Data regarding 193 (35 previously exposed and 158 not exposed healthcare workers) were collected retrospectively: the 35 seropositive cases included 25 female subjects and 10 male subjects with an overall mean age of 48.1 years (SD ± 9.7, range 31 – 69); the 158 seronegative cases included 74 female subjects and 84 male subjects with an overall mean age of 47.6 years (SD ± 10.0, range 22 - 70) (Table 1).
Table 1. Demographic data of previously exposed and not exposed cohorts of healthcare providers.
|
Male (age)
|
Female (age)
|
Total (mean ± SD)
|
|
n (mean ± SD)
|
Previously exposed subjects
|
10 (55.2 ± 9.5)
|
25 (45.2 ± 8.4)
|
35 (48.1 ± 9.7)
|
Not exposed subjects
|
84 (49.7 ± 9.7)
|
74 (45.2 ± 10.0)
|
158 (47.6 ± 10.0)
|
Total
|
94
|
99
|
193
|
Previously exposed subjects = subjects previously exposed to SARS-CoV-2
Not exposed subjects = subjects not previously exposed to SARS-CoV-2
n = number of subjects
mean = mean age
SD = standard deviation
In previously exposed to SARS-CoV-2, antibody response 20 days after the first dose of vaccine was statistically higher in comparison to pre-vaccination: median >2500.0 BAU/mL vs. 36.6 BAU/mL (IR 14.5 - 99.0) (Wilcoxon test, p <0.001) (Table 2, Figure 1).
In not exposed to SARS-CoV-2 subjects, overall antibody response 20 days after the first dose of vaccine was statistically significant in respect to pre-vaccination values: 18.9 BAU/mL (IR 4.3 - 58.2) vs. <0.4 BAU/mL (Wilcoxon test, p <0.001) (Table 2, Figure 1). Also the titers determined 8 days after the second dose revealed a statistically increasing trend in respect to the first dose: 2111.0 BAU/mL (IR 713.8 - >2500.0) vs. 18.9 BAU/mL (IR 4.3 - 58.2) (Wilcoxon test, p <0.001) (Table 2, Figure 1).
Table 2. Vaccine immune response monitoring in previously exposed and not exposed cohorts of healthcare providers.
|
Pre
|
Post I
|
Post II
|
|
median (IR) BAU/mL
|
Previously exposed subjects
|
36.6 (14.5-99.0)
|
>2500.0
|
---
|
Not exposed subjects
|
<0.4
|
18.9 (4.3-58.2)
|
2111.0 (713.8 - >2500.0)
|
Previously exposed subjects = subjects previously exposed to SARS-CoV-2
Not exposed subjects = subjects not previously exposed to SARS-CoV-2
Pre = anti - SARS-CoV-2 S titers before the first dose
Post I = anti - SARS-CoV-2 S titers 20 days after the first dose
Post II = anti - SARS-CoV-2 S titers 8 days after the second dose
median = median of anti - SARS-CoV-2 S titers
IR = Interquartile Range of anti - SARS-CoV-2 S titers
Comparing basal values and titers after the first dose of vaccine in the 2 groups, it was evident that previously exposed subjects presented significantly higher basal titers of antibodies in comparison to those not exposed (36.6 BAU/mL [IR 14.5 - 99.0] vs. <0.4 BAU/mL) and, as early as the first dose, previously exposed workers developed a significantly higher antibody response to SARS-CoV-2 respect to values of not exposed subjects (>2500.0 BAU/mL vs. 18.9 BAU/mL [IR 4.3 - 58.2]), Mann-Whitney test, p <0.001) (Table 2, Figure 1).
Further interesting information derived from analysis which compared antibody titers after the first dose of vaccine in the previously exposed cohort, in comparison to antibody titers after the second dose in the not exposed cohort, revealing values significantly higher (>2500.0 BAU/mL vs. 2111.0 BAU/mL [IR 713.8 - >2500.0], Mann-Whitney test, p <0.001) (Table 2, Figure 1).
Fold changes for subjects previously exposed to SARS-CoV-2 was very modest ( =1.8) (Table 3), given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for not exposed to SARS-CoV-2 subjects, mean fold change following the first dose was low ( =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose (Table 3). In the average, following the second dose, the FC of not exposed subjects was 3.5 in comparison to pre-vaccination and 1.9 in comparison to the titer obtained after the first dose of vaccine. In this cohort, given the high variability of FC, prompted us to divide it into 3 different groups, using two arbitrary antibody titers of 500.0 and 800.0 BAU/mL, whose FC values were 3.1 and 3.3, respectively (Table 3). The validation of such arbitrary values will be obtained in the following monitoring of those groups in order to verify and evaluate their relative susceptibility to further SARS-CoV-2 infection.
Table 3. Antibody titers’ fold changes (FC) in previously exposed and not exposed cohorts of healthcare providers to monitor vaccine immune responses.
Analyzed cohorts
|
Mean FC
|
min FC
|
max FC
|
n (%)
|
Previously exposed subjects
|
|
|
|
|
Post I / Pre
|
1.8
|
0.0
|
3.8
|
35 (100.0%)
|
Not exposed subjects
|
|
|
|
|
Post I / Pre
|
1.6
|
0.0
|
3.6
|
158 (100.0%)
|
Post II / Post I
|
1.9
|
0.2
|
3.8
|
158 (100.0%)
|
Post II / Pre
|
3.5
|
1.4
|
3.8
|
158 (100.0%)
|
Post II/Pre ≤ 3.1
|
2.6
|
1.4
|
3.1
|
30 (19.0%)
|
Post II/Pre 3.1< ≤ 3.3
|
3.2
|
3.1
|
3.3
|
12 (7.6%)
|
Post II/Pre 3.3< ≤ 3.8
|
3.7
|
3.3
|
3.8
|
116 (73.4%)
|
Post II/Pre = 3.8
|
3.8
|
|
|
72 (45.6%)
|
Previously exposed subjects = subjects previously exposed to SARS-CoV-2
Not exposed subjects = subjects not previously exposed to SARS-CoV-2
Pre = anti - SARS-CoV-2 S titers before the first dose
Post I = anti - SARS-CoV-2 S titers 20 days after the first dose
Post II = anti - SARS-CoV-2 S titers 8 days after the second dose
mean FC = mean fold changes of anti - SARS-CoV-2 S mean geometric titers
n (%) = number of subjects (percentage)