Six-month outcomes and effect of pulmonary rehabilitation among patients hospitalized with COVID-19: a retrospective cohort study

Figures & data

Figure 1. Flowchart of participants. COVID-19: coronavirus disease 2019; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Table 1. Demographics and clinical characteristics of patients.

	Total (N = 98)	Control (N = 71)	PR (N = 27)	p Value*
Male, no. (%)	45 (45.9)	36 (50.7)	9 (33.3)	.12
Age, years	47 ± 15	44 ± 13	54 ± 16	.002
Body weight, kg	61.2 ± 11.6	65.4 ± 12.6	61.1 ± 7.6	.10
BMI, kg/m^2	23.8 ± 3.0	23.8 ± 3.2	23.8 ± 2.5	.99
Clinical classification of COVID-19, no. (%)				.08
Mild cases	1 (1.0)	1 (1.4)	0 (0)
Moderate cases	73 (74.5)	56 (78.9)	17 (63.0)
Severe cases	18 (18.4)	10 (14.1)	8 (29.6)
Critical cases	6 (6.1)	4 (5.6)	2 (7.4)
Length of hospital stay, days	18 ± 9	17 ± 8	18 ± 9	.66
CT scan scores	2 ± 2	2 ± 1	3 ± 1	.11
Smoking status, no. (%)				.56
Smoking	9 (9.2)	7 (9.9)	2 (7.4)
Previously smoked	1 (1.0)	1 (1.4)	0 (0)
Never	88 (89.8)	63 (88.7)	25 (92.6)
Comorbidity, no. (%)^a	34 (34.7)	21 (29.6)	13 (48.2)	.10
Hypertension	11 (11.2)	8 (11.3)	3 (11.1)	.99
Diabetes mellitus	7 (7.1)	3 (4.2)	4 (14.8)	.09
Dyslipidaemia	8 (8.2)	6 (8.5)	2 (7.4)	.99
Cardiovascular disease	12 (12.2)	6 (8.5)	6 (22.2)	.09
Cerebrovascular disease	3 (3.0)	1 (1.4)	2 (7.4)	.18
Peptic ulcer	3 (3.06)	3 (4.23)	0 (0)	.56
Cancer	4 (4.1)	4 (5.6)	0 (0)	.57
Medications used during hospitalization, no. (%)
Glucocorticoid	32 (32.7)	20 (28.2)	12 (44.4)	.13
Lopinavir/ritonavir	78 (79.6)	57 (80.3)	21 (77.8)	.78
Arbidol	50 (51.0)	39 (54.9)	11 (40.7)	.21
Interferon	65 (66.3)	50 (70.4)	15 (55.6)	.17
Chloroquine phosphate	18 (18.4)	13 (18.3)	5 (18.5)	.98
Antibiotics	51 (52.0)	33 (46.4)	18 (66.7)	.07
Immunoglobulin	30 (30.6)	21 (29.6)	9 (33.3)	.72
CVD agents^b	24 (24.5)	15 (21.1)	9 (33.3)	.21
Physical activity, METs·min/week	2484.1 ± 2803.0	2530 ± 2582	2363 ± 3369	.79

PR: pulmonary rehabilitation group; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; BMI: body mass index; COVID-19: coronavirus disease-19; CT: computed tomography; CVD: cardiovascular disease.

Data are expressed as mean ± standard deviation (SD) for continuous variables and number (%) for categorical variables. Independent t-test and Chi-square test were used for assessing the difference between groups in continuous and categorical variables, respectively.

* p Value for comparison of control and PR groups.

^a Comorbidity accounts for hypertension, diabetes mellitus, dyslipidaemia, cardiovascular disease, cerebrovascular disease, peptic ulcer and cancer.

^b CVD agents include anti-platelets, anti-coagulants, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, diuretics, nitrate and digoxin.

Figure 2. (A) Clinical symptoms in the COVID-19 patients during hospitalization; (B) changes in exercise capacity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific immunoglobulins, T lymphocytes and biochemical and haematological biomarkers in the COVID-19 patients during the 6-month convalescence period. COVID-19: coronavirus disease-19; SD: standard deviation; 95% CI: 95% confidence interval; 6-MWD: six-minute walk distance; WBC: white blood cells; CD3+: mature human T lymphocytes; CD4+: helper/inducer T lymphocytes; CD8+: suppressor/cytotoxic T lymphocytes; WBC: white blood cell; Lymph.: lymphocytes; Neu.: neutrophils; Eos.: eosinophils; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen. *Any symptoms indicate if a patient has any of the following symptoms: fever, cough, fatigue, anorexia, sore throat, dyspnoea, myalgia, diarrhoea, headache and dizziness. †The value of relative change was calculated by the equation of (value of change/baseline value)×100. The absolute changes in variables during the 6-month convalescence period were assessed by paired t-test and Wilcoxon’s sign-rank test for normal and non-normal distribution variables, respectively.

Table 2. The effects of pulmonary rehabilitation on exercise capacity, immunity and blood chemistry in COVID-19 patients during the 6-month convalescence period.

	Control group		PR group		Unadjusted analysis^a		Adjusted analysis^b
	Baseline	Change	Baseline	Change	Diff. between changes		Diff. between changes
	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	95% CI	p Value	95% CI	p Value
Exercise capacity (N = 98, control 71, PR 27)
6-MWD, m	538 ± 68	60 ± 58	365.8 ± 59.0	254 ± 67	194 (167–221)	<.001	123 (66–181)	<.001
SARS-CoV-2 specific immunoglobulins (N = 77, control 55, PR 22)
IgG, U	13.9 ± 13.5	–5.1 ± 13.4	17.7 ± 14.4	–4.9 ± 15.6	0.3 (–7.4 to 8.0)	.84	–4.0 (–20.7 to 12.7)	.64
IgM, U	1.5 ± 2.5	–0.6 ± 2.6	1.6 ± 1.7	–1.0 ± 1.6	–0.4 (–1.4 to 0.6)	.44	–0.7 (–3.6 to 2.1)	.60
T lymphocytes (N = 38, control 25, PR 13)
CD3+, cells/µL	1161 ± 404	51 ± 271	1045 ± 424	63 ± 231	12 (–160 to 184)	.89	–82 (–462 to 299)	.67
CD4+, cells/µL	550 ± 200	40 ± 137	507 ± 219	45 ± 96	5 (–72 to 82)	.90	37 (–147 to 220)	.69
CD8+, cells/µL	565 ± 250	–4 ± 135	492 ± 262	12 ± 150	17 (–89 to 119)	.74	–107 (–309 to 94)	.29
CD4+/CD8+ ratio	1.1 ± 0.5	0.03 ± 0.2	1.2 ± 0.6	0.09 ± 0.2	0.05 (–0.09 to 0.2)	.46	0.1 (–0.3 to 0.4)	.69
Blood chemistry (N = 98, control 71, PR 27)
WBC, ×10^9 cells/L	6.5 ± 1.8	–0.5 ± 1.0	6.6 ± 2.1	–0.7 ± 1.2	–0.2 (–0.7 to 0.3)	.43	–1.0 (–2.1 to 0.2)	.10
Lymph., ×10^9 cells/L	1.8 ± 0.6	0.6 ± 0.6	1.6 ± 0.7	0.6 ± 0.5	0.01 (–0.2 to 0.2)	.98	–0.3 (–0.9 to 0.3)	.34
Neu., ×10^9 cells/L	4.2 ± 1.5	0.1 ± 1.0	4.4 ± 1.7	–0.1 ± 1.3	–0.3 (–0.9 to 0.3)	.28	–1.0 (–2.2 to 0.3)	.12
Eos., ×10^9 cells/L	0.13 ± 0.09	–0.01 ± 0.06	0.10 ± 0.09	0.01 ± 0.05	0.01 (–0.02 to 0.03)	.70	0.01 (–0.06 to 0.07)	.94
Haemoglobin, g/L	139.6 ± 14.5	9.5 ± 6.3	129.7 ± 20.7	7.6 ± 6.5	–1.9 (–4.8 to 1.0)	.19	–1.6 (–8.5 to 5.3)	.64
Platelets, ×10^9/L	225.9 ± 50.0	–28.6 ± 26.7	216.3 ± 93.3	–23.7 ± 26.0	5.0 (–6.9 to 16.9)	.40	17.1 (–11.9 to 46.1)	.24
ALT, U/L	29.3 ± 21.4	1.4 ± 11.7	22.8 ± 13.1	2.3 ± 3.6	0.9 (–2.0 to 3.9)	.58	2.8 (–8.3 to 14.0)	.62
AST, U/L	23.4 ± 9.5	1.3 ± 6.0	21.7 ± 6.0	0.8 ± 2.7	–0.5 (–2.3 to 1.2)	.54	–1.6 (–4.2 to 7.4)	.58
Total bilirubin, μmol/L	9.4 ± 3.9	1.7 ± 3.4	9.8 ± 4.4	1.5 ± 2.6	–0.3 (–1.6 to 1.0)	.67	–0.2 (–3.7 to 3.4)	.93
Total protein, g/L	73.1 ± 3.7	–1.0 ± 3.8	72.8 ± 5.1	–0.3 ± 2.8	0.6 (–0.8 to 2.0)	.36	1.1 (–2.8 to 5.0)	.58
Albumin, g/L	45.0 ± 3.3	0.6 ± 3.2	44.8 ± 3.4	0.5 ± 2.6	–0.1 (–1.3 to 1.2)	.92	1.3 (–2.0 to 4.6)	.45
Globulin, g/L	28.0 ± 4.1	–1.6 ± 3.7	28.0 ± 5.2	–0.9 ± 4.4	0.7 (–1.3 to 2.6)	.47	–0.3 (–4.5 to 4.0)	.90
Albumin/globulin ratio	1.7 ± 0.4	0.1 ± 0.3	1.7 ± 0.4	0.1 ± 0.4	–0.1 (–0.3 to 0.1)	.39	0.1 (–0.3 to 0.5)	.71
BUN, mmol/L	4.5 ± 1.0	0.9 ± 0.8	4.8 ± 1.2	0.9 ± 0.8	0.04 (–0.3 to 0.4)	.80	0.3 (–0.6 to 1.1)	.53
Uric acid, μmol/L	360.9 ± 84.7	12.9 ± 45.9	342.2 ± 95.6	6.2 ± 59.4	–6.7 (–32.3 to 18.9)	.60	–27.6 (–61.1 to 48.5)	.82
Creatinine, μmol/L	67.3 ± 13.2	0.9 ± 10.4	67.3 ± 21.1	0.9 ± 8.4	0.01 (–4.0 to 4.1)	.99	–1.4 (–12.3 to 9.4)	.80

PR: pulmonary rehabilitation; SD: standard deviation; 95% CI: 95% confidence interval; 6-MWD: six-minute walk distance; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; WBC: white blood cells; CD3+: mature human T lymphocytes; CD4+: helper/inducer T lymphocytes; CD8+: suppressor/cytotoxic T lymphocytes; WBC: white blood cell; Lymph.: lymphocytes; Neu.: neutrophils; Eos.: eosinophils; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen.

^a The difference between the changes across groups was assessed by independent t-test and Wilcoxon’s rank sum test for normal and non-normal distribution variables, respectively.

^b The difference between the changes across groups was evaluated by analysis of covariance (ANCOVA) with a covariate of propensity score that adjusted for sex, age, body weight, baseline exercise capacity (6-MWD), physical activity per week during 6-month convalescence period, and COVID-19 classification, comorbidity and the use of antibiotics during hospitalization.

Figure 3. The effect of pulmonary rehabilitation on exercise capacity in COVID-19 patients during the 6-month convalescence period in a dose-dependent way. The difference between changes in 6-minute walk distance (6-MWD) across groups was assessed by analysis of covariance (ANCOVA) with a covariate of propensity score that adjusted for sex, age, body weight, baseline 6-MWD, physical activity per week during the 6-month recovery period, and COVID-19 classification, comorbidity and the use of antibiotics during hospitalization. Post hoc analysis for each comparison was also performed. The mean difference and 95% confidence interval in the high-volume pulmonary rehabilitation group vs. control group are 165 (101–229) m; low-volume vs. control is 88 (22–154); high-volume vs. low-volume is 77 (34–120), p values for each assessment are marked on the figure accordingly (N = 98, control 71, low-volume PR 14, high-volume PR 13).

Data availability statement

The data that support the findings of this study are available from the corresponding author, SL, upon reasonable request.