Table 1.
Characteristics of included studies.
| Author (Year) | Study Design | Population | Sample Size | Intervention | Control Group | Outcomes | Results |
|---|---|---|---|---|---|---|---|
| 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). |
Abbreviations: F (Female); DS-12 (Dyspnea Severity Index 12); EQ-5D (EuroQol 5D); 6MWT (6 Minute Walking Test); RCT (Randomized Controlled Trial); MBS (Modified Borg Scale); 30STS (30 s Sit-to-Stand Test); MD12 (Multidimensional Dyspnea 12); BS (Borg Scale); NRS (Numeric Rating Scale); mMRC (Modified Medical Research Council Scale); BFI (Brief Fatigue Inventory); PHQ-9 (Patient Health Questionnaire-9); GAD-7 (General Anxiety Disorders 7); TUG (Time up and go Test); SF-12 (Short Form 36); SDS (Self-Rating Depression Scale); SAS (Self-Rating Anxiety Scale); SPPB (Short Physical Performance Battery); 4MWT (4 min walking test); 1MSTST (1 min Sit to Stand Test); FSS (Fatigue Severity Scale); SarQol (Sarcopenia and Quality of life Questionnaire); VAS (Visual Analogue Scale); SGRQ (Saint George Respiratory Questionnaire); BDI (Beck Depression Inventory); HADS (Hospital Anxiety and Depression Scale); WHOQOL-BREF (World Health Organization Quality of Life Questionnaire); 5TSTS (5 Times Sit-to-stand); MFIS (Modified Fatigue Impact Scale); C19YRS (Covid 19 Yorkshire Rehabilitation Scale); SF-36 (Short Form 36); ISWT (Incremental Shuttle Walking Test); FACIT (Functional Assessment of Chronic Illness Therapy); FSS (Fatigue Severity Scale); K-BILD (King’s Brief Interstitial Lung Disease Questionnaire); TDI (Transition Dyspnea Index); FAS (Fatigue Assessment Scale).