Low or Moderate Intensity Aerobic Training: Its Role in Clinical and Psychological Aspects of Community Dwelling COVID-19 Asymptomatic Older Adults With Sarcopenia Symptoms

Background: Sarcopenia is the major health concern and common consequence of COVID-19 in the aging population. Moreover, this clinical condition has not been considered in usual physical rehabilitation practice and nor its exercise protocol is well de�ned, which requires a meaningful study in this �eld. Objective: To �nd and compare the low and moderate intensity aerobic training protocols on clinical and psychological effects in community dwelling COVID-19 asymptomatic older adults with Sarcopenia symptoms. Methods: By using computer random table method the eligible participants were randomized into two groups. First group received low-intensity aerobic training (LAT; n = 38) and the second group received moderate-intensity aerobic training (MAT; n = 38) for 8 weeks. Clinical (muscle strength, muscle mass and physical performance) and psychological (kinesiophobia and quality of life) measures were measured at baseline, at 4th week, 8th week and at 6 month follow up. Results: Baseline demographic and clinical attributes show homogenous presentation among the study groups (p>0.05). After eight weeks of different aerobic trainings, and at the end of 6 months follow up, the hand grip strength, -3.0 (CI 95% -4.16 to -1.83), chair stand test -2.7 (-3.29 to -2.10), physical performance -0.08 (-0.10 to -0.05), kinesiophobia, 4.2 (3.25 to 5.14), and quality of life -5.7 (-8.4 to -2.9) shows more improvement (p<0.001) in LAT group than MAT group but in muscle mass both groups did not show any signi�cant difference (p>0.05). Conclusion: This study reports that low intensity aerobic training exercises improve the clinical (muscle strength and physical performance) and psychological (kinesiophobia and quality of life) aspects than moderate intensity aerobic training in COVID-19 asymptomatic older adults with Sarcopenia symptoms. At the same time both types of aerobic training exercises have negligible or little role in increasing the muscle quantity - cross sectional area.


Background
The world has been suffering from corona virus disease (COVID- 19) since December 2019 and it is declared as a pandemic disease by world health organization (WHO).It is a major health concern for humans, especially in the age group of 60 years and above, also, it is a social and economic burden on the society. 1 Corona virus enters into the body through nasopharyngeal root and infects almost all parts of the body.The special protein present in the spikes of the corona virus attaches with the angiotensin converter enzyme 2 receptor present on the cell membrane and easily penetrates into the cell. 2 People infected with COVID-19 not only shows it's signs and symptoms, but also show it's high life threatening risks according to the comorbidities such as; age above 60 years, respiratory problems, cardiac problems and diabetes. 3It is observed that, patients with COVID-19 undergoing physical inactivity, sedentary activity; prolong bed rest or sometimes on ventilator therapy may develop muscle weakness at a later stage.This group of population is also suffer from muscle pain; muscle atrophy, weight loss and anorexia. 1Sarcopenia is one such major issue in COVID-19 scenario which needs to be taken care of in the physiotherapy context.Sarcopenia is the major health concern and common consequence of COVID-19 in the aging population.The word, Sarcopenia (Greek, Sarx for " esh" and Penia for "loss") has been coined by Irwin Rosenberg in   1988, and de ned sarcopenia as a state of deterioration of muscle mass and its function by aging. 4In 2018, European Working Group on Sarcopenia in Older People (EWGSOP) recognized Sarcopenia as a disease of muscles with an international classi cation code of ICD-10-MC, which if untreated leads to poor quality of life and high mortality rate. 5The number of sarcopenia admission in hospitals has increased to 5 times that of the regular time in this COVID-19 situation. 6It is clinically characterized by diminished muscle functions with muscle atrophy. 7Sarcopenia is classi ed into primary and secondry, the primary type of sarcopenia can be seen in aging populations while the secondary type of sarcopenia is associated with other systemic diseases. 8 this present COVID-19 scenario, the requirement of social isolation leads physical inactivity and sedentary life style which accelerates muscle atrophy and diminish the muscle function. 9It also shows physiological changes in our body such as in ammatory changes, reduced albumin, decrease mitochondrial activities, disturbed neuromuscular junction conduction, hormonal imbalances, anorexia, insomnia, weight reduction, myalgia, loss of muscle mass and its properties. 10,11The in ammatory biomarker analysis shows increased C-reactive protein (CRP) and other in ammatory cytokines such as TNF-α, IL-1 and Il-6, these changes are due to ACE2 receptor mechanism.The changes in in ammatory cytokines are the causes of anorexia, insomnia and altered taste sensation. 12,13The main cause of weight reduction and myalgia is physical inactivity during this lock down phase following COVID-19 which was observed by Sheahan et al on animal studies. 14Considerable number of aged patients diagnosed with COVID-19 has respiratory problems, this result in secondary sarcopenia and such patients were recommended to do regular exercises to prevent these consequences. 15 this pandemic situation sarcopenia may cause high rate of mortality and physical disability.Izquierdo M et al stated that regular physical activities and exercise therapy is required to maintain the muscle mass and prevent atrophy in geriatric patients over the age of 60. 16 In the same way, aged patients who developed sarcopenia during COVID − 19 require regular physical activity and exercise to maintain the physiological and psychological traits.Furthermore, the recognition of sarcopenia as a high consideration for adverse health condition in aged COVID-19 patients has ignited a question for the researchers to attempt to devise an exercise protocol to overcome these consequences.Also, this clinical condition has not been considered in usual physical rehabilitation practice and nor its exercise protocol is well de ned, which requires a meaningful study in this eld.Hence this study was aimed to nd and compare the different aerobic training protocols on clinical and psychological effects in community dwelling COVID-19 asymptomatic older adults with Sarcopenia symptoms.The outcomes of the study could provide a new evidence and clear idea about the selection of exercise protocols in sarcopenia in clinical practice.The reports may also helpful for the therapists to prevent, delay, treat and reverse the symptoms of Sarcopenia in COVID-19 infection.

Trial Design
This is a randomized, double-blinded, prospective, controlled study conducted from January 2020 and August 2020.The study obtained the previous study ethical approval from department of ethical committee (DEC), Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia with the reference number of RHPT/020/044.The participant's consent form, intervention procedures and the outcome measures used were also approved by the DEC.All the participants selected for the nal study were instructed to complete the written informed consent form and they were undergone for baseline demographic and clinical measurements.By using computer random table -simple random sampling method the participants were randomized and allocated into three groups.First group received lowintensity aerobic training (LET; n = 38) and the second group received moderate-intensity aerobic training (MET; n = 38) for 8 weeks.

Participants
Participants were referred from local and government hospitals in Al-Kharj and Riyadh region of Saudi Arabia.The study registered both genders with the age range of 60-80 years with the positive diagnosis of asymptomatic COVID-19 infection.Sarcopenia (skeletal muscle loss) was identi ed through appendicular skeletal muscle mass index (ASMI, kg/m2).Based on AWGS criteria, ASMI score < 7.0 kg/m2 for men and < 5.7 kg/m2 for women were diagnosed as Sarcopenia 17 and were included in the study.Subjects with low muscle mass in observation, low hand grip strength (< 24 kg for men or < 16 kg for women) and slow gait speed (< 0.7 m/sec) were included.Participants with prior exercise training, under medication, history of lower limb surgeries, fractures, cardiac problems, respiratory problems, neurological problems, systemic problems and any other contra indications for aerobic training were excluded.The Fig. 1 shows the ow of study participants throughout the study.

Intervention
Participants (n = 38) in LAT group underwent low-intensity aerobic training for 8 weeks.All the participants were instructed about the guidelines for performing the LAT exercises by a trained physiotherapist with proper COVID-19 guidelines.The exercises performed by the participants were maintained in an exercise log book and was checked every week by a physiotherapist.Before every session, the vital signs such as temperature, blood pressure (BP), oxygen saturation, heart rate and physical status were measured.If the vital signs were not suitable, like temperature > 38 o C, BP > 160/100 mmHg and pulse rate > 100 beat per minute or < 50 beat per minute, participants were instructed not to do exercises on that day.
The intensity of the given exercise can be measured through maximum heart rate (MHR) and it can be calculated by subtracting the participant age from 220.In low intensity aerobic exercises 40 to 50 percentage of maximum heart rate can be used.Each session started with 15 minutes of warm-up, which includes stretching of upper limb and lower limb muscles.Following warm up, the participants were instructed do 30 minutes of low-intensity aerobic training (LAT) exercises, which includes 20 minutes of treadmill (Reebok Fitness, GT50) and 10 minutes of cycle ergometer (JX Fitness, JX-7056), followed with 10 minutes of cool down.In moderate intensity exercises the same protocol has been followed, but the intensity of exercises was xed between 50% to 70% of MHR. 18,19e progressive resistance training (PRT) was prescribed to all the participants in both the groups with weights based on individual personal strength assessment basis.The optimum resistance required for the muscle groups were decided based on one repetition maximum (RM).The major group muscles such as shoulder exors, shoulder extensors, shoulder abductors, elbow exors, elbow extensors, hip exors, hip extensors, knee exors, knee extensors, abdominal and back muscles were trained.Each group of muscles was trained for 10 repetitions for 3 sets with a rest period of 5 minutes.The resistance was increased gradually as per the individual requirements and the training was given 4 days in a week for 8 weeks. 20

Outcome measures
Hand grip strength It is a simple and cost effective test to measure the upper limb strength and it was measured with handheld dynamometer ( Camry digital hand dynamometer, EH 101 − 17).The participant was asked to press the handle as much as possible and the scores were noted.Three measurements were taken and the average value was included for data analysis and it is a valid and reliable tool to measure the upper limb strength. 21air stand test It is the test to measure the lower limb muscle strength, which measures the amount of time the participant taken to rise from the sitting position for ve times without any support.It was measured in seconds and reliable and validated test to measure lower limb muscle strength. 22

Muscle quantity
Muscle quantity or muscle mass was measured with Magnetic resonance imaging (MRI) scan (Philips Ingenia, 1.5 TS, MA, USA) and it is a non-invasive type of measurement.The three major muscle cross sectional areas such as mid of arm (biceps), mid of thigh (quadriceps) and mid-calf muscles were measured. 23

Physical performance
It is measured with gait speed test and the participant was asked to walk fast for 4 minutes and the speed was measured with digital stop watch.It is a reliable, simple and safe test to measure the physical performance in Sarcopenia patients. 24

Kinesiophobia
Tampa scale of kinesiophobia (TSK -11) was used to measure the fear of movement due to muscle weakness.It consists of 11 questions that include somatic factors and activity avoidance and was measured in 4 point likert scale.Highest scores indicate maximum fear and lowest scores indicate minimum fear of movement.It is a reliable and valid tool to measure kinesiophobia in aged patients with Sarcopenia. 25 Quality of life It was measured subjectively by SarQol questionnaire and the participant was asked to complete the questionnaire by himself.It measures the physical, psychological and social aspects of health of sarcopenia patients and it is a reliable and valid tool. 26

Sample size
The number of participants required was calculated through a basic data from the previous pilot study. 27he primary outcome variable selected was hand grip strength and 35 participants were required in each group with the objective of improving mean difference 40% and standard deviation of 2. When considering 10% drop out the number of subjects were increased to 38 in each group and totally 76 participants were recruited.The power of the study was set at 80% and the signi cance level was 0.05 and the sample size was calculated using G*Power (version 3.1.9.7) statistical science software.

Statistical analysis
The participants' demographic and clinical characters were presented and tabulated and analyzed for study homogeneity using Kolmogorov-Smirnov test.The baseline, after 4 weeks, 8 weeks and 6 months follow up measurements of primary and secondary variables were measured and presented as mean ± standard deviation (SD).Intention to treat analysis was presumed in the treatment effect analysis with replacing missing data.The 2 × 4 multiple analysis of variance (MANOVA) was performed to measure the group × time effect of each variables.Independent t test was performed to nd the difference between the treatment groups and repeated measures analysis of variance (ANOVA) was performed to nd the intra group effects.The whole statistical analysis was performed with IBM SPSS Statistics for Windows (version 20.0) and the statistical signi cant value was set at 0.05.

Results
Out of 121 screened participants, sixteen participants had other systemic problems, nine had joint degeneration, eight were awaiting some surgery and twelve participants were not given consent to participate in the study and (N = 76) were eligible to participate and they were randomized into two groups.The statistical test was conducted under intention to treat analysis principle and three subjects from LAT group and four subjects from MAT group were dropped at the end of 6 month follow up analysis (Fig. 1).The participant's demographic and clinical characters were analyzed between the groups for the study homogeneity by using Kolmogorov-Smirnov test and the test shows no signi cant difference in age, height, weight and body mass index (BMI) measures (p > 0.05) and the data represents suitable for further statistical analysis.The clinical exercise tness measures such as max VO 2 (Oxygen volume) and heart beat were measured for identifying to involve in aerobic exercise training, it also shows no signi cant difference and the data (p > 0.05) were presented as mean and SD in Table 1.

Discussion
This trial was conducted to compare and investigate the clinical (muscle strength, muscle mass and physical performance) and psychological (kinesiophobia and quality of life) effects of low or moderate intensity aerobic training in community dwelling COVID-19 asymptomatic older adults with Sarcopenia symptoms.The Sarcopenia and physical frailty in older people: multicomponent treatment strategies (SPRINTT) guidelines offered health practitioners to provide proper treatment strategies for older adults with Sarcopenia, which could be followed in COVID-19 scenario. 28Izquierdo M et al noted that older persons with Sarcopenia admitted in hospital or house quarantine for COVID-19 have to undergo regular exercise training for better outcomes. 29The reports of this trial stated that low intensity aerobic training (LAT) had better effects than moderate intensity aerobic training (MAT) in clinical and psychological effects and no or little change in muscle mass between the two groups.
Generally, aerobic exercises are safe physical activities which lead to whole body activation and induce the skeletal muscle properties.It promotes overall energy expenditure; improve physical tness and pathway for healthy aging. 30In respect to muscle properties, all type of aerobic exercises controls the adverse effects of aging, such as on in ammation process, mitochondrial function, cell apoptosis and insulin activity. 31Among the other types of aerobic training, LAT improves overall endurance by activating skeletal muscle oxidative capacity and improves blood ow to the cell.This is the greatest demand of mitochondria in the cell during physical activity and it becomes enhanced during LAT exercises. 32LAT exercise activates the muscle protein peroxisome proliferator activated receptor gamma coactivator-1 (PGC-1) and facilitates mitochondrial function and increase the energy expenditure. 31egarding muscle strength (hand grip strength, chair stand test and physical performance test), our reports show signi cant difference between the two groups.Goto K et al observed that the differences in the muscle strength in LAT and MAT exercise could be due to differences in energy metabolism or differences in training duration. 33The intra group analysis shows both groups have shown signi cant changes in muscle strength irrespective of exercise intensity.low intensity aerobic training group shows MCID (hand grip strength -3.00, chair stand test -2.70 and physical performance test -0.08)than moderate intensity aerobic training group.
At the same time, muscle quantity (arm, thigh and calf) -CSA did not show any statistical difference in LAT and MAT exercises which is in agreement with Pasini E et al, because these exercises did not have any role in altering the number and size of fast twitch muscle bers. 34Cadore EL et al., stated that the order of performing exercises (aerobic training followed with resistance training) plays an important role in improving the muscle strength and muscle mass, 35 but in our study aerobic training was given rst and then resistance training was given.This could be the cause for no changes in the muscle mass in both groups and the exact mechanism behind the effects of order of training was not clearly found.
Furthermore, it is observed that the little differences in LAT or MAT aerobic training in muscle quantity could be due to either demographic characters or exercise parameters. 36reover, inclusion of resistance exercises in the form of PRT would induce and recruit new satellite cells into the weak muscle bers and increase the number of myonucleus.This process would increases the strength and power of the muscle bers and it depends upon age of the person, food status, and type of training.During resistance exercises the muscle bers secrete muscle in ammatory cytokines which stimulate the satellite cells and increase the myonucleus in the muscles. 37Bowen TS noticed that in older adults there is substantial reduction in several muscle in ammatory cytokines and these hormonal and in ammatory changes have helped for the improvement in muscle strength and physical performance after LAT and MAT exercises. 38proving muscle strength is closely related with the improvement in activities of daily living (ADL), which may decrease kinesiophobia (fear of movement and fall) status.These overall changes improved the quality of life (QOL) of COVID-19 infected older adults with Sarcopenia symptoms as agreed by Rejeski et al, 39 and Binder et al 40

Declarations
Ethics approval and consent to participate: study obtained the study ethical approval from Department Ethical Committee (DEC), Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia with the reference number of RHPT/020/044.Written consent was obtained from all the participants.The patients included in this study have not been reported in any other submission by me or anyone else.
Consent for publication: No data is contained in this publication.

Figures
Figure 1

Few limitations have been
noticed during the execution of the whole trial.First, the authors felt the sample size of this trial was not su cient for generalization of the reports, even though the sample size was calculated by previous pilot study.Second, all the participants were undergoing training at same time at same place; hence there is possibility of sharing of study information and masking of participants could be doubtful.Third, the study did not analyze the correlation between the clinical and psychological effects after low and moderate intensity aerobic training exercises.Lastly, there is absence of control group, which may show the real time effects of LAT and MAT exercise.Therefore, future studies should include a control group with more samples and should analyze the correlation between the clinical and psychological effects after low and moderate intensity aerobic exercises in COVID-19 older adults with Sarcopenia symptoms.Combination of LAT or MAT exercises with PRT provides both the effects of aerobic and resistance training and can improve the clinical and psychological variables in community dwelling COVID-19 asymptomatic older adults with Sarcopenia symptoms.This study reports that low intensity aerobic training exercises improved the clinical (muscle strength and physical performance) and psychological (kinesiophobia and quality of life) aspects than moderate intensity aerobic training in COVID-19 asymptomatic older adults with Sarcopenia symptoms.At the same time, both types of aerobic training exercises have negligible or little role in increasing the muscle quantity -cross sectional area.The reports of the study would be helpful for the health professionals to prevent or postpone the negative consequences of Sarcopenia in older adults.High quality controlled clinical trials can be conducted at multicenter level with the involvement of multicomponent factors that can improve the health status of the COVID-19 infected older adults with Sarcopenia symptoms.

Table 1
Demographic details of low intensity and moderate intensity aerobic training groups LAT -Low intensity aerobic training, MAT -Moderate intensity aerobic training, BMI -Body mass index, VO 2 -Oxygen volume, HR -Heart rateThe 2 × 4 (group × time) multiple analysis of variance (MANOVA) of primary variables (hand grip strength and chair stand test) shows signi cant difference (p < 0.001), but muscle quantity (mid-arm, mid-thigh and mid-calf) failed to show the difference (p > o.o5) between the groups at various intervals.quantitymid-arm− 1.7 (CI 95% -3.96 to 0.56), mid-thigh − 3.1 (CI 95% -5.98 to -0.21) and mid-calf − 2.5 (CI 95% -4.94 to -0.05) measurements (Table2 &3).When calculated the effect size, the overall changes noted in hand grip strength (d = 1.17) and chair stand test (d = 1.40) of LAT group were categorized into large effect.The visual representation in Fig. 2 also shows more improvements in LAT group than MAT group.

Table 2
Pre and post analysis of low intensity and moderate intensity aerobic training groups *Signi cant, LAT -Low intensity aerobic training, MAT -Moderate intensity aerobic training, MRI -Magnetic resonance imaging, TSK -Tamba scale of kinesiophobia, SarQol -Sarcopenia quality of life *Signi cant, LAT -Low intensity aerobic training, MAT -Moderate intensity aerobic training, MRI -Magnetic resonance imaging, TSK -Tamba scale of kinesiophobia, SarQol -Sarcopenia quality of life

Table 3
Pre and post mean difference and con dence interval (upper limit and lower limit) scores of low intensity and moderate intensity aerobic training groups..001) in LAT group than MAT group.samegrowthcanbenoted in 8 weeks and 6 months follow up.At the end of 6 months follow up, again the physical performance, -0.08 (CI 95% -0.10 to -0.05), kinesiophobia level 4.2 (CI 95% 3.25 to 5.14) and quality life − 5.7 (CI 95% -8.4 to -2.9) showed more improvement (p < 0.001) in LAT group than MAT group (Table2&3).When calculated the effect size, the LAT group noted larger effects in physical performance (d = 1.6), kinesiophobia level (d = 2.04) and quality of life (d = 0.94) when compared to MAT group.The graphical presentation in Fig.2also shows more changes in the LAT group than MAT group.
44, against by Holviala et al.41The reports also suggest that LAT and MAT combined with progressive resistance training improved the psychological effects in older adults with Sarcopenia.Moreover, greater reduction in kinesiophobia status and improvement in quality of life were noted in LAT group than MAT group with MCID score (kinesiophobia -4.2, quality of life − 5.7)Granacher et al42have observed that PRE training for the upper/ lower extremities and trunk muscles provide the ability to work and reduce the kinesiophobia status of Sarcopenia patients.Combination of LAT or MAT exercises with PRE training provides both the effects of aerobic and resistance training, Also, the muscle reaction to different exercise training protocols may be reduced in older adults when compared to younger people, which shows the physiological reserve in different stages of life.43Thecombinedaerobic and progressive resistance training program may help to overcome this problem in sarcopenia patients as agreed by Cruz Jentoff AJ et al and Deutz NE et al.44,45Tieland et al 46 noticed that combined exercise training with adequate protein intake improve muscle strength, physical performance and quality of life in frail older patients than exercise training alone.
which can improve the overall quality of life.The difference in clinical and psychological variables in low intensity and moderate intensity aerobic training in older adults is due to its variations in parameters such as frequency, intensity, time and mode of execution of exercises.