key: cord-1030182-mv62vayd authors: Shachor-Meyouhas, Yael; Hussein, Khetam; Dabaja-Younis, Halima; Szwarcwort-Cohen, Moran; Almog, Ronit; Weissman, Avi; Mekel, Michal; Hyams, Gila; Horowitz, Nethanel A.; Gepstein, Vardit; Netzer, Itamar; Saban, Hagar Cohen; Petersiel, Neta; Tarabeia, Jalal; Halberthal, Michael title: Immunogenicity trends one and three months after second BNT162B2 vaccination among healthcare workers in Israel date: 2021-11-24 journal: Clin Microbiol Infect DOI: 10.1016/j.cmi.2021.11.014 sha: c377cd0c5170181bb7c91be499e13dbf62a3caac doc_id: 1030182 cord_uid: mv62vayd OBJECTIVES: We evaluated 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) one and three months after second vaccine dose. A multivariate mixed linear model was adjusted to participant’s data and fit to predict antibody levels after second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 and 1 month. Multivariate analyses identified factors associated with lower antibody levels. RESULTS: A total of 1,506 HCWs were tested for SARS-CoV-2 antibodies. Older age was associated with lower mean antibody levels (-1.22 AU/ml, p <0.001, 95% CI -1.43 – -1.01). In addition, male (-22.16AU/ml, p <0.001, 95% CI -27.93 – -16.39), underlying condition (-10.86AU/ml, p= 0.007, 95% CI -18.81 – -2.91) and immunosuppressive treatment (-28.57AU/ml, p = 0.002, 95% CI -46.85 – -10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri vaccination GCS 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 shortage. Since the World Health Organization (WHO) declared a pandemic for coronavirus disease-55 2019 (COVID-19), more than 3 million lives have been claimed worldwide; 6,363 were in 56 Israel by May 2021 [1] . In Israel, Pfizer/BioNTech BNT162b2 vaccination began in late 57 December. By late April 2021, more than 5 million Israeli citizens were fully vaccinated [2] . 58 Northern Israel's only tertiary medical centre has been involved with the vaccination 59 campaign from the beginning. Of its 5,499 healthcare workers (HCWs), 88% were fully 60 vaccinated. 61 The high effectiveness of the vaccine in Israel was published [3-5], but immunogenicity 62 data is sparse, mainly among immunocompromised or haemodialysis patients, and after the A prospective cohort study was conducted on fully vaccinated HCWs who consented to 69 participate and were tested for blood anti-spike SARS-CoV-2 levels one and three months 70 after the second vaccine dose in February and April 2021, respectively. The study was 71 conducted at Rambam Health Care Campus (RHCC), a 1,000 bed tertiary university hospital. LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy) was used to detect anti-73 spike S1/S2 IgG antibodies. The cut-off value was 15 AU/ml according to Israeli Ministry of 74 Health instructions [9] . 75 Primary outcome measures were the antibody levels difference at two time points (1 and 76 3 months) and the association between that difference and age, sex, underlying disease, 77 peri-vaccination GCS, immunosuppressive therapy, and allergic reactions or rash after Treatment with GCS was defined as either chronic or GCS treatment 1-2 days before or 85 after vaccine administration to relieve allergic reactions. Increased antibody levels after 3 months were defined as any antibody level increase 87 between 1 and 3 months. Individuals with increased antibody levels at 3 months were examined with Abbott 89 ARCHITECT SARS-CoV-2 IgG assay to detect anti-NC antibodies to rule out asymptomatic 90 oncological disease, 7 (0.5%). Peri-vaccination GCS or long-term immunosuppressive 115 therapy was reported by 74 (4.9%) HCWs. 116 Seven participants were diagnosed with SARS-CoV-2 infection, of which 6 were 117 diagnosed less than 7 days after the second vaccine dose. One participant was diagnosed 118 one and half months after the second dose; this individual was mildly symptomatic and had 119 increased antibody levels 3 months after vaccination. The difference in antibody levels between 3 and 1 month revealed a smaller absolute 168 decrease in antibody levels as age increased. However, the absolute antibody levels at 1 169 month were also lower as age increased, indicating that the relative reduction does not 170 differ by age. This finding should be further studied and correlated with clinical efficacy. Nevertheless, the fact that only 7 people had no measurable antibodies and were not 172 infected with SARS-CoV-2 is encouraging; these HCWs will be followed. Future studies 173 could provide insight regarding the decrease in antibody levels and its significance. Finally, a small group of HCWs experienced increased antibody levels between 1 and 3 178 months. No association was found; these HCWs should be further followed up, and more research is needed to understand this phenomenon and its clinical significance, which is 180 currently unknown. Our study had several limitations. Firstly, no information was available regarding cellular 188 however, that group was asymptomatic and exposed to fewer infected people. This group 189 should be further followed. J o u r n a l P r e -p r o o f MH conceived and designed the study; MSC did the laboratory testing 202 HDY and RA conducted the statistical analysis All authors read and approved the submission Acknowledgements: This study was performed in collaboration with the Israeli Ministry of Health. The 206 authors would like to thank Mira Shiloah WHO Coronavirus Disease (COVID-19) Dashboard Ministry of Health of Israel Ministry of Health Age-specific 257 differences in the dynamics of protective immunity to influenza Correlates of protection induced by vaccination Immunologic correlates of protection induced by vaccination COVID-19 264 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses