Trajectories of Seroprevalence and Neutralizing Activity of Antibodies against SARS-CoV-2 in Southern Switzerland between July 2020 and July 2021: An Ongoing, Prospective Population-Based Cohort Study

Abstract

Objectives: The COVID-19 pandemic continues, and evidence on infection- and vaccine-induced immunity is key. We assessed COVID-19 immunity and the neutralizing antibody response to virus variants across age groups in the Swiss population.

Study design: We conducted a cohort study in representative community-dwelling residents aged five years or older in southern Switzerland (total population 353,343), and we collected blood samples in July 2020 (in adults only, N = 646), November-December 2020 (N = 1457), and June-July 2021 (N = 885).

Methods: We used a previously validated Luminex assay to measure antibodies targeting the spike (S) and the nucleocapsid (N) proteins of the virus and a high-throughput cell-free neutralization assay optimized for multiple spike protein variants. We calculated seroprevalence with a Bayesian logistic regression model accounting for the population's sociodemographic structure and the test performance, and we compared the neutralizing activity between vaccinated and convalescent participants across virus variants.

Results: The overall seroprevalence was 7.8% (95% CI: 5.4-10.4) by July 2020 and 20.2% (16.4-24.4) by December 2020. By July 2021, the overall seroprevalence increased substantially to 72.5% (69.1-76.4), with the highest estimates of 95.6% (92.8-97.8) among older adults, who developed up to 10.3 more antibodies via vaccination than after infection compared to 3.7 times more in adults. The neutralizing activity was significantly higher for vaccine-induced than infection-induced antibodies for all virus variants (all p values < 0.037).

Conclusions: Vaccination chiefly contributed to the reduction in immunonaive individuals, particularly those in older age groups. Our findings on the greater neutralizing activity of vaccine-induced antibodies than infection-induced antibodies are greatly informative for future vaccination campaigns.

Keywords: COVID-19; acquired immunity; antibodies; cohort study; seroprevalence; vaccination.

Figure 1

Flow diagram of participants at each serosurvey of the “Corona Immunitas Ticino” study.

Figure 2

Seroprevalence estimates with 95% CI at each serosurvey (vertical red banners), and cumulative incidence rate of laboratory-confirmed COVID-19 cases in the region (solid line).

Figure 3

Temporal evolution of proportion of seropositive participants in different geographic regions of southern Switzerland (Ticino). The Italian Lombardy region borders the southern part of Ticino.

Figure 4

Rates of infection- and vaccine-induced immunity by age group at the third serosurvey in June 2021 (N = 885). Seronegatives = anti-SARS-CoV-2 antibodies not detected; infection-induced seropositives = both anti-S and anti-N antibodies positive irrespective of self-reported vaccination status or only anti-S antibodies positive in those who reported that they were not vaccinated; vaccine-induced seropositives = anti-S antibodies positive, anti-N antibodies negative, and self-reported vaccination. Individuals who were infected and vaccinated (S+ N+ vaccinated) (N = 29) are not reported.

Figure 5

SARS-CoV-2 antibodies’ neutralizing activity by variant in the sub-sample of seropositive participants at the third serosurvey in June–July 2021 (N = 250).

Figure 6

Neutralizing activity against SARS-CoV-2 variants by vaccination status across age groups in the sub-sample of seropositive participants at the third serosurvey in June–July 2021 (N = 250: 65+ years N = 125; 20–64 years N = 105; 14–19 years N = 20). The y-axis indicates the percentage of participants with an above IC₅₀ threshold neutralizing activity by self-reported vaccination status at the June–July 2021 serosurvey.