Demographic and clinical features
As shown in Table 1, among the 58 HCWs enrolled in the study, ten were male (17.2%), and the median age was 46 years (IQR 40.0-50.5) up to 2018. The majority of them were nurses who worked in the Emergency Department during the 2003 pandemic. Thirty-five patients were categorized as non-severe pneumonia in 2003, and 23 cases as severe pneumonia. Up to March 2018, most of them (47/58, 81.0%) were still full-time employed. Sixteen of them had hypertension, five had diabetes, and one had Sjogren's syndrome. Nearly half of the subjects complained of fatigue (27/58, 46.55%). Thirty-nine (39/56, 69.6%) SARS survivors had an mMRC score of 0–1 and 17 subjects (17/56,30.4%) had 2–3. (Table 2)
Table 1
Demographic data of SARS survivors and controls
|
The Severe Group
(N = 23)
|
The Non-Severe Group
(N = 35)
|
The Control Group
(N = 57)
|
F/T value
|
P-value
|
Age of onset
|
|
|
|
|
|
< 30 years
|
6 (26.1%)
|
18 (51.4%)
|
28 (49.1%)
|
4.294
|
0.117
|
≥ 30 years
|
17 (73.9%)
|
17 (48.6%)
|
29 (50.9%)
|
|
|
Gender
|
|
|
|
|
|
female
|
19 (82.6%)
|
29 (82.9%)
|
46 (80.7%)
|
0.082
|
0.960
|
male
|
4 (17.4%)
|
6 (17.1%)
|
11 (19.3%)
|
|
|
Occupations
|
|
|
|
|
|
Doctor
|
3 (13.0%)
|
4 (11.4%)
|
16 (28.1%)
|
9.079
|
0.169
|
Nurse
|
15 (65.2%)
|
25 (71.4%)
|
32 (56.1%)
|
|
|
Technician
|
3 (13.0%)
|
6 (17.1%)
|
8 (14.0%)
|
|
|
Others
|
2 (8.7%)
|
0
|
1 (1.8%)
|
|
|
Departments
|
|
|
|
|
|
Emergency room
|
11 (47.8%)
|
12 (39.3%)
|
26 (45.6%)
|
4.871
|
0.771
|
Cardiology
|
3 (13.0%)
|
3 (8.6%)
|
3 (5.3%)
|
|
|
Pulmonology
|
2 (8.7%)
|
2 (5.7%)
|
7 (12.3%)
|
|
|
Surgery
|
2 (8.7%)
|
3 (8.6%)
|
3 (5.3%)
|
|
|
Others
|
5 (21.7%)
|
15 (42.9%)
|
18 (31.6%)
|
|
|
Table 2
The lung status of SARS survivors assessed by mMRC score, pulmonary function tests, and chest CT.
|
The Severe Group
|
The Non-severe Group
|
F/T
|
P
|
mMRC scorea
|
N = 22
|
N = 34
|
|
|
0
|
5 (22.7%)
|
11 (32.4%)
|
4.785
|
0.310
|
1
|
11 (50.0%)
|
12 (35.3%)
|
|
|
2
|
3 (13.6%)
|
10 (29.4%)
|
|
|
3
|
3 (13.6%)
|
1 (2.9%)
|
|
|
Pulmonary function parametersb
|
N = 21
|
N = 31
|
|
|
FVC (L)
|
3.10 ± 0.59
|
3.52 ± 0.6
|
-2.517
|
0.015
|
FVC (%)
|
101.41 ± 14.52
|
104.69 ± 13.30
|
0.835
|
0.408
|
FVC% < 80%
|
0
|
0
|
-
|
-
|
FEV1(L)
|
2.48 ± 0.514
|
2.90 ± 0.453
|
3.313
|
0.003
|
FEV1 (%)
|
95.21 ± 12.46
|
101.61 ± 12.66
|
1.604
|
0.108
|
FEV1 % < 80%
|
4 (19.0%)
|
0
|
6.397
|
0༎011
|
FEV1/FVC (%)
|
79.23 ± 4.35
|
82.64 ± 4.80
|
2.611
|
0.012
|
FEV1/FVC < 70%
|
1 (4.8%)
|
0
|
1.505
|
0.220
|
DLCO (mmol/min/KPa)
|
6.86 ± 1.31
|
7.18 ± 1.43
|
0.807
|
0.424
|
DLCO (%)
|
84.01 ± 11.06
|
82.18 ± 12.42
|
-0.563
|
0.576
|
DLCO% < 80%
|
6 (28.6%)
|
13 (41.9%)
|
0.964
|
0.326
|
TLC (L)
|
5.05 ± 0.87
|
5.39 ± 0.71
|
1.599
|
0.116
|
TLC (%)
|
100.32 ± 10.83
|
103.93 ± 9.37
|
1.277
|
0.207
|
TLC% < 80%
|
0
|
0
|
-
|
-
|
RV/TLC (%)
|
38.69 ± 5.86
|
37.23 ± 5.77
|
-0.889
|
0.378
|
RV (%)
|
107.73 ± 13.66
|
111.70 ± 17.22
|
0.884
|
0.381
|
RV% > 120%
|
6 (28.6%)
|
12 (38.7%)
|
0.569
|
0.451
|
FEF25-75 (%)
|
65.95 ± 19.73
|
82.69 ± 20.36
|
2.946
|
0.005
|
FEF25-75 %< 65%
|
12 (57.1%)
|
7 (22.6%)
|
6.449
|
0.011
|
CT abnormalitiesc
|
N = 22
|
N = 33
|
|
|
GGO
|
6 (27.3%)
|
2 (6.0%)
|
16.360
|
< 0.001
|
interstitial fibrosis
|
7 (31.8%)
|
0
|
|
|
Others
|
5 (22.7%)
|
1 (3.0%)
|
|
|
a, b, c, The number of SARS survivors undertaking different tests. |
Immunological features 15 years after recovering from the SARS-CoV pneumonia
The results of CBC and biochemical tests were within the normal range, as well as serum immunoglobulin tests. There was no statistically significant difference among the severe group, the non-severe group, and the control group (p > 0.05). Complement 4 (C4) were a bit higher in the non-severe group, with values of 0.22 ± 0.06, 0.27 ± 0.18 and 0.22 ± 0.06 g/L, respectively, F = 3.547, p = 0.032. (Table 3).
T cell subsets were all within normal limits. The percentage of peripheral CD4+CD25+ Foxp3+regulatory T cells was slightly higher in the SARS survivors, as compared to the controls (3.85 ± 1.31% vs 3.34 ± 0.97%, respectively, T = 2.420, p = 0.018). (Fig. 2).
The serum antibody test results of SARS survivors showed that SARS-CoV N protein IgG antibody and S-RBD protein IgG antibody were positive in 11 (18.97%) and 12 (20.69%), respectively. (Fig. 3)
Table 3
Laboratory evaluation of immune status of SARS survivors.
|
The Severe Group
(N = 23)
|
The Non-Severe Group
(N = 35)
|
The Control Group
(N = 57)
|
F/T value
|
P-value
|
IgA (G/L)
|
2.20 ± 0.97
|
2.41 ± 0.97
|
2.21 ± 0.73
|
0.555
|
0.576
|
IgG (G/L)
|
11.84 ± 1.97
|
12.80 ± 2.32
|
12.94 ± 2.18
|
2.985
|
0.055
|
IgM (G/L)
|
0.98 ± 0.40
|
1.03 ± 0.38
|
1.09 ± 0.45
|
0.742
|
0.478
|
C3 (G/L)
|
0.88 ± 0.13
|
0.98 ± 0.18
|
0.94 ± 0.18
|
2.928
|
0.058
|
C4 (G/L)
|
0.22 ± 0.06
|
0.27 ± 0.18
|
0.22 ± 0.06
|
3.547
|
0.032
|
CD4+ (%)
|
50.69 ± 13.21
|
51.82 ± 10.25
|
51.20 ± 10.10
|
0.071
|
0.931
|
CD8+ (%)
|
40.82 ± 10.97
|
39.71 ± 10.61
|
38.48 ± 9.75
|
0.569
|
0.568
|
CD4 + CD25 + Foxp3+ (%)
|
3.84 ± 1.43
|
3.89 ± 1.12
|
3.34 ± 0.97
|
2.862
|
0.061
|
IgA, immunoglobulin A, normal value 0.82-4.53 g/L; IgG, immunoglobulin G, normal value 7.2-16.8 g/L; IgM, immunoglobulin M, normal value 0.46-3.04 g/L; C3, complement3, normal value 0.79-1.52 d/L, C4, complement4, normal value 0.16-0.38. |
Lung imaging results
CT abnormalities including ground-glass opacities, interstitial fibrosis, emphysema, bullae, and pleural thickening were observed in 14 SARS survivors, mostly (12/14, 85.6%) in the severe group. The most common abnormal lung radiologic findings were ground-glass opacities, detected in 8 (57.1%) cases. Seven cases presented with interstitial fibrosis. Less common changes included emphysema, bullae, and pleural thickening, and none of the survivors showed pleural effusion. We compared longitudinal series of chest CT in some cases of the severe group, and the abnormalities remained relatively stable 1 year after the disease onset. Dynamic CT changes of a patient in the severe group were shown in Figure 4.
Pulmonary function tests
Pulmonary function tests including spirometry, lung volume and diffusion capacities proceeded in 52 subjects. One severe case had moderate impairment of FVC (1/52, 1.92%), and no one showed restrictive ventilatory dysfunction. The FEF25-75% decreased in 19 patients (36.54%) with the mean (SD) 75.93 ± 21.57%. Diffusion capacity was impaired in 19 patients (36.54%), and the lowest was 62.2% of predicted values.
FEV1, FEV1/FVC and FEF25-75% were lower in the severe group than that in the non-severe group (FEV12.48 ± 0.514% vs 2.90 ± 0.453L, FEV1/FVC 79.23 ± 4.35% vs 82.64 ± 4.80%, FEF25-75% 65.95 ± 19.73% vs 82.69 ± 20.36%, p = 0.003, 0.012, and 0.005, respectively). There was no statistically significant difference in lung diffusing capacity of carbon monoxide between the two groups (84.01 ± 11.06% vs 82.18 ± 12.42%, p = 0.576). All the results of PFTs are provided in Table 2.