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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 commercially available high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. In this work, we leverage repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, to evaluate anti-Spike RBD antibody levels as a correlate of protection against Omicron BA.1/BA.2 infections during the December 2021-March 2022 epidemic wave. We do so by first modeling antibody dynamics in time with kinetic models. We then use these models to predict antibody trajectories into the time period where Omicron BA.1/BA.2 were the predominant circulating sub-lineages and use survival analyses to compare the hazard of having a positive SARS-CoV-2 test by antibody level, vaccination status and infection history. We find that antibody kinetics in our sample are mainly determined by infection and vaccination history, and to a lesser extent by demographics. After controlling for age and previous infections (based on anti-nucleocapsid serology), survival analyses reveal a significant reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave with increasing antibody levels, reaching up to a three-fold reduction for anti-S antibody vels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a eduction in hazard among uninfected participants. Taken together these results indicate that nti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an direct correlate of protection against Omicron BA.1/BA.2 for individuals with a history of revious SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will me next, these results provide reassuring insights into the continued interpretation of ARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.
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BackgroundMore than two years into the COVID-19 pandemic, it is generally assumed that 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. We thus aimed to estimate anti-SARS-CoV-2 antibodies seroprevalence and cross-variant neutralization capacity after Omicron became dominant in Geneva, Switzerland. MethodsWe conducted a population-based serosurvey between April 29th and June 9th, 2022, recruiting children and adults of all ages from age-stratified random samples of the Geneva general population. Anti-SARS-CoV-2 antibody presence was assessed using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein. Antibodies neutralization capacity against different SARS-CoV-2 variants was evaluated using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. Seroprevalence of anti-SARS-CoV-2 antibodies and neutralization capacity were estimated using Bayesian modeling frameworks accounting for the demographics, vaccination, and infection statuses of the Geneva population. ResultsAmong the 2521 individuals included in the analysis (55.2% women; 21.4% aged <18 years and 14.2% aged [≥] 65 years), overall seroprevalence of antibodies was 93.8% (95% credible interval: 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies based on a representative subsample of 1160 participants 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. In general, higher levels of neutralization activity against pre-Omicron variants were associated with vaccination, particularly having received a booster dose. Higher levels of neutralization activity against Omicron subvariants were associated with booster vaccination alongside recent infection. ConclusionMore than nine in ten individuals in the Geneva population have developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, but less than half of the population has antibodies with neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection appears to confer the greatest neutralization capacity, including against Omicron.
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AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSIt is now established that a significant proportion of adults experience persistent symptoms after SARS-CoV-2 infection. However, evidence for children and adolescents is still inconclusive. In this population-based study, we examine the proportion of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection, as assessed by serological status, and compare this to a seronegative control group. MethodsWe conducted a serosurvey in June-July 2021, recruiting 660 children and adolescents from 391 households selected randomly from the Geneva population. We tested participants for anti-SARS-CoV-2 antibodies targeting the nucleocapsid (N) protein to determine previous infection. A parent filled a questionnaire including questions on COVID-19-related symptoms lasting at least 2 weeks. FindingsAmong children seropositive for anti-SARS-CoV-2 antibodies, the sex- and age-adjusted prevalence of symptoms lasting longer than two weeks was 18.3%, compared to 11.1% among seronegative children (prevalence difference ({Delta}aPrev)=7.2%, 95%CI:1.5-13.0). Main symptoms declared among seropositive children were fatigue (11.5%) and headache (11.1%). For 8.6% (aPrev, 95%CI: 4.7-12.5) of seropositives, these symptoms were declared to be highly limiting of daily activities. Adolescents aged 12-17 years had a higher adjusted prevalence of persistent symptoms (aPrev=29.1%, 95%CI:19.4-38.7) than younger children. Comparing seropositive and seronegative adolescents, the estimated prevalence of symptoms lasting over four weeks is 4.4% ({Delta}aPrev, 95%CI:-3.8-13.6). InterpretationA significant proportion of children aged 12 to 17 years had symptoms lasting over two weeks after SARS-CoV-2 infection, with an estimated prevalence of symptoms lasting over 4 weeks of 4.4% in this age group. This represents a large number of adolescents in absolute terms, and should raise concern in the context of unknown long-term evolution of symptoms. Younger children appear to experience long-lasting symptoms less frequently, as no difference was observed between the seropositive and seronegative sample. Further studies with larger samples sizes are needed. FundingSwiss Federal Office of Public Health, Geneva General Directorate of Health, HUG Private Foundation, SSPH+, Fondation des Grangettes.
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BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape in the population and guide public health measures. We aimed to estimate the seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and six months into the vaccination campaign. MethodsWe conducted a population-based cross-sectional serosurvey between June 1 and July 7, 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 (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). ResultsWe included 3355 individuals, of which 1814 (54.1%) were women, 697 (20.8%) were aged <18 years and 449 (13.4%) were aged [≥]65 years, 2161 (64.4%) tested positive for anti-S antibodies, and 906 (27.0%) tested positive for anti-N antibodies. The total seroprevalence of anti-SARS-CoV-2 antibodies was 66.1% (95% credible interval, 64.1-68.0). We estimated that 29.9% (28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies only via vaccination. Seroprevalence estimates were similar across sexes, but differed markedly across age groups, being lowest among children aged 0-5 years (20.8% [15.5-26.7]) and highest among older adults aged [≥]75 years (93.1% [89.6-96.0]). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with a higher educational level. ConclusionsMost adults have developed anti-SARS-CoV-2 antibodies, while most teenagers and children remain 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 socioeconomically disadvantaged groups, and to minimize spread among children.