Longitudinal analysis of SARS-CoV-2 IgG antibody durability in Puerto Rico

Abstract

Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

Keywords: Antibody dynamics; COVID-19; Caribbean; Humoral immunity; Omicron; Vaccination.

Fig.1

Distribution of vaccine-induced, infection-induced, and hybrid (immunity derived from a combination of vaccination and infection) immunity^a against SARS-CoV-2 by age group, Puerto Rico, 2020–2022. ^aCombined detection of anti-S1 antibodies (produced by both COVID-19–vaccination and SARS-CoV-2 infection) and anti-N antibodies (specific to prior infection), along with vaccination history from vaccination cards. Vaccine-induced immunity: Individuals with history of ≥ 1 COVID-19 vaccination dose from vaccination card. Infection-induced immunity: Individuals with positive anti-N antibodies and positive anti-S1 antibodies. Hybrid immunity: Individuals with self-reported history of ≥ 1 COVID-19 vaccination dose and positive antibodies for both S1 and N antigens.

Fig.2

(A) Weekly distribution of SARS-CoV-2 N, RBD, and S1 antibody responses during the serosurvey period, represented as proportions of log-transformed median fluorescence intensity (log[MFI]) levels (e.g., < 3, 3–3.5, 3.5–4, etc.). The x-axis labels indicate months, with the number of participants tested each month shown in parentheses. The color gradient ranges from green (lower antibody levels) to red (higher antibody levels, e.g., log(MFI) ≥ 9.5), reflecting the intensity of the immune response over time. (B) Weekly COVID-19 case counts (confirmed and probable) reported to the Puerto Rico Department of Public Health for the Ponce Health Region, 2020–2022. These data are not part of the study cohort but are included to provide contextual information on regional COVID-19 trends. Departamento de Salud PR. COVID-19 en cifras en Puerto Rico. 2024 [cited 2024 May 17]; Available from: https://www.salud.pr.gov/estadisticas_v2.

Fig. 3

SARS-CoV-2 IgG antibody responses by days since last vaccine stratified by RT-PCR positivity in previous six months vs. no previous RT-PCR positivity and N negative (A) and antibody responses by days since last positive RT-PCR and vaccination status (B), Puerto Rico, 2020–2022. The lines are loess smoothing lines and shaded bands are 95% CIs.

Fig. 4

Paired SARS-CoV-2 IgG antibody responses for individuals at two time points six months apart among people who had received three vaccine doses by prior RT-PCR positivity, Puerto Rico, 2020–2022. *P < 0.05, **P < 0.01. NS: not significant.