/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Long COVID, reflected by persistent symptoms, including breathlessness and fatigue, after coronavirus disease-19 (COVID-19) infection, presents an unmet therapeutic need. In this study, the effects of a resistance exercise intervention on exercise capacity and health status in individuals with Long COVID were investigated. A two-arm randomized, controlled clinical trial including adults with a hospital or community diagnosis of COVID-19 in the preceding 12 months was undertaken. Participants were randomized to usual care or usual care plus a personalized resistance exercise intervention for 12 weeks. The primary outcome was the incremental shuttle walk test undertaken three months after randomization, with secondary outcomes including health-related quality of life (EQ-5D-5L), anxiety and depression (Patient Health Questionnaire) and grip strength. Adverse events and the DePaul Symptom Questionnaire (Short Form) were also assessed. Between May 2021 and April 2024, 233 individuals (median (interquartile range) 53.6 (43.8, 60.8) years; 146 (62.7%) female, 91 (39.1%) hospitalized with COVID-19) were randomized (n = 117 (50.2%) intervention group, n = 116 (49.8%) control group). The median (interquartile range) percentage adherence with the exercise intervention was 71.0 (47.8, 96.8). The mean (SD) distances achieved in the incremental shuttle walk test at baseline and at follow-up were 328 (225) m and 389 (249) m, in 224 and 193 individuals, respectively. The change in incremental shuttle walk test distance at three months compared to baseline was 83 (118) m in the intervention group (n = 94) and 47 (95) m in the control group (n = 98) (effect estimate (95%) confidence interval 36.4 (6.6, 66.2) m; p = 0.017). By three months, compared to the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 (0.01, 0.11); p = 0.020), Patient Health Questionnaire category (0.5 (0.2, 0.8); p = 0.013) and handgrip strength (2.54 (0.89, 4.19) kg; p = 0.003). In 99 individuals who completed the DePaul questionnaire, post-exertional malaise occurred in 40 (83.3%) individuals in the intervention group and 42 (82.4%) individuals in the control group. Five individuals in the control group and 1 individual in the intervention group experienced a serious adverse event (hospitalization) (p = 0.119). In conclusion, a 12-week program of personalized resistance exercise in a community- and post-hospitalized population with Long COVID improved exercise capacity, health-related quality of life, anxiety and depression, and grip strength. Adherence with exercise was high and post-exercise malaise and adverse events were not increased. Registration : Clinicaltrials.gov ID NCT04900961 Health sciences/Medical research/Outcomes research Health sciences/Health care/Disease prevention/Lifestyle modification Figures Figure 1 Figure 2 Introduction Symptoms, such as breathlessness and fatigue, lasting longer than three months after coronavirus disease-19 (COVID-19) infection represent ‘Long COVID’ [ 1 ]. The effects of Long COVID include persisting physical symptoms and psychological symptoms [ 2 – 7 ], and impairments in exercise capacity and health-related quality of life [ 5 – 7 ]. In 2024, the estimated prevalence of Long COVID in adults in England and Scotland was 3.3% (2 million people) and in the United States the prevalence estimate (95% confidence interval) was even higher (6.9% (6.5–7.2)). Given the paucity of evidence from randomized, controlled trials, Long COVID presents an unmet therapeutic need. Long COVID may involve single or multiple organ systems leading to new or worsening of preexisting, diagnosable conditions [ 1 , 2 , 4 – 6 ]. Individuals living with Long COVID may experience impairments in physical function [ 7 ] and skeletal muscle energetics [ 8 ], and a short-term reduction in physical activity can result in significant losses in muscle mass and function [ 9 ]. Pharmacological methods to increase muscle mass are few and the main method to improve muscle mass and function is via resistance exercise [ 10 ]. Few studies have investigated the effects of resistance exercise in people with Long COVID. A systematic review of exercise interventions indicated, in general, a benefit for exercise capacity, dyspnea and health-related quality of life, however the certainty of evidence was very low to moderate, biases may have overestimated treatment effects and there was a dearth of information on adverse events [ 11 ]. Accordingly, further high-quality studies with a focus on resistance exercise are needed. Building on our prior studies into the illness trajectory of Long COVID [ 6 ], we aimed to investigate the effects and safety of a resistance exercise intervention on exercise capacity and health status in individuals with Long COVID [ 12 ]. Results Between May 2021 and April 2024, 250 individuals were screened and 233 individuals (median (interquartile range) 53.6 (43.8, 60.8) years), 146 (62.7%) female) were randomized. One hundred and seventeen (50.2%) individuals were assigned to the intervention group, and one hundred and sixteen (49.8%) individuals were assigned to the control group. Almost two thirds of the population experienced symptoms ≥ 90 days following the diagnosis of COVID-19 (Table 1 ). Table 1 Characteristics of the study population at baseline (pre-randomization). All Standard care Intervention 233 116 117 Demographics Male, n (%) 87 (37.3%) 44 (37.9%) 43 (36.8%) Female, n (%) 146 (62.7%) 72 (62.1%) 74 (63.2%) Age, median (interquartile range) 53.6 (43.8, 60.8) 52.1 (43.6, 60.1) 54.6 (43.9, 60.8) Body mass index (kg/m 2 ) 29.8 (25.9, 33.7) 30.3 (26.0, 34.0) 29.3 (25.8, 33.2) Clinical presentation Group A 145 (62.2%) 72 (62.1%) 73 (62.4%) Group B 66 (28.3%) 33 (28.4%) 33 (28.2%) Group C 22 (9.4%) 11 (9.5%) 11 (9.4%) Hospitalized, n (%) 91 (39.1%) 45 (38.8%) 46 (39.3%) Ethnicity White 217 (93.1%) 110 (94.8%) 107 (91.5%) Asian 14 (6.0%) 6 (5.2%) 8 (6.8%) Other 2 (0.9%) 0 (0.0%) 2 (1.7%) Index of multiple deprivation, quintile Missing 1 0 1 1: most deprived 58 (25.0%) 36 (31.0%) 22 (19.0%) 2 39 (16.8%) 20 (17.2%) 19 (16.4%) 3 30 (12.9%) 13 (11.2%) 17 (14.7%) 4 37 (15.9%) 13 (11.2%) 24 (20.7%) 5 68 (29.3%) 34 (29.3%) 34 (29.3%) Smoking Never 147 (63.1%) 73 (62.9%) 74 (63.2%) Former 74 (31.8%) 37 (31.9%) 37 (31.6%) Current (< 10 per day) 4 (1.7%) 2 (1.7%) 2 (1.7%) Current (10–19 per day) 2 (0.9%) 0 (0.0%) 2 (1.7%) Current (≥ 20 per day) 6 (2.6%) 4 (3.4%) 2 (1.7%) Cardiovascular history Hypertension 59 (25.3%) 34 (29.3%) 25 (21.4%) Angina 13 (5.6%) 6 (5.2%) 7 (6.0%) Myocardial infarction 8 (3.4%) 5 (4.3%) 3 (2.6%) Stroke 9 (3.9%) 4 (3.4%) 5 (4.3%) Atrial fibrillation 9 (3.9%) 5 (4.3%) 4 (3.4%) Respiratory history COVID-19 pneumonia 70 (30.0%) 35 (30.2%) 35 (29.9%) Asthma 47 (20.2%) 25 (21.6%) 22 (18.8%) Chronic obstructive pulmonary disease 12 (5.2%) 8 (6.9%) 4 (3.4%) Sleep apnoea syndrome 6 (2.6%) 4 (3.4%) 2 (1.7%) Vital parameters Systolic blood pressure (mmHg) 129.0 (120.0, 140.5) 129.2 (120.0, 138.2) 127.8 (118.5, 143.1) Diastolic blood pressure 80.5 (72.5, 88.6) 79.8 (72.9, 88.6) 81.0 (72.5, 88.6) Heart rate (/min) 74.0 (66.0, 82.2) 76.0 (66.0, 84.2) 72.5 (65.8, 81.0) Respiratory rate (/min) 16.0 (14.0, 17.0) 16.0 (14.0, 16.0) 16.0 (14.0, 17.2) Oxygen saturation (%) 98.0 (97.0, 98.0) 98.0 (97.0, 98.0) 98.0 (97.0, 98.0) COVID-19 diagnosis, severity and treatment Days since symptom onset 144 (72, 480) 124 (72, 438) 152 (73, 480) Number (%) of individuals with symptoms ≥ 90 days 145 (62.2%) 72 (62.1%) 73 (62.4%) Diagnostic test for COVID-19 PCR test positive, n (%) 186 (79.8%) 90 (77.6%) 96 (82.1%) Serology test positive, n (%) 11 (4.7%) 8 (6.9%) 3 (2.6%) Lateral flow test positive, n (%) 96 (41.2%) 54 (46.6%) 42 (35.9%) Radiology diagnosis Chest x-ray, n (%) 67 (28.8%) 31 (26.7%) 36 (30.8%) Chest CT, n (%) 41 (17.6%) 17 (14.7%) 24 (20.5%) COVID-19 diagnosis by virology or radiology test, n (%) 231 (99.1%) 115 (99.1%) 115 (99.1%) WHO clinical severity scale No limitation of activities 33 (14.2%) 17 (14.7%) 16 (13.8%) Limitation of activities 128 (55.2%) 66 (56.9%) 62 (53.4%) Hospitalized, no oxygen therapy 26 (11.2%) 11 (9.5%) 15 (12.9%) Non-invasive ventilation of high-flow oxygen 10 (4.3%) 6 (5.2%) 4 (3.4%) Intubation and mechanical ventilation 1 (0.4%) 1 (0.9%) 0 (0.0%) Ventilation and additional organ support 0 (0.0%) 0 (0.0%) 0 (0.0%) Hospitalized, with oxygen therapy 34 (14.7%) 15 (12.9%) 19 (16.4%) History of vaccination for COVID-19, n % 221 (95.3%) 113 (97.4%) 108 (93.1%) History of COVID-19 reinfection, n % 44 (18.9%) 21 (18.1%) 23 (19.7%) Blood results C-reactive protein, mg/L 2.0 (1.0, 6.0) 3.0 (1.0, 7.0) 2.0 (1.0, 4.5) C-reactive protein > 5.0 mg/L 58 (27.6%) 34 (31.8%) 34 (31.8%) Hemoglobin, g/L 139.0 (130.0, 148.0) 139.0 (128.0, 150.5) 138.5 (130.0, 147.0) Hemoglobin < 120 g/L (females) 11 (7.7%) 8 (11.3%) 3 (4.2%) Hemoglobin < 130 g/L (males) 8 (9.4%) 6 (13.6%) 2 (4.9%) COVID-19 serology at 3-months, AU/mL 9896 (4516, 19878) 10494 (5694, 21127) 10494 (5694, 21127) Clinical presentation groups: Group A: Positive diagnosis with persisting symptoms for at least 4 weeks from onset of symptoms leading to medical review, but not admission; Group B: Positive diagnosis with post-discharge, persistent symptoms for at least 4 weeks following symptom onset; Group C: Positive diagnosis, in convalescent phase in hospital. The flow diagram is illustrated in Fig. 1 . The participants’ characteristics are described in Table 1 and Supplementary Tables S3 and S4. Intervention, adherence and primary outcome The median (interquartile range) percentage adherence with the exercise intervention was 71.0 (47.8, 96.8). The mean (SD) distances achieved in the incremental shuttle walk test at baseline and at follow-up were 328 (225) m and 389 (249) m, in 224 and 193 individuals, respectively (Supplementary Tables S5-S7). The reasons for stopping the shuttle walk test are also described in these tables. Prior to the follow-up assessment at 3-months, one participant (03011) experienced a lower limb injury unrelated to the protocol and was therefore unable to complete the primary outcome evaluation. This participant was in the standard care group. A list of withdrawals including the reason for individual participants and by randomised group is provided as a supplementary file. The primary outcome analysis is described in Table 2 and illustrated in Fig. 2 . The change in incremental shuttle walk test distance at three months compared to baseline was 83 (118) m in the intervention group (n = 94) and 47 (95) m in the control group (n = 98) (effect estimate (95%) confidence interval 36.4 (6.6, 66.2) m; p = 0.017). Table 2 Primary outcome analysis. All Standard care Intervention Randomized, n 233 116 117 Baseline ISWT distance (m) N (missing) 224 (9) 112 (4) 112 (5) Median (IQR) 270 (180, 430) 270 (180, 450) 270 (180, 422) [Min, Max] [10, 1230] [30, 1230] [10, 1030] 3-months follow-up ISWT distance (m) N (missing) 193 (2) 99 (1) 94 (1) Median (IQR) 340 (200, 520) 340 (195, 465) 350 (200, 528) [Min, Max] [40, 1290] [60, 1290] [40, 1080] Change in ISWT distance (m) N (missing) 192 (3) 98 (2) 94 (1) Median (IQR) 40 (0, 110) 30 (0, 90) 65 (10, 140) [Min, Max] [-170, 460] [-170, 440] [-170, 460] Linear regression intervention effect estimate Difference 36.4 95% confidence interval (6.6, 66.2) p-value p = 0.017 IQR = interquartile range; ISWT = incremental shuttle walk test distance; m = months; max = maximum; min = minimum; SD = standard deviation. There were no interactions in the primary outcome analysis by sex/gender, ethnicity, clinical presentation group, socioeconomic quintile, age or COVID-19 serology (Table 3 ). Table 3 The primary analysis extended to include terms which estimate the interaction between treatment effect and predefined subgroups. Number (missing) Change in ISWT distance (m) at three months Intervention effect estimate, 95% CI p-value p-value for interaction Group Male 73 (14) 50.0 (0.0, 120.0) 6.6 (-41.8, 55.0) p = 0.789 p = 0.128 Female 119 (27) 40.0 (0.0, 100.0) 54.7 (16.8, 92.5) p = 0.005 Ethnicity White or not stated 179 (38) 40.0 (0.0, 110.0) 38.1 (7.1, 69.2) p = 0.016 p = 0.558 Another ethnic group 13 (3) 40.0 (10.0, 100.0) 19.2 (-101.4, 139.9) p = 0.755 Clinical presentation group. Group A: Positive diagnosis with persisting symptoms for at least 4 weeks from onset of symptoms leading to medical review, but not admission 124 (21) 45 (0, 122.5) 31.1 (-6.2, 68.4) p = 0.103 p = 0.658 Group B: Positive diagnosis with post-discharge, persistent symptoms for at least 4 weeks following symptom onset 119 (27) 30.0 (-5.0, 90.0) 36.3 (-20.0, 92.6) p = 0.206 Group C: Positive diagnosis, in convalescent phase in hospital 13 (9) 80.0 (30.0, 130.0) 87.7 (-27.6, 203.0) p = 0.136 Index of Multiple Deprivation quintile. 1: most deprived 51 (7) 30.0 (-10.0, 80.0) 57.7 (-1.7, 117.0) p = 0.057 p = 0.771 2 29 (10) 80.0 (30.0, 130.0) 61.3 (-17.9, 140.5) p = 0.129 3 25 (5) 30.0 (0.0, 80.0) -6.2 (-91.2, 78.9) p = 0.887 4 29 (8) 40.0 (-10.0, 120.0) 27.3 (-54.2, 108.7) p = 0.511 5: least deprived 57 (11) 80.0 (0.0, 110.0) 39.8 (-15.8, 95.4) p = 0.160 Age, years Tertile 1: [20.9, 49.1) 65 (13) 70.0 (0.0, 140.0) 41.6 (-10.2, 93.4) p = 0.116 p = 0.922 Tertile 2: [49.1, 58.2) 63 (14) 30.0 (-5.0, 100.0) 27.0 (-26.1, 80.1) p = 0.318 Tertile 3: [58.2, 83.8] 64 (14) 40.0 (7.5, 90.0) 38.6 (-13.7, 90.8) p = 0.148 COVID-19 serology, AU/mL Tertile 1: [69, 5927) 61 (0) 40.0 (0.0, 120.0) 28.1 (-26.8, 83.0) p = 0.315 p = 0.732 Tertile 2: [5927, 14151) 61 (0) 10.0 (-40.0, 90.0) 25.6 (-29.6, 80.8) p = 0.363 Tertile 3: [14151, 354806] 59 (2) 10.0 (-40.0, 90.0) 53.7 (-0.5, 108.0) p = 0.052 ISWT = incremental shuttle walk test distance Secondary outcomes By three months post-randomization, compared to the control group, greater improvements in the intervention group were observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 (0.01, 0.11); p = 0.020), Patient Health Questionnaire category (0.5 (0.2, 0.8); p = 0.013) and handgrip strength (2.54 (0.89, 4.19) kg; p = 0.003) (Table 4 ; Supplementary Figures S1 -S3). No effects on any other outcomes were noted (Supplementary Tables S8-S22). Table 4 Secondary outcomes: change at three months from baseline and effect of the intervention. All Standard care Intervention Effect estimate (95% CI) p-value 233 116 117 Spirometry Change in Peak expiratory flow rate (L/m) N (Missing) 187 (8) 96 (4) 91 (4) Median (IQR) -5.00 (-46.00, 35.50) 3.50 (-41.25, 35.25) -8.00 (-50.00, 34.00) -0.64 (-22.74, 21.45) p = 0.954 Change in Forced vital capacity, L N (Missing) 187 (8) 96 (4) 91 (4) Median (IQR) 0.00 (-0.10, 0.20) 0.00 (-0.10, 0.20) 0.00 (-0.10, 0.20) 0.02 (-0.08, 0.13) p = 0.663 Change in Forced expiratory volume in one second, L N (Missing) 187 (8) 96 (4) 91 (4) Median (IQR) 0.00 (-0.10, 0.10) 0.00 (-0.10, 0.10) 0.00 (-0.10, 0.15) 0.01 (-0.12, 0.14) p = 0.914 Change in Forced expiratory volume / Forced expiratory volume ratio N (Missing) 187 (8) 96 (4) 91 (4) Median (IQR) 0.00 (-0.03, 0.02) 0.00 (-0.02, 0.02) 0.00 (-0.03, 0.02) -0.01 (-0.04, 0.02) p = 0.515 Physical function Change in grip strength, kg N (Missing) 193 (2) 99 (1) 94 (1) Median (IQR) 1.7 (-1.9, 4.6) 0.9 (-3.0, 3.5) 2.5 (-0.8, 5.8) 2.54 (0.89, 4.19) p = 0.003 Change in SPPB score category N (Missing) 174 (21) 86 (14) 88 (7) N (%) Improvement 38 (21.8%) 13 (15.1%) 25 (28.4%) N (%) No change 124 (71.3%) 69 (80.2%) 55 (62.5%) N (%) Deterioration 12 (6.9%) 4 (4.7%) 8 (9.1%) 1.6 (0.7, 3.7) p = 0.230 Change in Duke Activity Status Index N (Missing) 190 (5) 97 (3) 93 (2) Median (IQR) 3.35 (0.00, 9.88) 3.50 (-2.70, 9.00) 2.75 (0.00, 10.70) 0.81 (-2.16, 3.78) p = 0.593 Change in Duke Activity Status Index predicted VO2max, O2 ml/min/kg of body weight N (Missing) 190 (5) 97 (3) 93 (2) Median (IQR) 1.44 (0.00, 4.25) 1.50 (-1.16, 3.87) 1.18 (0.00, 4.60) 0.35 (-0.93, 1.62) p = 0.593 Change in International Physical Activity Questionnaire category N (Missing) 195 (0) 100 (0) 95 (0) N (%) Improvement 49 (25.1%) 22 (22.0%) 27 (28.4%) N (%) No change 110 (56.4%) 61 (61.0%) 49 (51.6%) N (%) Deterioration 36 (18.5%) 17 (17.0%) 19 (20.0%) 1.1 (0.6, 1.9) p = 0.753 Patient reported outcome measures Change in EQ-5D health utility score N (Missing) 195 (0) 100 (0) 95 (0) Median (IQR) 0.00 (-0.05, 0.14) 0.00 (-0.07, 0.07) 0.01 (-0.02, 0.21) 0.06 (0.01, 0.11) p = 0.020 Change in EQ-5D visual analogue scale N (Missing) 195 (0) 100 (0) 95 (0) Median (IQR) 5.0 (-2.5, 14.5) 0.0 (-3.5, 10.0) 5.0 (0.0, 15.0) 3.6 (-0.8, 7.9) p = 0.107 Change in PHQ-4 score category N (Missing) 193 (2) 99 (1) 94 (1) N (%) Improvement 52 (26.9%) 18 (18.2%) 34 (36.2%) N (%) No change 107 (55.4%) 61 (61.6%) 46 (48.9%) N (%) Deterioration 34 (17.6%) 20 (20.2%) 14 (14.9%) 0.5 (0.2, 0.8) p = 0.013 Change in Brief illness perception score N (Missing) 194 (1) 100 (0) 94 (1) Median (IQR) -4.00 (-12.00, 3.00) -2.50 (-9.25, 3.25) -6.00 (-13.75, 1.00) -3.49 (-7.21, 0.22) p = 0.066 Fatigue and breathlessness Change in fatigue severity score N (Missing) 194 (1) 100 (0) 94 (1) Median (IQR) -2 (-10, 2) 0 (-7, 3) -4 (-13, 1) -2.45 (-6.25, 1.35) p = 0.206 Fatigue visual analogue scale N (Missing) 192 (3) 98 (2) 94 (1) N (%) Improvement 91 (47.4%) 48 (49.0%) 43 (45.7%) N (%) No change 30 (15.6%) 16 (16.3%) 14 (14.9%) N (%) Deterioration 71 (37.0%) 34 (34.7%) 37 (39.4%) 0.9 (0.6, 1.6) p = 0.800 Change in MRC dyspnea score N (Missing) 195 (0) 100 (0) 95 (0) N (%) Improvement 59 (30.3%) 28 (28.0%) 31 (32.6%) N (%) No change 107 (54.9%) 57 (57.0%) 50 (52.6%) N (%) Deterioration 29 (14.9%) 15 (15.0%) 14 (14.7%) 0.9 (0.5, 1.5) p = 0.684 Change in Fried frailty N (Missing) 195 (0) 100 (0) 95 (0) N (%) Improvement 56 (28.7%) 28 (28.0%) 28 (29.5%) N (%) No change 123 (63.1%) 65 (65.0%) 58 (61.1%) N (%) Deterioration 16 (8.2%) 7 (7.0%) 9 (9.5%) 0.8 (0.4, 1.6) p = 0.568 Change in current clinical frailty N (missing) 191 (4) 98 (2) 93 (2) N (%) Improvement 77 (40.3%) 37 (37.8%) 40 (43.0%) N (%) No change 77 (40.3%) 39 (39.8%) 38 (40.9%) N (%) Deterioration 37 (19.4%) 22 (22.4%) 15 (16.1%) 0.7 (0.4, 1.1) p = 0.114 For continuous outcomes, a linear regression intervention effect estimate is provided for the follow-up value. This estimate has is adjusted for the baseline value and randomized group, as well as clinical presentation, history of COVID-19 pneumonia, age, and sex. A similar approach is taken for ordinal variables, and an ordinal regression intervention effect estimate provided. IQR = interquartile range; ISWT = incremental shuttle walk test distance; m = months; max = maximum; min = minimum; MRC = Medical Research Council; Patient health questionnaire-4 (PHQ-4); SD = standard deviation; SPPB – Short Physical Performance Battery Safety Adverse events No deaths occurred. Ten hospitalizations occurred (nine hospitalizations in five individuals in the control group and one hospitalization in the intervention group, deemed unrelated to the intervention) (Fisher test, p = 0.119) (Supplementary Table S28) Post-exercise malaise In 99 individuals who completed the DePaul questionnaire, post-exertional malaise occurred in 40 (83.3%) individuals in the intervention group and 42 (82.4%) individuals in the control group (Supplementary Table S24-S26). Costs The cost of the intervention on a per participant basis are described in (Supplementary Table S29). The cost per participant was estimated at £189.16 (US Dollar 244.87). Discussion A 12-week program of personalized resistance exercise in a population of community- and post-hospitalized individuals with Long COVID improved exercise capacity. The effect size exceeded the minimum clinically important difference of 35.0 m [ 13 ]. Health-related quality of life, anxiety and depression, and grip strength were also improved. Adherence with resistance exercise was reasonably high and post-exercise malaise and adverse events were not increased with the exercise intervention. The intervention cost was relatively inexpensive. The median age of the study population was 54 years, two thirds of the participants were female, and one quarter were from the most deprived quintile of the population in Scotland. Almost two thirds of individuals reported persisting symptoms ≥ 90 days after the diagnosis of COVID-19 and two in five individuals had received hospital care for COVID-19. Laboratory testing of immune serology in a blood sample provided by each participant at 3-months confirmed evidence of circulating IgG antibodies to SARS-CoV-2 in all (100%) of the participants consistent with prior COVID-19 and/or vaccination. The design of this trial was stimulated by our observations of persisting physical limitation within the illness trajectory of individuals following hospitalization for post-COVID-19 [ 6 ]. The results of our clinical trial now provide evidence that a 12-week personalized programme of resistance exercise improved exercise capacity and this effect was consistent across pre-specified groups including by age, sex/gender, ethnicity, socioeconomic quintile, clinical presentation group, and COVID-19 serology titre. This observation is important since it implies the benefit of resistance exercise is not limited to subgroups of individuals, but rather the potential benefits are generalizable to the wider patient population. Overall, the withdrawal rate was relatively low (8.2% overall), the adherence with the intervention was relatively high (median 71%), and no adverse events or serious adverse events occurred in relation to the intervention. The exercise programme was personalized according to the needs and preferences of the individual. Indeed, the programme was designed to be simple, require minimal equipment and be easy to follow for participants. The intervention was unsupervised, and designed to have minimal staff involvement, with the rationale being to implement a participant-led resistance exercise programme with minimal or no dependency on healthcare staff. The results of our study indicate the intervention should be generalizable in a range of settings including in primary and secondary care and in the community. The improvement in exercise capacity was associated with concomitant improvements in some but not all of the prespecified secondary outcomes. Health-related quality of life, psychological wellbeing and grip strength were improved indicating the intervention led to benefits in health and wellbeing and physical strength. Illness perception also improved but the change was not statistically significant. On the other hand, measures of physical activity, including objective measurement by accelerometry, did not improve. The reasons for this lack of change may be multifactorial, including the participants’ interactions with their environment, a lack of statistical power, and/or a true lack of effect. In other words, the intervention improves exercise capacity but does not alter general physical activity behavior. There are other clinical trials of exercise interventions in long COVID. In the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) trial [ 14 ], 585 adults (26–86 years) discharged from NHS hospitals at least three months previously after COVID-19 and with ongoing physical and/or mental health sequelae (post-COVID-19 condition) were randomized 1:1 to receive the intervention (n = 298) or usual care (n = 287). The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. Compared with usual care, the intervention led to improvements in health-related quality of life (adjusted mean difference in the patient reported outcomes measurement information system (PROMIS) preference score 0.03 (95% confidence interval 0.01 to 0.05), P = 0.02) at three months, driven by greater improvements in the PROMIS sub scores for depression (1.39 (0.06 to 2.71), P = 0.04), fatigue (2.50 (1.19 to 3.81), P < 0.001), and pain interference (1.80 (0.50 to 3.11), P = 0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P = 0.02). A systematic review of randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care identified 14 trials including 5 involving nonhospitalized populations [ 15 ]. Rehabilitation interventions were associated with improvements in functional exercise capacity (standard mean differences, -0.56; 95% credible intervals, -0.87 to -0.22), however, as mentioned previously, there was uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% credible intervals, 0.32 to 9.94). More recently, the Post-Hospitalisation COVID-19 Rehabilitation (PHOSP-R) consortium reported a randomized controlled trial of exercise-based rehabilitation in 181 participants (55% male, mean [SD] age 59 [ 12 ] years, length of hospital stay 12 [ 19 ] days) [ 16 ]. There was an improvement in the incremental shuttle walk test distance following face-to-face rehabilitation (mean 52 [95% CI 19 to 85]m, p = 0.002) and remote rehabilitation (mean 34 [95% CI 1 to 66]m, p = 0.047) compared to usual care alone. There were no differences between groups for health-related quality of life or self-reported symptoms. There are notable differences between PHOSP-R and our clinical trial. PHOSP-R exclusively enrolled individuals who had been hospitalized because of COVID-19, the intervention included mixed types of exercise (including aerobic exercise), education and self-management, and the duration of the intervention was 8-weeks, and no information was described on post-exercise malaise [ 16 ]. Our trial differed from PHOSP-R in several ways. In our trial, the sample size was modestly larger, most (61%) of the participants experienced COVID-19 in the community (Table 1 ), the intervention involved a personalized resistance exercise intervention, the duration of the intervention was longer (12-weeks), and post-exercise malaise was assessed and there was no evidence of an association with the exercise intervention. There were also differences in the characteristics of the populations: in PHOSP-R [ 16 ], a minority (45%) of the participants were female and 78% of the participants were white British whereas in our trial, 65% of the participants were female and 93% were white (reflecting the ethnicity/race characteristics of the population in Scotland). In addition, the intervention in our trial was associated with improvements in patient reported outcome measures including health-related quality of life, anxiety and depression, and grip strength. In PHOSP-R, the shuttle walk distance at baseline in the usual care group was 328 (277–380) m which is greater than that the distance achieved by participants in our trial (270 (180, 430) m) potentially reflecting a greater degree of physical limitation in the participants in our trial population. Our trial of a novel, personalized, pragmatic, resistance exercise intervention in a population of individuals with Long COVID adds evidence of patient benefits including exercise capacity, health-related quality of life, psychological well-being and safety with a relatively inexpensive intervention. The intervention incurs less cost (£189; US $ 245; Supplementary Table S29) than the REGAIN rehabilitation program for Long COVID (£1987) [ 17 ]. Future work will assess the health economic implications of a resistance exercise program in Long COVID. Limitations The incremental shuttle walk test is a pragmatic field test hence limited physiological information was collected. The intervention was not masked, as this is not possible in exercise studies, but the statistical analysis was carried out blind to the randomized group. The daily exercises were unsupervised and adherence was self-reported. Participants in the intervention group received more contact with site staff compared to participants in the control group, and this difference may have influenced the patient reported outcome measures. We suggest that improvements in exercise capacity and secondary outcomes provide confirmatory evidence of adherence and intervention effectiveness. The reasons for being lost-to-follow-up were not available. Conclusions In this multicenter, randomized trial, a 12-week program of personalized resistance exercise in a population of community- and post- hospitalized individuals with Long COVID led to improvements in exercise capacity, health-related quality of life, psychological wellbeing and grip strength. The intervention was not associated with an increase in adverse events or post-exertional malaise and adherence was reasonably high. This pragmatic, low-cost intervention may be a generalizable therapy for individuals with Long COVID. Abbreviations Incremental shuttle walk test (ISWT) Short performance physical battery (SPPB) National Health Service (NHS) Research Ethics Committee (REC) Severe angiotensin converting enzyme-2 (ACE2) Acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Coronavirus disease-19 (COVID-19) Cardiovascular disease (CVD) National Institute for Health and Care Excellence (NICE) Scottish Intercollegiate Guidelines Network (SIGN) Royal College of General Practitioners (RCGP) Cardiac Imaging in SARS-CoV-2 (COVID-19) (CISCO-19) Polymerase Chain Reaction (PCR) Intensive care unit (ICU) NHS Greater Glasgow and Clyde (NHSGGC) Rating of Perceived Exertion (RPE) Patient and Public Involvement (PPI) Adverse event (AE) Serious adverse event (SAE) Electronic case report form (eCRF) Post-hospitalization COVID-19 (PHOSP-COVID) Illness perception (Brief IPQ) Duke Activity Status Index (DASI) International Physical Activity Questionnaire (IPAQ-SF) Euroqol-5 dimension (EQ5D) Medical Research Council (MRC) Clinical Trials Unit (CTU) Standard operating procedures (SOPs) Statistical Analysis Plan (SAP) Consolidated Standards of Reporting Trials (CONSORT) Principal Investigator (PI) Related Unexpected Serious Adverse Event (RUSAE) Clinical Trial of an Investigational Medicinal Product (CTIMP) Post-exertional malaise (PEM) Graded exercise therapy (GET) Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) Robertson Centre for Biostatistics (RCB) Declarations Acknowledgements We thank the participants and staff who supported this study. Funding This study was funded by a project grant from the Chief Scientist Office (COV/LTE/20/10) and a British Heart Foundation Centre of Excellence Award (RE/18/6/34217). Data availability Data requests will be considered by the Steering Group, which includes representatives of the sponsor, the University of Glasgow, senior investigators independent of the research team and the chief investigator. The Steering Group took account of the scientific rationale, ethics, logistics and resource implications. Data access requests should be initially submitted by email to the chief investigator (C.B., corresponding author). The source data include the de-identified numerical data used for the statistical analyses. Data access will be provided through the secure analytical platform of the Robertson Centre for Biostatistics. This secure platform enables access to de-identified data for analytical purposes, without the possibility of removing the data from the server. 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Methods Study Design A parallel group, 1:1 randomized, controlled clinical trial in adults with a diagnosis of COVID-19 in the preceding 12 months was undertaken in NHS Scotland. Ethical approval was granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (reference: GN20CA537). The protocol schedule, amendments and enrolment by site are described in the Supplement (Tables S1-S2, respectively) and the study design has been published [12]. All participants provided written informed consent. The study was publicly registered before the first participant was randomized (Clinicialtrials.gov ID NCT04900961). Setting and Population Setting This multi-center trial included sites in Glasgow (Queen Elizabeth University Hospital and Glasgow Royal Infirmary) and Dundee (Ninewells Hospital) in Scotland. Population Participants were classified according to clinical presentation as not hospitalized due to COVID-19 but persisting symptoms for at least 4 weeks leading to medical review ( Group A ); discharged after hospitalization for COVID-19 and with persistent symptoms for at least 4 weeks ( Group B ); or convalescing in hospital after hospitalization for COVID-19 ( Group C ). Participants enrolled in the community were included in Groups A and B whereas participants enrolled during hospital admission were in Group C. Eligibility criteria Inclusion criteria Diagnosis of COVID-19 confirmed by: Virology PCR positive laboratory diagnosis and/or point of care test positive for COVID-19, or, Positive Lateral Flow Test, or, Positive COVID antibody Test; Within 12 months of diagnosis; Persistent symptoms for at least 4 weeks from symptoms onset (Groups A & B only); Presentation type - one of group A, B or C. Exclusion criteria Inpatient physiotherapy currently part of standard care post-ICU; No expectation of being able to walk within three months; Unable to provide informed consent; Unable to comply with the protocol; Known pregnancy. On 14 December 2022, given the reduction in incident cases of COVID-19 in the community, the initial eligibility period of 6 months from the diagnosis of COVID-19 (protocol versions 1, 2 and 3) was extended to 12 months (protocol versions 4). Control group The comparator was usual care for Long Covid in line with clinical practice guidelines from the National Institute for Healthcare Excellence 188 guideline [2], with no non-routine contacts from the clinical research team. Intervention An exercise programme was co-designed by exercise physiologists, physiotherapists and individuals with lived experience of Long COVID. Specifically, the intervention was developed through discussions with patient groups around the potential needs of the individual during the exercise intervention, such as staff contact, need for a seated (chair-based) exercise option, and personalization of the exercises, followed by practical exercise sessions involving patients who were hospitalized with COVID-19. For participants assigned to the intervention group, an instructional pack was provided by research nursing staff, supported by an exercise physiologist (S.G.), to participants. The pack included a guidance document, an exercise log and links to online videos (Supplement). The pack was given to participants during an initial face-to-face consultation where the nurse/therapist helped to select the most suitable category and level of exercise for the participant, and to demonstrate the exercises and ensure the participant was comfortable performing the exercise options. Every 2 weeks a member of the research team contacted each participant by telephone or online video consultation to ensure they were comfortable with the exercises and to help overcome any issues that may have arisen. If the participant was a hospital inpatient then the contact was undertaken daily, as needed. The intervention occurred in the community (Groups A and B) or in-hospital and then at home after discharge (Group C). Participants were asked to perform exercises daily. The number of exercise repetitions that lead to a validated resistance exercise specific Rating of Perceived Exertion (RPE) of 8-10 (3-5 in the first week) was determined [18]. The use of RPE to prescribe and titrate resistance exercise is as efficacious as other more complex methods but reported to be the most tolerable and enjoyable method [19]. The intervention was tailored according to the preferences of the participant and progress achieved. When a participant attained over 15-20 repetitions of each exercise, they were advised to move to the next difficulty level within each category, and once able to do this for the top level within the category, to then move to the next category. Similarly, if a participant was unable to manage 5 repetitions of each exercise, they were advised to move down a level and, if at the bottom level within a category, to then move down a category. Participants were encouraged to progress the level of exercise according to their preferences and not to exceed their perceived limit. They were advised that the number of repetitions would vary day to day, depending on symptoms, and if they were particularly fatigued then an interval day of rest without exercise was acceptable. There were 3 categories within the pack with exercise guidance provided according to the status of the participant: 1) bed-bound, 2) up-to-sit, or 3) ambulatory, and within each category the exercises had different levels of physical exertion to allow progression or regression, as appropriate. The exercises were: Bed-bound: lying chest-press, lying row, lying plantar flexion, lying leg press and bridging; Up-to-sit: seated chest-press, seated row, seated lateral raises, seated leg extension, seated plantar flexion, squats; Ambulatory: press-ups, standing lateral raises, seated rows, lunges, calf-raises, squats. Participants were asked to perform upper body exercise initially and bring in the lower body exercises in week 3. The exercise log was intended to be completed by the participant after an episode of exercise activity had been undertaken, whether it was completed and whether any adverse effects occurred. Additional information on the intervention is described in the Supplement. Randomization and Blinding The details of randomization and blinding are described in detail in the Supplement. Participants were allocated in a 1:1 ratio to usual care or usual care plus a personalized resistance exercise intervention for 12-weeks. Allocations were determined using a minimization algorithm with a small random element, designed to ensure balance with respect to study site, clinical presentation group (A, B, or C), history of COVID pneumonia, age (<40, 40-49, 50-59, 60-69. 70+), and sex. Allocations were assigned after baseline data collection, via the study-specific online data collection tool, developed and maintained by staff at the Robertson Centre for Biostatistics, University of Glasgow. Study participants and research staff delivering the intervention were unblinded to group allocations, but statistical staff were blind until the point of database lock. The Statistical Analysis Plan was finalized, and all statistical programs were written and validated prior to database lock and unblinding. Outcomes Primary outcome The primary outcome was the incremental shuttle walk test. This is an externally paced incremental walking test developed as a measure of exercise capacity [20]. Participants were required to walk around two marker cones, 9 m apart, placed 0.5 m from each endpoint (10 m course) with an initial speed of 0.5 m/s, increasing 0.17 m/s every minute. Audio cues (beeps) signal the time at which the participant should turn at the marker. The test has 12 levels (walking speeds) and the maximum duration of the test is therefore 12 minutes. No encouragement was given during the test: the only verbal cues provided referred to an impending increase in walking speed [21]. The incremental shuttle walk test performance was defined as the distance achieved [21] and oxygen saturation and heart rate were measured [22]. The duration of the incremental shuttle walk test correlates with peak oxygen consumption (ml/min/kg) and has population reference values for distance walked (m) [23]. The test has been evaluated and validated in several populations, including in healthy women [24], young men [25], in obese individuals [26] and patients with chronic respiratory disease [13, 20-22]. The incremental shuttle walk test is recognized for being safe and responsive to the effects of rehabilitation in populations with chronic respiratory disease [22] and stakeholder organizations support the use of this test as an efficacy measure in clinical trials [21]. The minimum clinically important difference is 35.0 m [13]. Secondary outcomes The following secondary outcomes were assessed: Respiratory function Spirometry Physical function 2. Handgrip strength 3. Short Physical Performance Battery (SPPB) [27] Patient reported outcome measures 4. Health-related quality of life (Euroqol-5 dimension (EQ5D)) [28] 5. Patient health questionnaire-4 (PHQ-4) [29] 6. Illness perception (Brief IPQ) [30] 7. Duke Activity Status Index (DASI) [31] 8. International Physical Activity Questionnaire (IPAQ-SF) short-form [32] Fatigue 9. Medical Research Council (MRC) dyspnea score Frailty 10. Fried frailty phenotype: five criteria: weight loss; exhaustion; grip strength; low physical activity; and slow walking pace [34] Clinical Frailty Scale [35] Clinical outcomes 12. Episodes of healthcare 13. Hospitalization for any reason. Additional prespecified outcomes Vital parameters of cardio-respiratory function e.g. oxygen saturation, heart rate, respiratory rate at baseline and during follow-up Adherence with exercise (intervention group) Post-exercise adverse events and malaise: adverse events during and after exercise were assessed in all participants. Following a protocol amendment, the DePaul Symptom Questionnaire (Short Form) was assessed in a subgroup. Accelerometery (Glasgow site) - Participants were issued with a GENEActiv (ActivInsights Ltd, United Kingdom) accelerometer and instructed to wear this 24 h per day for a 7-day period. The accelerometer was set to record at 100 Hz. Acceleration data were collected and calibrated to local gravity [36-38] and physical activity levels were quantified using GGIR, with methods previously described [39]. A valid day was defined as having >16 hours of data in it, and we excluded participants with less than 3 valid days of data or if wear data were not present for every 15 minutes of the 24-hour cycle, to ensure data was representative of a complete seven-day measure [40]. COVID-19 serology using the SARS-CoV-2 IgG II Quant assay [41] (Supplement). Costs of the intervention: the costs relating to staff time and consumables were estimated [42]. These included 1) the time of the exercise physiologist to design the intervention, prepare the exercise guideline to be used by the participants, provide training, support and supervision for healthcare staff in delivering the intervention, and support the follow-up calls with participants; 2) healthcare staff time to provide the intervention to the participant visit was estimated; 3) consumables i.e. resistance bands, and 4) transport costs for one visit to the site for the initial visit. Bias minimization Bias minimization procedures involved random allocation of the participants, masking of participants at the time of follow-up to baseline results, and retention strategies, such as by providing follow-up contacts to support the participants and minimize withdrawals. Outcome assessors were not blinded to group allocation. Statistics Sample size calculation A pre-determined sample size calculation was devised by bio statistician co-authors. The minimum clinically important between-group difference in the incremental shuttle walk test at follow-up (3-months) = 46 m, SD=105 [21], sample size for 80% power, 5% significance, no loss to follow-up (LTFU) = a minimum of 85 per group; allowing for LTFU and incomplete data, the sample size is n=110 per group (n=220 total). Statistical analyses The primary and secondary outcomes were analyzed using linear regression (continuous outcomes), logistic regression (binary outcomes), or proportional odds logistic regression (ordinal outcomes). All models were adjusted for the baseline value of the incremental shuttle walk test distance. Due to differing characteristics between sites, the model was not adjusted for site. In order to approximate normality in model residuals, a second model was fitted where ISWT distance at baseline and three months follow-up was square root transformed prior to analysis, the estimate provided in this case was on the square root scale. Estimates were provided from both models fitted to both the original data and the transformed data. Regression models were used to assess treatment effects within pre-specified subgroups, through the use of treatment-by-subgroup interactions. For linear regression analyses, the distribution of model residuals were visually assessed for Normality; where appropriate, outcomes were transformed to improve model fit. Tests of the proportional odds assumption (for treatment group) were used for ordinal regression models. All tests were two-tailed and assessed at the 5% significance level. Missing outcome data were not imputed, though for the primary outcome, a post hoc analysis was performed with multiple imputations for the missing outcomes. Because of the potential for type 1 error in the analyses of secondary outcomes, these outcomes should be interpreted as exploratory. The statistical analyses were conducted using R Studio and R version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) according to a pre-specified Statistical Analysis Plan (SAP). Additional Declarations Yes there is potential Competing Interest. Colin Berry is employed by the University of Glasgow which holds consultancy and research agreements for his work with Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, Merck, Servier, Novartis, Roche, Siemens Healthcare, and Zoll Medical. This study was funded by a project grant from the Chief Scientist Office (COV/LTE/20/10) and a British Heart Foundation Centre of Excellence Award (RE/18/6/34217). Supplementary Files CISCO21WithdrawalsFromStudy20250320.pdf Withdrawals-From-Study Visit CISCO21WithdrawalsFromIntervention20250320.pdf Withdrawals from Intervention CISCO21SAPv10signed.pdf Statistical Analysis Plan CISCO21ProtocolV4.020221214Final.pdf Protocol for the clinical trial CISCO21Supplement20250320.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6269439","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":434472888,"identity":"fcaa6a5e-dc75-4184-8fcf-33ef80818322","order_by":0,"name":"Colin Berry","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYFAC5oYDDAwHQCzGBwwFSBISOLUwwrUwGzAYEKmFAaqFTYIoLfztjY2HCxjuyJnPPmNW+cXAzl7evceA4UcNQ+LMBuxaJM4cbDg8g+GZscy5HLPbMgbJiRvPnDFg7DnGkDgbhy0GEokNh3kYDifO4OExuy1hwJxgOCN3AwNvA0PiPAJa6kFaiiUM6u1BWhj/EqElQQKohfGDwWHG+RK5G5hBtuByGNgvPAbPDGfwsBVLMxgcT9zAc/7DYZljEsa4vM/f3nz4M0/FHXkJHuaNH39UVNvLt7clPnxTYyM74wAOayDOAxEcBsw8IPYBcDThjkgkwP6A8QeQksfhnlEwCkbBKBi5AAChX1q8AmxzVAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4547-8636","institution":"University of Glasgow","correspondingAuthor":true,"prefix":"","firstName":"Colin","middleName":"","lastName":"Berry","suffix":""},{"id":434472889,"identity":"54f18c89-c953-4eb5-bbc4-a666921476c2","order_by":1,"name":"Gemma McKinley","email":"","orcid":"","institution":"University of 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Dundee","correspondingAuthor":false,"prefix":"","firstName":"Chim","middleName":"","lastName":"Lang","suffix":""},{"id":434472893,"identity":"7648fd7c-f2c8-4030-add3-2c98227f7b18","order_by":5,"name":"Adam Gill","email":"","orcid":"https://orcid.org/0009-0009-1120-0714","institution":"Queen Elizabeth University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Adam","middleName":"","lastName":"Gill","suffix":""},{"id":434472894,"identity":"6a9c9325-9951-4701-b437-827fe7d14f63","order_by":6,"name":"Andrew Morrow","email":"","orcid":"","institution":"University of Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Morrow","suffix":""},{"id":434472895,"identity":"cdecf4d0-b5f1-4c88-98b1-e9a8b0ca3ac1","order_by":7,"name":"Robert Sykes","email":"","orcid":"https://orcid.org/0000-0003-1010-5474","institution":"University of 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Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Welsh","suffix":""},{"id":434472899,"identity":"35466a4c-effb-44ab-b3dc-359f218b165b","order_by":11,"name":"Susan Dawkes","email":"","orcid":"","institution":"Edinburgh Napier University","correspondingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Dawkes","suffix":""},{"id":434472900,"identity":"9be2cfd4-dcb7-44f9-bea4-af71e4ccab4f","order_by":12,"name":"Alex McConnachie","email":"","orcid":"https://orcid.org/0000-0002-7262-7000","institution":"University of Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"McConnachie","suffix":""},{"id":434472901,"identity":"2a6baf0d-b4b1-4574-b898-5d719db47943","order_by":13,"name":"Stuart Gray","email":"","orcid":"https://orcid.org/0000-0001-8969-9636","institution":"University of Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Stuart","middleName":"","lastName":"Gray","suffix":""}],"badges":[],"createdAt":"2025-03-20 12:06:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6269439/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6269439/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79586455,"identity":"56d804ba-ea6b-46f8-8574-eb51e40d6b0e","added_by":"auto","created_at":"2025-03-31 12:32:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":634665,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram, including information on screened and randomized participants, and withdrawals (including the reasons). Recruitment ended when 170 individuals had been randomized.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/243ed72cda2d270f9632d3cb.png"},{"id":79587515,"identity":"d37f1611-d2a3-43c1-ab63-d8dfeff68dc5","added_by":"auto","created_at":"2025-03-31 12:40:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":210269,"visible":true,"origin":"","legend":"\u003cp\u003eIncremental shuttle walk test (ISWT) (mean ± 95% confidence interval) at baseline (blue) and 3-months follow-up (red) in the intervention and control groups, respectively.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/53bf4f7100248805a431aac0.png"},{"id":80841471,"identity":"fe8a5147-aa65-49fe-a3df-bfb1fc46264d","added_by":"auto","created_at":"2025-04-17 16:04:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2679566,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/942c0986-42a8-4994-93f4-237dbe270f9d.pdf"},{"id":79586465,"identity":"3c1df94d-7c99-487a-9e51-3699b004e3a0","added_by":"auto","created_at":"2025-03-31 12:32:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":75038,"visible":true,"origin":"","legend":"Withdrawals-From-Study Visit","description":"","filename":"CISCO21WithdrawalsFromStudy20250320.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/b9e57dcec84ca1d7907c3970.pdf"},{"id":79586456,"identity":"35598120-283e-4a5f-af29-668eeba59e19","added_by":"auto","created_at":"2025-03-31 12:32:32","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":76284,"visible":true,"origin":"","legend":"Withdrawals from Intervention","description":"","filename":"CISCO21WithdrawalsFromIntervention20250320.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/bc29bfb7df50e93ef856500c.pdf"},{"id":79586466,"identity":"56e2f9a5-3167-45cc-ad04-0275ff2b99e5","added_by":"auto","created_at":"2025-03-31 12:32:32","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":632451,"visible":true,"origin":"","legend":"\u003cp\u003eStatistical Analysis Plan\u003c/p\u003e","description":"","filename":"CISCO21SAPv10signed.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/b95d4ce7a595f03ab5c5b59f.pdf"},{"id":79588249,"identity":"f74533e8-4055-4c2d-9799-f2818e4c0215","added_by":"auto","created_at":"2025-03-31 12:48:32","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":468245,"visible":true,"origin":"","legend":"\u003cp\u003eProtocol for the clinical trial\u003c/p\u003e","description":"","filename":"CISCO21ProtocolV4.020221214Final.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/ecc24ac01fb440394a418945.pdf"},{"id":79586462,"identity":"52d73f3f-7d13-4f21-8c03-893d71513789","added_by":"auto","created_at":"2025-03-31 12:32:32","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1526302,"visible":true,"origin":"","legend":"","description":"","filename":"CISCO21Supplement20250320.docx","url":"https://assets-eu.researchsquare.com/files/rs-6269439/v1/db440a1a75dc4237a7233f33.docx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nColin Berry is employed by the University of Glasgow which holds consultancy and research agreements for his work with Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, Merck, Servier, Novartis, Roche, Siemens Healthcare, and Zoll Medical.\r\nThis study was funded by a project grant from the Chief Scientist Office (COV/LTE/20/10) and a British Heart Foundation Centre of Excellence Award (RE/18/6/34217).","formattedTitle":"Resistance Exercise Therapy for Long COVID: a Randomized, Controlled Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSymptoms, such as breathlessness and fatigue, lasting longer than three months after coronavirus disease-19 (COVID-19) infection represent \u0026lsquo;Long COVID\u0026rsquo; [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The effects of Long COVID include persisting physical symptoms and psychological symptoms [\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and impairments in exercise capacity and health-related quality of life [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In 2024, the estimated prevalence of Long COVID in adults in England and Scotland was 3.3% (2\u0026nbsp;million people) and in the United States the prevalence estimate (95% confidence interval) was even higher (6.9% (6.5\u0026ndash;7.2)). Given the paucity of evidence from randomized, controlled trials, Long COVID presents an unmet therapeutic need. Long COVID may involve single or multiple organ systems leading to new or worsening of preexisting, diagnosable conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIndividuals living with Long COVID may experience impairments in physical function [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and skeletal muscle energetics [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and a short-term reduction in physical activity can result in significant losses in muscle mass and function [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Pharmacological methods to increase muscle mass are few and the main method to improve muscle mass and function is via resistance exercise [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Few studies have investigated the effects of resistance exercise in people with Long COVID. A systematic review of exercise interventions indicated, in general, a benefit for exercise capacity, dyspnea and health-related quality of life, however the certainty of evidence was very low to moderate, biases may have overestimated treatment effects and there was a dearth of information on adverse events [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Accordingly, further high-quality studies with a focus on resistance exercise are needed.\u003c/p\u003e \u003cp\u003eBuilding on our prior studies into the illness trajectory of Long COVID [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], we aimed to investigate the effects and safety of a resistance exercise intervention on exercise capacity and health status in individuals with Long COVID [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween May 2021 and April 2024, 250 individuals were screened and 233 individuals (median (interquartile range) 53.6 (43.8, 60.8) years), 146 (62.7%) female) were randomized. One hundred and seventeen (50.2%) individuals were assigned to the intervention group, and one hundred and sixteen (49.8%) individuals were assigned to the control group. Almost two thirds of the population experienced symptoms\u0026thinsp;\u0026ge;\u0026thinsp;90 days following the diagnosis of COVID-19 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the study population at baseline (pre-randomization).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard care\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDemographics\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (37.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146 (62.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, median (interquartile range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.6 (43.8, 60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.1 (43.6, 60.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.6 (43.9, 60.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.8 (25.9, 33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.3 (26.0, 34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.3 (25.8, 33.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eClinical presentation\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73 (62.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (28.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalized, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (38.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (39.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e217 (93.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (94.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e107 (91.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIndex of multiple deprivation, quintile\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1: most deprived\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (31.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (19.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (16.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (16.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (20.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e147 (63.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (62.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (63.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (31.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (31.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent (\u0026lt;\u0026thinsp;10 per day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent (10\u0026ndash;19 per day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent (\u0026ge;\u0026thinsp;20 per day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCardiovascular history\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAngina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyocardial infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRespiratory history\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (20.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (21.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep apnoea syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVital parameters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129.0 (120.0, 140.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129.2 (120.0, 138.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127.8 (118.5, 143.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic blood pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.5 (72.5, 88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79.8 (72.9, 88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81.0 (72.5, 88.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate (/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.0 (66.0, 82.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.0 (66.0, 84.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.5 (65.8, 81.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory rate (/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.0 (14.0, 17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.0 (14.0, 16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.0 (14.0, 17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxygen saturation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.0 (97.0, 98.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.0 (97.0, 98.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98.0 (97.0, 98.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCOVID-19 diagnosis, severity and treatment\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays since symptom onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144 (72, 480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (72, 438)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e152 (73, 480)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber (%) of individuals with symptoms\u0026thinsp;\u0026ge;\u0026thinsp;90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73 (62.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDiagnostic test for COVID-19\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCR test positive, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e186 (79.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (77.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (82.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerology test positive, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateral flow test positive, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96 (41.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (46.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (35.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRadiology diagnosis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest x-ray, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest CT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (20.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 diagnosis by virology or radiology test, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e231 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWHO clinical severity scale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo limitation of activities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (14.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimitation of activities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (55.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (56.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalized, no oxygen therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-invasive ventilation of high-flow oxygen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation and mechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilation and additional organ support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalized, with oxygen therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (16.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of vaccination for COVID-19, n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e221 (95.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 (97.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108 (93.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of COVID-19 reinfection, n %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (19.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBlood results\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0 (1.0, 6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 (1.0, 7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0 (1.0, 4.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein\u0026thinsp;\u0026gt;\u0026thinsp;5.0 mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (27.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin, g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139.0 (130.0, 148.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139.0 (128.0, 150.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138.5 (130.0, 147.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;120 g/L (females)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;130 g/L (males)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 serology at 3-months, AU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9896 (4516, 19878)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10494 (5694, 21127)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10494 (5694, 21127)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eClinical presentation groups: Group A: Positive diagnosis with persisting symptoms for at least 4 weeks from onset of symptoms leading to medical review, but not admission; Group B: Positive diagnosis with post-discharge, persistent symptoms for at least 4 weeks following symptom onset; Group C: Positive diagnosis, in convalescent phase in hospital.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe flow diagram is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The participants\u0026rsquo; characteristics are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Supplementary Tables S3 and S4.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eIntervention, adherence and primary outcome\u003c/h2\u003e \u003cp\u003eThe median (interquartile range) percentage adherence with the exercise intervention was 71.0 (47.8, 96.8). The mean (SD) distances achieved in the incremental shuttle walk test at baseline and at follow-up were 328 (225) m and 389 (249) m, in 224 and 193 individuals, respectively (Supplementary Tables S5-S7).\u003c/p\u003e \u003cp\u003eThe reasons for stopping the shuttle walk test are also described in these tables. Prior to the follow-up assessment at 3-months, one participant (03011) experienced a lower limb injury unrelated to the protocol and was therefore unable to complete the primary outcome evaluation. This participant was in the standard care group. A list of withdrawals including the reason for individual participants and by randomised group is provided as a supplementary file.\u003c/p\u003e \u003cp\u003eThe primary outcome analysis is described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The change in incremental shuttle walk test distance at three months compared to baseline was 83 (118) m in the intervention group (n\u0026thinsp;=\u0026thinsp;94) and 47 (95) m in the control group (n\u0026thinsp;=\u0026thinsp;98) (effect estimate (95%) confidence interval 36.4 (6.6, 66.2) m; p\u0026thinsp;=\u0026thinsp;0.017).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary outcome analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard care\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRandomized, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline ISWT distance (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e224 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e112 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e270 (180, 430)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e270 (180, 450)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e270 (180, 422)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[Min, Max]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e[10, 1230]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[30, 1230]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e[10, 1030]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3-months follow-up ISWT distance (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e193 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e340 (200, 520)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e340 (195, 465)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e350 (200, 528)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[Min, Max]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e[40, 1290]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[60, 1290]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e[40, 1080]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in ISWT distance (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (0, 110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (0, 90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65 (10, 140)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[Min, Max]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e[-170, 460]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e[-170, 440]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e[-170, 460]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinear regression intervention effect estimate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDifference\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e36.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e95% confidence interval\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(6.6, 66.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ep-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIQR\u0026thinsp;=\u0026thinsp;interquartile range; ISWT\u0026thinsp;=\u0026thinsp;incremental shuttle walk test distance; m\u0026thinsp;=\u0026thinsp;months; max\u0026thinsp;=\u0026thinsp;maximum; min\u0026thinsp;=\u0026thinsp;minimum; SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere were no interactions in the primary outcome analysis by sex/gender, ethnicity, clinical presentation group, socioeconomic quintile, age or COVID-19 serology (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe primary analysis extended to include terms which estimate the interaction between treatment effect and predefined subgroups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber (missing)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChange in ISWT distance (m) at three months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntervention effect estimate, 95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value for interaction\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0 (0.0, 120.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003cp\u003e(-41.8, 55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (0.0, 100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.7\u003c/p\u003e \u003cp\u003e(16.8, 92.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWhite or not stated\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (0.0, 110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.1\u003c/p\u003e \u003cp\u003e(7.1, 69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnother ethnic group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (10.0, 100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.2\u003c/p\u003e \u003cp\u003e(-101.4, 139.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.755\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical presentation group.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A: Positive diagnosis with persisting symptoms for at least 4 weeks from onset of symptoms leading to medical review, but not admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (0, 122.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.1\u003c/p\u003e \u003cp\u003e(-6.2, 68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B: Positive diagnosis with post-discharge, persistent symptoms for at least 4 weeks following symptom onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.0 (-5.0, 90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.3\u003c/p\u003e \u003cp\u003e(-20.0, 92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup C: Positive diagnosis, in convalescent phase in hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80.0 (30.0, 130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87.7\u003c/p\u003e \u003cp\u003e(-27.6, 203.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex of Multiple Deprivation quintile.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1: most deprived\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.0 (-10.0, 80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.7\u003c/p\u003e \u003cp\u003e(-1.7, 117.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.771\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80.0 (30.0, 130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.3\u003c/p\u003e \u003cp\u003e(-17.9, 140.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.0 (0.0, 80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6.2\u003c/p\u003e \u003cp\u003e(-91.2, 78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (-10.0, 120.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.3\u003c/p\u003e \u003cp\u003e(-54.2, 108.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.511\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5: least deprived\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80.0 (0.0, 110.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.8\u003c/p\u003e \u003cp\u003e(-15.8, 95.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 1: [20.9, 49.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70.0 (0.0, 140.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.6\u003c/p\u003e \u003cp\u003e(-10.2, 93.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.922\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 2: [49.1, 58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.0 (-5.0, 100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0\u003c/p\u003e \u003cp\u003e(-26.1, 80.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 3: [58.2, 83.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (7.5, 90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.6\u003c/p\u003e \u003cp\u003e(-13.7, 90.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 serology, AU/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 1: [69, 5927)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.0 (0.0, 120.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.1\u003c/p\u003e \u003cp\u003e(-26.8, 83.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 2: [5927, 14151)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.0 (-40.0, 90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.6\u003c/p\u003e \u003cp\u003e(-29.6, 80.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTertile 3: [14151, 354806]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.0 (-40.0, 90.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.7\u003c/p\u003e \u003cp\u003e(-0.5, 108.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eISWT\u0026thinsp;=\u0026thinsp;incremental shuttle walk test distance\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSecondary outcomes\u003c/h3\u003e\n\u003cp\u003eBy three months post-randomization, compared to the control group, greater improvements in the intervention group were observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 (0.01, 0.11); p\u0026thinsp;=\u0026thinsp;0.020), Patient Health Questionnaire category (0.5 (0.2, 0.8); p\u0026thinsp;=\u0026thinsp;0.013) and handgrip strength (2.54 (0.89, 4.19) kg; p\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e; Supplementary Figures \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e-S3). No effects on any other outcomes were noted (Supplementary Tables S8-S22).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecondary outcomes: change at three months from baseline and effect of the intervention.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard care\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffect estimate (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpirometry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Peak expiratory flow rate (L/m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5.00 (-46.00, 35.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.50 (-41.25, 35.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-8.00 (-50.00, 34.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.64 (-22.74, 21.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.954\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Forced vital capacity, L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00 (-0.10, 0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (-0.10, 0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (-0.10, 0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02 (-0.08, 0.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.663\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Forced expiratory volume in one second, L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00 (-0.10, 0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (-0.10, 0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (-0.10, 0.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01 (-0.12, 0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.914\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Forced expiratory volume / Forced expiratory volume ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e187 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00 (-0.03, 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (-0.02, 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (-0.03, 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.01 (-0.04, 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.515\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in grip strength, kg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (Missing)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e193 (2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e99 (1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e94 (1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e1.7 (-1.9, 4.6)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.9 (-3.0, 3.5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e2.5 (-0.8, 5.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2.54 (0.89, 4.19)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in SPPB score category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (15.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (71.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (80.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.6 (0.7, 3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Duke Activity Status Index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.35 (0.00, 9.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.50 (-2.70, 9.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.75 (0.00, 10.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.81 (-2.16, 3.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Duke Activity Status Index predicted VO2max, O2 ml/min/kg of body weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.44 (0.00, 4.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.50 (-1.16, 3.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.18 (0.00, 4.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.35 (-0.93, 1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in International Physical Activity Questionnaire category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e195 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (25.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110 (56.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (61.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1 (0.6, 1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient reported outcome measures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in EQ-5D health utility score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (Missing)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e195 (0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e100 (0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e95 (0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.00 (-0.05, 0.14)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.00 (-0.07, 0.07)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01 (-0.02, 0.21)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.06 (0.01, 0.11)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in EQ-5D visual analogue scale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e195 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0 (-2.5, 14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 (-3.5, 10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.0 (0.0, 15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.6 (-0.8, 7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in PHQ-4 score category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (Missing)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e193 (2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e99 (1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e94 (1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (%) Improvement\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e52 (26.9%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e18 (18.2%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e34 (36.2%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (%) No change\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e107 (55.4%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e61 (61.6%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e46 (48.9%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (%) Deterioration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e34 (17.6%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e20 (20.2%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e14 (14.9%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.5 (0.2, 0.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Brief illness perception score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.00 (-12.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.50 (-9.25, 3.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6.00 (-13.75, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3.49 (-7.21, 0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue and breathlessness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in fatigue severity score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2 (-10, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (-7, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4 (-13, 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2.45 (-6.25, 1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.206\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue visual analogue scale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e192 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (47.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (49.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (37.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (34.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (39.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9 (0.6, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in MRC dyspnea score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e195 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (32.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107 (54.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (57.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (52.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9 (0.5, 1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in Fried frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (Missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e195 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (28.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (29.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123 (63.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (65.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58 (61.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8 (0.4, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChange in current clinical frailty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e191 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Improvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (37.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (43.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) No change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (39.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (40.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN (%) Deterioration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (19.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (22.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7 (0.4, 1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.114\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eFor continuous outcomes, a linear regression intervention effect estimate is provided for the follow-up value. This estimate has is adjusted for the baseline value and randomized group, as well as clinical presentation, history of COVID-19 pneumonia, age, and sex. A similar approach is taken for ordinal variables, and an ordinal regression intervention effect estimate provided. IQR\u0026thinsp;=\u0026thinsp;interquartile range; ISWT\u0026thinsp;=\u0026thinsp;incremental shuttle walk test distance; m\u0026thinsp;=\u0026thinsp;months; max\u0026thinsp;=\u0026thinsp;maximum; min\u0026thinsp;=\u0026thinsp;minimum; MRC\u0026thinsp;=\u0026thinsp;Medical Research Council; Patient health questionnaire-4 (PHQ-4); SD\u0026thinsp;=\u0026thinsp;standard deviation; SPPB \u0026ndash; Short Physical Performance Battery\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eSafety\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events\u003c/h2\u003e \u003cp\u003eNo deaths occurred. Ten hospitalizations occurred (nine hospitalizations in five individuals in the control group and one hospitalization in the intervention group, deemed unrelated to the intervention) (Fisher test, p\u0026thinsp;=\u0026thinsp;0.119) (Supplementary Table S28)\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePost-exercise malaise\u003c/h3\u003e\n\u003cp\u003eIn 99 individuals who completed the DePaul questionnaire, post-exertional malaise occurred in 40 (83.3%) individuals in the intervention group and 42 (82.4%) individuals in the control group (Supplementary Table S24-S26).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCosts\u003c/h2\u003e \u003cp\u003eThe cost of the intervention on a per participant basis are described in (Supplementary Table S29). The cost per participant was estimated at \u0026pound;189.16 (US Dollar 244.87).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eA 12-week program of personalized resistance exercise in a population of community- and post-hospitalized individuals with Long COVID improved exercise capacity. The effect size exceeded the minimum clinically important difference of 35.0 m [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Health-related quality of life, anxiety and depression, and grip strength were also improved. Adherence with resistance exercise was reasonably high and post-exercise malaise and adverse events were not increased with the exercise intervention. The intervention cost was relatively inexpensive.\u003c/p\u003e \u003cp\u003eThe median age of the study population was 54 years, two thirds of the participants were female, and one quarter were from the most deprived quintile of the population in Scotland. Almost two thirds of individuals reported persisting symptoms\u0026thinsp;\u0026ge;\u0026thinsp;90 days after the diagnosis of COVID-19 and two in five individuals had received hospital care for COVID-19. Laboratory testing of immune serology in a blood sample provided by each participant at 3-months confirmed evidence of circulating IgG antibodies to SARS-CoV-2 in all (100%) of the participants consistent with prior COVID-19 and/or vaccination.\u003c/p\u003e \u003cp\u003eThe design of this trial was stimulated by our observations of persisting physical limitation within the illness trajectory of individuals following hospitalization for post-COVID-19 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The results of our clinical trial now provide evidence that a 12-week personalized programme of resistance exercise improved exercise capacity and this effect was consistent across pre-specified groups including by age, sex/gender, ethnicity, socioeconomic quintile, clinical presentation group, and COVID-19 serology titre. This observation is important since it implies the benefit of resistance exercise is not limited to subgroups of individuals, but rather the potential benefits are generalizable to the wider patient population. Overall, the withdrawal rate was relatively low (8.2% overall), the adherence with the intervention was relatively high (median 71%), and no adverse events or serious adverse events occurred in relation to the intervention. The exercise programme was personalized according to the needs and preferences of the individual. Indeed, the programme was designed to be simple, require minimal equipment and be easy to follow for participants. The intervention was unsupervised, and designed to have minimal staff involvement, with the rationale being to implement a participant-led resistance exercise programme with minimal or no dependency on healthcare staff. The results of our study indicate the intervention should be generalizable in a range of settings including in primary and secondary care and in the community.\u003c/p\u003e \u003cp\u003eThe improvement in exercise capacity was associated with concomitant improvements in some but not all of the prespecified secondary outcomes. Health-related quality of life, psychological wellbeing and grip strength were improved indicating the intervention led to benefits in health and wellbeing and physical strength. Illness perception also improved but the change was not statistically significant. On the other hand, measures of physical activity, including objective measurement by accelerometry, did not improve. The reasons for this lack of change may be multifactorial, including the participants\u0026rsquo; interactions with their environment, a lack of statistical power, and/or a true lack of effect. In other words, the intervention improves exercise capacity but does not alter general physical activity behavior.\u003c/p\u003e \u003cp\u003eThere are other clinical trials of exercise interventions in long COVID. In the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) trial [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], 585 adults (26\u0026ndash;86 years) discharged from NHS hospitals at least three months previously after COVID-19 and with ongoing physical and/or mental health sequelae (post-COVID-19 condition) were randomized 1:1 to receive the intervention (n\u0026thinsp;=\u0026thinsp;298) or usual care (n\u0026thinsp;=\u0026thinsp;287). The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. Compared with usual care, the intervention led to improvements in health-related quality of life (adjusted mean difference in the patient reported outcomes measurement information system (PROMIS) preference score 0.03 (95% confidence interval 0.01 to 0.05), P\u0026thinsp;=\u0026thinsp;0.02) at three months, driven by greater improvements in the PROMIS sub scores for depression (1.39 (0.06 to 2.71), P\u0026thinsp;=\u0026thinsp;0.04), fatigue (2.50 (1.19 to 3.81), P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and pain interference (1.80 (0.50 to 3.11), P\u0026thinsp;=\u0026thinsp;0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P\u0026thinsp;=\u0026thinsp;0.02). A systematic review of randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care identified 14 trials including 5 involving nonhospitalized populations [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Rehabilitation interventions were associated with improvements in functional exercise capacity (standard mean differences, -0.56; 95% credible intervals, -0.87 to -0.22), however, as mentioned previously, there was uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% credible intervals, 0.32 to 9.94).\u003c/p\u003e \u003cp\u003eMore recently, the Post-Hospitalisation COVID-19 Rehabilitation (PHOSP-R) consortium reported a randomized controlled trial of exercise-based rehabilitation in 181 participants (55% male, mean [SD] age 59 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] years, length of hospital stay 12 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] days) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. There was an improvement in the incremental shuttle walk test distance following face-to-face rehabilitation (mean 52 [95% CI 19 to 85]m, p\u0026thinsp;=\u0026thinsp;0.002) and remote rehabilitation (mean 34 [95% CI 1 to 66]m, p\u0026thinsp;=\u0026thinsp;0.047) compared to usual care alone. There were no differences between groups for health-related quality of life or self-reported symptoms.\u003c/p\u003e \u003cp\u003eThere are notable differences between PHOSP-R and our clinical trial. PHOSP-R exclusively enrolled individuals who had been hospitalized because of COVID-19, the intervention included mixed types of exercise (including aerobic exercise), education and self-management, and the duration of the intervention was 8-weeks, and no information was described on post-exercise malaise [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our trial differed from PHOSP-R in several ways. In our trial, the sample size was modestly larger, most (61%) of the participants experienced COVID-19 in the community (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), the intervention involved a personalized resistance exercise intervention, the duration of the intervention was longer (12-weeks), and post-exercise malaise was assessed and there was no evidence of an association with the exercise intervention. There were also differences in the characteristics of the populations: in PHOSP-R [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], a minority (45%) of the participants were female and 78% of the participants were white British whereas in our trial, 65% of the participants were female and 93% were white (reflecting the ethnicity/race characteristics of the population in Scotland). In addition, the intervention in our trial was associated with improvements in patient reported outcome measures including health-related quality of life, anxiety and depression, and grip strength. In PHOSP-R, the shuttle walk distance at baseline in the usual care group was 328 (277\u0026ndash;380) m which is greater than that the distance achieved by participants in our trial (270 (180, 430) m) potentially reflecting a greater degree of physical limitation in the participants in our trial population.\u003c/p\u003e \u003cp\u003eOur trial of a novel, personalized, pragmatic, resistance exercise intervention in a population of individuals with Long COVID adds evidence of patient benefits including exercise capacity, health-related quality of life, psychological well-being and safety with a relatively inexpensive intervention. The intervention incurs less cost (\u0026pound;189; US\u003cspan\u003e$\u003c/span\u003e 245; Supplementary Table S29) than the REGAIN rehabilitation program for Long COVID (\u0026pound;1987) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Future work will assess the health economic implications of a resistance exercise program in Long COVID.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThe incremental shuttle walk test is a pragmatic field test hence limited physiological information was collected. The intervention was not masked, as this is not possible in exercise studies, but the statistical analysis was carried out blind to the randomized group. The daily exercises were unsupervised and adherence was self-reported. Participants in the intervention group received more contact with site staff compared to participants in the control group, and this difference may have influenced the patient reported outcome measures. We suggest that improvements in exercise capacity and secondary outcomes provide confirmatory evidence of adherence and intervention effectiveness. The reasons for being lost-to-follow-up were not available.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this multicenter, randomized trial, a 12-week program of personalized resistance exercise in a population of community- and post- hospitalized individuals with Long COVID led to improvements in exercise capacity, health-related quality of life, psychological wellbeing and grip strength. The intervention was not associated with an increase in adverse events or post-exertional malaise and adherence was reasonably high. This pragmatic, low-cost intervention may be a generalizable therapy for individuals with Long COVID.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIncremental shuttle walk test (ISWT)\u003c/p\u003e\n\u003cp\u003eShort performance physical battery (SPPB)\u003c/p\u003e\n\u003cp\u003eNational Health Service (NHS)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResearch Ethics Committee (REC)\u003c/p\u003e\n\u003cp\u003eSevere angiotensin converting enzyme-2 (ACE2)\u003c/p\u003e\n\u003cp\u003eAcute respiratory syndrome coronavirus-2 (SARS-CoV-2)\u003c/p\u003e\n\u003cp\u003eCoronavirus disease-19 (COVID-19)\u003c/p\u003e\n\u003cp\u003eCardiovascular disease (CVD)\u003c/p\u003e\n\u003cp\u003eNational Institute for Health and Care Excellence (NICE)\u003c/p\u003e\n\u003cp\u003eScottish Intercollegiate Guidelines Network (SIGN)\u003c/p\u003e\n\u003cp\u003eRoyal College of General Practitioners (RCGP)\u003c/p\u003e\n\u003cp\u003eCardiac Imaging in SARS-CoV-2 (COVID-19) (CISCO-19)\u003c/p\u003e\n\u003cp\u003ePolymerase Chain Reaction (PCR)\u003c/p\u003e\n\u003cp\u003eIntensive care unit (ICU)\u003c/p\u003e\n\u003cp\u003eNHS Greater Glasgow and Clyde (NHSGGC)\u003c/p\u003e\n\u003cp\u003eRating of Perceived Exertion (RPE)\u003c/p\u003e\n\u003cp\u003ePatient and Public Involvement (PPI)\u003c/p\u003e\n\u003cp\u003eAdverse event (AE)\u003c/p\u003e\n\u003cp\u003eSerious adverse event (SAE)\u003c/p\u003e\n\u003cp\u003eElectronic case report form (eCRF)\u003c/p\u003e\n\u003cp\u003ePost-hospitalization COVID-19 (PHOSP-COVID)\u003c/p\u003e\n\u003cp\u003eIllness perception (Brief IPQ)\u003c/p\u003e\n\u003cp\u003eDuke Activity Status Index (DASI)\u003c/p\u003e\n\u003cp\u003eInternational Physical Activity Questionnaire (IPAQ-SF)\u003c/p\u003e\n\u003cp\u003eEuroqol-5 dimension (EQ5D)\u003c/p\u003e\n\u003cp\u003eMedical Research Council (MRC)\u003c/p\u003e\n\u003cp\u003eClinical Trials Unit (CTU)\u003c/p\u003e\n\u003cp\u003eStandard operating procedures (SOPs)\u003c/p\u003e\n\u003cp\u003eStatistical Analysis Plan (SAP)\u003c/p\u003e\n\u003cp\u003eConsolidated Standards of Reporting Trials (CONSORT)\u003c/p\u003e\n\u003cp\u003ePrincipal Investigator (PI)\u003c/p\u003e\n\u003cp\u003eRelated Unexpected Serious Adverse Event (RUSAE)\u003c/p\u003e\n\u003cp\u003eClinical Trial of an Investigational Medicinal Product (CTIMP)\u003c/p\u003e\n\u003cp\u003ePost-exertional malaise (PEM)\u003c/p\u003e\n\u003cp\u003eGraded exercise therapy (GET)\u003c/p\u003e\n\u003cp\u003eMyalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS)\u003c/p\u003e\n\u003cp\u003eRobertson Centre for Biostatistics (RCB)\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe thank the participants and staff who supported this study.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study was funded by a project grant from the Chief Scientist Office (COV/LTE/20/10) and a British Heart Foundation Centre of Excellence Award (RE/18/6/34217).\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e\n\u003cp\u003eData requests will be considered by the Steering Group, which includes representatives of the sponsor, the University of Glasgow, senior investigators independent of the research team and the chief investigator. The Steering Group took account of the scientific rationale, ethics, logistics and resource implications.\u003c/p\u003e\n\u003cp\u003eData access requests should be initially submitted by email to the chief investigator (C.B., corresponding author). The source data include the de-identified numerical data used for the statistical analyses. Data access will be provided through the secure analytical platform of the Robertson Centre for Biostatistics. This secure platform enables access to de-identified data for analytical purposes, without the possibility of removing the data from the server. Requests for transfer of de-identified data will be considered by the Steering Group, and, if approved, a collaboration agreement would be expected. The Steering Group will consider any cost implications, and cost recovery would be expected on a not-for-profit basis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEly EW, Brown LM, Fineberg HV; National Academies of Sciences, Engineering, and Medicine Committee on Examining the Working Definition for Long Covid. Long Covid Defined. N Engl J Med. 2024 Nov 7;391(18):1746-1753. doi: 10.1056/NEJMsb2408466. Epub 2024 Jul 31. PMID: 39083764.\u003c/li\u003e\n\u003cli\u003eCOVID-19 rapid guideline: managing the long-term effects of COVID-19 https://www.nice.org.uk/guidance/ng188 \u003c/li\u003e\n\u003cli\u003eAl-Aly Z, Davis H, McCorkell L, Soares L, Wulf-Hanson S, Iwasaki A, Topol EJ. Long COVID science, research and policy. Nat Med. 2024 Aug;30(8):2148-2164. doi: 10.1038/s41591-024-03173-6. Epub 2024 Aug 9. PMID: 39122965.\u003c/li\u003e\n\u003cli\u003eCai M, Xie Y, Topol EJ, Al-Aly Z. Three-year outcomes of post-acute sequelae of COVID-19. 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Br Med J, 1960; 1665. https://www.bmj.com/content/bmj/2/5213/1665.1.full.pdf \u003c/li\u003e\n\u003cli\u003eFried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146. PMID: 11253156.\u003c/li\u003e\n\u003cli\u003eRockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 30;173(5):489-95. doi: 10.1503/cmaj.050051. PMID: 16129869; PMCID: PMC1188185.\u003c/li\u003e\n\u003cli\u003evan Hees VT, Fang Z, Langford J, Assah F, Mohammad A, da Silva IC, Trenell MI, White T, Wareham NJ, Brage S. Autocalibration of accelerometer data for free-living physical activity assessment using local gravity and temperature: an evaluation on four continents. J Appl Physiol (1985). 2014 Oct 1;117(7):738-44. doi: 10.1152/japplphysiol.00421.2014. Epub 2014 Aug 7. PMID: 25103964; PMCID: PMC4187052.\u003c/li\u003e\n\u003cli\u003evan Hees VT, Gorzelniak L, Dean Le\u0026oacute;n EC, Eder M, Pias M, Taherian S, Ekelund U, Renstr\u0026ouml;m F, Franks PW, Horsch A, Brage S. Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity. PLoS One. 2013 Apr 23;8(4):e61691. doi: 10.1371/journal.pone.0061691. PMID: 23626718; PMCID: PMC3634007.\u003c/li\u003e\n\u003cli\u003eMigueles JH, Rowlands AV, Huber F, Sabia S, van Hees VT. GGIR: A Research Community\u0026ndash;Driven Open Source R Package for Generating Physical Activity and Sleep Outcomes From Multi-Day Raw Accelerometer Data. Journal for the Measurement of Physical Behaviour. 2019;2(3): 188-196. https://doi.org/10.1123/jmpb.2018-0063https://journals.humankinetics.com/view/journals/jmpb/2/3/article-p188.xml \u003c/li\u003e\n\u003cli\u003eSabia S, van Hees VT, Shipley MJ, Trenell MI, Hagger-Johnson G, Elbaz A, Kivimaki M, Singh-Manoux A. Association between questionnaire- and accelerometer-assessed physical activity: the role of sociodemographic factors. Am J Epidemiol. 2014 Mar 15;179(6):781-90. doi: 10.1093/aje/kwt330. Epub 2014 Feb 4. PMID: 24500862; PMCID: PMC3939851.\u003c/li\u003e\n\u003cli\u003eDoherty A, Jackson D, Hammerla N, Pl\u0026ouml;tz T, Olivier P, Granat MH, White T, van Hees VT, Trenell MI, Owen CG, Preece SJ, Gillions R, Sheard S, Peakman T, Brage S, Wareham NJ. Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study. PLoS One. 2017 Feb 1;12(2):e0169649. doi: 10.1371/journal.pone.0169649. PMID: 28146576; PMCID: PMC5287488.\u003c/li\u003e\n\u003cli\u003eSARS-CoV-2 IgG II Quant immunoassay. https://www.corelaboratory.abbott/int/en/offerings/segments/infectious-disease/sars-cov-2.html \u003c/li\u003e\n\u003cli\u003eJones, Karen C. and Weatherly, Helen and Birch, Sarah and Castelli, Adriana and Chalkley, Martin and Dargan, Alan and Forder, Julien E. and Gao, Minyue and Hinde, Seb and Markham, Sarah and Premji, Shainur and Findlay, D. and Teo, H. (2024) Unit Costs of Health and Social Care 2023 Manual. Technical report. Personal Social Services Research Unit (University of Kent) \u0026amp; Centre for Health Economics (University of York), Kent, UK 10.22024/UniKent/01.02.105685. (doi:10.22024/UniKent/01.02.105685) (KAR id:105685).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy Design\u003c/h2\u003e\n\u003cp\u003eA parallel group, 1:1 randomized, controlled clinical trial in adults with a diagnosis of COVID-19 in the preceding 12 months was undertaken in NHS Scotland. Ethical approval was granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (reference: GN20CA537). The protocol schedule, amendments and enrolment by site are described in the Supplement (Tables S1-S2, respectively) and the study design has been published [12]. All participants provided written informed consent. The study was publicly registered before the first participant was randomized (Clinicialtrials.gov ID NCT04900961).\u003c/p\u003e\n\u003ch2\u003eSetting and Population\u003c/h2\u003e\n\u003ch3\u003eSetting\u003c/h3\u003e\n\u003cp\u003eThis multi-center trial included sites in Glasgow (Queen Elizabeth University Hospital and Glasgow Royal Infirmary) and Dundee (Ninewells Hospital) in Scotland.\u003c/p\u003e\n\u003ch3\u003ePopulation\u003c/h3\u003e\n\u003cp\u003eParticipants were classified according to clinical presentation as not hospitalized due to COVID-19 but persisting symptoms for at least 4 weeks leading to medical review (\u003cem\u003eGroup A\u003c/em\u003e); discharged after hospitalization for COVID-19 and with persistent symptoms for at least 4 weeks (\u003cem\u003eGroup B\u003c/em\u003e); or convalescing in hospital after hospitalization for COVID-19 (\u003cem\u003eGroup C\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eParticipants enrolled in the community were included in Groups A and B whereas participants enrolled during hospital admission were in Group C.\u003c/p\u003e\n\u003ch2\u003eEligibility criteria\u003c/h2\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003col\u003e\n \u003cli\u003eDiagnosis of COVID-19 confirmed by:\u003col style=\"list-style-type: lower-alpha;\"\u003e\n \u003cli\u003eVirology PCR positive laboratory diagnosis and/or point of care test positive for COVID-19, or,\u003c/li\u003e\n \u003cli\u003ePositive Lateral Flow Test, or,\u003c/li\u003e\n \u003cli\u003ePositive COVID antibody Test;\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003eWithin 12 months of diagnosis;\u003c/li\u003e\n \u003cli\u003ePersistent symptoms for at least 4 weeks from symptoms onset (Groups A \u0026amp; B only);\u003c/li\u003e\n \u003cli\u003ePresentation type - one of group A, B or C.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003col\u003e\n \u003cli\u003eInpatient physiotherapy currently part of standard care post-ICU;\u003c/li\u003e\n \u003cli\u003eNo expectation of being able to walk within three months;\u003c/li\u003e\n \u003cli\u003eUnable to provide informed consent;\u003c/li\u003e\n \u003cli\u003eUnable to comply with the protocol;\u003c/li\u003e\n \u003cli\u003eKnown pregnancy.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOn 14 December 2022, given the reduction in incident cases of COVID-19 in the community, the initial eligibility period of 6 months from the diagnosis of COVID-19 (protocol versions 1, 2 and 3) was extended to 12 months (protocol versions 4).\u003c/p\u003e\n\u003ch2\u003eControl group\u003c/h2\u003e\n\u003cp\u003eThe comparator was usual care for Long Covid in line with clinical practice guidelines from the National Institute for Healthcare Excellence 188 guideline [2], with no non-routine contacts from the clinical research team.\u003c/p\u003e\n\u003ch2\u003eIntervention\u003c/h2\u003e\n\u003cp\u003eAn exercise programme was co-designed by exercise physiologists, physiotherapists and individuals with lived experience of Long COVID. Specifically, the intervention was developed through discussions with patient groups around the potential needs of the individual during the exercise intervention, such as staff contact, need for a seated (chair-based) exercise option, and personalization of the exercises, followed by practical exercise sessions involving patients who were hospitalized with COVID-19.\u003c/p\u003e\n\u003cp\u003eFor participants assigned to the intervention group, an instructional pack was provided by research nursing staff, supported by an exercise physiologist (S.G.), to participants. The pack included a guidance document, an exercise log and links to online videos (Supplement). The pack was given to participants during an initial face-to-face consultation where the nurse/therapist helped to select the most suitable category and level of exercise for the participant, and to demonstrate the exercises and ensure the participant was comfortable performing the exercise options. Every 2 weeks a member of the research team contacted each participant by telephone or online video consultation to ensure they were comfortable with the exercises and to help overcome any issues that may have arisen. If the participant was a hospital inpatient then the contact was undertaken daily, as needed.\u003c/p\u003e\n\u003cp\u003eThe intervention occurred in the community (Groups A and B) or in-hospital and then at home after discharge (Group C). Participants were asked to perform exercises daily. The number of exercise repetitions that lead to a validated resistance exercise specific Rating of Perceived Exertion (RPE) of 8-10 (3-5 in the first week) was determined [18]. The use of RPE to prescribe and titrate resistance exercise is as efficacious as other more complex methods but reported to be the most tolerable and enjoyable method [19]. The intervention was tailored according to the preferences of the participant and progress achieved. When a participant attained over 15-20 repetitions of each exercise, they were advised to move to the next difficulty level within each category, and once able to do this for the top level within the category, to then move to the next category. Similarly, if a participant was unable to manage 5 repetitions of each exercise, they were advised to move down a level and, if at the bottom level within a category, to then move down a category. Participants were encouraged to progress the level of exercise according to their preferences and not to exceed their perceived limit. They were advised that the number of repetitions would vary day to day, depending on symptoms, and if they were particularly fatigued then an interval day of rest without exercise was acceptable.\u003c/p\u003e\n\u003cp\u003eThere were 3 categories within the pack with exercise guidance provided according to the status of the participant: 1) bed-bound, 2) up-to-sit, or 3) ambulatory, and within each category the exercises had different levels of physical exertion to allow progression or regression, as appropriate. The exercises were:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eBed-bound: lying chest-press, lying row, lying plantar flexion, lying leg press and bridging;\u003c/li\u003e\n \u003cli\u003eUp-to-sit: seated chest-press, seated row, seated lateral raises, seated leg extension, seated plantar flexion, squats;\u003c/li\u003e\n \u003cli\u003eAmbulatory: press-ups, standing lateral raises, seated rows, lunges, calf-raises, squats.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eParticipants were asked to perform upper body exercise initially and bring in the lower body exercises in week 3. The exercise log was intended to be completed by the participant after an episode of exercise activity had been undertaken, whether it was completed and whether any adverse effects occurred. Additional information on the intervention is described in the Supplement.\u003c/p\u003e\n\u003ch2\u003eRandomization and Blinding\u003c/h2\u003e\n\u003cp\u003eThe details of randomization and blinding are described in detail in the Supplement. Participants were allocated in a 1:1 ratio to usual care or usual care plus a personalized resistance exercise intervention for 12-weeks. Allocations were determined using a minimization algorithm with a small random element, designed to ensure balance with respect to study site, clinical presentation group (A, B, or C), history of COVID pneumonia, age (\u0026lt;40, 40-49, 50-59, 60-69. 70+), and sex. Allocations were assigned after baseline data collection, via the study-specific online data collection tool, developed and maintained by staff at the Robertson Centre for Biostatistics, University of Glasgow. Study participants and research staff delivering the intervention were unblinded to group allocations, but statistical staff were blind until the point of database lock. The Statistical Analysis Plan was finalized, and all statistical programs were written and validated prior to database lock and unblinding.\u003c/p\u003e\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003ch3\u003ePrimary outcome\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the incremental shuttle walk test. This is an externally paced incremental walking test developed as a measure of exercise capacity [20].\u003c/p\u003e\n\u003cp\u003eParticipants were required to walk around two marker cones, 9 m apart, placed 0.5 m from each endpoint (10 m course) with an initial speed of 0.5 m/s, increasing 0.17 m/s every minute. Audio cues (beeps) signal the time at which the participant should turn at the marker. The test has 12 levels (walking speeds) and the maximum duration of the test is therefore 12 minutes. No encouragement was given during the test: the only verbal cues provided referred to an impending increase in walking speed [21]. The incremental shuttle walk test performance was defined as the distance achieved [21] and oxygen saturation and heart rate were measured [22].\u003c/p\u003e\n\u003cp\u003eThe duration of the incremental shuttle walk test correlates with peak oxygen consumption (ml/min/kg) and has population reference values for distance walked (m) [23]. The test has been evaluated and validated in several populations, including in healthy women [24], young men [25], in obese individuals [26] and patients with chronic respiratory disease [13, 20-22]. The incremental shuttle walk test is recognized for being safe and responsive to the effects of rehabilitation in populations with chronic respiratory disease [22] and stakeholder organizations support the use of this test as an efficacy measure in clinical trials [21]. The minimum clinically important difference is 35.0 m [13].\u003c/p\u003e\n\u003ch3\u003eSecondary outcomes\u003c/h3\u003e\n\u003cp\u003eThe following secondary outcomes were assessed:\u003c/p\u003e\n\u003ch4\u003eRespiratory function\u003c/h4\u003e\n\u003col\u003e\n \u003cli\u003eSpirometry\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch4\u003ePhysical function\u003c/h4\u003e\n\u003cp\u003e2. Handgrip strength\u003c/p\u003e\n\u003cp\u003e3. Short Physical Performance Battery (SPPB) [27]\u003c/p\u003e\n\u003ch4\u003ePatient reported outcome measures\u003c/h4\u003e\n\u003cp\u003e4. Health-related quality of life (Euroqol-5 dimension (EQ5D)) [28]\u003c/p\u003e\n\u003cp\u003e5. Patient health questionnaire-4 (PHQ-4) [29]\u003c/p\u003e\n\u003cp\u003e6. Illness perception (Brief IPQ) [30]\u003c/p\u003e\n\u003cp\u003e7. Duke Activity Status Index (DASI) [31]\u003c/p\u003e\n\u003cp\u003e8. International Physical Activity Questionnaire (IPAQ-SF) short-form [32]\u003c/p\u003e\n\u003ch4\u003eFatigue\u003c/h4\u003e\n\u003cp\u003e9. Medical Research Council (MRC) dyspnea score\u003c/p\u003e\n\u003ch4\u003eFrailty\u003c/h4\u003e\n\u003cp\u003e10. Fried frailty phenotype: five criteria: weight loss; exhaustion; grip strength; low physical activity; and slow walking pace [34]\u003c/p\u003e\n\u003col start=\"11\"\u003e\n \u003cli\u003eClinical Frailty Scale [35]\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch4\u003eClinical outcomes\u003c/h4\u003e\n\u003cp\u003e12. Episodes of healthcare\u003c/p\u003e\n\u003cp\u003e13. Hospitalization for any reason.\u003c/p\u003e\n\u003ch2\u003eAdditional prespecified outcomes\u003c/h2\u003e\n\u003col\u003e\n \u003cli\u003eVital parameters of cardio-respiratory function e.g. oxygen saturation, heart rate, respiratory rate at baseline and during follow-up\u003c/li\u003e\n \u003cli\u003eAdherence with exercise (intervention group)\u003c/li\u003e\n \u003cli\u003ePost-exercise adverse events and malaise: adverse events during and after exercise were assessed in all participants. Following a protocol amendment, the DePaul Symptom Questionnaire (Short Form) was assessed in a subgroup.\u003c/li\u003e\n \u003cli\u003eAccelerometery (Glasgow site) - Participants were issued with a GENEActiv (ActivInsights Ltd, United Kingdom) accelerometer and instructed to wear this 24 h per day for a 7-day period. The accelerometer was set to record at 100 Hz. Acceleration data were collected and calibrated to local gravity [36-38] and physical activity levels were quantified using GGIR, with methods previously described [39]. A valid day was defined as having \u0026gt;16 hours of data in it, and we excluded participants with less than 3 valid days of data or if wear data were not present for every 15 minutes of the 24-hour cycle, to ensure data was representative of a complete seven-day measure [40].\u003c/li\u003e\n \u003cli\u003eCOVID-19 serology using the SARS-CoV-2 IgG II Quant assay [41] (Supplement).\u003c/li\u003e\n \u003cli\u003eCosts of the intervention: the costs relating to staff time and consumables were estimated [42]. These included 1) the time of the exercise physiologist to design the intervention, prepare the exercise guideline to be used by the participants, provide training, support and supervision for healthcare staff in delivering the intervention, and support the follow-up calls with participants; 2) healthcare staff time to provide the intervention to the participant visit was estimated; 3) consumables i.e. resistance bands, and 4) transport costs for one visit to the site for the initial visit.\u003c/li\u003e\n\u003c/ol\u003e\n\u003ch2\u003eBias minimization\u003c/h2\u003e\n\u003cp\u003eBias minimization procedures involved random allocation of the participants, masking of participants at the time of follow-up to baseline results, and retention strategies, such as by providing follow-up contacts to support the participants and minimize withdrawals. Outcome assessors were not blinded to group allocation.\u003c/p\u003e\n\u003ch2\u003eStatistics\u003c/h2\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eA pre-determined sample size calculation was devised by bio statistician co-authors. The minimum clinically important between-group difference in the incremental shuttle walk test at follow-up (3-months) = 46 m, SD=105 [21], sample size for 80% power, 5% significance, no loss to follow-up (LTFU) = a minimum of 85 per group; allowing for LTFU and incomplete data, the sample size is n=110 per group (n=220 total).\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eThe primary and secondary outcomes were analyzed using linear regression (continuous outcomes), logistic regression (binary outcomes), or proportional odds logistic regression (ordinal outcomes). All models were adjusted for the baseline value of the incremental shuttle walk test distance.\u003c/p\u003e\n\u003cp\u003eDue to differing characteristics between sites, the model was not adjusted for site. In order to approximate normality in model residuals, a second model was fitted where ISWT distance at baseline and three months follow-up was square root transformed prior to analysis, the estimate provided in this case was on the square root scale. Estimates were provided from both models fitted to both the original data and the transformed data.\u003c/p\u003e\n\u003cp\u003eRegression models were used to assess treatment effects within pre-specified subgroups, through the use of treatment-by-subgroup interactions. For linear regression analyses, the distribution of model residuals were visually assessed for Normality; where appropriate, outcomes were transformed to improve model fit. Tests of the proportional odds assumption (for treatment group) were used for ordinal regression models. All tests were two-tailed and assessed at the 5% significance level. Missing outcome data were not imputed, though for the primary outcome, a post hoc analysis was performed with multiple imputations for the missing outcomes. Because of the potential for type 1 error in the analyses of secondary outcomes, these outcomes should be interpreted as exploratory. The statistical analyses were conducted using R Studio and R version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) according to a pre-specified Statistical Analysis Plan (SAP).\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6269439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6269439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLong COVID, reflected by persistent symptoms, including breathlessness and fatigue, after coronavirus disease-19 (COVID-19) infection, presents an unmet therapeutic need. In this study, the effects of a resistance exercise intervention on exercise capacity and health status in individuals with Long COVID were investigated.\u003c/p\u003e \u003cp\u003eA two-arm randomized, controlled clinical trial including adults with a hospital or community diagnosis of COVID-19 in the preceding 12 months was undertaken. Participants were randomized to usual care or usual care plus a personalized resistance exercise intervention for 12 weeks. The primary outcome was the incremental shuttle walk test undertaken three months after randomization, with secondary outcomes including health-related quality of life (EQ-5D-5L), anxiety and depression (Patient Health Questionnaire) and grip strength. Adverse events and the DePaul Symptom Questionnaire (Short Form) were also assessed.\u003c/p\u003e \u003cp\u003eBetween May 2021 and April 2024, 233 individuals (median (interquartile range) 53.6 (43.8, 60.8) years; 146 (62.7%) female, 91 (39.1%) hospitalized with COVID-19) were randomized (n\u0026thinsp;=\u0026thinsp;117 (50.2%) intervention group, n\u0026thinsp;=\u0026thinsp;116 (49.8%) control group). The median (interquartile range) percentage adherence with the exercise intervention was 71.0 (47.8, 96.8). The mean (SD) distances achieved in the incremental shuttle walk test at baseline and at follow-up were 328 (225) m and 389 (249) m, in 224 and 193 individuals, respectively. The change in incremental shuttle walk test distance at three months compared to baseline was 83 (118) m in the intervention group (n\u0026thinsp;=\u0026thinsp;94) and 47 (95) m in the control group (n\u0026thinsp;=\u0026thinsp;98) (effect estimate (95%) confidence interval 36.4 (6.6, 66.2) m; p\u0026thinsp;=\u0026thinsp;0.017). By three months, compared to the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 (0.01, 0.11); p\u0026thinsp;=\u0026thinsp;0.020), Patient Health Questionnaire category (0.5 (0.2, 0.8); p\u0026thinsp;=\u0026thinsp;0.013) and handgrip strength (2.54 (0.89, 4.19) kg; p\u0026thinsp;=\u0026thinsp;0.003). In 99 individuals who completed the DePaul questionnaire, post-exertional malaise occurred in 40 (83.3%) individuals in the intervention group and 42 (82.4%) individuals in the control group. Five individuals in the control group and 1 individual in the intervention group experienced a serious adverse event (hospitalization) (p\u0026thinsp;=\u0026thinsp;0.119).\u003c/p\u003e \u003cp\u003eIn conclusion, a 12-week program of personalized resistance exercise in a community- and post-hospitalized population with Long COVID improved exercise capacity, health-related quality of life, anxiety and depression, and grip strength. Adherence with exercise was high and post-exercise malaise and adverse events were not increased.\u003c/p\u003e \u003cp\u003e \u003cb\u003eRegistration\u003c/b\u003e: Clinicaltrials.gov ID NCT04900961\u003c/p\u003e","manuscriptTitle":"Resistance Exercise Therapy for Long COVID: a Randomized, Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 12:32:27","doi":"10.21203/rs.3.rs-6269439/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fe6edd33-9a3c-4564-9e5e-c20b61ac59ac","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46265175,"name":"Health sciences/Medical research/Outcomes research"},{"id":46265176,"name":"Health sciences/Health care/Disease prevention/Lifestyle modification"}],"tags":[],"updatedAt":"2025-04-17T15:56:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 12:32:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6269439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6269439","identity":"rs-6269439","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}