Immunogenicity and SARS-CoV-2 Infection following the Fourth BNT162b2 Booster Dose among Health Care Workers

Abstract

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.

Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses

“…In our analysis of antibody dynamics in previously infected and uninfected participants using linear regression, we observed that the previously infected group maintained more sustained antibody levels over time compared with the uninfected group 13 , 14 . In uninfected participants, predicted antibody levels fell below 1000 arbitrary units per milliliter (AU/mL) in approximately 220 days; in those previously infected, the predicted antibody levels remained above 1000 AU/mL even after 400 days (Fig.…”

“…Our population-based follow-up study corroborated that individuals with prior infection maintained their antibody levels over time following additional vaccinations, compared with those not previously infected with COVID-19. Previous reports suggest that antibody levels below 1000 binding antibody units per milliliter (BAU/mL) are associated with a significantly increased risk of Omicron-strain infection 13 , 14 . The unadjusted linear regression performed to visually illustrate the temporal changes in antibody titers between groups in our study also suggested that individuals with prior infection retained antibody levels exceeding 1000 AU/mL, often considered indicative of reduced infection risk, for over 400 days.…”

Humoral Immunogenicity of mRNA Booster Vaccination after Heterologous CoronaVac-ChAdOx1 nCoV-19 or Homologous ChAdOx1 nCoV-19 Vaccination in Patients with Autoimmune Rheumatic Diseases: A Preliminary Report

“…The attenuated response to the VOC epitopes was reported in infected patients with the prior Wuhan-Hu-1-like antigen vaccination, compared with unvaccinated infected patients [ 32 ]. Recently, during the Omicron VOC outspreading, multiple studies demonstrated that the fourth (second booster) dose raised a milder immune response and rapidly waned, compared to the previous vaccination [ 36 , 37 ]. This phenomenon might be explained by the OAS theory.…”