MME & RC’S
M. A. RANGOONWALA COLLEGE OF PHYSIOTHERAPY &
RESEARCH CENTER, PUNE
A Synopsis for
Bachelor of Physiotherapy
MUHS, Nashik
EFFECT OF AEROBIC EXERCISE ON COGNITION
AND FATIGUE IN POST COVID SYNDROME IN
MIDDLE AGE ADULTS - AN EXPERIMENTAL STUDY
GUIDEDR. SANAT KULKARNI (M.P.T)
ASSISTANT PROFESSOR
ByAAMENA ZAHRA SHAIKH
1
“EFFECT OF AEROBIC EXERCISE ON COGNITION
AND FATIGUE IN POST COVID SYNDROME IN
MIDDLE AGE ADULT - AN EXPERIMENTAL STUDY”
2
CERTIFICATE
MME & RC’S
M. A. Rangoonwala College of Physiotherapy & Research, Pune.
This is to certify that Ms. Aamena Zahra Shaikh is a bonafide student of MME & RC’s
M.A. Rangoonwala College of Physiotherapy & Research, Pune. The synopsis titled
“EFFECT OF AEROBIC EXERCISE ON COGNITION AND FATIGUE IN POST
COVID SYNDROME IN MIDDLE AGE ADULT - AN EXPERIMENTAL STUDY”
will be carried out for the fulfilments of the Bachelor of Physiotherapy (B.P.T) Degree
under my supervision and guidance to my complete satisfaction.
Principal:
Dr. (Mrs.) Ronika Agarwal
Principal
Guide:
Dr. Sanat Kulkarni (M.P.T)
Assistant Professor
3
DECLARATION
This is to declare that the work presented in this synopsis titled “EFFECT OF
AEROBIC EXERCISE ON COGNITION AND FATIGUE IN POST COVID
SYNDROME IN MIDDLE AGE ADULT - AN EXPERIMENTAL STUDY” was
carried out by me at the M.M.E. & R.C’s M.A. Rangoonwala College of Physiotherapy
& Research, under the guidance of Dr. Sanat Kulkarni (M.P.T) Professor at M.M.E. &
R.C’s Rangoonwala College of Physiotherapy & Research, Pune.
Place: Pune
Date:
AAMENA ZAHRA SHAIKH
4
ACKNOWLEDGEMENT
First of all, I would like to thank the Almighty for this opportunity and proper
guidance. It is my pleasure to express my gratitude to Dr. Mrs. Ronika Agarwal,
principal of M.M.E. & R.C.’s M. A. Rangoonwala College of Physiotherapy &
Research, Pune. I acknowledge the constant support, valuable input and tireless effort
of my guide Dr. Sanat Kulkarni (M.P.T)
I thank the teaching staff of M. A. Rangoonwala College of Physiotherapy &
Research, Pune. Last but not the least I extend my humble gratitude to my beloved
parents, family members and friends for the unconditional love and support.
5
INDEX
S/NO:
TOPICS
PAGE NO:
1
INTRODUCTION
7
2
NEED FOR STUDY
14
3
REVIEW OF LITERATURE
15
4
AIMS AND OBJECTIVES
23
5
METHODOLOGY
24
6
PROCEDURE
28
7
STATISTICAL ANALYSIS
36
8
BIBLIOGRAPHY
51
9
APPENDIX-A
59
10
APPENDIX-B
60
6
1. INTRODUCTION
1.1. Definition
1.2. Anatomy
1.3. Pathogenesis
1.4. Prevalence
1.5. Classification
1.6. Outcome Measures
1.7. Treatment options
1.1 DEFINITION
Coronavirus disease 2019 (COVID-19) is associated with respiratory dysfunction in
the upper respiratory tract and was first reported to WHO as pneumonia of unknown
etiology in Hubei Province, Wuhan City, China, on December 31, 2019.[1] Coronavirus
disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2).[2] Apart from causing a respiratory distress syndrome, COVID-19 is a
systemic disease that affects multiple organs.[3]
Symptoms associated with SARS-CoV-2 infection are heterogeneous and can affect
many different systems such as respiratory (cough, sore throat, rhinorrhea, dyspnea),
musculoskeletal (myalgia), gastrointestinal (diarrhoea, vomiting), and neurological
[headaches, myopathy, ageusia (loss of taste of sense), anosmia (loss of smell)].[4]
Elderly subjects with comorbidities—namely, hypertension, coronary artery disease,
obesity and diabetes are more susceptible to SARS-CoV-2 infection with more severe
symptoms and worse outcomes.[5] COVID-19 diagnosis was done through the real-time
reverse transcription PCR test (RT-PCR).[6]
The Guideline published by the National Institute for Health and Care Excellence
(NICE), the Scottish Intercollegiate Guidelines Network, and the Royal College of
General Practitioners has defined long COVID as “signs and symptoms developed
7
during or following a disease consistent with COVID-19 and which continue for more
than four weeks but they are not explained by alternative diagnoses”.[7] NICE defines
Long COVID as signs and symptoms that continue or develop after acute COVID-19,
including both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and
post-COVID-19 syndrome (12 weeks or more).[51] Fatigue and cognitive and dyspnea
manifestations, comprises of ’post-acute sequelae of SARS-CoV-2’, which is referred to
as ‘long COVID.[8] In the coming months, emphasis will gradually involve post-acute
care of COVID-19 survivors.[9] It is expected that COVID-19 may have a major impact
on physical, cognitive, mental and social health status, also in patients with mild disease
presentation.[9] Cognitive deficits were widespread in those with and without ICU stays
and occurred most commonly of oral processing speed and verbal fluency as well as of
learning and memory.[6] Cognition is the ability to learn, solve problems, remember, and
appropriately use stored information.[10] Fatigue can be defined as a subjective
experience, which includes symptoms such as rapid, persisting lack of energy,
exhaustion, physical and mental tiredness, and uninterestedness.[11]
Cognitive fatigue is defined as decline in the cognitive functioning, during sustained
mental work. The affected cognitive functions, overall named “cognitive control”,
include vigilance, executive attention, working memory, judgment and long-term
memory recall. The feeling that people may experience during or after prolonged
periods of cognitive and/or physical activity is called “mental fatigue”. Alterations in
the neural circuits may partially account for both cognitive and mental fatigue.[12]
1.2 Anatomy
It has been reported that SARS-CoV2 enters the human body through the mucosa of
nose and oropharynx, and may eventually get deposited in the lungs. Other organs
expressing angiotensin-converting enzyme 2 (ACE2) receptors on the surface of the
cells such as heart, kidney, and intestines are also prone to be infected by the SARSCoV2, different stages of pulmonary interstitial damages along with parenchymal
changes are observed CT manifestations of lung shows consolidation, reticular pattern,
crazy paving pattern, air broncho-gram including the airway changes, pleural changes,
sub-pleural curvilinear line, and fibrosis. [13]
8
1.3. Pathogenesis
Extant literature indicates that pro-inflammatory cytokines moderate serotonin
levels, hypothalamic–pituitary–adrenal (HPA) axis self-regulation, microglial cells,
and neuroplasticity, leading to negative regulation of brain function. This
phenomenon has been commonly observed among the elderly, who are known to be
more at risk for the increased inflammation and serious complications following the
SARS-CoV-2 infection due to cytokine storms. [14]
Proposed mechanisms underlying neurological impact in COVID-19. Systemic
inflammation induced by COVID-19, as well as brain invasion by viral proteins or
SARS-CoV-2 can add up to cause blood-brain barrier (BBB) dysfunction, brain
microvascular damage, and brain inflammation. Activation of toll-like receptors
(TLRs) and accumulation of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL6) in the brain, either by local production or from the periphery, triggers synaptic
damage, leading to depressive and cognitive symptoms in COVID-19 patients.[3]
Inflammation is a potential driver of cognitive decline and depressive symptoms in
COVID-19: COVID-19 patients show elevated blood and CSF biomarkers of
inflammation, neuronal damage, and astrocytic activation, associated with
neurological symptoms and disease severity. IL-6 and TNF-⍺ are critical mediators
of the inflammatory response in COVID-19. Blood levels of IL-6 predict disease
progression and correlate with COVID-19 severity and mortality. Blood TNF-α is
high in critically ill COVID-19 patients.[3]
The abnormal misfolding and aggregation of proteins in patients who survive and
recover from their acute SARS-Cov2 infection can thus theoretically lead to brain
degeneration decades later.[13] There are multiple mechanisms whereby SARS-CoV2 infection can exacerbate persistent fatigue and/or cognitive impairment.[8]
9
1.4. Prevalence
It is estimated that 10% to 35% of patients those not requiring hospitalisation
develop post-COVID symptoms, regardless of co-morbidities while incidence rates
up to 80% have been reported among hospitalised patients and among patients with
severe illnesses.[15]
Recent evidence indicates that elderly population have higher risk of severe disease
and mortality due to COVID-19, particularly those with comorbidities.[16] Follow-up
studies carried out which indicates that a significant proportion of COVID-19
survivors experience persistent neuropsychological alterations, including anxiety,
depression, and cognitive impairment.[3] 78% of the survivors performed poorly in at
least one cognitive domain, with the most significant impact on executive functions
and motor coordination.[3] In contradistinction to other persistent symptoms which
may be self-limiting, fatigue and cognitive impairment appear to endure and may
potentially worsen over time in susceptible individuals, as evidenced by similar
proportion of affected individual.[8] Frequently reported factors associated with
greater incidence of Post Covid Syndrome (PCS) symptoms amongst studies included
female sex, older age, greater severity of acute illness, and pre-existing
comorbidities.[8]
Subset
of
individuals
consistently
exhibited
markers
of
inflammation following the resolution of acute COVID-19 infection, suggesting
hyper-inflammation is the cause of fatigue and/or cognitive impairment in PCS.[8]
Meta-analysis conducted by Cuban, et al., revealed that the proportion of individuals
experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32
(95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of
individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001;
n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in
proinflammatory markers and considerable functional impairment in a subset of
individuals. [8]
10
1.6 Treatment
Pharmacological treatment for COVID-19- Anticoagulant therapy (studies reported
increased thromboembolic events and improved outcomes with anticoagulation
therapy in COVID-19 patients), Remdesivir (broad-spectrum antiviral medication),
corticosteroids (showed anti-inflammatory benefits), IL-6 inhibitors (inhibits IL-6 proinflammatory cytokine), ACE inhibitors (anti-inflammatory, anti-fibrotic, vasodilatory
effects), Statin (inhibitory effect of statins on coagulopathy, endothelial dysfunction, and
inflammation).[23]
Symptomatic treatment/supportive care during the mild phase of COVID-19: For
headache, fever and myalgia- adequate hydration, acetaminophen, non-steroidal antiinflammatory drug (NSAID). Cough, and dyspnea- breathing exercises education and
medications which included Dextromethorphan, Benzonatate (100–200 mg three times
daily) prescribed. In Phase I, the early infective phase, supportive care and symptomatic
treatment are needed. In phase II, the pulmonary phase, treatment aims at inhibiting viral
entry or replication. Drugs used during this phase are famotidine, monoclonal antibodies,
nanobodies, ivermectin, remdesivir, camostat mesylate and other antiviral agents. In
phase III, the hyper-inflammatory phase, tocilizumab, dexamethasone, selective
serotonin reuptake inhibitors (SSRI), and melatonin are used.[24]
Respiratory rehabilitation regimen for patients discharged after COVID-19 infection
were published which showed significant improvement in the respiratory function,
quality of life, and anxiety in a group of older patients who participated in the respiratory
rehabilitation program which included respiratory muscle training, coughing techniques,
diaphragmatic training, stretching exercises, and home exercises comprising two sessions
per week for 6 weeks, once a day for 10 minutes.[25]
11
The American College of Sports Medicine (ACSM) defines aerobic exercise as any
activity that uses large muscle groups, can be maintained continuously and is rhythmic
in nature.[26]
Physical activity improves cognitive performance by increasing
neuroelectric activity, brain volume, and blood flow in brain networks that mediate
attention, learning, and
enhancement
in
memory.[27] Aerobic exercise
produces an immediate
immune functions.[28] Regular release of muscle-derived anti-
inflammatory cytokines (IL-6, IL-7, IL-10, IL-15), linked with the inhibition of proinflammatory cytokines (IL-1β, IL-18, TNF-α), plays important role in the beneficial
effects of exercise on immunity.[29]
1.7. Outcome Measures
1. Mini Mental State Examination (MMSE):
The Mini-Mental Status Exam (MMSE) is one of the most widely used tests for
cognitive assessment and one of the most frequently studied dementia screening tests. It
consists of questions with a maximum MMSE score of 30 points. According to a
systemic review and meta-analysis, the sensitivity and specificity of MMSE for
dementia detection were 81% and 89%, respectively.[18] Reliability is 0.95.[19] It
measures cognitive domains which includes visuospatial, language, concentration,
working memory, memory recall and orientation.[20]
2. The Chalder Fatigue Scale (CFQ 11):
It is a self-administered questionnaire for measuring the extent and severity of
fatigue. It provides a brief tool to measure both physical and psychological fatigue. Each
of the 11 items are answered on a 4-point scale ranging from the asymptomatic to
maximum symptomology, such as ‘Better than usual’, ‘No worse than usual’, ‘Worse
than usual’ and ‘Much worse than usual’. Using the Likert scoring method, responses on
the extreme
left receive a score of 0, increasing to 1, 2 or 3 as they become more
12
symptomatic. The respondent’s global score can range from 0 to 33. The global score
also spans two dimensions—physical fatigue (measured by items 1–7) and
psychological fatigue (measured by items 8–11). Reliability coefficients for the CFQ
11 is 0.90 in likert scoring method. [22]
3. Trail Making Test A & B:
The Trail Making Test is a neuropsychological test of visual attention and task
switching. It can provide information about visual search speed, scanning, speed of
processing, mental flexibility, as well as executive functioning. There are 2 parts to the
TMT. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet
of paper. In Part A, the circles are numbered 1 – 25, and the patient should draw lines
to connect the numbers in ascending order. In Part B, the circles include both numbers
(1 – 13) and letters (A – L); as in Part A, the patient draws lines to connect the circles
in an ascending pattern, but with the added task of alternating between the numbers
and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the
circles as quickly as possible, without lifting the pen or pencil from the paper. Time
the patient as he or she connects the "trail." If the patient makes an error, point it out
immediately and allow the patient to correct it. Errors affect the patient's score only in
that the correction of errors is included in the completion time for the task. It is
unnecessary to continue the test if the patient has not completed both parts after five
minutes have elapsed.Test -retest ability: For intervals of 3 weeks to 1 year, test-retest
reliability is moderate to high for Part A (r=0.79) and Part B (r=0.89).[42]
13
NEED FOR STUDY
COVID-19 is a novel disease involving multiple systems and some symptoms
which are persistent even after recovery from covid-19. After recovery from
covid-19 cognitive impairment and fatigue is a growing problem. By preserving
this function, we can help them remain independent for as long as possible, which
can improve their quality of life. By being physically active, eating a healthy diet,
keeping their mind active they will improve in these functions. Cognitive skills
occupy a vital role in an individual’s overall development, as they include some of
the brain’s core functions such as thinking, reading, learning, retaining
information, and paying attention and are used to solve problems, remember tasks
and make decisions which are . All this affects the quality of our learning and
performance. Cognition is critical for functional independence as people age,
including whether someone can live independently, manage finances, take
medications correctly, and drive safely. In addition, intact cognition is vital for
humans to communicate effectively, including processing and integrating sensory
information and responding appropriately to others. Physical and mental fatigue
are different, but they often occur together. Fatigue prevent a person from fulfilling
their daily tasks. Fatigue and cognitive impairment are amongst the most common
and debilitating symptoms of post-COVID-19 syndrome. Aerobic exercises can
activates cerebral cortical neuron excitability, it reduces the neuro-inflammation in
brain by increasing anti inflammatory cytokines and decreasing pro-inflammatory
IL-6, TNF alpha.
As COVID-19 is a novel disease and there is a dearth of literature on individuals
with symptoms such as cognitive impairment and fatigue in post covid syndrome,
also there is no sufficient literature on physiotherapy intervention for the same so
this following study is aimed to see if there are any positive effects of aerobic
exercises on cognitive impairment and fatigue in Post Covid Syndrome.
14
REVIEW OF LITERATURE
1. A randomised clinical trial was conducted in the year 2022 by Florent, et. al
which included patients with long COVID-19 and mean age 60. Two intervention:
(1) Rehabilitation: centre-based exercise training program (8 weeks, 3 times per
week); (2) control: individuals had to maintain their daily habits. The study lasted
for 10 weeks including 1 week of testing at baseline and 1 week post-intervention, in
addition to the 8 training weeks. Outcome measure: cardiorespiratory fitness (VO2
peak: mL/kg/min) measured by a maximal cardiopulmonary exercise test, functional
capacity assessed using 6 min walking test, the Timed Up-and-Go test and the Sit-toStand test, brain health assessed using Montreal Cognitive Assessment (MoCA) and
neuropsychological tests to assess different components of cognition: the Hopkins
Verbal Learning Test (verbal memory), the Digit Span (short-term memory and
working memory), an oral version of the Trail-Making Test (executive functions),
as well as phonological and semantic verbal-fluency test (language and executive
functions). The study concluded that cardiopulmonary and brain functions are
frequently impaired after COVID-19 infection and cardiopulmonary rehabilitation is
the cornerstone to the management of people affected by chronic pulmonary and
cardiovascular diseases in individuals living with long COVID-19. [30]
2. A systematic review and meta-analysis was conducted by Lucia, et. al, in the year
2022 on cognitive effects of coronavirus disease 2019 (COVID-19) in adults with no
prior history of cognitive impairment, mean age = 56.05 years, evaluation time
ranged from acute phase to 7 months post-infection. Impairment in executive
functions, attention, and memory were found in post-COVID-19 patients. The metaanalysis revealed that people with COVID-19 had poorer general cognitive
functioning, compared to people without COVID-19 measured by MoCA between
assessment in the acute phase and 6 months after infection.[32]
15
3. A systemic review was conducted by Natalia, et. al in the year 2022 on evidences
which indicates that COVID-19 is associated with neuro-inflammation, along with
blood-brain barrier dysfunction. Current evidence demonstrates that patients with preexisting cognitive and neuropsychiatric deficits show worse outcomes upon infected by
SARS-CoV-2 and thus COVID-19 survivors had increased risk of developing dementia
and mood disorders. Considering the high prevalence of COVID-19 patients who
recovered had alarming prevalence of dementia and depression which had lead to longterm neurological abnormalities in COVID-19 survivor.[3]
4. A systematic review and meta-analysis was conducted by Qing, et. al in the year
2022, on one-year follow-up studies on Post-COVID symptoms regarding long-term
sequelae in COVID-19. Fatigue/weakness (28%), dyspnoea (18%), arthromyalgia
(26%), depression (23%), anxiety (22%), memory loss (19%), concentration difficulties
(18%) and insomnia (12%) were found to be the most prevalent symptoms at one-year
follow-up. Low prevalence of nausea, vomiting, diarrhoea, abdominal pain, and loss of
appetite was found at one-year follow-up. [38]
5. A study was done by Pratip, et. al, in the year 2022 who gave epidemiological finding
of Maharashtra for first and second waves of Covid-19. State recorded 28.6% of the
countrywide fatalities due to COVID-19. 95% of the infections in Maharashtra recorded
successful recovery. Statistical comparison of the total number of cases with the
population densities of districts revealed moderate association of 51% during the first
wave and 45% for the second wave. [37]
6. A systemic review and meta analysis was done by Mohamad Salim, et. al, in the
2022 to estimate the prevalence of persistent symptoms and signs at least 12 weeks after
acute COVID-19 at different follow-up periods. The most commonly reported
symptoms were fatigue (32%), dyspnea (25%), sleep disorder (24%), and difficulty
concentrating (22%), at 3 to <6-month follow-up; effort
intolerance (45%), fatigue
(36%), sleep disorder (29%), and dyspnea (25%), at 6 to <9-month follow-up; fatigue
(37%) and dyspnea
16
(21%) at 9 to <12 months; and fatigue (41%), dyspnea (31%), sleep disorder (30%),
and myalgia (22%), at >12-month follow-up. Large proportion of patients experienced
post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of
COVID-19.[35]
7. A study was conducted by Enya Daynes, et. al in the year 2021 on patients with
post-COVID symptoms who were given comprehensive recovery programme.
Individuals with mean age 58 were taken. The rehabilitation programme was of 6
weeks in duration, with two supervised sessions per week. The programme comprised
of aerobic exercise (walking/ treadmill based), strength training of upper and lower
limbs, demonstrated statistically significant improvements in exercise capacity,
respiratory symptoms, fatigue and cognition. The outcomes were: the incremental and
endurance shuttle walking test (ISWT/ESWT), COPD Assessment Test (CAT),
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT), Hospital
Anxiety and Depression Scale (HADS), EuroQual 5 domains (EQ5D) and the Montreal
Cognitive Assessment (MoCA). Participants improved by 112 meter on the
Incremental Shuttle Walking Test and 544 seconds on the Endurance Shuttle Walking
Test.[31]
8. A systemic review was done by Soraya Mouffak, et. al in the year 2021 on recent
advances in management of COVID-19. They concluded that in Phase I, the early
infective phase, supportive care and symptomatic treatment was needed. In phase II,
the pulmonary phase, treatment was aimed at inhibiting viral entry or replication.
Drugs used during this phase was famotidine, monoclonal antibodies, nanobodies,
ivermectin, remdesivir, camostat mesylate and other antiviral agents. In phase III, the
hyper-inflammatory phase, tocilizumab, dexamethasone, selective serotonin reuptake
inhibitors (SSRI), and melatonin was used.[24]
9. A study by César et. al in the year 2021 had proposed the classification based on
relapsing nature of post-COVID symptoms: Potentially infection related-symptoms (up
to 4–5 weeks), acute post-COVID symptoms from week 5 to week 12), long post-
17
COVID symptoms (from week 12 to week 24), and persistent post-COVID symptoms
(lasting more than 24 weeks).[7]
10. A narrative review was done by Amaya, et. al in the year 2021 which summaries the
up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of
the disease and explained how regular exercise can improve the symptoms and reduce the
long-term effects of COVID-19. It explains how exercise
have benefits on
immunological health, cardiovascular health, to manage physical syndrome, pulmonary
complications, how it stimulates brain plasticity and increases psychological well-
being.[29]
11. A systematic review and meta-analysis was done by Felicia, et. al in the year 2021 on
81 studies. The pooled proportion of individuals exhibiting cognitive impairment amongst
COVID-19 patients 12 or more weeks following diagnosis was found to be 0.22. The
pooled proportion of individuals experiencing fatigue amongst COVID-19 patients 12 or
more weeks following diagnosis was 0.32. Marked increase in the numbers of CD4+ T
cells expressing the inflammatory cytokines interleukin (IL)-2, interferons (IFN)-γ, and
tumor necrosis factor (TNF)-α in individuals with prior COVID-19 as compared with
healthy donors. They established that approximately a third of the included individuals
experienced persistent fatigue and over a fifth of individuals exhibited cognitive
impairment 12 or more weeks following COVID-19 diagnosis and subset of individuals
exhibited markers of systemic inflammation and Post COVID Syndrome was associated
with marked levels of functional impairment.[8]
12. A study was done by Udina, et. al in the year 2021 to assess pre-post impact on
physical performance of multi-component therapeutic exercise for post-COVID-19
rehabilitation in a post-acute care facility. The 30-minute 7 days/week multi-component
therapeutic exercise intervention combined: a) Resistance training (1-2 sets with 8-10
repetitions each & intensity between 30-80% of the Repetition Maximum) b) Endurance
training (up to 15-minutes aerobic training with a cycle ergometer, steps or
walking)
18
c) Balance training (walking with obstacles, changing directions or on unstable
surfaces). Each session was individualised to each patient’s physical condition.
Outcomes: Short Physical Performance Battery; Barthel Index, ability to walk
unassisted and single leg stance. Our comprehensive assessment included: pre-COVID
functional status with the Barthel Index and Lawton Index and frailty status with the
Clinical Frailty Scale (CFS); cognitive function at post-acute admission with the
Montreal Cognitive Assessment (MoCA) for global cognition and the Symbol Digit
Modalities Test (SDMT) for attention and processing speed. Study concluded that adults
and older adults surviving COVID-19 seem to improve their functional status, despite
previous admission to ICU, through a short, individualised, multicomponent therapeutic
exercise intervention.[39]
13. A systemic review was done by Ghadha in the year 2021 on neuropathological
impact of COVID-19. This review demonstrated the need to understand the
neuropathology of COVID-19 & to manage the current borderless outbreak of SARSCoV-2 and its comorbidities. The mechanism of action included: SARS-COV-2-induced
cytokine storm followed by multiple organ failure (MOF),
the neuropathogenic
mechanisms of SARS-COV-2 (systemic hypoxia, cytokine storm, direct invasion).[1]
14. A cross-sectional study was conducted by Jacqueline, et. al in the year 2021 to
assess cognitive functioning using well validated neuropsychological measures: Number
Span forward (attention) and backward (working memory), Trail Making Test Part A
and Part B (processing speed and executive functioning, respectively), phonemic and
category fluency (language), and the Hopkins Verbal Learning Test–Revised (memory
encoding, recall and recognition). The mean age was 49 (38-59) years, and the mean
(SD) time from COVID-19 diagnosis was 7.6 months inclusion criteria included no
history of dementia. Study revealed that hospitalized patients were more likely to have
impairments in attention, executive functioning, category fluency, memory encoding,
and memory recall than those in the outpatient group. Patients
19
treated in the ED were more likely to have impaired category fluency and memory
encoding than those treated in the outpatient setting.[40]
15. A study was conducted by Sherry, et. al in the year 2021 which was aimed to find
out the prevalence of fatigue & evaluating the correlation between fatigue & quality
of life in post covid-19 patients. Mean age: 35.63 ± 14.59. Outcome measure: Chalder
fatigue questionnaire (CFQ-11) and WHO quality of life- brief questionnaire
(WHOQOL-Brief). Study concluded that fatigue is highly prevalent in post-covid
population and with higher levels of fatigue, quality of life deteriorates.[34]
16. A study was done by Lisa, et. al in the year 2020 which provided considerations
for post acute rehabilitation for survivors of COVID-19. They concluded that to avoid
aggravating respiratory distress or dispersing the virus unnecessarily, respiratory
rehabilitation should not begin too early, initially, aerobic activity should be kept to
less than 3 metabolic equivalents of task. Later, progressive aerobic exercise should
be increased to 20-30 minutes, 3-5 times a week. Study also concluded that firstly, tp
consider details of how patients may present including co-morbidities, complications
from an ICU stay with or without intubation, and the effects of the virus on multiple
body systems, secondly, they have suggested procedures regarding the design of
inpatient rehabilitation units for COVID-19 survivors and considerations for
outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy,
occupational therapy, speech-language pathology) following COVID-19 have been
proposed with respect to recovery of the respiratory system as well as recovery of
mobility and function. [2]
17. An examination was done by Liam, et. al in the 2020 on prevalence of fatigue in
individuals recovered from the acute phase of COVID-19 illness using the Chalder
Fatigue Questionnaire Score (CFQ-11), they also examined potential predictors of
fatigue. Mean age 49, at median of 10 weeks after initial COVID-19 symptoms 52.3%
20
out of 128 participants reported persistent fatigue. No association between COVID-19
severity was found. This study highlights the importance of assessing those subjects
recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of
initial illness and
the burden of fatigue, the impact on return to work and the
importance of following all patients diagnosed with COVID-19 and not merely those
who required hospitalisation. [36]
18. A systemic review was done by M. Alawna, et. al, in the year 2020 to
systematically analyse the effects of aerobic exercise on immunological biomarkers to
provide safe aerobic exercise recommendations and specifications for non-athletes
patients with COVID-19 . The most used exercise prescriptions included walking,
cycling, or running. The duration of exercise ranged from 18 to 60 min with an
intensity of 55% to 80% of VO2max or 60%-80% of maximum heart rate. The
frequency range was 1 to 3 times/week. The modes of aerobic exercise were mainly
cycling or walking. The mainly increased immunological biomarkers included
leukocytes, lymphocytes, neutrophils, monocytes, eosinophils, IL-6, CD16-56, CD16,
CD4, CD3, CD8 and CD19. This study is unique because it is first one which provided
safe aerobic exercise prescriptions for patients with COVID-19 to improve their
immune functions and help to decrease the disease severity and death rate without any
exhaustion. [28]
19. A study was conducted by Hong-Mei, et. al in the year 2019 which gave
recommendations for respiratory rehabilitation in adults with coronavirus disease 2019.
For COVID-19 inpatients, the aim of respiratory rehabilitation was to ameliorate
dyspnea, alleviate anxiety and depression, reduce complications, prevent and improve
dysfunction, reduce morbidity, preserve functions, and improve quality of life as much
as possible. it included positioning management, early mobilisation, respiratory
management.[31]
21
20. A study was done by Min, et. al in the year 2016 to examine the validity and reliability
of the MMSE-2 for assessing patients with mild cognitive impairment (MCI) and
Alzheimer’s disease (AD). The usefulness of the MMSE-2 as a screening measure for
detecting early cognitive change, which has not been detectable through the MMSE, was
examined. MMSE was used to assess seven areas of cognitive functioning and it had
shown to have both good test-retest reliability 0.95. [19]
21. A systemic review was conducted by Craig in the year 2015 on Chalder Fatigue
Questionnaire (CFQ 11). Reliability coefficient ranging from 0.90 for the Likert scoring
method. The authors established that a global binary fatigue score of 3 or less represents
scores of those who are not fatigued, with scores of 4 or more equating to ‘severe fatigue’.
The respondent’s global score ranges from 0 to 33. The global score
includes two
dimensions—physical fatigue (measured by items 1–7) and psychological fatigue
(measured by items 8–11). It provides a brief tool to measure both physical and
psychological fatigue. [22]
22. A study was done by Martina, et. al, in the year 2015 based on the effects of Physical
Exercise on Neuro-inflammation, Neuroplasticity, Neurodegeneration, and Behaviour in
Animal Models in Clinical Setting. Training reduced the levels of TNF-α and IL-1β in the
hippocampus and prevented cognitive impairment in the mouse over expressing a mutated
form of the amyloid precursor protein. They observed increased levels of neurotrophic
factors, elevated expression of anti-inflammatory cytokines, and reduced levels of proinflammatory cytokines and activated microglia after physical training. [33]
23. Christopher R Bowie and Philip Harvey (2006) conducted a study on Administration
and interpretation of the Trail Making Test. The Trail Making Test is an accessible
neuropsychological instrument that provides the examiner with information on a wide
range of cognitive skills and can be completed in 5–10 min. Its background, psychometric
properties, administration procedures and interpretive guidelines are provided in this
protocol. The TMT provides information on visual search, scanning, speed of processing,
mental flexibility and executive functions. The interrupter reliability on both parts was
high (rPart A= 0.79 ; rPart B = .89) [42]
22
AIMS AND OBJECTIVES
Aim of the study:
To study the effect of aerobic exercise on cognition, fatigue and executive function in
Post COVID-19 Syndrome in middle aged adult population.
Objectives of the study:
•
To study the effects of aerobic exercise on cognition using Mini Mental State
Examination in Post COVID-19 Syndrome in middle aged adult population.
•
To study the effects of aerobic exercise on physical and mental fatigue using Chalder
Fatigue scale in Post COVID-19 Syndrome in middle aged adult population.
•
To study the effects of aerobic exercise on executive function using Trail Making Test
A & B in Post COVID-19 Syndrome in middle aged adult population.
23
METHOD AND METHODOLOGY:
Type of Study: Quasi -Experimental study
Study Design: Pre and post experimental study
Type of Sampling: Purposive sampling
Sample Size: 32
Treatment Duration: 3 weeks ( 4 sessions / week) on alternate days
Inclusion criteria:
1. Had COVID-19 symptoms and confirmed positive for SARS-CoV-2 via RTPCR
2. Age between 40 to 65 years, both male and female
3. > 12 weeks from onset of covid infection
4. Mild to moderate COVID-19 infection [52]
Exclusion criteria:
1. Patients clinically diagnosed with Neurological condition.
2. High resting heart rate (>100 beats/min)
3. High blood pressure ( >140/90 mmHg)
4. Blood oxygen saturation (<95%)
5. Patients on beta blockers.
6. Severe COVID-19 infection.
24
Material:
• Assessment performa
• Sphygmomanometer
• Outcome measure scales
• Oxymeter
• Treadmill
• Cycle ergometer
• Stepper
25
OUTCOME MEASURES
1. Mini mental state examination (MMSE):
The Mini-Mental Status Exam (MMSE) is one of the most widely used tests for
cognitive assessment and one of the most frequently studied dementia screening tests. It
consists of questions with a maximum MMSE score of 30 points. According to a
systemic review and meta-analysis, the sensitivity and specificity of MMSE for dementia
detection were 81% and 89%, respectively.[18] Reliability is 0.95.[19] It measures
cognitive domains which includes visuospatial, language, concentration, working
memory, memory recall and orientation.[20]
2. The Chalder Fatigue Scale (CFQ 11)
It is a self-administered questionnaire for measuring the extent and severity of
fatigue. It provides a brief tool to measure both physical and psychological fatigue. Each
of the 11 items are answered on a 4-point scale ranging from the asymptomatic to
maximum symptomology, such as ‘Better than usual’, ‘No worse than usual’, ‘Worse
than usual’ and ‘Much worse than usual’. Using the Likert scoring method, responses on
the extreme left receive a score of 0, increasing to 1, 2 or 3 as they become more
symptomatic. The respondent’s global score can range from 0 to 33. The global score
also spans two dimensions—physical fatigue (measured by items 1–7) and psychological
fatigue (measured by items 8–11). Reliability coefficients for the CFQ 11 is 0.90 in likert
scoring method.[22]
26
3. Trail Making Test A & B:
The Trail Making Test is a neuropsychological test of visual attention and task
switching. It can provide information about visual search speed, scanning, speed of
processing, mental flexibility, as well as executive functioning. There are 2 parts to the
TMT. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet
of paper. In Part A, the circles are numbered 1 – 25, and the patient should draw lines
to connect the numbers in ascending order. In Part B, the circles include both numbers
(1 – 13) and letters (A – L); as in Part A, the patient draws lines to connect the circles
in an ascending pattern, but with the added task of alternating between the numbers
and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the
circles as quickly as possible, without lifting the pen or pencil from the paper. Time
the patient as he or she connects the "trail." If the patient makes an error, point it out
immediately and allow the patient to correct it. Errors affect the patient's score only in
that the correction of errors is included in the completion time for the task. It is
unnecessary to continue the test if the patient has not completed both parts after five
minutes have elapsed.Test -retest ability: For intervals of 3 weeks to 1 year, test-retest
reliability is moderate to high for Part A (r=0.79) and Part B (r=0.89).[42]
27
PROCEDURE
Institutional ethical committee clearance was taken before commencing with the project.
Subjects satisfying the inclusion and exclusion criteria were included in the study and
written informed consent was taken after the complete explanation of the procedure and the
protocol.
Subjects were assessed through proforma and informed consent was taken. Pre-test
cognitive impairment was measured by Mini Mental State Examination, executive function
was assessed using Trail Making Test A & B, physical and mental fatigue was measured
by Chalder Fatigue Questionnaire .
The pre and post intervention Chalder Fatigue Scale, Mini Mental State Examination, Trail
Making Test A & B was documented and there will be only one group;
Group - n = 32
Intervention was carried out for 3 weeks.
28
INTERVENTIONS
The American College of Sports Medicine (ACSM) defines aerobic exercise as
any activity that uses large muscle groups, can be maintained continuously and is
rhythmic in nature.[26]
One study concluded that two weeks of moderate-intensity aerobic exercise
decreased the severity and progression of COVID-19 associated disorders and quality
of life. Also, the two weeks of aerobic exercise produced a positive effect on the
immune system by increasing the amounts of Leucocytes,
Lymphocytes,
Immunoglobulin A.[28]
•
Frequency: 4 days/week for 3 weeks on Alternate days
•
Intensity : Mild intensity based on patient’s tolerance.
•
Time:
5 mins warm up (cross over touch and reach, arm circles, hip rotations) ,
30 mins (stationery cycling without resistance, Step aerobic, treadmill walking),
terminating
5 mins cool down (Diaphragmatic exercise, standing quadriceps stretch, calf
stretch against wall, standing forward bend, cross arm stretch)
Total duration 40 mins
•
Type: Aerobic exercise which includes stationery cycling without resistance,
step aerobics and treadmill walking.
29
Rehabilitation evaluation:
•
•
•
•
•
•
•
Blood Pressure
Pulse rate
Oxygen saturation
mMRC dyspnea scale
MMSE to assess cognitive impairment
Chalder Fatigue Questionnaire to assess physical and mental fatigue.
Trail Making Test A & B to assess executive function.
Exercise termination criteria:
• Chest pain
• Respiratory symptoms like breathlessness and fatigue worsening.
•
•
•
•
•
•
Severe cough
Chest tightness
Dizziness
Blurred vision
Giddiness
Tachycardia
Warm up : Cross over touch and reach, arm circles, hip rotations.
The warm-up should be gradual and sufficient to increase muscle and core
temperature without causing fatigue.
The warm-up period leads to:
■ An increase in muscle temperature to
increase the efficiency of muscular
contraction.
■ An increased need for oxygen to meet the energy demands for the muscle.
■ Dilatation of the previously constricted capillaries which increases blood
circulation.
■ An increase in venous return.
30
Cross-body toe-touch:
It is a version of the toe-touch stretch where instead of both hands reaching down
toward both feet, one hand at a time reaches for the opposing foot. It stretches the
hamstrings and trains the torso to twist and rotate. Perform alternate reaching on right
and then left, of total 10 repetitions i.e. 5 repetitions on each side.
Arm circles:
It helps to warm up the shoulders, arms, chest and upper back.
Steps to performStand straight with your feet shoulder-width apart. Raise and extend the arms to the
sides without bending the elbows. Slowly rotate both arms forward, making small
circles in clockwise direction. Complete a set in one direction and then switch,
rotating backward i.e in anti-clockwise direction. Perform clockwise motion of 5
repetitions and then anti-clockwise for 5 repetition of both arms simultaneously.
Hips rotations:
Stand with feet wider than shoulder width apart and legs straight with hands on your
hips and your head straight. Making a larger circle with your hips, moving from side,
to back, around the other side, and finally front. Perform this 10 times clockwise and
10 times anti-clockwise.
31
Cool down: Diaphragmatic exercise, light jogging, standing forward bend, standing
quadriceps stretch and calf stretch.
The purpose of the cool-down period is to:
■ Prevent pooling of the blood in the extremities and to maintain venous return.
■ Prevent fainting by increasing the return of blood to the heart and brain as cardiac
output and venous return decreases.
■ Enhance the recovery period with the oxidation of metabolic waste and
replacement of the energy stores and prevent delayed onset muscle soreness.
Diaphragmatic Breathing:
Patient in semi-reclining position. Place one hand over the abdomen just below the
anterior costal margin. Ask the patient to breathe in slowly and deeply through the
nose. Have the patient keep the shoulders and upper chest relaxed. Allowing the
abdomen to rise slightly. Then, relax and exhale slowly through the mouth. Perform
this 3 times.
Standing quadriceps stretch:
Stand in front of a wall with straight back and avoid bending or slouching. Gently
pull your heel up by grasping the ankle (not your toes) and back until you feel a
stretch in the front of your thigh. Hold for about 30 seconds. Switch to other leg and
repeat. 5 repetition on each side.
Standing forward bend:
Stand with your feet about shoulders width apart and bend forward from the hips.
Keeping your legs straight, bend as far as possible & try to touch your toes. Hold this
position for 30 seconds, breathing slowly and steadily, not holding your breath.
32
Calf stretch:
While holding on to a chair or wall, keep one leg back with your knee straight and
your heel flat on the floor. Slowly bend your elbows and front knee and move your
hips forward until you feel a stretch in your calf. Hold this position for 30 seconds,
3sets. Switch leg positions and repeat with your other leg.
Cross arm stretch:
Bring your left arm across the front of your body at your chest height. Through your
right hand hold your left arm and stretch left shoulder by pushing it towards the
opposite shoulder. Hold this stretch for 30 seconds, 3 sets. Repeat on the opposite
side.
Aerobic Exercise:
Stationery cycling - 10 mins
Treadmill walking - 10 mins
Step aerobics - 10 mins,
Treadmill walking; Walk on treadmill for 10 minutes
Stationery cycling: Start off pedalling for 10 minutes.
Step aerobics:
Step onto the stepper with the right foot first.
1.
Step up with the right foot then step up with left foot.
2.
Now, Step down backward with the right foot for 5 mins
3.
Perform the same by stepping onto the stepper with the left foot first for
next 5 mins.
33
Arm rotations
Diaphragmatic breathing
Cross body toe touch
Hip rotations
34
Calf Stretch
Treadmill walking
v
v
Stationery Cycling
Standing forward bend
35
STATISTICAL ANALYSIS
Method of data analysis
•
Statistical Product and Service Solution (SPSS) version 21 for Windows
(Armonk,NY:IBM corp) software was used to analyse the data.
•
Statistical analysis was done by using tools of descriptive statistics such as Mean,
and SD for representing quantitative data.
•
Probability p<0.05, considered as significant as alpha error set at 5% with
confidence interval of 95% set in the study. Power of the study was set at 80% with
beta error set at 20%
•
Normality of data was checked using Shapiro Wilk test.
•
Paired t test was used to compare study parameters from baseline to post -study time
interval.
•
Chi square test was used for comparing demographic variables like age group,
gender.
36
STATISTICAL ANALYSIS
The data collected pre and post intervention was subjected to following test.
Intra group analysis was taken to study the effects of treatment pre and post intervention.
Sample size calculation:
Point prevalence of 45% is estimated as
n = Z2P (1-P)/d2
p = prevalence of disease 45% (0.45)
z = 1.96
d = error i.e. 0.03
n = (1.96)2(0.45) (1-0.45)/0.03
= 0.9405 ÷ 0.03
= 31.35 ~ 32
= 32
Total sample size is 32
37
RESULTS
Table 1: Age group comparison
Around 13 (40.6%) subjects were in age group of 40-50 years, 14 (43.8%) subjects were in
age group of 51-60 years and 5 (15.6%) were from 61-65 years. On overall comparison
between different age groups, there was found to be no statistical significant (p>0.05)
difference among different age groups.
Graph 1: Representing comparison of age.
38
Table 2: Gender Comparison
In respect to gender distribution, around 14 (43.7%) were male and 18 ( 56.3%) were
female. No statistical significant (p>0.05) difference was found between male and female
distribution.
Pie Chart 1: Representing the distribution of gender.
39
Table 3: Intragroup comparison of study parameters pre and post study
MMSE score was 28.71 (2.0) which increased to 29.15 (1.41) and the difference was not
found to be of statistical significance
Graph 2: Representing pre and post values of MMSE
scoring
40
Table 4: Intragroup comparison of fatigue parameters pre and post study
Physical fatigue score reduced from 12.34 (2.63) which decreased to 8.06 (1.93) and the
difference was found to be of highly statistical significance (p<0.001).
Mental fatigue score reduced from 5.21 (1.67) which decreased to 4.56 (1.31) but the
change was not found to be of statistical significance (p>0.05)
Cumulative score i.e. Chadder Fatigue Score which decreased from 17.56 (3.35) to 12.62
(2.82) and the difference was found to be of highly statistical significance (p< 0.001)
41
Graph 3: Representing pre and post values of
Chalder Fatigue Scale.
Table 5 : Intragroup comparison of Trail making test A and B (in seconds) from
pre to post study respectively.
42
Trail making test A which took 62.09 (22.55) which decreased to 50 (17.59) and the
difference was found to be of statistical difference (p<0.05)
Trail making test B which took 156.31 (66.51) which decreased to 126.44 (56.02) but
the difference was not found to be of statistical significance (p>0.05)
Graph 4: Representing pre and post values of
Trail Making test A and B
43
Tests of Normality
Kolmogorov-Smirnova
Statistic
Shapiro-Wilk
df
Sig.
Statistic
df
Sig.
mmsepre
.301
32
.000
.691
32
.000
chalderpre
.191
32
.004
.934
32
.050
physicalpre
.132
32
.165
.964
32
.354
mentalpre
.229
32
.000
.911
32
.012
TRAILAPRE
.106
32
.200*
.953
32
.176
trailbpre
.158
32
.040
.942
32
.086
mmsepost
.318
32
.000
.645
32
.000
chaldpost
.103
32
.200*
.975
32
.639
physicalpost
.175
32
.014
.957
32
.221
mentalpost
.210
32
.001
.915
32
.015
trailapost
.139
32
.119
.932
32
.043
trailbpost
.182
32
.009
.886
32
.003
a. Lilliefors Significance Correction
*. This is a lower bound of the true significance.
Case Processing Summary
Cases
Valid
N
Missing
Percent
N
Total
Percent
N
Percent
mmsepre
32
50.0%
32
50.0%
64
100.0%
chalderpre
32
50.0%
32
50.0%
64
100.0%
physicalpre
32
50.0%
32
50.0%
64
100.0%
mentalpre
32
50.0%
32
50.0%
64
100.0%
TRAILAPRE
32
50.0%
32
50.0%
64
100.0%
trailbpre
32
50.0%
32
50.0%
64
100.0%
mmsepost
32
50.0%
32
50.0%
64
100.0%
chaldpost
32
50.0%
32
50.0%
64
100.0%
physicalpost
32
50.0%
32
50.0%
64
100.0%
mentalpost
32
50.0%
32
50.0%
64
100.0%
trailapost
32
50.0%
32
50.0%
64
100.0%
trailbpost
32
50.0%
32
50.0%
64
100.0%
DISCUSSION
The aim of the present study was to
investigate the effects of a 3-week (4-
session/week) aerobic exercise program on cognition, fatigue & executive function
with respect to MMSE, Chalder Fatigue Scale, Trail Making Test A & Trail Making
Test B in post covid-19 subjects in middle aged adult. In this study we recruited males
and females between the age group of 40 and 45 years who were affected by COVID19. In total, there were 32 subjects who participated.
The period of middle age is assumed to begin between the ages of 35-45 years and to
end at the age of 65 years [44].
Cognition, fatigue (physical & mental fatigue), executive function was assessed using
MMSE, Chalder Fatigue Scale, Trail Making Test A & B respectively. The
intervention consisted of aerobic exercise. M. Alawna's study concluded that two
weeks of moderate-intensity aerobic exercise reduced the severity and progression of
COVID-19 associated disorders and quality of life. Furthermore, two weeks of aerobic
exercise produced a positive effect on the immune system by increasing the amounts of
Leucocytes, Lymphocytes, Immunoglobulin A.[28]
Before beginning with the protocol, assessment was performed which included blood
pressure, pulse rate, oxygen saturation & outcome measures. The protocol included
prior warm-up session for 5 minutes (cross over touch and reach, arm circles, hip
rotations), followed by 20 minutes of aerobic exercise that included 10 minutes of
treadmill walking, 10 minutes of step aerobics, and 10 minutes of stationary cycling.
The protocol was terminated with a cool-down session for 5 minutes involving
diaphragmatic breathing exercise, bending toe touch, standing quadriceps stretch, calf
stretch against wall.
45
The modes of exercise used in previous studies were mostly cycling or walking.
Treadmill walking or cycling were said to be a suitable exercise method for sedentary
patients with Covid-19. The performed interventions in short-term studies were cycling
and walking. The duration used was approximately 18-60 minutes and was performed
1-2 times a week.[45]
MMSE was used to assess cognition and has a reliability of 0.95.[20] Chalder fatigue
scale was used to measure physical as well as mental fatigue. It has a reliability of
0.90.[42] Trail Making Test was used to measure executive function. It consists of two
parts, Part A and Part B with reliability of 0.79 and 0.89 respectively.[42]
The outcome measures were recorded pre and post intervention. The most commonly
reported symptom was fatigue, with the prevalence of 32%, 36%, 47%, 41% in 3-<6
months, 6-<9 months, 9-<12 months, >12 months respectively. It has a prevalence of
41% (94% CI).[35]
This is supported by systematic review and meta-analysis by Alessandro de Sire, et al.,
showed that nearly all patients experienced COVID-19-related fatigue in the post
COVID phase. Despite a paucity of evidence in the literature for COVID-19-related
fatigue treatment, several studies have confirmed that physical exercise might be
effective in the reducing this symptom in chronic and immune-mediated diseases. With
recent evidences, the biological mechanisms of chronic fatigue in post COVID-19
patients are thought to be inflammatory overregulation.[43]
In this study, the age group ranged between 40-65 years. As table 1 suggests age wise
comparison of Post COVID patients, categorised as 40-50 years, 51-60 years, 61-65
years which is depicted in pie chart 1. There was no statistically significant difference
between different age groups when all age groups were compared.
46
Table 2 demonstrates that the study had 32 participants, out of which 14 were male
(43.7%) & 18 female (56.3%) which is represented in pie chart 2. There was found to
be no statistical significance difference between male & female distribution. This
suggested that there is an increased incidence of Long COVID in female than in male.
This is consistent with the previous study by Francesca Bar, metal.[46] Some preliminary
studies have shown an increased prevalence of fatigue or other symptoms among
female.[46] Hormone might play a role in perpetuating the hyper-inflammatory status
even after recovery.[46]
Frequently reported factors associated with greater incidence of Post Covid Syndrome
(PCS) symptoms amongst studies included female sex, older age, greater severity of
acute illness, and pre-existing comorbidities.[8]
Table 3 suggests intragroup comparison of study parameters pre & post values of
MMSE. For MMSE pretest mean value was 28.71 & in post test it was 29.15 & the p
value was 0.317 since the p values were > 0.05, which indicates that there’s no
significant variability in pre & post value of the group, as seen in graph 2.
Now, for Chalder Fatigue Score pretest mean value was 17.56 & in post test it was
12.62 & the p value was 4.93 since the p value were found to be <0.001 which showed
there was high significant variability in pre & post value of the group. This indicates
the treatment was effective in improving fatigue levels as represented in the graph. This
could be due to decrease in the pro-inflammatory cytokines and an increase in antiinflammatory cytokines.
To be more specific with physical & mental fatigue, so for Physical Fatigue pretest
mean value was 12.34 & in post test it was 8.06 & the p value was 4.28 Since the p
values were <0.001, which indicates that there’s high significant variability in pre &
post value of the group. This indicates the treatment was effective in improving
physical fatigue through aerobic exercise as depicted in the graph 3.
47
For Mental Fatigue pretest mean value was 5.21 & in post test it was 4.56 & the p
value was 0.65 Since the p values were 0.087, which indicates that there’s no
significant variability in pre & post value of the group. This outcome is supported by
by Bruno, et al,. 2022, in their quasi experimental study, they had recruited adults over
18 years post COVID.[47]
The intervention lasted 12 sessions and consisted of moderate intensity continuous
aerobic and resistance exercise twice a week.[47] Following the cardiopulmonary
rehabilitation programme, 36% of patients reported being "Not at all tired" and 28%
reported being "able to do everything I normally do." 65.4% of patients reported
“Better, and a definitive improvement that has made a real and worthwhile
difference“.[47]
Finally, for the Trail Making Test A, pre-test mean value was 62.09, the post-test mean
value was 50, and the p value was 12.09. Because the p values were 0.02, this suggests
that there was significant variability in the group's pre and post results. As seen in
graph 4, this shows that the treatment was helpful in enhancing executive function. For
Trail Making Test B, the pretest mean value was 156.31, the post test mean value was
126.44, and the p value was 29.87. Because the p values were 0.057, there was no
significant variability in the group's pre and post values. According to Sarah Hauben
and Bruno Bronchere, physical exercises and increased physical activity levels not only
improve motor outcomes but also cognitive. [48]
One short-term study concluded that there was significant increase in leukocytes
(Leuk), lymphocytes (Linf), neutrophils (Neut), monocytes(Mon), eosinophils (Eosin),
IL-6, CD16-56,CD16, CD4, CD3, CD8, CD19, and granulocytes(Gran). It also showed
significant increases in all immunomarkers except monocytes and granulocytes.
Immunological markers differently increased in some of the included studies as
follows: IL-616, CD16-5617, CD1618, CD319, CD419,21, CD819, and CD1919. Also,
CD3 and CD18 as well as CD4 and CD8 significantly decreased.[45]
48
In this study, as table 1 suggests age wise comparison of Post & post
Exercise training may act to reduce inflammatory pathways via the following three
value of the group. This indicates the treatment was effective in
putative mechanisms: (1) by reducing the expression of the TLRs; (2) by increasing the
improving fatigue levels as represented in graph.
levels of anti-inflammatory cytokines such as IL-10 and IL-37, which in turn will inhibit
the TLR-inflammation pathway and counteract the inflammatory response induced by
the inflammasomes; and (3) by activating the AMPK-activated protein kinase (AMPK)
in the lung, reducing the inflammatory processes by allowing for the transformation of
Ang II to Ang 1-7. A 3-week swim training protocol in mice had protective effects
against LPS-induced systemic inflammation (as measured by reduced circulating
con-centrations of TNFα, IL-6, and IL-1β) and lung inflammation (30). Similar results
were reported after a 4-week treadmill running pro-gram.[49]
Cognitive impairment can persist. Cognitive impairment can affect 70%-100% of
patients at discharge; 46%-80% still have it one year later, and 20% still have it after 5
years. All components of cognition can be affected, including attention, visual-spatial
abilities, memory, executive function, and working memory.[2]
Our study the need to overcome the literature gap regarding the rehabilitation approach
in patients affected by such a disabling COVID-19 consequence. Long COVID may
result in severe disability that significantly affects the patient’s functionality and healthrelated quality of life. In this context, it is essential to identify and treat this undermining
condition, and rehabilitation could play a key role in reducing post-COVID-19 fatigue.
Thus, our findings suggest that this short-term exercise program may have positive
effects on physical fatigue and executive function in this population.
49
CONCLUSION
The following study underlined the need to overcome the literature gap regarding the
rehabilitation approach in patients affected by COVID-19. Long COVID may result in a
severe disability that significantly affects the patients’ functioning and quality of life in
terms of their health.
In this context, it is essential to identify and treat this undermining condition, and
rehabilitation could play a key role in reducing post-COVID-19 fatigue.
Thus, our findings suggest that this short-term exercise program may have positive
effects on physical fatigue and executive function in this population.
Our results imply that rehabilitation might play a key role in post-COVID-19 patients,
especially regarding its impact on fatigue, but further studies are still needed to provide
a stronger conclusion and further clinical evidence to highlight the effects of
rehabilitation in these subjects.
50
LIMITATIONS
1. Future studies can have a longer follow-up period to assess the long term effects of
the aerobic exercise on fatigue and cognition.
2. Additional outcome measures - future studies can include more outcome measures
of attention, memory, and processing speed using neuropsychological battery test to
provide a more comprehensive assessment of cognitive function.
By addressing these limitations, future studies can provide a more robust and
comprehensive understanding of the effects of aerobic exercise on cognition and
fatigue in middle-aged adults with post-COVID syndrome.
51
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JMIR public health and surveillance. 2020 May 8;6(2):e19462.
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crossroads of COVID-19, cognitive deficits and depression. Neuropharmacology. 2022
May 15;209:109023.
4. Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Florencio LL,
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Appendix A
“EFFECT OF AEROBIC EXERCISE ON COGNITION AND
FATIGUE IN POST COVID SYNDROME IN MIDDLE AGE
ADULT POPULATION - AN EXPERIMENTAL STUDY”
DECLARATION OF CONSENT
I______________________________ agree to participate in this research study. The
purpose and nature of study has been explained to me. I have had the procedure explained
to me and the investigator has answered my question concerning the procedure involved
in the study. I am participating voluntarily and also understand the consequences
associated with participation. I may withdraw from the study any time without
compromise. I also agree that the result of this research study can be used for presentation
or publication on the understanding that anonymity will be fully preserved.
Signature of Investigator
Signature of Subject
Date:
60
Appendix B
PRE AND POST TRAINING ASSESSMENT
NAME:
AGE:
ADDRESS:
GENDER:
MOBILE NO.:
Resting Heart Rate (HRR):
Maximum Heart Rate (MHR):
Outcome measure
Pre training
Post training
MMSE score:
Chalder Fatigue Score
(total score):
Physical fatigue:
Mental fatigue:
Trail Making Test A
Trail Making Test B
61
62
63
64
65
66
67
68
69
70