Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection.

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. These results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

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.

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.

Persistent symptoms after SARS-CoV-2 infection in children: a cross-sectional population-based serological study.

OBJECTIVES: To estimate the prevalence of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection. DESIGN: A random sample of children and adolescents participated with their family members to a serological survey including a blood drawing for detecting antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein and a questionnaire on COVID-19-related symptoms experienced since the beginning of the pandemic. SETTING: The study took place in the canton of Geneva, Switzerland, between June and July 2021. PARTICIPANT: 660 children aged between 2 and 17 years old. PRIMARY AND SECONDARY OUTCOME: The primary outcome was the persistence of symptoms beyond 4 weeks comparing seropositive and seronegative participants. The type of declared symptoms were also studied as well as associated risk factors. RESULTS: Among seropositive children, the sex-adjusted and age-adjusted prevalence of symptoms lasting longer than 2 weeks was 18.3%, compared with 11.1% among seronegatives (adjusted prevalence difference (ΔaPrev)=7.2%, 95% CI: 1.5% to 13.0%). Among adolescents aged 12-17 years, we estimated the prevalence of experiencing symptoms lasting over 4 weeks to be 4.4% (ΔaPrev,95% CI: -3.8% to 13.6%), whereas no seropositive child aged 2-11 reported symptoms of this duration. The most frequently declared symptoms were fatigue, headache and loss of smell. CONCLUSIONS: We estimated the prevalence of experiencing persistent symptoms lasting over 4 weeks to be around 4% among adolescents, which represents a large absolute number, and should raise awareness and concern. We did not observe meaningful differences of persistent symptoms between seropositive and seronegative younger children, suggesting that they may be less affected than their older counterparts.

Seroprevalence of anti-SARS-CoV-2 antibodies 6 months into the vaccination campaign in Geneva, Switzerland, 1 June to 7 July 2021.

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions.AimWe estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between 1 June and 7 July 2021, recruiting participants from age- and sex-stratified random samples of the general population. We tested participants for anti-SARS-CoV-2 antibodies targeting the spike (S) or nucleocapsid (N) proteins using the Roche Elecsys immunoassays. We estimated the anti-SARS-CoV-2 antibodies seroprevalence following vaccination and/or infection (anti-S antibodies), or infection only (anti-N antibodies).ResultsAmong 3,355 individuals (54.1% women; 20.8% aged < 18 years and 13.4% aged ≥ 65 years), 2,161 (64.4%) had anti-S antibodies and 906 (27.0%) had anti-N antibodies. The total seroprevalence was 66.1% (95% credible interval (CrI): 64.1-68.0). We estimated that 29.9% (95% Crl: 28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies via vaccination. Seroprevalence estimates differed markedly across age groups, being lowest among children aged 0-5 years (20.8%; 95% Crl: 15.5-26.7) and highest among older adults aged ≥ 75 years (93.1%; 95% Crl: 89.6-96.0). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with higher educational level.ConclusionMost of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining vulnerable to infection. As the SARS-CoV-2 Delta variant spreads and vaccination rates stagnate, efforts are needed to address vaccine hesitancy, particularly among younger individuals and to minimise spread among children.