Biomedicines | Free Full-Text | Efficacy of Pulmonary Rehabilitation in Post-COVID-19: A Systematic Review and Meta-Analysis

Studies with Subacute COVID-19 Patients Abodonya et al. (2021) [39] RCT Adults with subacute COVID-19 n = 42
Int: n = 21 (19% F), Age: 48.3 ± 8.5
Con: n = 21 (23.8% F) Age: 47.8 ± 9.2 Duration
2 weeks.
Intervention
Breathing exercises. Usual care Dyspnea (DS-12)
Quality of life (EQ-5D)
Physical function (6MWT) Intra-group analysis found statistically differences in intervention group in dyspnea (p = 0.001), quality of life (p < 0.001) and 6MWT (p < 0.001).
Between group comparison, intervention group reported statistically significant differences compared to control in all outcomes with medium-large size effects. Barhagi et al. (2021) [40] RCT Adults with subacute COVID-19 n = 80 (38.75% F)
Int: n = 40, Age: 57.1 ± 18.7
Con: n = 40
Age: 58 ± 17.13 Duration
Three days.
Intervention
Breathing exercises. Usual care Dyspnea (MBS) After end of treatment, intervention group improved dyspnea with statistically differences compared to usual care (p = 0.007). Fereydounnia et al. (2022) [41] RCT Adults with subacute COVID-19 n = 50
(42% F)
Int: n = 25, Age: 49.44 ± 14.78
Con: n = 25, Age: 45 ± 12.75 Duration
1 week.
Intervention
Myofascial release and breathing exercises. Breathing exercises Dyspnea (MBS)
Physical function (6MWT)
Fatigue (Borg) Intervention group improved dyspnea with statistically differences at the end of the treatment compared to control (p < 0.01).
No statistically differences were found in terms of physical function (p = 0.033) or fatigue (p = 0.034) improvement compared to control. González-Gerez et al. (2021) [42] RCT Adults with subacute COVID-19 n = 38
Int: n = 19 (47.4% F), Age: 40.79 ± 9.84
Con: n = 19 (42.1% F), Age: 40.32 ± 12.53 Duration
1 week.
Intervention
Breathing exercises. Telerehabilitation. Usual care Physical function (6MWT; 30STS)
Dyspnea (MD12; BS) Statistically differences were found in terms of improving dyspnea (p < 0.001) and physical function (p = 0.001), in intervention, with no differences in control group.
Between group analysis found statistically differences favoring intervention compared to control improving dyspnea (p < 0.001) and physical function (p = 0.001). Hayden et al. (2021) [43] Observational Adults with subacute COVID-19 n = 108
(45.4% F)
Age: 55.6 ± 10.1 Duration
3 weeks.
Intervention
Aerobic and strength training. Nutritional, psychological, and physical therapy support were included. No control Dyspnea (NRS/mMRC)
Physical function (6MWT)
Quality of life (EQ-5D)
Fatigue (BFI)
Depression and Anxiety (PHQ-9, GAD-7) Dyspnea improved at rest (p < 0.001) and on exertion (p < 0.001) after treatment.
Physical function improved after treatment (p < 0.001).
Quality of life, fatigue, anxiety, and depression improved after treatment (p < 0.001) Hockele et al. (2022) [44] Observational Adults with subacute COVID-19 n = 29
(51.7% F)
Age: 54.4 ± 14.6 Duration
6–8 weeks.
Intervention
Aerobic and strength training. No control Physical function (6MWT, TUG)
Dyspnea (mMRC) Physical function improved after treatment with statistically significant differences compared to baseline in 6MWT (p < 0.001) and TUG (p = 0.023). Dyspnea improved after treatment with differences compared to baseline (p = 0.003). Li et al. (2021) [45] RCT Adults with subacute COVID-19 n = 119
(55.46% F)
Int: n = 59, Age: 49.17 ± 10.75
Con: n = 60, Age: 52.03 ± 11.10 Duration
6 weeks. 6 months follow-up.
Intervention
Aerobic, strength and breathing exercises. Telerehabilitation. Usual care Physical function (6 MWT)
Dyspnea (mMRC)
Quality of life (SF-12) Intervention group improved physical function after treatment (p < 0.001) and at follow-up with statistically differences (p < 0.001).
Perceived dyspnea improved after treatment with differences compared to control (p = 0.001) but without differences at follow-up (p = 0.162).
Physical component of SF-12 improved with differences after treatment (p = 0.004) and at follow-up (p = 0.045). However, mental component found no differences at any point (p = 0.116; p = 0.164). Liu et al. (2020) [46] RCT Adults with subacute COVID-19 n = 72
Int: n = 36 (33.3% F), Age: 69.4 ± 8
Con: n = 36 (30.6% F)
Age: 68.9 ± 7.6 Duration
6 weeks.
Intervention
Breathing exercises. Usual care Physical function (6MWT)
Quality of life (SF-36)
Anxiety and Depression (SDS, SAS) Physical function improved with statistically differences in intervention group compared with baseline (p < 0.05), without statistically improvements in control group. Intervention group improved with statistically differences compared to control group (p < 0.05).
Quality of life improved with statistically differences compared to baseline in intervention group (p < 0.05) and not on control group. Between group analysis found that intervention group improved with statistically differences in all items of SF-36 compared to control group (p < 0.05).
Anxiety improved with statistically significant differences between groups favoring intervention (p < 0.05), but not depression. Llurda-Almuzara et al. (2022) [47] RCT Adults with subacute COVID-19 n = 70
Int: n = 35, Age: 49.5 ± 13.7
Con: n = 35
Age: 55.1 ± 20.9 Duration
8 weeks.
Intervention
Aerobic, strength and breathing exercises. Telerehabilitation. Usual care Physical function (SPPB, 4MWT) Physical function improved with moderate significant effects in intervention group compared to control. Lobanov et al. (2022) [48] RCT Adults with subacute COVID-19 n = 23
Int: n = 14
Con: n= 9 Duration
2 weeks.
Intervention
Aerobic exercises in pool. Exercise without pool. Physical function (6MWT)
Quality of life (EQ-5D)
Dyspnea (BS) Physical function improved with statistically significant differences compared to baseline (p = 0.047 both groups), with greater improvement in intervention group.
Quality of life improved in anxiety/depression domain with statistically differences in control group (p = 0.043), but not in intervention group (p = 0.69).
Dyspnea improved after treatment, but without statistical differences compared to baseline in any group. Martín et al. (2021) [49] Observational Adults with subacute COVID-19 n = 27
Int: n = 14 (21.4% F), Age: 60.8 ± 10.4
Con: n = 13 (53.8% F), Age: 61.9 ± 10.7 Duration
6 weeks.
Intervention
Aerobic and strength exercises. Usual Care Physical function (1MSTST)
Dyspnea (BS) After treatment, statistically differences were found in 1min-STS favoring intervention group (p = 0.004).
No differences were found in terms of dyspnea improvement (p = 0.560). Nagy et al. (2022) [50] RCT Adults with subacute COVID-19 n = 52
Int: n = 26, Age: 40 ± 3.36
Con: n = 26, Age: 39.7 ± 3.55 Duration
6 weeks.
Intervention
Myofascial release and breathing exercises. Breathing exercises Dyspnea (mMRC)
Physical function (6MWT)
Fatigue (FSS) Dyspnea, physical function, and fatigue improved with statistical differences compared to baseline in both groups (p < 0.05). Additionally, intervention group resulted in statistically significant differences compared to control (p < 0.001). Nambi et al. (2022) [51] RCT Adults with subacute COVID-19 n = 76
Int: n = 38, Age: 63.2 ± 3.1
Con: n = 38
Age: 64.1 ± 3.2 Duration
8 weeks.
Intervention
Exercise at low intensity Exercise at high intensity Quality of life (SarQol) Both groups improved quality of life after treatment with statistical differences compared to baseline (p = 0.001). However, patients allocated to low intensity group improved with better results in SarQol compared to baseline than those allocated to high intensity training. Pehlivan et al. (2022) [52] RCT Adults with subacute COVID-19 n = 34
Int: n = 17 (18% F), Age: 50.76 (32–82)
Con: n = 17 (35% F), Age: 43.24 (23–71) Duration
6 weeks.
Intervention
Aerobic, strength and breathing exercises. Telerehabilitation. Usual care Physical function (TUG/SPPB)
Dyspnea (mMRC)
Fatigue (VAS)
Quality of life (SGRQ)
Depression (BDI) Although both groups improved outcomes, intra-group differences were only found mMRC (p = 0.035), TUG (p = 0.005) and SGRQ (p = 0.002) at intervention group, while not statistically differences were found in control group at the end of treatment.
Between-groups analysis revealed statistically significant differences in terms of SGRQ improvement favor to intervention (p = 0.042).
No significant changes were found after treatment in depression levels neither intra-group or between group comparison. Puchner et al. (2021) [53] Observational Adults with subacute COVID-19 n = 23
(30% F)
Age: 57 ± 10 Duration
3–4 weeks.
Intervention
Aerobic, strength and breathing exercises. Nutritional and psychological counseling. No control Physical function (6MWT) Physical function improved after treatment with statistically differences compared to baseline (p < 0.001). Rodríguez-Blanco et al. (2021) [54] RCT Adults with subacute COVID-19 n = 36
Int: n = 18 (50% F), Age: 39.39 ± 11.74
Con: n = 18 (55.5% F), Age: 41.33 ± 12.13 Duration
1 week.
Intervention
Strength exercises. Telerehabilitation. Usual care Physical function (6MWT/30STS)
Dyspnea (BS) Intervention group improved physical function after treatment with statistically differences compared to usual care (p < 0.001).
However, although dyspnea improved in intervention group and did not improve in control group after treatment, differences were not significant (p = 0.074). Rutkowski et al. (2022) [55] RCT Adults with subacute COVID-19 n = 32
(68% F)
Age: 57.8 ± 4.9 Duration
3 weeks.
Intervention
Virtual reality exercise Exercise without virtual reality Depression and Anxiety (HADS)
Quality of life (WHOQOL-BREF)
Physical function (6MWT) Intervention group (p < 0.001) and control group (p < 0.05) improved anxiety and depression after treatment compared to baseline levels.
No significant changes were found in any group in terms of quality-of-life improvement after treatment.
Physical function improved in both groups. However, patients in intervention group showed more improvements in walked distance after treatment than control group. Teixeira do Amaral et al. (2022) [56] RCT Adults with subacute COVID-19 n = 32
Int: n = 12, Age: 51.9 ± 10.2
Con: n = 20, Age: 53.3 ± 11.6 Duration
12 weeks.
Intervention
Aerobic and strength exercises. Telerehabilitation. Usual care Physical function (6MWT, TUG, 5TSTS) Both groups all physical function outcomes compared to baseline, but without statistically significant differences within-group or between groups. Studies with long COVID-19 patients Albu et al., 2022 [57] Observational Adults with long COVID-19 n = 40
(40% female)
Mean Age: 52 ± 11.4 y/o Duration
8 weeks
Intervention
Education
Aerobic, strength and breathing exercises.
Psychological counseling.
Intensity
Personalized according to patient status. No control Physical performance (SPPB)
Fatigue (MFIS)
Quality of life (WHOQOL-BREF) After 8 weeks of rehabilitation, significant improvements in physical performance were found in SPPB compared to baseline with statistically differences (p = 0.001).
Fatigue was improved after intervention with statistically differences for all measured domains (p = 0.001).
Quality of life improved in physical, psychological, and environmental domains with statistical differences (p = 0.001), but not at social domain (p = 0.15). Cahalan et al., 2022 [58] Observational Adults with long COVID-19 n = 27
(85% f)
Mean age: 48.4 ± 10.1 y/o Duration
10 weeks.
Intervention
Breathing exercises, psychological advice. Telerehabilitation.
Intensity
Not reported. None Dyspnea (C19YRS)
Fatigue (C19YRS)
Anxiety/Depression (C19YRS) Statistical improvements were found after treatment in terms of dyspnea (p < 0.001), as well as in fatigue (p = 0.03).
Although anxiety and depression improved after treatment, no significant differences were found (p = 0.08 for anxiety, p = 0.337 for depression). Calvo-Paniagua 2022 [59] Quasi-experimental Adults with long COVID-19 n = 68
(61.8% f)
Mean age: 48.5 ± 9.7 y/o Duration
7 weeks.
Intervention
Aerobic, strength and breathing exercises. Telerehabilitation.
Intensity
Not reported. None Dyspnea (mMRC)
Quality of life (SGRQ)
Physical performance (6MWT) Dyspnea improved significantly after intervention and at follow-up (p < 0.001).
Quality of life improved significantly after intervention and at follow-up (p < 0.001).
Physical performance improved with statistically differences after intervention and at follow-up (p < 0.001). Compagno et al., 2022 [60] Observational Adults with long COVID-19 n = 30
(40% female)
Mean Age: 58.37 ± 11.6 y/o Duration
8–20 weeks
Intervention
Aerobic and strength exercises.
Psychological counseling.
Intensity
Aerobic exercise at low and mid intensity. Strength at 30–50% 1RM. No control Quality of life (SF-36)
Anxiety (SAS)
Depression (SDS) Quality of life improved after intervention with statistically differences (p < 0.05).
Anxiety and depression improved with statistically differences after treatment (both p < 0.05). Daynes et al., 2021 [61] Observational Adults with long COVID-19 n = 30
(48% female)
Mean Age: 58 ± 16 y/o Duration
6 weeks, with two supervised sessions per week.
Intervention
Aerobic and strength exercises.
Intensity
Not reported. No control Physical performance (ISWT)
Fatigue (FACIT)
Anxiety and depression (HADS)
Quality of life (EQ-5D) ISWT improved after treatment with statistically differences compared to baseline (p < 0.01).
Fatigue improved with statistical differences at the end of treatment (p < 0.01), while anxiety and depression improved, but without statistically significant differences (p = 0.5 for anxiety and p = 0.1 for depression).
Quality of life improved after treatment compared to baseline (p = 0.05). Del Corral 2022 [62] RCT Adults with long COVID-19 G1: n = 22, mean age: 48.9 ± 8.3 y/o; 77% f
G2: n = 22, mean age: 45.3 ± 12.8 y/o; 73% f
G3: n = 22, mean age: 46.5 ± 9.6 y/o, 64% f
G4: n = 22, mean age: 45 ± 10.2 y/o, 73% f Duration
8 weeks.
Intervention
Group 1: Inspiratory breathing exercises.
Group 2: Inspiratory and expiratory breathing exercises.
Telerehabilitation.
Intensity
20–80% of maximal inspiratory pressure Group 3: Sham inspiratory exercises.
Group 4: Sham inspiratory and expiratory exercises.
Sham procedures were with device without resistance Quality of life (EQ-5D)
Physical performance (1MSTST)
Anxiety/Depression (HADS) All groups improved quality of life after intervention compared to baseline (p < 0.05), except group 4.
At 4 weeks follow-up, no statistical differences were found between groups improving quality of life.
Physical performance improved with large effects in intervention groups compared with sham groups after intervention (p < 0.01), but without differences when comparing both intervention groups.
Differences were not found between groups after 4 weeks follow-up in terms of physical performance improving.
Although all groups improved psychological status, no statistical differences were found across groups. Estébanez-Pérez 2022 [63] Quasi-Experimental Adults with long COVID-19 n = 32
(71.9% f)
Mean age: 45.93 ± 10.65 y/o Duration
4 weeks.
Intervention
Aerobic and strength training. Telerehabilitation.
Intensity
Aerobic exercises at low to moderate intensity. Strength training not reported. None Physical performance (SPPB, 1MSTST) 1mSTS and SPPB improved with statistically significant effects after treatment (p < 0.05). Groenveld 2022 [64] Observational Adults with long COVID-19 n = 47
(68% f)
Mean age: 54 (21–70) Duration
6 weeks
Intervention
Virtual reality-based exercise. Telerehabilitation.
Intensity
Adjusted to patient. None Fatigue (BS)
Physical performance (6MWT, TUG, 30CST)
Quality of life (SF-12, PHQ)
Anxiety/Depression (HADS) Fatigue improved with clinical differences after treatment (p = 0.03).
Significant differences were found in 6MWT (p < 0.001) and 30CST (p = 0.02) after intervention.
Three patients performed TUG instead of 6MWT, with improvements after treatment.
Statistical differences were found improving quality of life for physical sphere (p < 0.049) and mental sphere (p < 0.01) measured with SF-12, as well as with PHQ (p = 0.04)
Symptoms measured with HADS decreased, but without statistical differences (p = 0.08). Hasenoehrl et al., 2022 [65] Quasi-experimental Adults with long COVID-19 Group 1 (mild symptoms): n = 10
(60% female), mean age: 42.9 ± 12.4 y/o
Group 2 (severe symptoms): n = 18
(89% female), mean age: 47.4 ± 10.1 y/o Duration
8 weeks of supervised strength training, 2 times per week
Intervention
Aerobic and strength exercises.
Intensity
Strength exercises performed at 7–10 RPE. Aerobic exercises at moderate intensity. No control Physical performance (6 MWT/30 STST) Both groups improved significantly 30 STST (p < 0.001) and 6 MWT (p < 0.001) after intervention. Jimeno-Almanzán et al., 2022 [36] RCT Adults with long COVID-19 n = 80
(69% female)
Mean Age: 45.3 ± 8.0 y/o Duration
8 weeks.
Intervention
G1: Strength and breathing exercises.
G2: Strength exercises.
G3: Breathing exercises.
Intensity
Strength at 50% 1 RM.
Breathing exercises at 12–15 RPE. G4: Usual care Dyspnea (mMRC)
Quality of life (SF-12)
Anxiety and Depression (GAD-7/PHQ-9)
Fatigue (FSS) All outcomes improved in all study groups after intervention.
After 8 weeks of intervention, no differences between groups were detected in mMRC, GAD-7 and SF-12.
Fatigue and depression improved with differences in training groups (G1 and G2, p = 0.007).
Breathing training group (G3) improved with differences in physical domain of SF-12 (p < 0.05).
No relevant changes were observed in control group (G4) pre-post intervention. Jimeno-Almanzán et al., 2022a [66] RCT Adults with long COVID-19 n = 39
(74.4% female)
Mean Age: 45.2 ± 9.5 y/o Duration
8 weeks.
Intervention
Strength exercises.
Intensity
50% 1RM. Usual care Dyspnea (mMRC)
Quality of life (SF-12)
Anxiety and Depression (GAD-7/PHQ-9)
Fatigue (FSS)
Physical performance (5TSTST) Intervention group resulted in statistically differences compared to control in physical domain of SF-12 (p = 0.024), fatigue (p < 0.05), depression symptoms (p = 0.021), and physical performance (p = 0.009).
Although all studied outcomes improved in both groups, no statistical differences were found in other outcomes such as dyspnea improvement or anxiety. Lloyd-Evans 2022 [67] Observational Adults with long COVID-19 n = 110 (68.1% f)
Mean age: 46.3 ± 10.8 Duration
8–12 weeks
Intervention
Aerobic and strength exercises. Telerehabilitation.
Intensity
Not reported. None Quality of life (EQ-5D) Statistically significant differences were found improving quality of life (p < 0.01). McNarry 2022 [68] RCT Adults with long COVID-19 n = 148
(111 int, 86% f/37 con, 95% f)
Mean age: 46.76 ± 12.03 (int)/46.13 ± 12.73 (con) Duration
8 weeks, unsupervised.
Intervention
Breathing exercises. Telerehabilitation.
Intensity
80% of sustained maximal inspiratory pressure. Usual care Quality of life (K-BILD)
Dyspnea (TDI) Although quality of life improved within-group, no statistically significant differences were found between groups.
Dyspnea improved with statistical differences favoring intervention compared to control (p = 0.005). Nopp et al., 2022 [69] Observational Adults with long COVID-19 n = 58
(43.1% female)
Mean Age: 46.8 ± 12.6 y/o Duration
6 weeks.
Intervention
Aerobic, strength and breathing exercises.
Intensity
Not reported. No Control Physical performance (6 MWT/1 MSTST)
Dyspnea (mMRC)
Quality of life (EQ-5D)
Fatigue (FAS) After intervention, patients improved 6 MWT and 1 MSTST with statistical differences (p < 0.001).
Dyspnea improved with statistical differences compared to baseline (p < 0.001).
Quality of life improved after treatment (p < 0.001).
Fatigue improved after treatment with statistical differences (p < 0.001). Okan 2022 [70] RCT Adults with long COVID-19 n = 52
(26 int, 42.3% f/26 con, 53.8% f)
Mean age: 48.85 ± 10.85 (int)/52.19 ± 14.84 (con) Duration
5 weeks, one session supervised.
Intervention
Aerobic and breathing exercises. Telerehabilitation.
Intensity
Aerobic exercises at moderate intensity. Breathing not reported. Usual care Dyspnea (mMRC)
Physical performance (6 MWT)
Quality of life (SGRQ) Both groups improved dyspnea. However, it was significantly lower in intervention group than in control group (p < 0.001).
Quality of life improved with statistical differences in intervention group compared to control after treatment (p < 0.001).
Physical performance improved with statistically significant differences in intervention group compared to control (p < 0.001). Philip 2022 [71] RCT Adults with long COVID-19 n = 150
(81% f)
Mean age: 49 ± 12 Duration
6 weeks.
Intervention
Breathing exercises. Telerehabilitation.
Intensity
Not reported. Usual care Quality of life (SF-36)
Dyspnea (DS-12)
Anxiety (GAD-7) Intervention group improved mental component of SF-36 with statistical differences compared to control (p = 0.047), while no differences in physical component (p = 0.54).
Dyspnea improved in both groups compared to baseline, but without differences between groups (p = 0.38).
Although anxiety improved in both groups, no statistical differences were found between group (p = 0.085).