Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; United States; coronavirus disease; healthcare workers; respiratory infections; severe acute respiratory syndrome coronavirus 2; vaccine-preventable diseases; viruses; zoonoses.

Figure 1

Vaccine-induced binding and neutralizing antibody responses observed among US healthcare worker participants in the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study, January–August 2021. A) MFI levels of vaccine-induced spike IgG binding before and after second vaccination in serum samples diluted 1:400 (n = 227 participants). Horizontal line indicates the positive or negative spike IgG threshold. B) Spike IgG binding antibodies (BAU/mL) quantified from serum samples collected 1 month (mean 36.9 days, range 23–81 days) and 6 months (mean 201.1 days, range 151–237 days) postvaccination (n = 187 participants). Wilcoxon matched-pairs signed rank test performed; y-axis is log₂-scale. C) Neutralizing antibody titers against severe acute respiratory syndrome coronavirus 2 wild-type and Delta variant from serum samples collected 1 month (mean 30.8 days, range 28–42 days) and 6 months (mean 200.1 days, range 189–219 days) postvaccination (n = 49 participants). Friedman ANOVA with Dunn’s multiple comparisons performed post-hoc; y-axis is log₂-scale. All errors bars represent the geometric mean and 95% CIs. BAU, binding antibody units; IC₅₀, 50% inhibitory concentration; MFI, median fluorescence intensity.

Figure 2

Timeline of antibody responses and SARS-CoV-2 infections among US healthcare worker participants in the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study, January–August 2021 (17 unvaccinated and 227 vaccinated participants). Each horizontal bar represents the infection, vaccination, and serologic status obtained monthly in all participants who had not been diagnosed with SARS-CoV-2 by PCR or S protein IgG seroconversion by January 31, 2021. White spaces indicate no data. Gray bars represent negative S protein IgG. Red bars indicate month of SARS-CoV-2 diagnosis by PCR positivity or S protein IgG seroconversion. Yellow bars indicate S protein IgG seroconversion after SARS-CoV-2 diagnosis in unvaccinated persons, and orange bars indicate presence of both S protein and NP antibodies in unvaccinated persons. Light green bars indicate S protein IgG seroconversion after vaccination. Dark green bars indicate detection of NP IgG in addition to S protein antibodies at timepoints postvaccination. S, spike protein; NP, nucleocapsid protein; ICU, intensive care unit; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.