Seroprevalence of anti-SARS-CoV-2 antibodies and cross-variant neutralization capacity after the Omicron BA.2 wave in Geneva, Switzerland: a population-based study

Abstract

Background: More than two years into the COVID-19 pandemic, most of the population has developed anti-SARS-CoV-2 antibodies from infection and/or vaccination. However, public health decision-making is hindered by the lack of up-to-date and precise characterization of the immune landscape in the population. Here, we estimated anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland.

Methods: We conducted a population-based serosurvey between April 29 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population.

Findings: Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) ranged from 79.5% (77.1-81.8) against the Alpha variant to 46.7% (43.0-50.4) against the Omicron BA.4/BA.5 subvariants. Despite having high seroprevalence of infection-induced antibodies (76.7% [69.7-83.0] for ages 0-5 years, 90.5% [86.5-94.1] for ages 6-11 years), children aged <12 years had substantially lower neutralizing activity than older participants, particularly against Omicron subvariants. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants.

Interpretation: While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron.

Funding: General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

Keywords: Anti-SARS-CoV-2 antibodies; Neutralizing antibodies; Omicron; Seroprevalence; Switzerland; Variants of concern.

Fig. 1

Seroprevalence of anti-SARS-CoV-2 antibodies in the general population of Geneva, Switzerland, April 29 to June 9, 2022. Seroprevalence estimates in total sample and by age group (in years) and origin of antibody response. Symbols indicate the antibody origin: dot indicates antibodies developed after infection; triangle indicates antibodies developed after infection and/or vaccination. Vertical bars represent 95% credible intervals.

Fig. 2

Seroprevalence of neutralizing antibodies against main SARS-CoV-2 variants in the general population of Geneva, Switzerland, April 29 to June 9, 2022. Panels show the effect of covariates tested in the model: age and infection and vaccination statuses (self-reported)—though sex was included as covariate, it showed no apparent effect, so it is excluded here, but estimates are shown in appendix pp 13, 25–27. Estimates of neutralizing capacity against Beta, Gamma, and Lambda variants are shown in appendix pp 13, 25–27. Global seroprevalence estimates for anti-S and anti-N antibodies are included in black in the two left panels for comparison purposes. Symbols indicate the antibody origin: dot indicates antibodies developed after infection (anti-N); triangle indicates antibodies developed after infection and/or vaccination (anti-S); and square indicates neutralizing antibodies (cell-free surrogate neutralization assay). Vertical bars represent 95% credible intervals.