Patient vaccination status and breakthrough infections
Regarding vaccination status,among the 314 patients, 21(6.6%) were unvaccinated, 136 (42.6%) were partially vaccinated and 159 (50.8%) were fully vaccinated. Time between final vaccination and diagnosis was 127 ± 80 days. About the type of vaccine, most(242,77%) received the inactivated vaccine, followed by 49 (16.1%) received the adenovirusvector vaccine, 2 (0.6%) received the recombinant vaccine. Of the patients with breakthrough infection, 94 (70.4%) received the inactivated vaccine, 17 (14.7%) received the adenovirusvector vaccine, and 2 (1.7%) received the recombinant vaccine.
Proportions of chest CT scores and imaging features by vaccination status
Chest CT examination results of 314 patients over 14 years old were shown in Table 1. About patients who had a score 0, 7 (33.3%) were unvaccinated patients, 72 (53.7%) were partially vaccinated patients, and 108 (67.9%) were fully vaccinated patients. The proportion of score 0 CT scans was higher in the fully vaccinated group than in the unvaccinated group (P=0.024). Among patients with CT scores 1, the proportion of patients in the unvaccinated group was higher than that in the partial vaccinated group and the fully vaccinated group, but the difference was not statistically significant (P=0.091). Among patients with CT scores 2, the proportion of unvaccinated patients and partially vaccinated patients was significantly higher than that of fully vaccinated patients (P=0.038).
Table 1. CT scores and imaging features by vaccination status
|
|
Unvaccinated
|
Partially vaccinated
|
Fully vaccinated
|
P value
|
Morphological feature
|
|
|
|
|
Subpleural lines
|
21.4% (3/14)
|
25.8% (16/62)
|
20.8% (11/53)
|
0.872
|
Consolidation
|
71.4% (10/14)
|
61.3% (38/62)
|
50.9%(27/53)
|
0.302
|
GGO
|
92.2% (13/14)
|
95.2% (59/62)
|
94.3% (50/53)
|
0.869
|
Thickened pleura
|
42.9% (6/14)
|
22.6%(14/62)
|
22.6%(12/53)
|
0.264
|
Crazy paving sign
|
50.0% (7/14)
|
38.7% (24/62)
|
32.1% (17/53)
|
0.441
|
Distribution
|
|
|
|
|
Subpleural
|
92.9% (13/14)
|
87.1% (54/62)
|
90.6% (48/53)
|
0.981
|
Peribronchovascular
|
0% (0/14)
|
6.5% (4/62)
|
3.8% (2/53)
|
|
Diffuse
|
7.1% (1/14)
|
6.5% (4/62)
|
5.7% (3/53)
|
|
CT score
|
|
|
|
|
0
|
33%(7/21)a
|
54% (72/134)a
|
68% (108/159)b
|
0.024
|
1
|
48% (10/21)
|
32% (43/134)
|
26% (41/159)
|
0.091
|
2
|
19% (4/21)a
|
14% (19/134) a
|
6% (10/159)b
|
0.038
|
Note. GGO= ground-glass opacity. Each subscript indicates a subset of the vaccination status categories, and at the 0.05 level, the column proportions of these categories do not differ significantly from each other.
|
Clinical characteristics and laboratory data by vaccination status
Baseline clinical characteristics by vaccination status are presented in Table 2. The mean age between different vaccination status grouop are similar (P=0.063). The proportion of patients with at least one comorbidities was higher in the unvaccinated(11, 52.4%) group than in the fully vaccinated(38, 23.9%) group (P=0.023). In detail, diabetes and chronic lung disease were higher in unvaccinated group. The length of hospital stay in the three groups were similar(P=0.080).
Table 2
Clinical Characteristics and Laboratory examination of patients by Vaccination Status
Parameter
|
Unvaccinated
|
Partially vaccinated
|
Fully vaccinated
|
P value
|
Age
|
56 ± 20
|
45 ± 16
|
45 ± 13
|
0.063
|
Gender
|
|
|
|
0.191
|
Male
|
28.6% (6/21)
|
40.2% (54/134)
|
47.2% (75/159)
|
|
Female
|
71.4% (15/21)
|
59.8% (80/134)
|
52.8% (84/159)
|
|
BMI
|
24.34 (23.73, 26.35)
|
24.97 (22.16, 27.43)
|
25.56 (22.59, 28.4)
|
0.248
|
Comorbidities
|
52.4% (11/21)a
|
27.6% (37/134)a,b
|
23.9% (38/159)b
|
0.023
|
Hypertension
|
33.3% (7/21)
|
17.9% (24/134)
|
22.6% (36/159)
|
0.235
|
Diabetes
|
38.1% (8/21))a
|
14.2% (19/134)b
|
4.4% (7/159)c
|
< 0.001
|
Heart cerebrovascular disease
|
14.3% (3/21)
|
8.2% (11/134)
|
7.5% (12/159)
|
0.574
|
Chronic lung disease
|
14.3% (3/21)a
|
0.7% (1/134)b
|
0% (0/159)b
|
< 0.001
|
Smoking
|
19.0% (4/21)
|
19.4% (26/134)
|
10.1% (16/159)
|
0.066
|
Initial symptoms
|
81% (17/21)
|
81.3% (109/134)
|
85.5% (136/159)
|
0.599
|
Fever
|
23.8% (5/21)
|
28.4% (38/134)
|
31.4% (50/159)
|
0.706
|
Cough
|
33.3% 7/21)
|
47.8% (64/134)
|
51.6% (82/159)
|
0.278
|
Rhinorrhea
|
14.3% (3/21)
|
14.2% (19/134)
|
14.5% (23/159)
|
0.998
|
Sore throat
|
28.6% (6/21)a
|
50.7% (68/135)a,b
|
57.9% (92/159)b
|
0.033
|
Myalgia
|
9.5% (2/21)
|
7.5% (10/135)
|
6.9% (11/159)
|
0.908
|
Loss of sensory
|
0% (0/21)
|
0.7% (1/134)
|
3.1% (5/159)
|
0.393
|
Weak
|
9.5% (2/21)
|
6.7% (9/134)
|
8.8% (14/159)
|
0.776
|
Length of hospital stay (day)
|
13 (12, 15)
|
13 (12,15)
|
12 (11,14)
|
0.080
|
Inflammatory marks
|
|
|
|
|
CRP(>5.0mg/L)
|
52.4% (11/21)a,b
|
34.3% (46/134)b
|
48.4% (77/159)a
|
0.033
|
IL-6(>7.0pg/mL)
|
71.4% (15/21)
|
46% (57/134)
|
46.4% (71/159)
|
0.090
|
Antibody
|
|
|
|
|
IgG(S/CO)
|
1.07 ± 3.89a
|
43 ± 69.31b
|
52.1 ± 55.6c
|
< 0.001
|
IgM(S/CO)
|
0.10 ± .010a
|
0.50 ± 1.38b
|
0.73 ± 1.61c
|
< 0.001
|
Blood routine
|
|
|
|
|
WBC count > 10,000/µl
|
33.3% (7/21)a
|
19.4% (26/134)a, b
|
11.9% (19/159)b
|
0.026
|
Neutrophil count < 2000/µl
|
42.9% (9/21)a
|
22.4% (30/134)a, b
|
12.6% (20/159)b
|
0.002
|
Lymphocyte count < 1000/µl
|
52.4% (11/21)a
|
29.1% (39/134)a, b
|
20.8% (33/159)b
|
0.006
|
Platelet count < 150,000/µl
|
33.3% (7/21)a
|
9.0% (12/134)b
|
7.5% (12/159)b
|
0.002
|
LDH (> 250U/L)
|
9.5% (2/21)
|
1.5% (2/134)
|
2.6% (4/159)
|
0.102
|
Note. CRP = C-reactive protein, IL-6 = interleukin-6, LDH = Lactate dehydrogenase. Each subscript indicates a subset of the vaccination status categories, and at the 0.05 level, the column proportions of these categories do not differ significantly from each other.
|
Laboratory tests showed that there were statistically significant differences in abnormal percentages of white blood cell count, neutrophil count, lymphocyte count and platelet count among the unvaccinated group and fully vaccinated (P<0.05), low platelet count rate in fully vaccinated group and partially vaccinated group was lower than that in unvaccinated group (P=0.002). For the Inflammatory marks, C-reactive protein (CRP) elevation was more common in the unvaccinated group and the fully vaccinated group (P=0.033), IL-6 elevation shows a similar level between three groups, the difference was not significant(P=0.09). In the antibody indices, The IgM and IgG level of the fully and partial vaccinated groups was significantly higher than that of the unvaccinated group and unvaccinated group(P<0.001).
Table 2. Clinical Characteristics and Laboratory examination of patients by Vaccination Status is in this area
Proportions of chest CT scores by vaccination status and virus type
Compared with previous studies on the imaging performance of patients with immune breakthrough in Table 3, CT scores in the unvaccinated group and fully vaccinated group were similar in Omicron and other type variant. In partially vaccinated group, the proportion of patients with negative CT performance in this study (54%) was larger than that in other type variant (30%), the proportion of patients with CT score 1 in Omicron variant (32%) was less than that in other type (53%) (P=0.005), and the proportion of patients with CT score 2 showed no significant different[14](Figure 3).
Table 3. The CT score by Vaccination Status between different virus type
|
CT score
|
Unvaccinated
|
P value
|
Partially vaccinated
|
P value
|
Fully vaccinated
|
P value
|
Omicron
|
Other type
|
Omicron
|
Other type
|
Omicron
|
Other type
|
0
|
33%(7/21)
|
22%(71/326)
|
0.257
|
54% (72/134)a
|
30% (19/64)b
|
0.005
|
68% (108/159)
|
59% (13/22)
|
0.688
|
1
|
48% (10/21)
|
64%(209/326)
|
|
32% (43/134)a
|
53% (34/64)b
|
|
26% (41/159)
|
32% (7/22)
|
|
2
|
19% (4/21)
|
14%(46/326)
|
|
14% (19/134)
|
17% (11/64)
|
|
6% (10/159)
|
9% (2/22)
|
|
Note. Data on other types of COVID-19 are from published paper[14]. Each subscript indicates a subset of the virus type categories, and at the 0.05 level, the column proportions of these categories do not differ significantly from each other.
|
Figure 3. CT scores grade of the patients that underwent chest CT during hospitalization by vaccination status between Omicron and other type infection.
Clinical characteristics and laboratory examination by vaccination status and virus type
The demographics and baseline clinical characteristics and laboratory examination of by vaccination status between Omicron and other varian are presented in Table 4. In Partially vaccinated patients, a higher proportion of women were infected with Omicron (59.7%) than other type (47.2%) (P=0.044). Among unvaccinated patients, a higher proportion of Omicron infected patients (52.4%) had at least one comorbidities than pther type infected patients (26.2%) (P=0.008). While among partially and fully vaccinated patients, the proportion of omicron infected patients with at least one comorbidities (27.6%, 23.9%) was lower than the other types (57.5%, 55.3%) (p<0.001).
Table 4
Clinical Characteristics by Vaccination Status between different virus type
Parameter
|
Unvaccinated
|
P value
|
Partially vaccinated
|
P value
|
Fully vaccinated
|
P value
|
Omicron
|
Other type
|
Omicron
|
Other type
|
Omicron
|
Other type
|
Age (years)
|
56 ± 20
|
43 ± 15
|
-
|
45 ± 17
|
59 ± 14
|
-
|
45 ± 13
|
65 ± 18
|
-
|
Sex
|
|
|
|
|
|
|
|
|
|
Male
|
28.6% (6/21)
|
47.9% (281/587)
|
0.082
|
40.3% (54/134)
|
52.8% (67/127)
|
0.044
|
47.2% (75/159)
|
59.6% (28/47)
|
0.135
|
Female
|
71.4% (15/21)
|
52.1% (306/587)
|
|
59.7% (80/134)
|
47.2% 60/127)
|
|
52.8% (84/159)
|
40.4% (19/47)
|
|
Smoking history
|
19% (4/21)
|
21.8% (128/587)
|
0.763
|
19.4% (26/134)
|
16.5% (21/127)
|
0.547
|
10.1% (16/159)
|
12.8% (6/47)
|
0.598
|
Comorbidities
|
|
|
|
|
|
|
|
|
|
Any comorbidities
|
52.4% (11/21)
|
26.2% (154/587)
|
0.008
|
27.6% (37/134)
|
57.5% (73/127)
|
< 0.001
|
23.9% (38/159)
|
55.3% (26/47)
|
< 0.001
|
Hypertension
|
33.3% (7/21)
|
16.2% (95/587)
|
0.039
|
17.9% (24/134)
|
44.1% (56/127)
|
< 0.001
|
22.6% (36/159)
|
38.3% (18/47)
|
0.032
|
Diabetes
|
38.1% (8/21)
|
9.7% (57/587)
|
< 0.001
|
14.2% (19/134)
|
26.8% (34/127)
|
0.011
|
4.4% (7/159)
|
19,1% (9/47)
|
0.001
|
Cardiovascular disease
|
14.3% (3/21)
|
3.4% (20/587)
|
0.01
|
8.2% (11/134)
|
8.7% (11/127)
|
0.895
|
7.5% (12/159)
|
21.3% (10/47)
|
0.007
|
Initial laboratory findings
|
|
|
|
|
|
|
|
|
|
WBC count > 10,000/µl
|
9.5% (2/21)
|
2.9% (17/587)
|
0.137
|
0.7% (1/134)
|
1.6% (2/127)
|
0.53
|
3.8% (6/159)
|
0% (0/47)
|
0.207
|
Lymphocyte count < 1000/µl
|
52.3% (11/21)
|
23.3% (137/587)
|
0.02
|
14.9% (39/134)
|
18.9% (24/127)
|
0.054
|
20.7% (33/159)
|
27.7% (13/47)
|
0.318
|
Platelet count < 150,000/µl
|
33.3% (7/21)
|
17.5% (103/587)
|
0.081
|
8.9% (12/134)
|
22.8% (29/127)
|
0.002
|
7.5% (12/159)
|
14.9% (7/47)
|
0.151
|
LDH > 250 U/L
|
9.5% (2/21)
|
41.2% (242/587)
|
0.004
|
1.5% (2/134)
|
48.8% (62/127)
|
< 0.001
|
2.5% (4/159)
|
34% (16/47)
|
< 0.001
|
CRP > 50 mg/L
|
4.8% (1/21)
|
11% (63/587)
|
0.331
|
0% (0/134)
|
13.4% (17/127)
|
< 0.001
|
0.6% (1/159)
|
17% (8/47)
|
< 0.001
|
Clinical outcomes
|
|
|
|
|
|
|
|
|
|
Length of hospital stay
|
13.4 ± 3.6
|
10.1 ± 30.8
|
-
|
13.4 ± 3.2
|
11.5 ± 4.8
|
-
|
12.7 ± 3.3
|
12.2 ± 5.8
|
-
|
Note. Data on other types of COVID-19 are from published paper[14]. CRP = C-reactive protein, IL-6 = interleukin-6, LDH = Lactate dehydrogenase.
|
About laboratory findings, with the exception of unvaccinated patients, the proportion of CRP elevation in partially vaccinated and fully vaccinated omicron patients was significantly lower than that in other types of patients(P<0.001). The proportion of lactate dehydrogenase (LDH) increase under different vaccination status was significantly lower in omicron infection than in other types of infection(P<0.05). The proportion of patients with reduced lymphocyte counts in unvaccinated omicron infected patients(52.3%) was significantly higher than that of other types infections(23.3%) (P=0.02). The platelet count reduction rate of partially vaccinated omicron infected patients(8.9%) was lower than that of other types of patients(22.8%) (P=0.002).
Table 4. Clinical Characteristics by Vaccination Status between different virus type is in this area
The relationship between vaccination and antibody and changes of CT findings
We analyzed the CT scores of all examinations during hospitalization, the vaccination status and antibody were compared according to the progress of CT findings in Table S1 and Figure S1. After adjusted odds ratios for disease progression are summarized in Table 5. Adjusted multivariate analysis showed older age and low IgG levels are associated with an increased risk of disease progression (Figure 4).
Table 5. Odds Ratios for progression of disease
|
Parameter
|
OR
|
P value
|
Vaccination status
|
|
|
Unvaccinated
|
Reference
|
|
Partially vaccinated
|
1.37 (0.05-36.78)
|
0.853
|
Fully vaccinated
|
1.05 (0.04-25.54)
|
0.977
|
Age
|
1.04 (1.01-1,06)
|
0.002
|
BMI (>24)
|
2.03 (1.06-3.89)
|
0.032
|
Comorbidities
|
|
|
Diabetes
|
0.90 (0.31-2.60)
|
0.842
|
Heart cerebrovascular disease
|
1.82 (0.58-5.7)
|
0.303
|
Days after vaccination (day)
|
1.00 (1.00-1.01)
|
0.77
|
Inflammatory marks
|
|
|
IL-6(>7.0pg/mL)
|
1.75 (0.95-3.22)
|
0.074
|
Antibody
|
|
|
IgG(S/CO)
|
0.91 (0.95-0.98)
|
<0.001
|
IgM(S/CO)
|
1.29 (0.97-1.72)
|
0.082
|
Blood routine
|
|
|
Lymphopenia (<0.8x109g/L)
|
1.82 (0.78-4.25)
|
0.163
|
Note. BMI= body mass index, IL-6 = interleukin- 6, OR = odds ratio. Data in parentheses are 95% confidence intervals. The analysis was performed using a logistic regression model.
|
Figure 4. Clinical and laboratory parameters related to disease progression, 0: no progression, 1: progression. (A) The relationship between age and disease progression. (B)The relationship between IgG levels and disease progression.
The days after vaccination was inversely correlated with serum IgG levels (β=-0.0338, P<0.001), was positively correlated with disease progression (r=0.0006, P=0.7621), also negatively correlated with positive IgG level (ɑ=-0.1612, P<0.001). With the extension of inoculation time, the mediating effect of serum IgG increased the chance of disease progression. There was a positive correlation between vaccination status and serum IgG level (β=-0.0337, P<0.001), was negatively correlated with disease progression (r=0.0882, P=0.693), also negatively correlated with positive IgG level (ɑ=17.437, P=0.002). The dose of vaccinations increased and the serum IgG mediated effect reduced the rate of disease progression (Figure 5).
Figure 5. Mediating role of IgG in the relationship between vaccination characteristics and disease progression. (A) DAYS: days after vaccination; RESULT: progression of disease. IgG level had a complete mediating effect between days after vaccination and disease progression (ɑ=-0.1612). (B) DOSE: vaccination Status. RESULT: progression of disease. IgG level had a complete mediating effect between vaccination status and disease progression (ɑ=17.4347).