THE EFFECTS OF A PULMONARY REHABILITATION PROGRAMME  
ON FUNCTIONAL CAPACITY AND STRENGTH OF RESPIRATORY MUSCLES  
IN PATIENTS WITH POST-COVID SYNDROME
Lana VRANIĆ 1, Zrinka BILOGLAV 2     , Petar MEDAKOVIĆ 3     , Jasminka TALAPKO 4     , Ivana ŠKRLEC 4* 
1 Clinic for Lung Diseases Jordanovac, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
2 Department of Medical Statistics, Epidemiology and Medical Informatics, School of Public Health 
Andrija Štampar, University of Zagreb School of Medicine, 10000 Zagreb, Croatia
3 Department of Radiology, Polyclinic Croatia, 10000 Zagreb, Croatia
4 Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia
Received: Sep 28, 2023
Accepted: Apr 23, 2024
Original scientific article
*Correspondence: iskrlec@fdmz.hr
10.2478/sjph-2024-00017 Zdr Varst. 2024;63(3):123-131
123
UČINEK PROGRAMA PLJUČNE REHABILITACIJE NA FUNKCIONALNO 
SPOSOBNOST IN MOČ DIHALNIH MIŠIC PRI BOLNIKIH Z DOLGIM COVIDOM
© National Institute of Public Health, Slovenia. 
Vranić L, Biloglav Z, Medaković P, Talapko J, Škrlec I. The effects of a pulmonary rehabilitation programme on functional capacity and strength of respiratory muscles in patients with 
post-COVID syndrome. Zdr Varst. 2024;63(3):123-131. doi: 10.2478/sjph-2024-0017.
ABSTRACT
Keywords: 
Dyspnea
Post-COVID syndrome
Pulmonary 
function tests
Pulmonary  
rehabilitation
Respiratory muscle 
strength
IZVLEČEK
Ključne besede: 
dispneja
dolgi covid
testi pljučne funkcije
pljučna rehabilitacija
moč dihalnih mišic
Aim: The aim of this study was to estimate the effects of a pulmonary rehabilitation programme (PR) on the 
functional capacity and respiratory muscle strength of patients with post-COVID syndrome. 
Methods: A cross-sectional study was conducted using hospital data on patients who participated in a pulmonary 
rehabilitation programme at the Clinic for Lung Diseases, University Hospital Centre Zagreb, Croatia, between 
January 2021 and December 2022. Data on the spirometry, respiratory muscle strength, and functional exercise 
capacity of patients were collected at baseline and three weeks after the start of rehabilitation. The study 
included 80 patients (43 females, 37 males) with a mean age of 51±10 years.
Results: A significant increase in respiratory muscle strength (P<0.001) was observed after pulmonary 
rehabilitation, with effect sizes ranging from small to large (Cohen’s d from 0.39 to 1.07), whereas the effect 
for PImax expressed as a percentage was large (Cohen’s d=0.99). In addition, the pulmonary rehabilitation 
programme significantly improved the parameters of the six-minute walk test in patients, and the parameters of 
lung function, FVC, FEV1, and DLCO also improved significantly after PR (P<0.05).
Conclusion: The results showed that the pulmonary rehabilitation programme has clinically significant effects on 
functional capacity and respiratory muscle strength in patients with post-COVID syndrome.
Cilj: Cilj te študije je bil oceniti učinek programa pljučne rehabilitacije na funkcionalno sposobnost in moč 
dihalnih mišic pri bolnikih z dolgim covidom. 
Metode: Opravili smo presečno študijo na podlagi bolnišničnih podatkov o bolnikih, ki so med januarjem 2021 
in decembrom 2022 sodelovali v programu pljučne rehabilitacije v Kliniki za pljučne bolezni v Univerzitetnem 
bolnišničnem centru v Zagrebu. Podatke o spirometriji, moči dihalnih mišic in funkcionalni zmogljivosti za 
telesno aktivnost bolnikov smo zbrali ob izhodišču in tri tedne po začetku rehabilitacije. Študija je vključevala 
80 bolnikov (43 žensk, 37 moških) povprečne starosti 51±10 let.
Rezultati: Ugotovili smo bistveno povečanje moči dihalnih mišic (P < 0,001) po pljučni rehabilitaciji, pri čemer 
so bile velikosti učinka od majhnih do velikih (Cohen d od 0,39 do 1,07), učinek za PImax, izražen v odstotku, pa 
je bil velik (Cohen d = 0,99). Poleg tega je program pljučne rehabilitacije precej izboljšal parametre 6-minutnega 
sprehoda pri bolnikih, parametri pljučne funkcije FVC, FEV1 in DLCO pa so se po pljučni rehabilitaciji prav tako 
znatno izboljšali (P < 0,05).
Zaključek: Rezultati so pokazali, da ima program pljučne rehabilitacije pri bolnikih z dolgim covidom klinično 
pomemben učinek na funkcionalno sposobnost in moč dihalnih mišic.
1 INTRODUCTION
In late 2019, the WHO declared a COVID-19 pandemic (1), 
with the severity ranging from asymptomatic to mild forms 
of the disease, to multiple organ failure and death (2). 
In addition to the acute phase, a distinction is also made 
with regard to post-COVID syndrome or long COVID. 
This refers to a duration of disease symptoms – such as 
shortness of breath, fatigue, chest pain, and cough – for 
more than two months after onset (3, 4). SARS-CoV-2 virus 
reduces respiratory muscle strength independently or in 
combination with other factors, resulting in shortness 
of breath in patients in acute and post-COVID phases 
(5). Pathophysiological mechanisms include direct 
myopathic effects on respiratory muscles (4) or damage to 
neurological control of breathing (6). 
The pulmonary rehabilitation (PR) programme, based 
on 2013 recommendations of the American Thoracic 
Society (ATS) and European Respiratory Society (ERS), 
aims to improve the health status of patients with chronic 
respiratory diseases (7). Patients with chronic obstructive 
pulmonary disease commonly use PR, but it is effective 
with many other pulmonary diseases, such as COVID-19 
and post-COVID syndrome. In the long term, it improves 
the physical and psychological health of patients with 
chronic lung diseases (7). It improves the quality of 
life by improving cardiorespiratory and bone-muscular 
function, reducing dyspnea and fatigue intensity (8). 
During rehabilitation, the patient’s condition is regularly 
assessed. Exercises are adjusted with a gradual increase in 
load, and the same tests are performed at the beginning 
and end of PR programme (9). 
Exercises to strengthen respiratory muscles are an 
important part of PR programme for post-COVID patients 
(10). Various respiratory muscle strengthening devices are 
used in rehabilitation, such as an inspiratory muscle training 
(IMT) device, positive expiratory pressure device (PEP), and 
Respifit S (an inspiratory muscle training device). The IMT 
device increases the strength of the patient’s respiratory 
muscles and is more effective than breathing exercises (11), 
while IMT exercises improve respiratory muscle strength 
and lung function in COPD patients (12). The efficacy of 
these exercises has already been demonstrated in patients 
with some other diagnoses. Morgan et al. examined 
respiratory muscle-strengthening exercises in post-
COVID-19 patients, and their review found that pulmonary 
function improved in all but one of included studies, and 
dyspnea and quality of life improved significantly (13). This 
led to a hypothesis that PR programmes positively affect 
functional capacity and respiratory muscle strength in 
patients with post-COVID syndrome. This study aimed to 
investigate a PR programme’s effects on lung functional 
capacity and respiratory muscles strength in patients with 
post-COVID syndrome. 
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
124
2 MATERIALS AND METHODS
2.1 Patients
This cross-sectional study was approved by the Ethics 
Committee of University Hospital Centre Zagreb 
(No.02/013AG). It was conducted in accordance with 
guidelines for the safety of subjects participating in such 
studies, including the Declaration of Helsinki. It included 
analyses of data collected during routine PR.
Patients who had recovered from COVID-19 and, after 
clinical evaluation by a specialist, had participated in and 
fully completed the PR programme at the Clinic for Lung 
Diseases Jordanovac University Hospital Centre Zagreb 
from January 2021 to December 2022, were eligible for 
this study. They had been infected with SARS-CoV-2 over 
two months before starting rehabilitation. All the patients 
were required to present a test upon arrival to exclude 
current SARS-CoV-2 infection. All the data for the study 
were obtained from the hospital information system.
The study included 80 patients aged 25 to 68 (Table 1). 
The proportion of women was higher, at 53.8% vs. 46.3%.
Characteristics of patients (N=80, 43 females,  
37 males).
*BMI–body mass index
Variable All patients Females 
(n=43)
Males  
(n=37)
Table 1.
Mean age (years)
Age (interval)
Age (mode)
Age (median) 
BMI>30kg/m2*
Comorbidity 
50.96±10.22
25–68
49
51.5
37 (46.3%)
56 (70%)
50.46±10.53
25–68
49
51
17 (39.5%) 
32 (74.4%) 
51.54±9.97
28-68
52
52
20 (54.1%)
24 (64.9%)
2.2 Rehabilitation programme
During the three-week PR programme, the patients 
attended rehabilitation sessions five times a week. 
They participated in a three-hour rehabilitation activity 
each session, including tests, education, exercises, and 
check-ups. Since the PR programme occurred during the 
pandemic, all the patients were required to present a 
negative test upon arrival to rule out SARS-CoV-2 infection. 
Staff and patients wore protective clothing during the 
exercises and pulmonary function tests.
The patient was first examined by a specialist 
who determined whether there were any clinical 
contraindications to performing PR tests. If there were 
no contraindications, then the tests followed. Pulmonary 
function tests (spirometry, diffusion, PImax, PEmax) 
were performed first. The pulmonary function tests were 
performed sitting with the feet flat on the floor. The 
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
125
patient wore comfortable clothing that did not constrict 
them anywhere, and thus made breathing difficult. After 
10 minutes, when the patient had rested sufficiently, the 
six-minute walk test (6MWT) began. 
The PR programme took place in a room specially 
equipped for exercise with all the necessary devices. The 
PR programme was held at two times, at 8 am and noon, 
and each session lasted three hours. During this time, 
the patients learned diaphragmatic breathing exercises, 
exercises to strengthen the muscles of the extremities 
with the help of supports, and exercises to strengthen the 
respiratory muscles with the help of various devices (IMT, 
PEP, Respifit S), they also performed endurance exercises 
(cycling, walking on treadmill) and learned Nordic walking 
techniques. Nurses and physiotherapists supervised the 
patients during all the exercises. In addition to correct 
execution, during each activity the patients’ blood oxygen 
saturation and pulse rate were monitored, so that they 
would not be subjected to an effort that was too intense 
for them at that moment. PR aims to ensure that patients 
learn the correct breathing techniques and use them daily 
to improve their quality of life.
Patients who trained on an IMT or PEP device were later given 
this device to continue training after the PR programme. 
In contrast, the Respifit S was used exclusively during 
rehabilitation and under the supervision of medical staff.
2.3 Pulmonary function tests and respiratory muscle 
strength
Pulmonary function tests were performed with a 
Schiller LFX8 spirometer according to the ATS and ERS 
standards using the standardized quality control protocol 
ERS93&GLI2017 (14, 15). The following parameters were 
compared: forced expiratory volume in one second 
(FEV1), forced vital capacity (FVC), and ratio of FEV1/
FVC, i.e., the Tiffeneau index and diffusion capacity of 
lungs for carbon monoxide (DLCO) to evaluate the effects 
of PR on lung function (16). Patients had to have at least 
three technically correct measurements for the results to 
be acceptable. The results were then compared with the 
expected values for patient age, sex, height, and weight. 
Values greater than 80% for FEV1, FVC, and DLCO and >70% 
for the Tiffeneau index were considered normal (17).
Respiratory muscle strength was determined, with PImax 
indicating the maximal inspiratory pressure and PEmax 
the maximal expiratory pressure. Measurements for 
both values were taken at least twice. Any result >80% 
of patient’s reference value, as determined by age, sex, 
height, and weight, was considered the lowest normal 
value for PImax and PEmax.
2.4 Six-minute walk test and grade of dyspnea
The 6MWT determines the functional exercise capacity 
of patients with moderate to severe lung disease (18), 
based on the maximum distance a patient can walk in a 
given period (19). The patient’s vital signs at rest (arterial 
pressure, peripheral blood oxygen saturation (SpO2), and 
pulse) were measured at the test’s beginning and end. 
The degree of dyspnea at rest was determined using 
the modified Borg scale from 0 to 10, where 0 indicated 
complete absence of dyspnea and 10 the most severe 
dyspnea (20). At the end of the 6MWT test, measurements 
were repeated to determine whether vital signs had 
changed or SpO2 had decreased during fast walking. 
2.5 Statistical methods
Data are presented as the arithmetic mean and standard 
deviation (SD), arithmetic mean difference, and 95% 
confidence interval (95%CI). The differences in pulmonary 
function tests before and after completion of the PR 
programme were calculated using Student’s t-test for 
paired samples. The comparison of proportions was 
assessed with a chi-square test. Differences between PR 
initiation time after COVID-19 were tested by one-way 
ANOVA. Effect sizes were calculated for all differences 
in measured outcomes after the PR programme using 
Cohen’s d index. The SPSS statistical programme (26.0, 
SPSS, USA) was used for statistical analysis, and P<0.05 
was considered significant.
3 RESULTS 
Most patients (71.3%) started the rehabilitation programme 
more than four months after having COVID-19 (Figure 1). 
The distribution of patients depends on the time of 
initiation of PR after COVID-19 (N=80, 43 females,  
37 males).
Figure 1.
Over half of the patients had decreased respiratory 
muscle strength (<80%) and functional capacity before the 
PR programme. After rehabilitation, 51.3% and 16.3% of 
patients had PImax and PEmax values <80% of the predicted 
threshold, respectively, whereas only 21.3% had a 6MWT 
distance <80% of the predicted reference value (Table 2).
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
126
Pathological values of pulmonary parameters and respiratory muscle strength before and after the PR programme (N=80, 43 
females, 37 males)
The effects of the PR programme on muscle strength (N=80, 43 females, 37 males).
*Student’s t-test for paired samples.
*Chi-square test. 
Variable
Variable
Baseline n(%)
Baseline 
M±SD
After PR
M±SD
P* Cohen’s dMean difference
(95%CI)
After PR n(%) P* Cohen’s d
Table 2.
Table 3.
PImax<80% 
PEmax<80%
FVC<80%
FEV1<80%
FEV1/FVC<70%
DLCO<80%
6MWT<80 %
PImax
PImax(%)
PEmax
PEmax(%)
FVC
FVC(%)
FEV1
FEV1(%)
FEV1/FVC
DLCO
DLCO(%)
6MWT(m)
6MWT(%)
SpO2 (before 6MWT)
SpO2 (after 6MWT)
Dyspnea (Borg)
Heart rate
57 (71.3)
28 (35)
14 (17.5)
19 (23.8)
16 (20)
15 (18.8)
44 (55)
69.90±26.49
64.74±25.01
92.16±30.03
90.80±27.26
4.14±1.28
98.16±18.28
3.04±0.93
90.61±18.97
74.28±11.62
24.34±7.58
95.23±21.57
442.76±96.22
77.72±16.06
96.59±2.10
94.15±4.89
3.53±2.32
81.43±12.67
88.06±26.23
80.84±24.57
100.66±30.49
99.78±25.82
4.33±1.29
100.49±16.97
3.15±0.96
92.16±18.58
73.47±11.93
24.96±7.81
95.88±21.72
503.11±105.15
87.68±13.86
97.14±1.64
94.60±4.29
2.63±1.94
113.65±18.27
<0.001
<0.001
<0.001
0.001
<0.001
0.001
0.001
0.001
0.122
0.007
0.011
<0.001
<0.001
0.006
0.036
<0.001
<0.001
1.07
0.99
0.44
0.39
0.48
0.39
0.42
0.39
0.18
0.35
0.33
0.91
1.08
0.33
0.25
0.44
1.75
18.16 (-21.94–(-14.38))
16.10 (-19.72–(-12.48))
8.50 (-12.78–(-4.22))
8.98 (-14.13–(-3.82))
-0.14 (-0.21–(-0.07))
-2.92 (-4.64–(-1.19))
-0.08 (-0.13–(-0.04))
-2.36 (-3.76–(-0.97))
0.68 (-0.18–1.54)
-1.17 (-2.02–(-0.33))
-4.03 (-7.11–(-0.95))
-66.92  (-84.01– (-49.82))
-9.66 (-11.78–(-7.55))
-0.64 (-1.09–(-0.19))
-0.56 (-1.09–(-0.04))
0.95 (0.44–1.45)
-32.22 (-36.39)–(31.99))
41 (51.3)
13 (16.3)
8 (10)
14 (17.5)
18 (22.5)
13 (16.3)
17 (21.3)
<0.001
<0.001
0.251
0.338
0.699
0.677
0.007
0.89
0.15
0.06
0.59
0.41
0.26
0.65
The effects of PR on patients’ respiratory muscle strength 
(Table 3) showed significant differences (P<0.001), with 
small to large effect sizes. The effect and difference are 
very large for PImax. The mean value of PImax increased 
by 18.16 cmH2O and PEmax by 8.50 cmH2O. The results for 
all other pulmonary function parameters in patients with 
COVID-19 syndrome showed significant improvement after 
PR (P<0.05), except for the Tiffeneau index. However, 
the effect sizes of PR ranged from very small to small, 
with a Cohen’s d index from 0.18 to 0.48. PR significantly 
improved functional capacity as measured by 6MWT, with 
a large effect size. Peripheral oxygen saturation improved 
significantly, but the effect size was small. A significant 
reduction in dyspnea, as measured on the modified Borg 
scale, was observed after PR, with a small effect.
In Table 4, we compared the outcomes after PR between 
patient groups according to the time elapsed between 
onset of COVID-19 and start of rehabilitation. Significant 
differences (P<0.05) were observed for higher PImax in 
patients who started rehabilitation after two to three 
months than in those who started rehabilitation more 
than four months after the onset of COVID-19. The lowest 
values of PImax were measured in patients who started 
rehabilitation more than four months after disease onset. 
Post-hoc analysis showed that PImax in terms of cmH2O was 
significantly higher in patients who started PR two to three 
months after disease onset than in patients who started 
rehabilitation more than four months after it (Tukey 
P=0.024). The same was true for PImax in percentage terms 
(Tukey P=0.012). For PImax, no significant difference was 
found between patients who started PR two to three months 
after COVID-19 and patients who started rehabilitation 
three to four months after COVID-19 (Tukey P=0.369). For 
PEmax, there was no significant difference with regard to 
the time when rehabilitation started after COVID-19. The 
time elapsed from disease onset to initiation of PR had no 
significant effect on other spirometric pulmonary function 
test results or DLCO, 6MWT, and dyspnea. A post-hoc 
analysis showed that patients who started PR two to three 
months after disease onset had a significantly higher heart 
rate than patients who started rehabilitation more than 
four months after it (Tukey P=0.038). 
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
127
Differences in outcomes of the PR programme according to the time elapsed between disease onset and the beginning of 
rehabilitation (N=80, 43 females, 37 males).
*ANOVA test. 
Variable 2 to 3 months 
(n=16)
M±SD
3 to 4 months 
(n=7)
M±SD
P* Cohen’s dMore than 4 months
(n=57)
M±SD
Table 4.
PImax
PImax(%)
PEmax
PEmax(%)
FVC
FVC(%)
FEV1
FEV1(%)
FEV1/FVC
DLCO
DLCO(%)
6MWT(m)
6MWT(%)
SpO2 (before 6MWT)
SpO2 (after 6MWT)
Dyspnea 
Heart rate
21.44±24.07
19.88±22.78
7.56±21.62
8.38±20.33
0.31±0.34
5.47±6.69
0.15±0.21
3.87±4.82
1.48±4.89
2.99±3.59
8.33±10.36
525.87±105.47
88.07±11.06
97.60±0.99
94.40±3.38
1.97±1.64
84.19±16.14
17.86±14.38
16.43±13.29
2.86±25.24
0.57±23.32
0.02±0.27
1.29±8.75
0.02±0.18
1.00±6.71
2.35±5.04
3.61±5.04
14.86±15.12
468.43±146.46
91.17±17.52
97.43±1.40
93.71±3.15
2.93±1.43
81.71±10.45
0.032
0.021
0.180
0.785
0.363
0.269
0.124
0.812
0.327
0.275
0.709
0.483
0.798
0.374
0.813
0.332
0.047
3.36
3.29
3.30
3.86
3.33
5.92
3.29
4.96
6.16
3.20
4.41
4.78
6.33
59.08
22.07
1.35
6.43
17.28±15.05
15.00±14.51
9.46±18.01
10.18±24.00
0.11±0.28
2.40±7.45
0.08±0.19
2.38±6.14
0.23±3.10
0.29±2.91
1.14±11.12
501.21±99.61
87.16±12.68
96.96±1.81
94.78±4.68
2.78±2.07
80.57±11.87
4 DISCUSSION 
COVID-19 and post-COVID syndrome, relatively new clinical 
entities for acute and chronic patients’ health problems, 
have become subject of numerous studies. The results of 
this study support the clinical use of a PR programme with 
post-COVID-19 patients, since it significantly improved 
most indicators of pulmonary function. 
At the end of rehabilitation, the values of FEV1, FVC, 
DLCO, 6MWT, and respiratory muscle strength improved 
significantly, with effect sizes ranging from small to large 
(Cohen’s d from 0.35 to 1.08). In contrast, the Tiffeneau 
index remained unchanged, as both the numerator (FEV1) 
and denominator (FVC) improved significantly. Lung 
function increased in litres from 4.14±1.28 to 4.33±1.29 for 
FVC and from 3.04±0.93 to 3.15±0.96 for FEV1. Functional 
capacity increased in metres from 442.76±96.22 to 
503.11±105.15, with an increase in the predicted value from 
77.7% to 87.7%. In addition to the significant effects of PR 
on lung function, a previous study of older adults who had 
recovered from COVID-19 confirmed a positive impact on 
other areas of health, such as quality of life and anxiety. In 
that study, a six-week PR programme included 10-minute 
exercises twice weekly to strengthen respiratory muscles 
and the diaphragm, as well as stretching exercises (21). 
After hospitalization, post-COVID patients usually have 
muscle weakness and difficulty breathing after exercise. 
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
128
For them, rehabilitation is crucial to improving fitness and 
muscle strength because the muscles of whole body are 
weakened in addition to respiratory muscles (22).
PR significantly improved PImax, PEmax, and respiratory 
muscle strength. A total of 71.3% of patients had a 
pathological value <80% of the predicted value for PImax 
at the first measurement, and 51.3% of them at the last 
measurement. For PEmax, pathological values were 
found in 35% of patients at the first measurement and in 
6.3% of them at the last measurement. Vieira da Costa 
et al. confirmed the improvement of respiratory muscle 
strength after PR in a study of nine post-COVID patients 
with different clinical presentations, dry cough, shortness 
of breath, and chest pain (23). In addition to improving 
lung function and respiratory strength, the endurance of 
the respiratory muscles and diaphragm, main respiratory 
muscle, and quadriceps all improved (23). Villelabeitia-
Jaureguizar et al. studied SARS-CoV-2 patients who were 
treated with invasive mechanical ventilation in an intensive 
care unit, and then performed low-intensity respiratory 
muscle exercises after discharge (24). The results suggest 
that low-intensity respiratory muscle training improves 
respiratory strength and quality of life associated with 
health status and shortness of breath.
In this study the COVID-19 patients who took part in the PR 
programme recovered better and faster than those who did 
not participate in it. Their muscle strength, balance, and 
psychosocial status also improved significantly compared to 
patients who suffered only respiratory failure. Long-term 
ICU treatment significantly damages muscle function in the 
short term, limits physical performance, and reduces quality 
of life. Al Chikhania at al. suggest that PR programmes may 
reduce posttraumatic stress (25). The increased PImax and 
PEmax values after PR indicate that improved inspiratory 
and expiratory muscle strength is associated with greater 
mobility of the chest wall and diaphragmatic movements 
(10, 26). Respiratory muscle training improves muscle 
strength, airway resistance, and diaphragm thickness. 
It also reduces dyspnea, as weakness of the respiratory 
muscles is associated with shortness of breath (10).
The development of fibrosis is partly genetically 
determined. The angiotensin-converting enzyme-2 
gene is expressed in the myofiber membrane of the 
diaphragm, allowing infiltration of the SARS-CoV-2 virus 
and increasing gene expression involved in fibrosis (4,27). 
COVID-19 also changes the function of the diaphragm and 
decreases its thickness (27). A decrease in diaphragm 
muscle significantly increases the risk of pneumonia, 
and low thickness and density at CT are predictors for 
a severe form of COVID-19 (28). Diaphragm thickness at 
the end of expiration decreased In COVID-19 patients, 
and the thickening proportion increased (29). Various 
pathophysiological mechanisms are involved in the damage 
to the respiratory muscles that occurs with COVID-19, such 
as the decreased contractility of the respiratory muscles, 
myopathy of the respiratory muscles caused by the virus, 
unilateral paralysis of diaphragm due to unilateral injury 
of the phrenic nerve, severe atrophy and weakness due 
to dysfunction of the diaphragm, and baseline respiratory 
muscle weakness (4). COVID-19 may also affect neural 
control of breathing and cause unilateral diaphragm 
paralysis, unrelated to mechanical ventilation and normal 
lung parenchyma (6, 30).
Fibrous abnormalities and lung fibrosis affect about one-
third of COVID-19 patients (31). Risk factors include older 
age, chronic comorbidities, use of mechanical ventilation 
during the acute phase of COVID-19, and female gender. 
The development and progression of pulmonary fibrosis is 
influenced by each individual’s genetic background, i.e., the 
genes involved in innate antiviral defence, inflammatory 
lung injury, and the ABO system of blood groups (31, 32). 
Aging increases lung parenchyma stiffness and facilitates 
pulmonary fibrosis progression (33). For all these reasons, 
it is obvious why exercise in PR alleviates the severe 
symptoms of post-COVID-19 pulmonary fibrosis (34). 
The results are consistent with a systematic review, which 
showed that PR significantly improved exercise tolerance 
as determined by 6MWT (35). PR improves the pulmonary 
function parameters and reduces anxiety, depression, 
and symptoms of dyspnea and fatigue. Moreover, the 
lung function parameters and respiratory muscle strength 
were significantly better in patients who took part in a PR 
programme than in patients who did not (35).
The time between onset of COVID-19 and start of PR had no 
significant effects on most of the parameters of lung function, 
except PImax, suggesting that the time of starting PR is 
not as important clinically as simply starting rehabilitation 
in terms of achieving faster recovery and improvement in 
quality of life in post-COVID syndrome patients. 
The PR programme is effective in patients recovering 
from severe acute respiratory syndrome (SARS). In 
these patients, pulmonary abnormalities are present 
in up to 75.4% of patients six months after onset of the 
disease (36), and abnormalities in pulmonary function 
are present in one-third one year after SARS (37). Some 
studies reported reductions in DLCO scores ranging from 
11% to 45% among patients after one year, while the 6MWT 
results improved (38). Wu et al. showed radiological 
abnormalities resembling pulmonary fibrosis seven years 
after SARS (39). The results of studies on SARS patients, in 
whom the consequences of damage to pulmonary function 
are visible seven years after onset of the disease, point 
to the importance of a timely PR programme in post-
COVID-19 patients. Although the short-term consequences 
of COVID-19, such as weakened lung function, decreased 
muscle strength, and reduced mobility, are described in 
detail, further studies are needed to determine whether 
COVID-19 permanently impairs lung function. In this way, 
rehabilitation programmes in the acute and later phases 
of the disease can be maximally individualized and thus 
enable the best possible quality of life for each person (40).
In the context of all the previously mentioned studies on 
patients who have recovered from COVID-19, the use of the 
PR programme has been shown to have numerous positive 
effects, with sufficient supporting evidence. This complex 
programme includes physical activity and breathing 
exercises that increase respiratory muscle strength and 
lung function. The results are clinically significant since, 
at the end of rehabilitation, the patients had the ability 
to walk a greater distance with a lower grade of dyspnea. 
The use of the correct breathing patterns and exercises 
helped the patients to make tremendous efforts and 
achieve a higher workload with less breathlessness. This 
underscores the importance of referring patients in the 
post-COVID phase for PR. Learning the correct breathing 
patterns, strengthening specific limb muscles, increasing 
fitness, strengthening the respiratory muscles, improving 
the pulmonary function parameters, and increasing the 
functional capacity all help to improve the quality of life. 
Corral et al. have shown that an inspiratory and expiratory 
muscle training programme effectively improves the 
quality of life of people with long-term COVID-19 
symptoms (41). In addition, a systematic review with a 
meta-analysis found that rehabilitation interventions are 
associated with significant improvements in quality of life, 
functional exercise capacity, and dyspnea in post-COVID 
patients (42).
It should be noted that the programme investigated in this 
study is neither financially nor technically demanding for 
medical personnel. A clinical psychologist was included in 
the PR programme and had an important role in treating 
people with post-COVID syndrome, since anxiety and 
depression are not uncommon in this population (43). 
However, psychological monitoring of patients during PR 
has shown that this medical intervention can improve 
mental health.
4.1 Study limitations 
One of the limitations of this work is that it is a single-centre 
study. All patients who met the inclusion criteria and had 
a clinical indication for participation in a PR programme 
were included in the study. Given such a sampling frame, 
which implies consecutive sampling, it was impossible 
to estimate the required sample size before study was 
conducted. Moreover, data are lacking on the patients’ 
premorbid respiratory status, which might have influenced 
the measured parameters of lung function and respiratory 
muscle strength even before the disease, and whether 
SARS-CoV-2 infection was responsible for their worsening 
or was a clinical course of another, underlying condition.
Nevertheless, these limitations could not significantly 
affect the study’s results because most patients (91.3%) 
who participated in PR had not previously received 
pulmonary treatment. The collected data did not include 
information on the clinical presentation of COVID-19 and 
hospitalizations. In the Croatian health system, secondary 
and tertiary medical institutions are not linked by a 
single hospital information system, and it is impossible 
to conduct multicentre studies. Although the severity 
of clinical presentation could be associated with other 
comorbidities affecting respiratory muscle strength 
and functional capacity, it could not be subsequently 
categorized based on secondary use of the collected data. 
Undoubtedly, further research is needed to determine 
whether clinical improvement in post-COVID syndrome is 
attributable to the natural course of the disease, or if PR is 
crucial in improving the patient’s quality of life. However, 
identifying and quantifying the consequences of COVID-19 
and its dynamics over time requires a longitudinal study, 
extensive clinical follow-up, and many participants. Still, 
the methodological approach adopted in the current work 
makes it possible to compare the results with those of 
previous studies, although the statistical associations 
that it obtained have some limitations, usually due to the 
cross-sectional research design.
5 CONCLUSION 
PR significantly strengthens the respiratory muscles in 
patients with post-COVID syndrome, particularly in terms 
of PImax, by 18.16 litres, it improves lung functional 
capacity–FVC by 0.14 and FEV1 by 0.08, and reduces 
dyspnea by 0.95. Besides statistical significance, these 
positive effects on respiratory muscle strength have 
clinical relevance. The pulmonary function parameters 
of FVC, FEV1, and DLCOS significantly improved in the 
patients, as did endurance based on the results of the 
6MWT test. The time elapsed between disease onset and 
starting the PR programme was not found to be significant 
in improving lung function, but it did affect respiratory 
muscle strength.
ACKNOWLEDGMENT 
We would like to acknowledge and thank all the subjects 
who participated in the survey.  
CONFLICT OF INTEREST
The authors declare there is no conflict of interest.
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
129
FUNDING
The study received no funding
ETHICAL APPROVAL 
Ethical approval to conduct the study was obtained from 
the Ethics Committee of the University Hospital Centre 
Zagreb (No. 02/013 AG).
Informed consent: The manuscript does not contain any 
individual person’s data in any form.
AVAILABILITY OF DATA AND MATERIALS
All data and materials used in this study were collected 
from the hospital’s information system and are available 
upon reasonable request. 
CONTRIBUTIONS
All the authors contributed equally to the manuscript, 
read and approved the final version of the manuscript, 
and agreed to be accountable for all aspects of the work.
ORCID
Lana VRANIĆ: 
no ORCID number
Zrinka Biloglav: 
https://orcid.org/0000-0002-3245-001X
Petar Medaković: 
https://orcid.org/0000-0002-7173-8286
Jasminka Talapko: 
https://orcid.org/0000-0001-5957-0807
Ivana Škrlec: 
https://orcid.org/0000-0003-1842-930X
REFERENCES 
1. Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Bio-
medica. 2020;91(1):157–60. doi: 10.23750/ABM.V91I1.9397.
2. Pavli A, Theodoridou M, Maltezou HC. Post-COVID syndrome: 
Incidence, clinical spectrum, and challenges for primary healthcare 
professionals. Arch Med Res. 2021;52(6):575–81. doi: 10.1016/J.
ARCMED.2021.03.010. 
3. Jalušić Glunčić T, Muršić D, Basara L, Vranić L, Moćan A, Janković 
Makek M, et al. Overview of symptoms of ongoing symptomatic and 
post-COVID-19 patients who were reffered to pulmonary rehabilitation 
- first single-centre experience in Croatia. Psychiatr Danub. 
2021;33(suppl 4):565–571.
4. Severin R, Franz CK, Farr E, Meirelles C, Arena R, Phillips SA, et al. 
The effects of COVID-19 on respiratory muscle performance: Making 
the case for respiratory muscle testing and training. Eur Respir Rev. 
2022;31(166):220006. doi: 10.1183/16000617.0006-2022.
5. Hockele LF, Sachet Affonso JV, Rossi D, Eibel B. Pulmonary and 
functional rehabilitation improves functional capacity, pulmonary 
function and respiratory muscle strength in post COVID-19 patients: 
Pilot clinical trial. Int J Environ Res Public Health. 2022;19(22):14899. 
doi: 10.3390/IJERPH192214899. 
6. Maurie F, Godbert B, Perrin J. Respiratory distress in SARS-CoV-2 
without lung damage: Phrenic paralysis should be considered in 
COVID-19 infection. Eur J Case Reports Intern Med. 2020;7(6):001728. 
doi: 10.12890/2020_001728. 
7. Spruit MA, Singh SJ, Garvey C, Zu Wallack R, Nici L, Rochester C, et al. 
An official American Thoracic Society/European Respiratory Society 
statement: Key concepts and advances in pulmonary rehabilitation. 
Am J Respir Crit Care Med. 2013;188(8):e13-64. doi: 10.1164/
RCCM.201309-1634ST. 
8. Huang Y, Tan C, Wu J, Chen M, Wang Z, Luo L, et al. Impact of 
coronavirus disease 2019 on pulmonary function in early convalescence 
phase. Respir Res. 2020;21(1):163. doi: 10.1186/S12931-020-01429-6. 
9. McNarry MA, Berg RMG, Shelley J, Hudson J, Saynor ZL, Duckers J, 
et al. Inspiratory muscle training enhances recovery post COVID-19: 
A randomised controlled trial. Eur Respir J. 2022;60(4). doi: 
10.1183/13993003.03101-2021. 
10. Romaszko-Wojtowicz A, Szalecki M, Olech K, Doboszyńska A. 
Assessment of the function of respiratory muscles in patients after 
COVID-19 infection and respiratory rehabilitation. Trop Med Infect Dis. 
2023;8(1):57. doi: 10.3390/TROPICALMED8010057. 
11. Chung Y, Huang TY, Liao YH, Kuo YC. 12-week inspiratory muscle 
training improves respiratory muscle strength in adult patients with 
stable asthma: A randomized controlled trial. Int J Environ Res Public 
Health. 2021;18(6):1–17. doi: 10.3390/IJERPH18063267. 
12. Figueiredo RIN, Azambuja AM, Cureau FV, Sbruzzi G. Inspiratory 
muscle training in COPD. Respir Care. 2020;65(8):1189–1201. doi: 
10.4187/RESPCARE.07098.
13. Morgan SP, Visovsky C, Thomas B, Klein AB. Respiratory muscle 
strength training in patients post-COVID-19: A systematic review. Clin 
Nurs Res. 2024;33(1):60–69. doi: 10.1177/10547738231201994.
14. Brusasco V, Crapo R, Viegi G. Coming together: The ATS/ERS consensus 
on clinical pulmonary function testing. Eur Respir J. 2005;26(1):1–2. 
doi: 10.1183/09031936.05.00034205.
15. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, 
et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–338. 
doi: 10.1183/09031936.05.00034805.
16. Moore VC. Spirometry: Step by step. Breathe. 2012;8(3):232–240. doi: 
10.1183/20734735.0021711.
17. Graham BL, Steenbruggen I, Barjaktarevic IZ, Cooper BG, Hall GL, 
Hallstrand TS, et al. Standardization of spirometry 2019 update: An 
official American Thoracic Society and European Respiratory Society 
technical statement. Am J Respir Crit Care Med. 2019;200(8):E70–E88. 
doi: 10.1164/RCCM.201908-1590ST.
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
130
18. Agarwala P, Salzman SH. Six-minute walk test: Clinical role, 
technique, coding, and reimbursement. Chest. 2020;157(3):603–611. 
doi: 10.1016/J.CHEST.2019.10.014.
19. Crapo RO, Casaburi R, Coates AL, Enright PL, MacIntyre NR, McKay 
RT, et al. ATS statement: guidelines for the six-minute walk test. 
Am J Respir Crit Care Med. 2002;166(1):111–117. doi: 10.1164/
AJRCCM.166.1.AT1102.
20. Johnson MJ, Close L, Gillon SC, Molassiotis A, Lee PH, Farquhar MC, 
et al. Use of the modified Borg scale and numerical rating scale to 
measure chronic breathlessness: A pooled data analysis. Eur Respir J. 
2016;47(6):1861–1864. doi: 10.1183/13993003.02089-2015.
21. Liu K, Zhang W, Yang Y, Zhang J, Li Y, Chen Y. Respiratory rehabilitation 
in elderly patients with COVID-19: A randomized controlled study. 
Complement Ther Clin Pract. 2020;39:101166. doi: 10.1016/J.
CTCP.2020.101166.
22. Zhao HM, Xie YX, Wang C. Recommendations for respiratory 
rehabilitation in adults with coronavirus disease 2019. Chin Med J 
(Engl). 2020;133(13):1595–1602. doi: 10.1097/CM9.0000000000000848.
23. da Costa KV, de Souza ITC, dos Santos Felix JV, Brandão CBF, de Souza 
Fernandes VM, Favero ABL, et al. Efficacy of a rehabilitation protocol 
on pulmonary and respiratory muscle function and ultrasound 
evaluation of diaphragm and quadriceps femoris in patients with 
post-COVID-19 syndrome: A series of cases. Monaldi Arch chest Dis. 
2022;93(1). doi: 10.4081/MONALDI.2022.2206.
24. Villelabeitia-Jaureguizar K, Calvo-Lobo C, Rodríguez-Sanz D, 
Vicente-Campos D, Castro-Portal JA, López-Cañadas M, et al. Low 
intensity respiratory muscle training in COVID-19 patients after 
invasive mechanical ventilation: A retrospective case-series study. 
Biomedicines. 2022;10(11):2807. doi: 10.3390/BIOMEDICINES10112807.
25. Al Chikhanie Y, Veale D, Schoeffler M, Pépin JL, Verges S, Hérengt 
F. Effectiveness of pulmonary rehabilitation in COVID-19 respiratory 
failure patients post-ICU. Respir Physiol Neurobiol. 2021;287:103639. 
doi: 10.1016/J.RESP.2021.103639.
26. Padkao T, Boonla O. Relationships between respiratory muscle 
strength, chest wall expansion, and functional capacity in healthy 
nonsmokers. J Exerc Rehabil. 2020;16(2):189. doi: 10.12965/
JER.2040080.040.
27. Cesanelli L, Satkunskiene D, Bileviciute-Ljungar I, Kubilius R, 
Repečkaite G, Cesanelli F, et al. The possible impact of COVID-19 
on respiratory muscles structure and functions: A literature review. 
Sustainability. 2022;14(12):7446. doi: 10.3390/SU14127446.
28. Parlak S, Beşler MS, Gökhan MB. Association of diaphragm thickness 
and density measured on chest CT with disease severity in 
COVID-19 patients. Am J Emerg Med. 2022;61:29–33. doi: 10.1016/J.
AJEM.2022.08.029.
29. Hadda V, Raja A, Suri TM, Khan MA, Mittal S, Madan K, et al. Temporal 
evolution of diaphragm thickness and diaphragm excursion among 
subjects hospitalized with COVID-19: A prospective observational study. 
Respir Med Res. 2023;83:100960. doi: 10.1016/J.RESMER.2022.100960.
30. Shahid M, Nasir SA, Shahid O, Nasir SA, Khan MW. Unilateral 
diaphragmatic paralysis in a patient with COVID-19 pneumonia. 
Cureus. 2021;13(11):e19322. doi: 10.7759/CUREUS.19322.
31. Duong-Quy S, Vo-Pham-Minh T, Tran-Xuan Q, Huynh-Anh T, Vo-Van 
T, Vu-Tran-Thien Q, et al. Post-COVID-19 pulmonary fibrosis: facts—
challenges and futures: a narrative review. Pulm Ther. 2023;9(3):295.
doi:10.1007/S41030-023-00226-Y.
32. 32.  Kramberger M, Biloglav Z, Talapko J, Škrlec I. The association 
of abo and rhd blood groups with covid-19 mortality of patients 
hospitalized in the COVID ward at general hospital Karlovac. Med 
Flum. 2023;59(2):161–169. doi: 10.21860/MEDFLUM2023_300574.
33. Lyu Q, Wen Y, Zhang X, Addinsall AB, Cacciani N, Larsson L. Multi-
omics reveals age-related differences in the diaphragm response to 
mechanical ventilation: A pilot study. Skelet Muscle. 2021;11(1):11. doi: 
10.1186/S13395-021-00267-4.
34. Reina-Gutiérrez S, Torres-Costoso A, Martínez-Vizcaíno V, Núñez de 
Arenas-Arroyo S, Fernández-Rodríguez R, Pozuelo-Carrascosa DP. 
Effectiveness of pulmonary rehabilitation in interstitial lung disease, 
including coronavirus diseases: A systematic review and meta-
analysis. Arch Phys Med Rehabil. 2021;102(10):1989-1997.e3. doi: 
10.1016/J.APMR.2021.03.035.
35. Soril LJJ, Damant RW, Lam GY, Smith MP, Weatherald J, Bourbeau 
J, et al. The effectiveness of pulmonary rehabilitation for post-
COVID symptoms: A rapid review of the literature. Respir Med. 
2022;195:106782. doi: 10.1016/J.RMED.2022.106782.
36. Ng CK, Chan JWM, Kwan TL, To TS, Chan YH, Ng FYY, et al. Six-month 
radiological and physiological outcomes in severe acute respiratory 
syndrome (SARS) survivors. Thorax. 2004;59(10):889–891. doi: 10.1136/
THX.2004.023762.
37. Ong KC, Ng AWK, Lee LSU, Kaw G, Kwek SK, Leow MKS, et al. 1-year 
pulmonary function and health status in survivors of severe acute 
respiratory syndrome. Chest. 2005;128(3):1393–1400. doi: 10.1378/
CHEST.128.3.1393.
38. Ahmed H, Patel K, Greenwood DC, Halpin S, Lewthwaite P, Salawu A, et 
al. Long-term clinical outcomes in survivors of severe acute respiratory 
syndrome and Middle East respiratory syndrome coronavirus outbreaks 
after hospitalisation or ICU admission: A systematic review and meta-
analysis. J Rehabil Med. 2020;52(5):jrm00063. doi: 10.2340/16501977-
2694.
39. Wu X, Dong D, Ma D. Thin-section computed tomography manifestations 
during convalescence and long-term follow-up of patients with severe 
acute respiratory syndrome (SARS). Med Sci Monit. 2016;22:2793–2799. 
doi: 10.12659/MSM.896985.
40. Boutou AK, Georgopoulou A, Pitsiou G, Stanopoulos I, Kontakiotis T, 
Kioumis I. Changes in the respiratory function of COVID-19 survivors 
during follow-up: A novel respiratory disorder on the rise? Int J Clin 
Pract. 2021;75(10):e14301. doi: 10.1111/IJCP.14301.
41. del Corral T, Fabero-Garrido R, Plaza-Manzano G, Fernández-de-las-
Peñas C, Navarro-Santana M, López-de-Uralde-Villanueva I. Home-
based respiratory muscle training on quality of life and exercise 
tolerance in long-term post-COVID-19: Randomized controlled 
trial. Ann Phys Rehabil Med. 2023;66(1):101709. doi: 10.1016/J.
REHAB.2022.101709.
42. Pouliopoulou D V., Macdermid JC, Saunders E, Peters S, Brunton L, 
Miller E, et al. Rehabilitation interventions for physical capacity and 
quality of life in adults with post–COVID-19 condition: A systematic 
review and meta-analysis. JAMA Netw Open. 2023;6(9):e2333838. doi: 
10.1001/JAMANETWORKOPEN.2023.33838.
43. Badinlou F, Lundgren T, Jansson-Fröjmark M. Mental health outcomes 
following COVID-19 infection: Impacts of post-COVID impairments 
and fatigue on depression, anxiety, and insomnia — a web survey in 
Sweden. BMC Psychiatry. 2022;22(1):743. doi: 10.1186/S12888-022-
04405-0.
10.2478/sjph-2024-0017 Zdr Varst. 2024;63(3):123-131
131