key: cord-0308579-60azzrku
authors: Stringhini, S.; Zaballa, M.-E.; Pullen, N.; Perez-Saez, J.; de Mestral, C.; Loizeau, A.; Lamour, J.; Pennacchio, F.; Wisniak, A.; Dumont, R.; Baysson, H.; Richard, V.; Lorthe, E.; Semaani, C.; Balavoine, J.-F.; Pittet, D.; Vuilleumier, N.; Chappuis, F.; Kherad, O.; Azman, A. S.; Posfay-Barbe, K.; Kaiser, L.; Guessous, I.; Group, the Specchio-COVID19 Study
title: Seroprevalence of anti-SARS-CoV-2 antibodies six months into the vaccination campaign in Geneva, Switzerland
date: 2021-08-13
journal: nan
DOI: 10.1101/2021.08.12.21261929
sha: 0f35e107d77d276d4ade806f46a4cf3280ef8bae
doc_id: 308579
cord_uid: 60azzrku

Background: Up-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. Methods: We 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). Results: We 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). Considering the presence of anti-N antibodies, 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. Conclusions: Most 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.

Background: Up-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.

We 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).

We 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. .0]). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with a higher educational level.

Most 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. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

As the Delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drives a surge in new infections worldwide, 1 vaccination rates stagnate in the USA and much of Europe, 2,3 undermining public health efforts to achieve herd immunity and curb the pandemic. Up-todate seroprevalence estimates of anti-SARS-CoV-2 antibodies in the general population remain scarce, yet they are critical in monitoring the progression of infection-and vaccination-induced immune response and informing public health decisions. 4 The state of Geneva, Switzerland, with a population of about half a million people, has been heavily affected by the pandemic, with 62196 confirmed cases (122 per 1000 inhabitants) and 746 deaths reported by August 11, 2021. 5 Previous serosurveys of the Geneva population revealed that one in ten individuals had developed anti-SARS-CoV-2 antibodies by April-June 2020 following infection, and only two in ten individuals had done so by November-December 2020, 6 before mass vaccination began. To date, the only serosurvey conducted after the third wave of the COVID-19 pandemic in the general population reported a total anti-SARS-CoV-2 antibodies seroprevalence of 17.3% in the Portuguese population up to March 2021, including a seroprevalence of 13.1% among self-reported unvaccinated participants. 7 Using a representative sample of the general population, we aimed to assess the seroprevalence of anti-SARS-CoV-2 antibodies 15 months after the first confirmed case (February 26, 2020) and six months after the vaccination campaign began (December 28, 2020; Pfizer and Moderna vaccines).

We conducted a cross-sectional serosurvey between June 1 and July 7, 2021, recruiting participants from a random sample of individuals aged 0-64 years provided by the Swiss Federal Office of Statistics, and an age-and sex-stratified random sample of individuals aged 18-24 years and ≥50 years from a previous serosurvey using the same methodology (Addendum S1 in Supplementary Material). 6, 8 The Geneva Cantonal Commission for Research Ethics approved this study (Project N° 2020-00881). Participants gave written consent, provided a venous blood sample, and completed a is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.12.21261929 doi: medRxiv preprint questionnaire. To detect anti-SARS-CoV-2 antibodies, we used the Roche Elecsys anti-SARS-CoV-2 S and N immunoassays (Roche Diagnostics), both with sensitivity and specificity approaching 100% (Addendum S2-S3). 9

To estimate seroprevalence (% and 95% credible intervals), we expanded previous Bayesian modelling frameworks that accounted for age, sex, immunoassay performance, and household clustering, 6, 8 to jointly model the antibody response measured by the two immunoassays while additionally accounting for vaccination information. Since the vaccines used to date in Geneva elicit no response to the SARS-CoV-2 N-protein, we used participants' two-marker antibody profiles to estimate the proportion having any anti-SARS-CoV-2 antibody and the proportion having antibodies due to infection (but could also have been vaccinated). Full details of the statistical model are provided in the supplementary material (Addendum S4). We stratified seroprevalence estimates by sex, age group, and, for ages ≥18 years, education level, and calculated prevalence ratios for sex, age, and education level groups. The model was coded in the probabilistic programming language Stan using the Rstan package 10 and R version 4.1. 11

The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. SS and GP had access to all the data in the study and SS had final responsibility for the decision to submit for publication.

We included 3355 participants, of whom 1814 (54.1%) were women, 697 (20.8%) were aged <18 years and 449 (13.4%) ≥65 years. Among participants aged ≥18 years, 203 (8.1%) had up to primary education level and 1499 (59.5%) tertiary education level (Table 1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.12.21261929 doi: medRxiv preprint positive for anti-N antibodies ( Table 1 ). The overall seroprevalence estimate was 66.1% (95% CrI 64.1-68.0), including a seroprevalence of 29.9% (28.0-31.9) for infection-derived antibodies ( Figure   1 ). Seroprevalence estimates were similar across sexes, but varied widely across age groups (Table 1 and Figure 1 ), being lowest among children aged 0-5 years (20.8% [15.5-26.7 Among adults with a tertiary education level, 878 (58.6%) reported receiving at least one COVID-19 vaccine dose ≥14 days before their blood draw (Table 1 and Table S1) (Table 1) ; the corresponding prevalence ratio for overall antibody seroprevalence was 0.85 (0.77-0.93) among participants with up to primary education relative to those with a tertiary education level (Table S2 ). The seroprevalence of infection-induced antibodies was similar across education groups.

In this seroprevalence survey, we found that, by July 7, 2021, 66.1% of the population of Geneva, Switzerland, had developed antibodies against SARS-CoV-2 after vaccination and/or infection. We also found that 29.9% of the population had been infected-almost triple the 10.8% seroprevalence reported in April-June, 2020, 8 and an 8.8 point increase from the 21.1% seroprevalence reported in November-December, 2020, 6 before the vaccination campaign began (Table S3) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.12.21261929 doi: medRxiv preprint percentage point increase), suggesting the third COVID-19 wave, comprised primarily of the Alpha (B.1.1.7) variant, 12 may have particularly affected these age groups (Table S3) .

Additionally, we observed marked age differences in seroprevalence, which closely reflect the agerelated infection risk observed in Geneva and elsewhere throughout the pandemic 6, 8, 13 and, subsequently, the progression of the age-dependent vaccination eligibility in the population since December 2020. 14 For instance, the 20.8% seroprevalence in children aged 0-5 years-a 5.9

percentage point increase in a six-month period-indicates their consistently reported lower infection risk, and the fact that, to date, vaccination in Switzerland remains approved only for individuals aged ≥12 years. The 16.2% seroprevalence of infection-induced antibodies in adults aged ≥75 years mirrors their previously reported lower infection risk 6, 8 and the fact that they were the first age group targeted by the vaccination campaign; with a reported 92.6% vaccination rate-and an associated estimated total seroprevalence of 93.1%-individuals in this age group were potentially protected from further SARS-CoV-2 infection (Table 1 and Table S3 ).

We also found that vaccination uptake differed by education level, with a higher proportion of individuals with a tertiary education level reporting being vaccinated than individuals with lower education levels, which reflects socioeconomic inequalities in COVID-19 vaccination reported in the United States and Israel. 15, 16 The proportion having anti-S antibodies was correspondingly higher among individuals with a tertiary education level, though the proportion of anti-N antibodies was similar across education groups, reflecting findings from our previous seroprevalence study, 17 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.12.21261929 doi: medRxiv preprint intention or willingness to get vaccinated against SARS-CoV-2 than more socioeconomically privileged individuals. [21] [22] [23] [24] [25] [26] Strengths of this study include the large sample that is representative of the general population, the measurement of antibodies against both the SARS-CoV-2 S and N proteins, and the robust novel modelling framework accounting for both immunoassays and vaccination status. Limitations include the fact that, as with most seroprevalence surveys, 27 the sample was generally more socioeconomically advantaged than the general population (Table S4) , which may have led to overestimation of vaccinederived antibody seroprevalence-however, the proportion of vaccinated individuals in our sample was similar to that observed in the general population of Geneva (Table S5) ; the fact that we only included formal residents and that we only assessed education as a socioeconomic indicator, which may have precluded the identification of inequalities based on other indicators; and, finally, the fact that, since we did not perform neutralization assays, our estimates may not completely reflect SARS-CoV-2 protective immunity. 28 This study provides the first seroprevalence estimates of SARS-CoV-2 antibodies in a representative sample of the general population after the third pandemic wave and the start of mass vaccination. Our findings highlight how mass vaccination has closed the immunity gap in most of the adult population-particularly among older individuals who are at the greatest risk of severe COVID-19 outcomes. 29 They attest to the efficacy of free-of-charge vaccination programs in promoting immunization against the virus while highlighting the need to strengthen efforts to address vaccine hesitancy. 21, 23 Importantly, our findings also show that the large majority of children and teenagers, and a large proportion of young and middle-aged adults, lack anti-SARS-CoV-2 antibodies, leaving behind a large reservoir in the population to sustain transmission in the critical months to come. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.12.21261929 doi: medRxiv preprint the manuscript and created tables. All authors contributed to the interpretation of results and read and approved the final manuscript.

None of the authors have any competing interests to report. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint a Serology based on Roche Elecsys anti-SARS-CoV-2 S immunoassay and N immunoassay, respectively.

b Seroprevalence estimates reported as % and 95% credible interval, adjusted for test performance of both immunoassays and post-stratified to account for age distribution in the Geneva general population and for household clustering of infection and vaccination. N = 3355 for total, and sex-and age-stratified estimates; N = 2520 for education-stratified estimates, excluding participants aged <18 years. Seroprevalence of antibodies of any antibodies is based on proportion of participants with any anti-SARS-CoV-2 antibodies; seroprevalence of infection antibodies is based on proportion of participants who were naturally infected (but could also have been vaccinated). c Self-reported having received at least 1 dose of the COVID-19 vaccine >14 days before blood sample was drawn. 

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Figure 1. Confirmed SARS-CoV-2 infection cases and estimated seroprevalence of anti-SARS-CoV-2 antibodies in the general population of

Confirmed SARS-CoV-2 infection cases in the general population of

in which the 0-5 age group only included children aged 5 years 8 ; second serosurvey from