Effect of Combined Exercise Training Physical and Functional Capacity in Post-Covid Patients

DOI: https://doi.org/10.21203/rs.3.rs-2010104/v1

Abstract

The purpose of this study was to investigate the effects of supervised moderate combined exercise training in patients with post-COVID in the physical and functional capacity. Forty-one patients completed 6-week combined moderate exercise training. In baseline and after intervention, patients were assessments of screening, including clinical data and anthropometrics performed functional tests, which consisted of handgrip strength test, chair sit and reach test, arm curl test, 30-sec sit to stand test, timed up and go, and six-minute walk test (6MWT). Primary outcomes were results of functional tests, and secondary outcomes were clinical data. Handgrip strength (p < 0.001), flexibility (p = 0.01), strength of upper (p = 0.01) and lower limbs (p < 0.001), gait speed (p < 0.001) and 6MWT (p < 0.001) improved after rehabilitation. Resting heart rate, systolic and diastolic blood pressure were lower after intervention (p = 0.01; p = 0.05; p = 0.03, respectively). No one difference was observed in persistent symptoms (p > 0.05). In conclusion, exercise training promoted great physical, functional and cardiovascular benefits for post-COVID patients.

Introduction

After the outbreak in 2019, coronavirus disease (COVID-19) developed into a major public health issue [1]. In the acute phase, about 30% of patients develop acute respiratory distress syndrome (ARDS) by massive alveolar damage and require hospitalization [2]. Besides pulmonary damage, a longer length of stay in hospital could be related to functional decline after discharge because of skeletal muscle impairments in patients with COVID-19 [3]. In fact, some patients could develop sequelae and/or persistence of symptoms after acute recovery, and about 60% of patients still presented fatigue post-viral infection [4]. Hence, patients tend to show reduced functional capacity and exercise intolerance due pulmonary and/or neuromuscular impairments [5].

In other pulmonary or neuromuscular diseases, like chronic obstructive pulmonary disease (COPD) [6], idiopathic fibrosis [7], myopathies [8], and chronic fatigue syndrome (CFS) [9], exercise training is safe and effective to improve functional capacity. For these patients, previous studies have showed a large range of benefits after interventions by exercise, such as: improved forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) [10], reduced breathlessness and fatigue [11, 12], attenuated of inflammatory response [13]; maintenance (without worsening) of oxidative stress levels [14], with functional gains. Interestingly, some of these variables are abnormal in COVID-19 patients, and they are related to Long COVID syndrome. Therefore, physical exercise could be a possible candidate to improve some of these variables in COVID-19 patients.

The physical exercise as a rehabilitation tool has been discussed since the beginning of the elaboration of recovery strategies for COVID-19 patients, and their importance has been demonstrated within the context that involves the treatment of this disease, because the potential benefits of exercise are related to cardiovascular, neurological, respiratory, immune and musculoskeletal systems [15, 16]. Moreover, some studies have showed an inverse relationship between physical activity level and prevalence of hospitalization [17], severity of COVID [18, 19], and length of stay in hospital [20]. Initially, due the pulmonary damage, it was believed that exercise intolerance in post-COVID patients was related only to respiratory system impairment, but analyzing inpatient and outpatient frailty it was identified that peripheral factors are the major determinants [5], indicating to increase the practice of physical exercise in the many rehabilitation scenarios.

Therefore, the aim of this study was to investigate the effects of a supervised moderate combined exercise training in patients with post-COVID in the physical and functional capacity. We hypothesized that exercise training would improve physical and functional capacity.

Methods

Subjects

A statistical power analysis was performed using G*power 3.1 software (Kiel University, Germany). The number of participants required was calculated based in Liu et al. [21], and primary outcome was the 6MWT. Twenty-two participants were required to achieve a power of 0.80 and an alpha of 0.05.

Fifty patients previous diagnosed with COVID-19 by quantitative PCR viral test (qPCR) or blood test (serology) were recruited after being discharged from University Hospital of State University of Ponta Grossa. Of these, nine patients withdrew from the study, and forty-one completed and were included in analyses. The exclusion criteria were: a) patients under 18 years old; b) any other chronic disease with exacerbation; c) less than 7 days hospitalized by COVID-19; d) interval between discharge and enrolment in the rehabilitation > 3 months. The procedures were approved by the Human Research Ethics Committee (protocol number 4.429.866) and conducted in line with principles of the Declaration of Helsinki. All participants were informed about the aim and study protocols and signed an informed consent form prior to the enrolment.

Study design

All study participants underwent baseline assessments of screening, including clinical data and anthropometrics. Thereafter, they performed functional tests, which consisted of handgrip strength test, chair sit and reach test, arm curl test, 30-sec sit to stand test, timed up and go, and six-minute walk test (6MWT). During the subsequent six weeks, the patients completed supervised moderate combined exercise training twice a weekly. Finally, the subjects were reassessed performing the same baseline procedure.

Anthropometric and Functional Assessments

The patients’ weight and height was measured without shoes using a digital scale and a stadiometer, respectively. Blood pressure was measured with a digital pulse monitor (Omron, model HEM-6124, Japan) and fat mass was determined using a bioelectrical impedance (Sanny, model BIA1010, Brazil). Comorbidities and long-COVID symptoms also were registered.

Handgrip strength test was performed using a hydraulic dynamometer (Saehan, model Sh5001, South Korea), permitting 3 attempts in dominant hand, and the best result was recorded [22]. The sit and reach test was performed with a standard sit and reach box and participants were instructed to maintain the palms facing downwards, and the hands on top of each other, and the subjects reached forward along the measuring line as far as possible; 3 attempts were performed and the best value was used [23]. Arm curl test was performed with the dominant hand and the subjects were encouraged to curl the weight through the full range of motion of the elbow as many as possible for 30 seconds; men used a 4 kg dumbbell and women used a 2 kg dumbbell [24]. A 30-second sit to stand test (STS) was performed in a 43cm-chair and the participants were instructed to stand up and sit down with arms crossed against the chest as possible for 30 seconds; after 2 attempts the better result was used [24]. The Timed Up and Go (TUG) test was performed on a 3m flat line and patients were advised to stand up the chair, move as quickly until a cone, turn around and walk back to the chair and seat down [25]. 6MWT was performed on a 10m flat line and the participants were encouraged to walk as much distance as possible for 6 minutes [24].

Intervention

Intervention was planned according to the FITT principle. All patients completed six weeks of twice weekly supervised moderate combined exercise training. Completion of protocol was defined as having attended at least 9 of 12 sessions (75% of training frequency). It was performed 20 minutes of aerobic training (treadmill, cycle ergometer, step up) and 25 minutes of resistance training (chest press, low back row, seated leg press, knee extension in a machine). All sessions contained a warm-up and cool down period. It was measured peripheral oxygen saturation and blood pressure at the beginning and ending, and heart rate was continually monitored during the whole session period. Sessions are designed to achieve a 3–6 points in a perceived exertion scale (Borg 1–10), and the loads of training were adjusted according to the exercise tolerance of the participants throughout the intervention.

Primary Outcome

The primary outcome was result in functional tests, which were handgrip, flexibility, strength of upper and lower limbs, gait speed and 6MWT after intervention. For 6MWT, a value of 30.5 m, previously established in the literature to adults with pathology, was used as the minimal clinically important difference (MCID) for defining response [26].

Secondary Outcome

The secondary outcomes were clinical data, which was: resting cardiovascular variables (heart rate, systolic blood pressure and diastolic blood pressure), persistent symptoms (cough, dyspnea and musculoskeletal pain) and modified Barthel questionnaire.

Statistical analyses

Data are presented as mean and standard deviation or absolute and relative frequency. Shapiro-Wilk test was used to analyze normality data. Differences between baseline vs post-intervention were analyzed by Student t test and Wilcoxon test. For categorical analyses, the chi-squared test was used. Analyses were performed using SPSS v. 24 for Windows. A p value ≤ 0.05 was considered to be statistically significant.

Results

Baseline characteristics of the subjects are presented in Table 1.

Table 1

Characteristics of the subjects (n = 41).

Age (years)

49.18 ± 10.72

Sex (M/F)

18/23

Body Mass (kg)

81.53 ± 13.74

Height (cm)

163.24 ± 8.09

Body fat (%)

39.01 ± 10.04

LOS in hospital (days)

39.08 ± 22.74

Invasive ventilation (%)

37 (90.3)

Pulmonary thromboembolism (%)

19 (46.3)

Values in mean ± standard deviation or absolute and relative frequency. LOS = length of stay.

Table 2 shows results of intervention in the functional tests. There was an improvement in handgrip strength, flexibility, strength of upper and lower limbs, gait speed and 6MWT after intervention. In MCID criteria, 82,9% were defined as responders in 6MWT.

Table 2

Primary outcomes.

Functional tests

Baseline

Post-intervention

p

Handgrip strength (kgf)

19.20 ± 8.96

25.48 ± 9.11

< 0.001*

Sit and reach test (cm)

18.11 ± 9.42

20.01 ± 9.63

0.01*

Arm curl test (rpt)

14.24 ± 5.49

18.63 ± 4.06

< 0.001*

STS (rpt)

9.02 ± 3.75

13.00 ± 2.16

< 0.001*

TUG (s)

11.20 ± 5.82

7.87 ± 2.50

< 0.001*

6MWT (m)

252.93 ± 129.09

379.06 ± 122.92

< 0.001*

Values in mean ± standard deviation. STS = 30-second sit to stand test. TUG = timed up and go. 6MWT = six-minute walk test. * p ≤ 0.05.

In secondary outcomes, resting HR, SBP and DBP values are lower after intervention compared to baseline (p = 0.01; p = 0.05; p = 0.03, respectively) and modified Barthel index was improved significantly (p < 0.001). There was not any effect in persistent symptoms (p > 0.05).

Table 3

Secondary outcomes.

Cardiovascular variables

Baseline

Post-intervention

p

HR (bpm)

97.46 ± 14.40

89.61 ± 9.79

0.01*

SBP (mmHg)

130.82 ± 19.10

122.32 ± 15.05

0.05*

DBP (mmHg)

84.49 ± 13.49

77.66 ± 11.88

0.03*

Persistent Symptoms

Cough (%)

12 (29.3)

7 (17.1)

0.19

Dyspnea (%)

10 (24.4)

7 (17.1)

0.41

Musculoskeletal pain (%)

11 (26.8)

5 (12.2)

0.10

Modified Barthel index

46.60 ± 5.29

49.80 ± 0.97

< 0.001*

Values in mean ± standard deviation or absolute and relative frequency. HR = heart rate. SBP = systolic blood pressure. DBP = diastolic blood pressure. * p ≤ 0.05.

Discussion

The present study examined the effects of a combined exercise training in the physical and functional capacity in post-COVID patients. The main findings showed that exercise training improved physical and functional capacity, and reduced resting heart rate, systolic and diastolic blood pressure.

An important finding of the present study is the great improvement in functional capacity after supervised combined exercise training, corroborating others with similar protocols and outcomes [2732]. The handgrip strength increased in our study ~ 32,7% post-COVID rehabilitation. This result presented a higher improvement when compared to Mayer et al. [31] study, that evaluated handgrip strength after 8-week moderate-intensity rehabilitation and observed an improvement of ~ 15,1% and Nambi et al. [32] with post-COVID sarcopenic patients in which observed improvement of ~ 10,9% after 8-week low-intensity rehabilitation. This magnitude difference probably occurred due Mayer et al. [31] performed an ICU recovery previous to outpatient rehabilitation and Nambi et al. [32] analyze community-dwelling elderly with post-COVID, and both studies had higher baseline values than compared to present study. About STS, De Souza et al. [28] showed a significant improvement after 6-week home-based rehabilitation (~ 53,5%). Although De Souza et al. [28] evaluated in non-ICU patients, the magnitude of improvement was similar to observed in our study (~ 44,1%) after a supervised exercise training in severe patients. It is according to Dalbosco-Salas et al. [33] results, which they showed that non-hospitalized, non-ICU and ICU COVID patients had similar improvement in STS after telerehabilitation, but hospitalized patients had lower baseline values. Therefore, rehabilitation with physical exercise is effective to improve STS in post-COVID patients.

The present study also demonstrated that after intervention there was a better performance in flexibility and upper limb strength tests. There are not, to our knowledge, studies that examined effects of exercise rehabilitation in flexibility and upper limb strength. Some of the severe patients develop critical illness polyneuropathy [34], and this adverse outcome could be related to a lower upper limb strength and flexibility after discharge from hospital.

Mayer et al. [31] and Udina et al. [35] demonstrated a faster gait speed after intervention, although Mayer et al. [31] observed an improvement only in supervised rehabilitation, but not in telerehabilitation, and Udina et al. [35] observed that ICU patients had greater change in gait speed test after early rehabilitation. Our findings corroborate these previous studies, which showed a great improvement in gait speed test after supervised rehabilitation with mostly ICU patients. Betschart et al. [27] and Everaerts et al. [29] evaluated 6MWT and showed a changed of 88 m (95% CI, 52–125 m) and 86 m (95% CI, 53–175 m) in 8 and 6 weeks of exercise training, respectively. The present study showed a change of 121.8 ± 69.1 m (~ 49,8%) in 6 weeks of intervention, but baseline values were lower than above-mentioned studies. Hermann et al. [30] and Liu et al. [21] also observed a great change in 6MWT after intervention (baseline = 241.3 ± 154.4 m, change ~ 56%; baseline = 162.7 ± 72.0 m, change ~ 31%, respectively) with post-invasive ventilation patients and elderly patients, respectively, and their baseline values were similar to the present study, however, Liu et al. [21] did not use physical exercise for their pulmonary rehabilitation. These results demonstrated that higher changed occurred in the group of patients with lower baseline 6MWT. Thus, the present study reinforces that physical exercise is a key component in the rehabilitation of post-COVID patients and their benefits are related to whole-body conditioning.

After 6 weeks intervention, resting heart rate, systolic and diastolic blood pressure in post-COVID patients presented lower values when compared to baseline. Resting heart rate declines with exercise training and it is strongly associated with higher cardiorespiratory fitness [36, 37]. In general, some mechanisms could be related to lower resting heart rate after exercise training, and in healthy subjects is due to intrinsic heart rate mechanism [36]. In addition, post-COVID patients may present dysautonomia [38], and mechanisms of heart rate control could be different in these patients, although further studies are necessary to investigate this hypothesis. Angeli et al. [39] observed that blood pressure increased during hospitalization from patients hospitalized by COVID-19, and about 45% persist with higher blood pressure when compared to admission, due a reduction of the angiotensin 1–7, a potent vasodilator, and ACE2 receptor deficiency. In turn, Cornelissen and Smart [40] observed in a meta-analysis that combined exercise training does not reduce systolic blood pressure, but it is effective to reduce diastolic blood pressure. Notwithstanding, Naci et al. [41] showed lower systolic blood pressure after exercise training, but the authors observed that the decrease in systolic blood pressure after exercise training is more pronounced in patients with higher cut-off values. These findings demonstrated that response of blood pressure after exercise intervention is similar to healthy, although the mechanisms could be different.

The percentage of patients with persistent symptoms was not significantly modified after intervention. Nevertheless, in a cohort study, Seeßle et al. [42] showed that frequency of dyspnea and fatigue were higher after 12 months from discharge by COVID when compared to 5 months after discharge, and patients reporting at least 1 symptom presented reduced exercise capacity and reduced physical quality of life. The physiopathology of Long COVID syndrome still needs to be clearly defined, however, there are cardiorespiratory, immune, neurological and hormonal involvement [43]. On the other hand, physical exercise is effective to reduce symptoms and improve quality of life in many chronic diseases [44], and in the context of COVID, exercise could be an inhibitor from spiral related to inflammation [45]. Furthermore, persistent symptoms could be related to sedentary behavior, and engaging in exercise intervention should prevent exacerbation of these symptoms after discharge from COVID.

Some limitations of the present study were: there is not a control group, and it is not possible to distinguish results from rehabilitation to spontaneous physical recovery. Because of COVID-19 is very debilitating condition, all the patients were forwarded to rehabilitation. The sample of the study was formed by severe patients, but not by disability patients, and these results may not be reliable in disability or bed rest patients. Follow-up was not evaluated, and it is not possible to extrapolate these results over time.

Conclusion

A supervised moderate combined exercise training promoted great physical and functional benefits for post-COVID patients. Similarly, exercise training reduced resting heart rate and blood pressure and induced a full functional independence.

Declarations

Acknowledgments

The authors are grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) for the scholarship granted to the post-graduate student participating in the study.

Declaration of interest statement

The authors report no conflicts of interest.

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