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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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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.
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ObjectivesThis cohort study including essential workers, assessed the{square}risk and incidence of SARS-CoV-2{square}infection during the second surge of COVID-19 according to baseline serostatus and occupational sector. MethodsEssential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralized registry compiling SARS-CoV-2 infections. Primary outcome was the number of virologically-confirmed infections from serological assessment (between May and September 2020) to January 25, 2021, according to baseline antibody status and stratified by three pre-defined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). Secondary outcomes included the incidence of infection. Results10457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645, and 3755 workers were classified under "Other essential occupations"). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during follow-up with no significant between-occupational group difference. ConclusionsA ten-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least six months after infection. Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSRisk of SARS-CoV-2 reinfection is low in the general population and among healthcare workers. What are the new findings?A ten-fold reduction of risk of being virologically tested positive reinfection is observed among anti-SARS-CoV-2 seropositive essential workers of different activity sectors, regardless of their occupation-related risk of exposure. How might this impact on policy or clinical practice in the foreseeable future?Vaccination could be delayed in individuals with previous history of SARS-CoV-2 infection with serologic confirmation, regardless of their occupational exposure. These observations need to be confirmed for new SARS-CoV-2 variants.
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BackgroundThe COVID-19 pandemic has affected billions of people around the world both directly through the infection itself and indirectly through its economic, social and sanitary impact. Collecting data over time is essential for the understanding of the disease spread, the incidence of COVID19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. ObjectiveThe objective of the study was to set up a longitudinal follow-up of adult participants of serosurveys carried out in the Canton of Geneva, Switzerland, during the COVID-19 pandemic. MethodsSerosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/). Upon registration, an initial questionnaire assessed socio-demographic and lifestyle characteristics (including housing conditions, physical activity, diet, alcohol and tobacco consumption), anthropometry, general health, and experience related to COVID-19 (symptoms, COVID-19 test results, quarantines, hospitalizations). Weekly, participants were invited to fill in a short questionnaire with updates on self-reported COVID-19-compatible symptoms, SARS-CoV-2 infection testing and vaccination. A more detailed questionnaire about mental health, well-being, risk perception, and changes in working conditions was proposed monthly. Supplementary questionnaires were proposed at regular intervals to assess more in depth the impact of the pandemic on physical and mental health, vaccination adherence, health care consumption and changes in health behaviors. At baseline, serology testing allowed to assess the spread of SARS-CoV-2 infection among the general population and subgroups of workers. Additionally, seropositive participants and a sample of randomly selected participants were invited for serologic testing at regular intervals in order to monitor both the seropersistance of anti-SARS-CoV-2 antibodies and the seroprevalence of anti-SARS-CoV-2 antibodies in the population of the Canton of Geneva. Ethics and disseminationThe study was approved by the Cantonal Research Ethics Commission of Geneva, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the Specchio-COVID19 platform, social media posts, press releases, and through regular scientific dissemination methods (open-access articles, conferences). Article summaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThis is a large study with a diversified recruitment among the general population and mobilized workers. It will contribute to obtain a clearer picture of the impact of the COVID-19 pandemic, for both the general population and targeted subpopulations. C_LIO_LIA major strength of the study is the combined use of serological testing and questionnaires. While regular serological testing will help us to model evolution of the pandemic, self-reported data on socioeconomic characteristics, COVID-19-compatible symptoms, and general and mental health will allow us to monitor the progression of the COVID-19 pandemic as well as to thoroughly analyze its effects on several dimensions of health. C_LIO_LIThe longitudinal component of the study will provide insight into the extent and duration of immunity, as well as the long-term impact of the pandemic and the sanitary, social and economic measures associated with it. C_LIO_LIThe main limitation is that Specchio-COVID19 is based on self-reports with a risk of information bias. However, considering the pandemic context, participants are generally engaged to participate and to contribute to COVID-19 research. Further, at least half of the sample is based on random selection in the general population. C_LIO_LIThe study is primarily being conducted online, which may limit the generalizability of the findings, especially for the elderly and vulnerable populations, although internet access is extensive in Switzerland. Nonetheless, participants can use paper questionnaires to contribute to the major assessments. C_LI
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Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. The reliability of serologic studies for quantifying the proportion of the population that have been infected depends on the extent of antibody decay as well as on assay performance in detecting both recent and older infections. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. In a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals tested with three widely-used immunoassays, antibodies persisted for at least 8 months after infection, although detection depended on immunoassay choice, with one of them missing up to 40% of past infections. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. As the immune landscape becomes more complex with naturally-infected and vaccinated individuals, assay choice and appropriate assay-performance-adjustment will become even more important for the interpretation of serologic studies.
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BackgroundAntigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. MethodsWe conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS. Results402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values [≤] 26.7 ([≥] 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. InterpretationBased on our findings, the diagnostic performance of the Panbio Covid-19 RDT with OPS samples meet the criteria required by the WHO for Ag-RDTs (sensitivity[≥]80% and specificity [≥]97%).
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BackgroundPopulation-based serological surveys provide a means for assessing the immunologic landscape of a community, without the biases related to health-seeking behaviors and testing practices typically associated with rt-PCR testing. This study assesses SARS-CoV-2 seroprevalence over the first epidemic wave in Canton Geneva, Switzerland, as well as biological and socio-economic risk factors for infection and symptoms associated with IgG seropositivity. Methods and findingsBetween April 6 and June 30, 2020, former participants of a yearly representative cross-sectional survey of the 20-75-year-old population of the canton of Geneva were invited to participate in a seroprevalence study, along with household members five years and older. We collected blood and tested it for anti-SARS-CoV-2 immunoglobulins G (IgG). Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. We included 8344 participants (53.5% women, mean age 46.9 years). The population-level seroprevalence over the 12-week study period was 7.8 % (95% Credible Interval (CrI) 6.8-8.9), accounting for sex, age and household random effects. Seroprevalence was highest among 18-49 year olds (9.5%, 95%CrI 8.1-10.9), with young children (5-9 years) and those >65 years having significantly lower seroprevalence (4.3% and 4.7-5.4% respectively). Men were more likely to be seropositive than women (relative risk 1.2, 95%CrI 1.1-1.4). Odds of seropositivity were reduced for female retirees (0.46, 95%CI 0.23-0.93) and unemployed men (0.35, 95%CI 0.13-1.0) compared to employed individuals, and for current smokers (0.36, 95%CI 0.23-0.55) compared to never-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. Symptoms most strongly associated with seropositivity were anosmia/dysgeusia, loss of appetite, fever, fatigue and myalgia and/or arthralgia. Thirteen percent of seropositive participants reported no symptoms. ConclusionsOur results confirm a low population seroprevalence of anti-SARS-CoV-2 antibodies after the first wave in Geneva, a region hard hit by the COVID-19 pandemic. Socioeconomic factors were not associated with seropositivity in this sample. The elderly and young children were less frequently seropositive, though it is not clear how biology and behaviors shape these differences. These specificities should be considered when assessing the need for targeted public health measures.
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BackgroundAntigen-detecting rapid diagnostic tests for SARS-CoV-2 offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. MethodsWe performed a prospective, single-center, point of care validation of two antigen-detecting rapid diagnostic tests (Ag-RDT) in comparison to RT-PCR on nasopharyngeal swabs. FindingsBetween October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioCovid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. InterpretationWe provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of [≥]80% sensitivity and [≥]97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value. FundingFoundation of Innovative Diagnostics (FIND), Fondation privee des HUG, Pictet Charitable Foundation.
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BackgroundAssessing the burden of COVID-19 based on medically-attended case counts is suboptimal given its reliance on testing strategy, changing case definitions and the wide spectrum of disease presentation. Population-based serosurveys provide one avenue for estimating infection rates and monitoring the progression of the epidemic, overcoming many of these limitations. MethodsTaking advantage of a pool of adult participants from population-representative surveys conducted in Geneva, Switzerland, we implemented a study consisting of 8 weekly serosurveys among these participants and their household members older than 5 years. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available enzyme-linked immunosorbent assay (Euroimmun AG, Lubeck, Germany). We estimated seroprevalence using a Bayesian regression model taking into account test performance and adjusting for the age and sex of Genevas population. ResultsIn the first three weeks, we enrolled 1335 participants coming from 633 households, with 16% <20 years of age and 53.6% female, a distribution similar to that of Geneva. In the first week, we estimated a seroprevalence of 3.1% (95% CI 0.2-5.99, n=343). This increased to 6.1% (95% CI 2.69.33, n=416) in the second, and to 9.7% (95% CI 6.1-13.11, n=576) in the third week. We found that 5-19 year-olds (6.0%, 95% CI 2.3-10.2%) had similar seroprevalence to 20-49 year olds (8.5%, 95%CI 4.99-11.7), while significantly lower seroprevalence was observed among those 50 and older (3.7%, 95% CI 0.99-6.0, p=0.0008). InterpretationAssuming that the presence of IgG antibodies is at least in the short-term associated with immunity, these results highlight that the epidemic is far from burning out simply due to herd immunity. Further, no differences in seroprevalence between children and middle age adults are observed. These results must be considered as Switzerland and the world look towards easing restrictions aimed at curbing transmission.