Kinetics of SARS-CoV-2 Serum Antibodies Through the Alpha, Delta, and Omicron Surges Among Vaccinated Health Care Workers at a Boston Hospital

Abstract

Background Longitudinal serology studies can assist in analyzing kinetics of antibodies to the SARS-CoV-2 virus, helping to inform public health decision-making. Our study aims to characterize circulating antibody trends over 18 months in vaccinated participants with and without evidence of COVID-19 infection. Methods A cohort of healthcare workers employed at Boston Medical Center were followed, collecting serum samples and survey data over six timepoints from July 2020 through December 2021 (n = 527). History of SARS-CoV-2 infection, vaccination and booster status were confirmed, where possible, using electronic medical records. Serum was assessed for the qualitative detection of anti-N IgG and the semi-quantitative detection of anti-S IgG antibody levels. Piecewise regression models were utilized to characterize the antibody kinetics overtime. Results Anti-S IgG titers remained above the positivity threshold following infection and/or vaccination throughout the 18-month follow-up. Among participants with no evidence of COVID-19 infection, titers declined significantly faster in the initial 90 days post-full vaccination (β=-0.056) from December 2020 to March 2021 compared to the decline observed following booster dose uptake (β=-0.023) (p < 0.001). Additionally, COVID-19 infection prior to vaccination significantly attenuated the decline of anti-S IgG when compared to the infection-naïve participants following vaccine uptake (p < 0.001). Lastly, fewer boosted participants contracted Omicron (12.7%) than fully vaccinated (17.6%). Among the Omicron-positive participants, anti-S IgG titers were lower, but not significantly, than those who did not test positive when comparing by vaccination status. Conclusions These findings provide novel 18-month kinetics of anti-S IgG antibodies and further highlight the durability of hybrid immunity, underlining the strong humoral response stimulated by combined infection and vaccination.

Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study

“…Similarly, the small increase following a second infection was based on a confirmed second case in only 19 participants. The sharper decline after the 3 rd and 4 th vaccine dose than after the 2 nd is not consistent with some earlier reports which suggested a slower decline after the third dose [10] [12]. The reasons for this difference are uncertain.…”

“…In those with a recognized infection, this may again reflect a further unrecognized infection, or perhaps different rates of decay of anti-RBD IgG and nucleocapsid post infection [27]. The greater response in those with at least one dose of mRNA-1273 vaccine compared to those receiving only BNT162b2 is consistent with the literature [4] [12] [13] as is the lower IgG response with non-mRNA vaccines [7] [28] [29].…”

“…The current study was much larger and the follow-up after the third vaccine dose somewhat longer (mean 3.3 months) than in the previous studies cited here. Ikezaki et al [10] collected samples from 52 HCWs 2 months after the third vaccine dose and Dodge et al [12] from 212 HCWs 2-3 months after the third dose. The statistical approach differed between the studies.…”

“…The statistical approach differed between the studies. The analysis by Dodge et al [12] suggesting a shallower decay slope after the third vaccine considered only a subgroup in a cross-sectional analysis rather than a longitudinal analysis of IgG values which would have controlled for between-participant factors. Ikezaki et al [10] reported a percentage decline after the 2 nd and 3 rd vaccines without giving more detail.…”

“…At that point in the pandemic there was little knowledge about the effectiveness of vaccinations or the decay in immunological response, although this rapidly became available from clinical trials [1][2][3] and observational studies [4][5]6] [7]. Much useful data has come from cohort studies of HCWs [8] [9] [10] [11] [12] that were set up close to the start of vaccination against COVID-19, but long-term follow-up with repeated measures beyond the first months of vaccination are less in evidence [12] [13]. Using data from a serology sub-cohort of Canadian HCWs, we sought to establish an overall model of the relation between anti-receptor binding domain (anti-RBD) IgG to the spike protein of the SARS-CoV-2 virus (anti-RBD IgG titer) and the pattern of SARS-CoV-2 vaccinations and infections over time.…”