Title Page
Summary
Contents
Introduction 13
Methods 15
1. Study design and participants 15
2. Definitions 17
3. Specimen collection 17
4. Estimation of SARS-CoV-2 variants of the previous infection 18
5. Immunological evaluation of the study cohort 18
6. Statistical analysis 22
Results 23
1. Baseline characteristics 23
2. Baseline antibody responses and subsequent SARS-CoV-2 infection 26
3. Participants with subsequent infection stratified by baseline SARS-CoV-2 antibody titer 33
4. Receiver operating characteristic curves of each immune marker 39
5. Protective factors against subsequent SARS-CoV-2 infection 42
6. Stratified analysis according to the baseline serum antibody level 45
7. Subgroup analysis 1-month after bivalent vaccine administration 49
8. Predictive performance of baseline serum immune markers 58
Discussion 60
Conclusions 64
References 65
국문요약 69
Table 1. Demographics and baseline characteristics of study participants according to the subsequent SARS-CoV-2 infection 25
Table 2. Cox-proportional hazard model for prediction of subsequent infection using baseline antibody levels 43
Table 3. Cox-proportional hazard model for the 1-month subgroup analysis for prediction of subsequent infection. 51
Table 4. Demographics and baseline characteristics of study participants according to the bivalent vaccine administration 54
Table 5. Predictive performance of baseline serum Wuhan S1-IgG, BA.5 S1-IgG, and neutralizing antibody against BA.5 at optimal cutoff values for protection against subsequent SARS-CoV-2 infection 59
Figure 1. SARS-CoV-2 variants in analyzed sequence and epidemic curve during the entire period of the COVID-19 pandemic, South Korea 16
Figure 2. Correlation between serum binding antibody and neutralizing antibody 21
Figure 3. Schematic diagram of the study participants 24
Figure 4. Baseline serum SARS-CoV-2 S1-IgG and neutralizing antibody levels according to the subsequent SARS-CoV-2 infection. 27
Figure 5. Baseline saliva SARS-CoV-2 S1-IgA levels according to the subsequent SARS-CoV-2 infection. 28
Figure 6. The baseline antibody levels according to the previous infection history. 30
Figure 7. Correlation between time from previous SARS-CoV-2 infection and baseline antibody levels 32
Figure 8. Participants with subsequent infection stratified by baseline SARS-CoV-2 antibody levels. A. By serum Wuhan-Hu-1 S1-IgG. B. By serum BA.5 S1-IgG. C. By serum neutralizing antibody against BA.5. D. By saliva Wuhan-Hu-1 S1-IgA. E. By saliva... 38
Figure 9. Receiver operating characteristic curves of baseline serum Wuhan-Hu-1 S1-IgG, BA.5 S1-IgG, and neutralizing antibody against BA.5 for distinguishing subsequent infection. 40
Figure 10. Receiver operating characteristic curves of saliva Wuhan-Hu-1 S1-IgA and BA.5 S1-IgA for distinguishing subsequent infection. 41
Figure 11. Cumulative incidence of subsequent infection by baseline serum antibody levels higher and lower than cutoff values determined by ROC curves. A. Wuhan-Hu-1 S1-IgG. B. BA.5 S1-IgG. C. Neutralizing antibody against BA.5. 46
Figure 12. Comparison of cumulative incidence of subsequent infection according to the previous SARS-CoV-2 infection stratified by baseline serum antibody level. A. Participants with low baseline antibody levels. B. Participants with high baseline antibody levels. 48
Figure 13. Receiver operating characteristic curves for 1-month subgroup analysis with serum Wuhan-Hu-1 S1-IgG, BA.5 S1-IgG, and neutralizing antibody against BA.5 for distinguishing subsequent infection. 50
Figure 14. Cumulative incidence of subsequent SARS-CoV-2 infection according to the bivalent vaccine administration in the 1-month subgroup analysis. 53
Figure 15. Serum antibody levels before and after bivalent booster vaccine. 57