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INTRODUCTION: The fourth SARS-CoV-2 vaccine dose was found to protect against infection and more importantly against severe disease and death. It was also shown that the risk of symptomatic or severe disease was related to the antibody levels after vaccination or infection, with lower protection against the BA.4 BA.5 Omicron variants. The aim of our study was to assess the impact of the fourth dose on infection and perception of illness seriousness among healthcare workers (HCWs) at a tertiary health care campus in Haifa, Israel, and to investigate the possible protective effect of antibody levels against infection. METHODS: We conducted a prospective cohort study among fully vaccinated HCWs and retired employees at Rambam Healthcare Campus (RHCC), a tertiary hospital in northern Israel. Participants underwent serial serological tests at 1, 3, 6, 9, 12 and 18 months following the second BNT162b2 vaccine dose. Only a part of the participants chose to receive the fourth vaccine. A multivariable logistic regression was conducted to test the adjusted association between vaccination, and the risk of infection with SARS-CoV-2. Kaplan-Meier SARS-CoV-2 free "survival" analysis was conducted to compare the waning effect of the first and second, third and fourth vaccines. Receiver Operating Characteristic (ROC) curve was plotted for different values of the sixth serology to identify workers at risk for disease. RESULTS: Disease occurrence was more frequent among females, people age 40-50 years old and those with background chronic lung disease. The fourth vaccine was found to have better protection against infection, compared to the third vaccine; however, it also had a faster waning immunity compared to the third vaccine dose. Antibody titer of 955 AU/mL was found as a cutoff protecting from infection. CONCLUSIONS: We found that the fourth vaccine dose had a protective effect, but shorter than the third vaccine dose. Cutoff point of 955 AU/mL was recognized for protection from illness. The decision to vaccinate the population with a booster dose should consider other factors, including the spread of disease at the point, chronic comorbidities and age, especially during shortage of vaccine supply.
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This study assessed humoral response to the third BNT162b2 dose among healthcare workers (HCW). This prospective cohort study of HCW tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) at 1, 3, 6, 9, and 12 months after receiving the second BNT162b2 vaccine dose (tests 1, 2, 3, 4, and 5, respectively). A third (booster) vaccination dose was introduced before test 4. Linear regression model was used to determine the humoral response following vaccine doses. For each serology test, changes in log-transformed antibody concentrations over time, adjusted for age, sex, underlying diseases, steroid treatment, and smoking were described using the general linear mix model. Serology tests were performed at 3, 6, 9, and 12 months after the second vaccine dose in 1113, 1058, 986, and 939 participants, respectively. The third dose was received by 964 participants before the 9-month tests, 797 of whom participated in the 9- and 12-month serology tests. A significant inverse correlation was noted between time from third dose and antibody concentrations (Spearman correlation −0.395; p < 0.001). Age (p < 0.0001; CI 95% −0.005−−0.004), heart disease (p < 0.0001; CI 95% −0.177−−0.052), immunodeficiency (p < 0.0001; CI 95% 0.251−−0.106), and smoking (p < 0.0001; CI 95% −0.122−−0.040) were significantly associated with decreased antibody concentrations. Female sex (p = 0.03; CI 95% 0.013−0.066) was associated with increased antibody concentrations. The third booster dose had a better effect on immunogenicity, with higher antibody concentrations among tested HCW. Heart disease, smoking, and other known risk factors were associated with decreased antibody concentrations.
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OBJECTIVES: We evaluated the antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity. METHODS: This prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post-vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) 1 and 3 months after the second vaccine dose. A multivariate mixed linear model was adjusted to participants' data and fit to predict antibody levels after the second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 months and 1 month. Multivariate analyses identified factors associated with lower antibody levels. RESULTS: In total 1506 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Older age was associated with lower mean antibody levels (-1.22 AU/mL, p < 0.001, 95%CI -1.43 to -1.01). In addition, male sex (-22.16 AU/mL, p < 0.001, 95%CI -27.93 to -16.39), underlying condition (-10.86 AU/mL, p 0.007, 95%CI -18.81 to -2.91) and immunosuppressive treatment (-28.57 AU/mL, p 0.002, 95%CI -46.85 to -10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri-vaccination glucocorticosteroid treatment were not correlated with antibody levels. CONCLUSIONS: Most HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortages.