Interplay of Digital Proximity App Use and SARS-CoV-2 Vaccine Uptake in Switzerland: Analysis of Two Population-Based Cohort Studies.

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic. Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes. Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40-1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62-1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38-0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27-0.78 [CSM]) compared to participants who did not get vaccinated. Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions.

Maintaining brain health across the lifespan.

Across the lifespan, the human body and brain endure the impact of a plethora of exogenous and endogenous factors that determine the health outcome in old age. The overwhelming inter-individual variance spans between progressive frailty with loss of autonomy to largely preserved physical, cognitive, and social functions. Understanding the mechanisms underlying the diverse aging trajectories can inform future strategies to maintain a healthy body and brain. Here we provide a comprehensive overview of the current literature on lifetime factors governing brain health. We present the growing body of evidence that unhealthy alimentary regime, sedentary behaviour, sleep pathologies, cardio-vascular risk factors, and chronic inflammation exert their harmful effects in a cumulative and gradual manner, and that timely and efficient intervention could promote healthy and successful aging. We discuss the main effects and interactions between these risk factors and the resulting brain health outcomes to follow with a description of current strategies aiming to eliminate, treat, or counteract the risk factors. We conclude that the detailed insights about modifiable risk factors could inform personalized multi-domain strategies for brain health maintenance on the background of increased longevity.

Investigating the association of measures of epigenetic age with COVID-19 severity: evidence from secondary analyses of open access data.

BACKGROUND: Epigenetic modifications may contribute to inter-individual variation that is unexplainable by presently known risk factors for COVID-19 severity (e.g., age, excess weight, or other health conditions). Estimates of youth capital (YC) reflect the difference between an individual's epigenetic - or biological - age and chronological age, and may quantify abnormal aging due to lifestyle or other environmental exposures, providing insights that could inform risk-stratification for severe COVID-19 outcomes. This study aims to thereby a) assess the association between YC and epigenetic signatures of lifestyle exposures with COVID-19 severity, and b) to assess whether the inclusion of these signatures in addition to a signature of COVID-19 severity (EPICOVID) improved the prediction of COVID-19 severity. METHODS: This study uses data from two publicly-available studies accessed via the Gene Expression Omnibus (GEO) platform (accession references: GSE168739 and GSE174818). The GSE168739 is a retrospective, cross-sectional study of 407 individuals with confirmed COVID-19 across 14 hospitals in Spain, while the GSE174818 sample is a single-center observational study of individuals admitted to the hospital for COVID-19 symptoms (n = 102). YC was estimated using the (a) Gonseth-Nusslé, (b) Horvath, (c) Hannum, and (d) PhenoAge estimates of epigenetic age. Study-specific definitions of COVID-19 severity were used, including hospitalization status (yes/no) (GSE168739) or vital status at the end of follow-up (alive/dead) (GSE174818). Logistic regression models were used to assess the association between YC, lifestyle exposures, and COVID-19 severity. RESULTS: Higher YC as estimated using the Gonseth-Nusslé, Hannum and PhenoAge measures was associated with reduced odds of severe symptoms (OR = 0.95, 95% CI = 0.91-1.00; OR = 0.81, 95% CI = 0.75 - 0.86; and OR = 0.85, 95% CI = 0.81-0.88, respectively) (adjusting for chronological age and sex). In contrast, a one-unit increase in the epigenetic signature for alcohol consumption was associated with 13% increased odds of severe symptoms (OR = 1.13, 95% CI = 1.05-1.23). Compared to the model including only age, sex and the EPICOVID signature, the additional inclusion of PhenoAge and the epigenetic signature for alcohol consumption improved the prediction of COVID-19 severity (AUC = 0.94, 95% CI = 0.91-0.96 versus AUC = 0.95, 95% CI = 0.93-0.97; p = 0.01). In the GSE174818 sample, only PhenoAge was associated with COVID-related mortality (OR = 0.93, 95% CI = 0.87-1.00) (adjusting for age, sex, BMI and Charlson comorbidity index). CONCLUSIONS: Epigenetic age is a potentially useful tool in primary prevention, particularly as an incentive towards lifestyle changes that target reducing the risk of severe COVID-19 symptoms. However, additional research is needed to establish potential causal pathways and the directionality of this effect.

Association of plasma zinc levels with anti-SARS-CoV-2 IgG and IgA seropositivity in the general population: A case-control study.

INTRODUCTION: Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data. METHODS: Case-control study comparing the first PCR-confirmed COVID-19 symptomatic cases in the Vaud Canton (May to June 2020, n = 199) and controls (random population sample, n = 447), seronegative for IgG and IgA. The replication analysis included seropositive (n = 134) and seronegative (n = 152) close contacts from confirmed COVID-19 cases. Anti-SARS-CoV-2 IgG and IgA levels against the native trimeric spike protein were measured using the Luminex immunoassay. We measured plasma Zn, Se and Cu concentrations by ICP-MS, and 25-hydroxy-vitamin D3 (25(OH)D3) with LC-MS/MS and explored associations using multiple logistic regression. RESULTS: The 932 participants (54.1% women) were aged 48.6 ± 20.2 years (±SD), BMI 25.0 ± 4.7 kg/m2 with median C-Reactive Protein 1 mg/l. In logistic regressions, log2(Zn) plasma levels were negatively associated with IgG seropositivity (OR [95% CI]: 0.196 [0.0831; 0.465], P < 0.001; replication analyses: 0.294 [0.0893; 0.968], P < 0.05). Results were similar for IgA. We found no association of Cu, Se, and 25(OH)D3 with anti-SARS-CoV-2 IgG or IgA seropositivity. CONCLUSION: Low plasma Zn levels were associated with higher anti-SARS-CoV-2 IgG and IgA seropositivity in a Swiss population when the initial viral variant was circulating, and no vaccination available. These results suggest that adequate Zn status may play an important role in protecting the general population against SARS-CoV-2 infection. REGISTRY: CORONA IMMUNITAS:: ISRCTN18181860.

Seroprevalence trends of anti-SARS-CoV-2 antibodies and associated risk factors: a population-based study.

PURPOSE: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time. METHODS: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models. RESULTS: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake. CONCLUSIONS: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed.

Prevalence of SARS-CoV-2 infection and associated risk factors among asylum seekers living in asylum centres: A cross-sectional serologic study in Canton of Vaud, Switzerland.

Background: Understanding the factors influencing SARS-CoV-2 transmission in asylum seekers and refugees living in centres is crucial to determine targeted public health policies protecting these populations fairly and efficiently. In response, this study was designed to explore the pandemic's spread into asylum centres during the first wave of the pandemic in Switzerland. Specifically, it aimed to identify the risk factors associated with a positive anti-SARS-CoV-2 seroprevalence test after the first semi-confinement period (16 March to 27 April 2020) amongst asylum seekers and refugees living in centres. Methods: This research is part of SérocoVID, a seroepidemiologic study of SARS-CoV-2 infection conducted in the canton of Vaud, Switzerland. Migrants living in two asylum centres, one known to have had an epidemic outbreak, were invited to participate in this study. Anti-SARS-CoV-2 IgG and IgA antibodies targeting the spike viral protein were measured in all participants using a Luminex immunoassay. Each participant also completed a questionnaire measuring socio-demographic characteristics, medical history (comorbidities, smoking status, BMI, flu-like symptoms), health literacy, public health recommendations (wearing a masque in a public area, social distancing and hands cleaning), behaviours and exposures (daily life activities, number of contacts weekly). The association of these independent variables with the serologic test result were estimated using a multivariable logistic regression model. Findings: A total of 124 participants from the two asylum centres took part in the study (Centre 1, n = 82; Centre 2, n = 42). The mean participation rate was 36.7%. The seroprevalence in Centres 1 and 2 were 13% [95% CI 0.03, 0.14] and 50% [0.34, 0.65], respectively. Next, 40.63% of SARS-CoV-2 positive people never developed symptoms (asymptomatic cases), and no one had severe forms of the Covid-19 disease requiring hospitalisation. Participants report high compliance with public health measures, especially hygiene rules (96.3% of positive answers) and social distancing (88.7%). However, only 11.3% said they always wore a masque in public. After adjusting for individual characteristics, infection risk was lower amongst people with high health literacy (aOR 0.16, p = 0.007 [0.04, 0.60]) and smokers (aOR 0.20, p = 0.013 [0.06, 0.69]). Conclusion: Despite the lack of severe complications of Covid-19 disease in this study, findings suggest that developing targeted public health measures, especially for the low health literacy population, would be necessary to limit the risk of outbreaks in asylum centres and improve this population's safety. Further investigations and qualitative approach are required to understand more finely how living conditions, risks and behaviours such as tobacco consumption, and the adoption of protective measures impact SARS-CoV-2 infection.

Life-course socioeconomic factors are associated with markers of epigenetic aging in a population-based study.

Adverse socioeconomic circumstances negatively affect the functioning of biological systems, but the underlying mechanisms remain only partially understood. Here, we explore the associations between life-course socioeconomic factors and four markers of epigenetic aging in a population-based setting. We included 684 participants (52 % women, mean age 52.6 ± 15.5 years) from a population and family-based Swiss study. We used nine life-course socioeconomic indicators as the main exposure variables, and four blood-derived, second generation markers of epigenetic aging as the outcome variables (Levine's DNAmPhenoAge, DunedinPoAm38, GrimAge epigenetic age acceleration (EAA), and the mortality risk score (MS)). First, we investigated the associations between socioeconomic indicators and markers of epigenetic aging via mixed-effect linear regression models, adjusting for age, sex, participant's recruitment center, familial structure (random-effect covariate), seasonality of blood sampling, and technical covariates. Second, we implemented counterfactual mediation analysis to investigate life-course and intermediate mechanisms underlying the socioeconomic gradient in epigenetic aging. Effect-size estimates were assessed using regression coefficients and counterfactual mediation parameters, along with their respective 95 % confidence intervals. Individuals reporting a low father's occupation, adverse financial conditions in childhood, a low income, having financial difficulties, or experiencing unfavorable socioeconomic trajectories were epigenetically older and had a higher mortality risk score than their more advantaged counterparts. Specifically, this corresponded to an average increase of 1.1-1.5 years for Levine's epigenetic age (ß and 95 %CI range, ß (minimum and maximum): 1.1-1.5 95 %CI[0.0-0.2; 2.3-3.0]), 1.1-1.5 additional years for GrimAge (ß: 1.1-1.5 95 %CI[0.2-0.6; 1.9-3.0]), a 1-3 % higher DunedinPoAm38 age acceleration (ß: 0.01-0.03 95 %CI[0.00; 0.03-0.04]), and a 10-50 % higher MS score (ß: 0.1-0.4 95 %CI[0.0-0.2; 0.3-0.4]) for the aforementioned socioeconomic indicators. By exploring the life-course mechanisms underlying the socioeconomic gradient in epigenetic aging, we found that both childhood and adulthood socioeconomic factors contributed to epigenetic aging, and that detrimental lifestyle factors mediated the relation between socioeconomic circumstances in adulthood and EAA (31-89 % mediated proportion). This study provides emerging evidence for an association between disadvantaged life-course socioeconomic circumstances and detrimental epigenetic aging patterns, supporting the "sensitive-period" life-course model. Counterfactual mediation analyses further indicated that the effect of socioeconomic factors in adulthood operates through detrimental lifestyle factors, whereas associations involving early-life socioeconomic factors were less clear.

SARS-CoV-2 Seroprevalence in Employees of Four Essential Non-Health Care Sectors at Moderate/High Risk of Exposure to Coronavirus Infection: Data From the "First Wave".

OBJECTIVE: The aim of this study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in Swiss non-health care employees at a moderate to high risk of exposure: bus drivers and supermarket, laundry service, and mail-sorting center employees. METHODS: Data on 455 essential workers included demographics, SARS-CoV-2 exposure and use of protective measures. Anti-SARS-CoV-2 immunoglobulins G and A targeting the spike protein were measured between May and July 2020. RESULTS: The overall crude seroprevalence estimate (15.9%; 95% confidence interval [CI], 12.6% to 19.7%) among essential workers was not significantly higher than that of the general working-age population (11.2%; 95% CI, 7.1% to 15.2%). Seroprevalence ranged from 11.9% (95% CI, 6.3% to 19.8%) among bus drivers to 22.0% (95% CI, 12.6% to 19.7%) among food supermarket employees. CONCLUSIONS: We found no significant difference in seroprevalence between our sample of essential workers and local working-age population during the first lockdown phase of the COVID-19 pandemic. Having a seropositive housemate was the strongest predictor of SARS-CoV-2 seropositivity.

Blood DNA methylation signatures of lifestyle exposures: tobacco and alcohol consumption.

BACKGROUND: Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic changes incurred with differing levels of lifestyle exposures. This study describes and validates two novel epigenetic signatures of tobacco (EpiTob) and alcohol (EpiAlc) consumption and investigates their association with disease outcomes. METHODS: The epigenetic signatures, EpiTob and EpiAlc, were developed using data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) (N = 689). Epigenetic and phenotypic data available from the 1921 (N = 550) and 1936 (N = 1091) Lothian Birth Cohort (LBC) studies, and two publicly available datasets on GEO Accession (GSE50660, N = 464; and GSE110043, N = 94) were used to validate the signatures. A multivariable logistic regression model, adjusting for age and sex, was used to assess the association between self-reported tobacco or alcohol consumption and the respective epigenetic signature, as well as to estimate the association between CVD and epigenetic signatures. A Cox proportional hazard model was used to estimate the risk of mortality in association with the EpiTob and EpiAlc signatures. RESULTS: The EpiTob signature was positively associated with self-reported tobacco consumption for current or never smokers with explained variance ranging from 0.49 (LBC1921) to 0.72 (LBC1936) (pseudo-R2). In the SKIPOGH, LBC1921 and LBC1936 cohorts, the epigenetic signature for alcohol consumption explained limited variance in association with self-reported alcohol status [i.e., non-drinker, moderate drinker, and heavy drinker] (pseudo-R2 = 0.05, 0.03 and 0.03, respectively), although this improved considerably when measuring self-reported alcohol consumption with standardized units consumed per week (SKIPOGH R2 = 0.21; LBC1921 R2 = 0.31; LBC1936 R2 = 0.41). Both signatures were associated with history of CVD in SKIPOGH and LBC1936, but not in LBC1921. The EpiTob signature was associated with increased risk of all-cause and lung-cancer specific mortality in the 1936 and 1921 LBC cohorts. CONCLUSIONS: This study found the EpiTob and EpiAlc signatures to be well-correlated with self-reported exposure status and associated with long-term health outcomes. Epigenetic signatures of lifestyle exposures may reduce measurement issues and biases and could aid in risk stratification for informing early-stage targeted interventions.

Determinants of COVID-19 Vaccine Hesitancy During the Pandemic: A Cross-Sectional Survey in the Canton of Vaud, Switzerland.

Objectives: COVID-19 vaccine hesitancy is a major obstacle in the fight against the pandemic. This study aimed to identify the local determinants of vaccine hesitancy in the context of COVID-19 to better inform future immunization campaigns. Methods: The study, conducted in February 2021, included 1,189 randomly selected inhabitants of the canton of Vaud, Switzerland. Online questionnaires investigated determinants of the intention to vaccinate. Previously validated scores (Cronbach's alphas >0.70) were applied to our data for inclusion in the ordinal logistic regression model. Results: Individuals were more likely to vaccinate if they were 40 years or older, wealthy, reported a high educational attainment, or reported comorbidities. Doubts regarding vaccine safety and efficacy, mistrust in authorities and a propensity for natural immunity were identified as the main local hindrances to the COVID-19 vaccination. Conclusion: Outreach to people at risk of severe COVID-19 is particularly relevant in the pandemic context to help mitigate vaccine hesitancy in the canton of Vaud, and should take into consideration the level of education. Further investigation is needed to better understand reasons for mistrust in authorities.

Adherence to Coronavirus Disease 2019 Preventive Measures in a Representative Sample of the Population of the Canton of Vaud, Switzerland.

Objectives: We quantified adherence to COVID-19 preventive measures and explored associated factors, after the first and during the second Swiss epidemic waves. Methods: With an observational cohort study in a representative sample of individuals aged 15 years and more, we analysed the association between self-reported adherence to COVID-19 preventive measures (respect of simple hygiene rules; respect of social distancing rules; wearing a mask) and socio-demographic factors, the existence of a chronic disease, and the existence of a previous confirmed COVID-19 episode. Results: Highest adherence was to simple hygiene rules, followed by social distancing rules and mask wearing, with a slight decrease for simple hygiene rules and a strong increase for mask wearing between visits. Men were significantly less likely to respect simple hygiene rules and wear a mask in public. Participants aged 65 years and more (versus 25-64 years) and those with at least one chronic disease (versus none) were two times more likely to respect social distancing rules and wear a mask. Conclusion: Adherence to social distancing rules and mask wearing was rather poor, especially compared to other countries.

Performance of the Digital Dietary Assessment Tool MyFoodRepo.

Digital dietary assessment devices could help overcome the limitations of traditional tools to assess dietary intake in clinical and/or epidemiological studies. We evaluated the accuracy of the automated dietary app MyFoodRepo (MFR) against controlled reference values from weighted food diaries (WFD). MFR's capability to identify, classify and analyze the content of 189 different records was assessed using Cohen and uniform kappa coefficients and linear regressions. MFR identified 98.0% ± 1.5 of all edible components and was not affected by increasing numbers of ingredients. Linear regression analysis showed wide limits of agreement between MFR and WFD methods to estimate energy, carbohydrates, fat, proteins, fiber and alcohol contents of all records and a constant overestimation of proteins, likely reflecting the overestimation of portion sizes for meat, fish and seafood. The MFR mean portion size error was 9.2% ± 48.1 with individual errors ranging between -88.5% and +242.5% compared to true values. Beverages were impacted by the app's difficulty in correctly identifying the nature of liquids (41.9% ± 17.7 of composed beverages correctly classified). Fair estimations of portion size by MFR, along with its strong segmentation and classification capabilities, resulted in a generally good agreement between MFR and WFD which would be suited for the identification of dietary patterns, eating habits and regime types.

PhenoExplorer: An Interactive Web-based Platform for Exploring (Epi)Genome-Wide Associations Using a Swiss Population-based Study.

The recent advent of high-throughput sequencing technologies has allowed exploring the contribution of thousands of genomic, epigenomic, transcriptomic, or proteomic variants to complex phenotypic traits. Here, we sought to conduct large-scale (Epi)Genome-Wide Association Studies (GWAS/EWAS) to investigate the associations between genomic (Single Nucleotide Polymorphism; SNP) and epigenomic (Cytosine-Phospho-Guanine; CpG) markers, with multiple phenotypic traits in a population-based context. We used data from SKIPOGH, a family- and population-based cohort conducted in the cities of Lausanne, Geneva, and Bern (N=1100). We used 7,577,572 SNPs, 420,444 CpGs, and 825 phenotypes, including anthropometric, clinical, blood, urine, metabolite, and metal measures. GWAS analyses assessed the associations between SNPs and metabolites and metals (N=279), using regression models adjusted for age, sex, recruitment center, and familial structure, whereas EWAS analyses explored the relations between CpGs and 825 phenotypes, additionally adjusting for the seasonality of blood sampling and technical nuisance. Following the implementation of GWAS and EWAS analyses, we developed a web-based platform, PhenoExplorer, aimed at providing an open access to the obtained results. Of the 279 phenotypes included in GWAS, 103 displayed significant associations with 2804 SNPs (2091 unique SNPs) at Bonferroni threshold, whereas 109 of the 825 phenotypes included in EWAS analyses were associated with 4893 CpGs (2578 unique CpGs). All of the obtained GWAS and EWAS results were eventually made available using the in-house built web-based PhenoExplorer platform, with the purpose of providing an open-access to the tested associations. In conclusion, we provide a comprehensive outline of GWAS and EWAS associations performed in a Swiss population-based study. Further, we set up a web-based PhenoExplorer platform with the purpose of contributing to the overall understanding of the role of molecular variants in regulating complex phenotypes.

Prevalence of SARS-CoV-2 in Household Members and Other Close Contacts of COVID-19 Cases: A Serologic Study in Canton of Vaud, Switzerland.

BACKGROUND: Research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission within households and other close settings using serological testing is scarce. METHODS: We invited coronavirus disease 2019 (COVID-19) cases diagnosed between February 27 and April 1, 2020, in Canton of Vaud, Switzerland, to participate, along with household members and other close contacts. Anti-SARS-CoV-2 immunoglobulin G antibodies were measured using a Luminex immunoassay. We estimated factors associated with serological status using generalized estimating equations. RESULTS: Overall, 219 cases, 302 household members, and 69 other close contacts participated between May 4 and June 27, 2020. More than half of household members (57.2%; 95% CI, 49.7%-64.3%) had developed a serologic response to SARS-CoV-2, while 19.0% (95% CI, 10.0%-33.2%) of other close contacts were seropositive. After adjusting for individual and household characteristics, infection risk was higher in household members aged ≥65 years than in younger adults (adjusted odds ratio [aOR], 3.63; 95% CI, 1.05-12.60) and in those not strictly adhering to simple hygiene rules like hand washing (aOR, 1.80; 95% CI, 1.02-3.17). The risk was lower when more than 5 people outside home were met during semiconfinement, compared with none (aOR, 0.35; 95% CI, 0.16-0.74). Individual risk of household members to be seropositive was lower in large households (22% less per each additional person). CONCLUSIONS: During semiconfinement, household members of a COVID-19 case were at very high risk of getting infected, 3 times more than close contacts outside home. This highlights the need to provide clear messages on protective measures applicable at home. For elderly couples, who were especially at risk, providing external support for daily basic activities is essential.

Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses to the spike (S) protein monomer, S protein native trimeric form, or the nucleocapsid (N) proteins were evaluated in cohorts of individuals with acute infection (n = 93) and in individuals enrolled in a postinfection seroprevalence population study (n = 578) in Switzerland. Commercial assays specific for the S1 monomer, for the N protein, or within a newly developed Luminex assay using the S protein trimer were found to be equally sensitive in antibody detection in the acute-infection-phase samples. Interestingly, compared to anti-S antibody responses, those against the N protein appear to wane in the postinfection cohort. Seroprevalence in a "positive patient contacts" group (n = 177) was underestimated by N protein assays by 10.9 to 32.2%, while the "randomly selected" general population group (n = 311) was reduced by up to 45% relative to the S protein assays. The overall reduction in seroprevalence targeting only anti-N antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was significantly more sensitive compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.IMPORTANCE In the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and postinfection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection, but that responses against N appear to wane in the postinfection phase where those against the S protein persist over time. The most sensitive serological assay in both acute and postinfection phases used the native S protein trimer as the binding antigen, which has significantly greater conformational epitopes for antibody binding compared to the S1 monomer protein used in other assays. We believe these results are extremely important in order to generate correct estimates of SARS-CoV-2 infections in the general population. Furthermore, the assessment of antibody responses against the trimeric S protein will be critical to evaluate the durability of the antibody response and for the characterization of a vaccine-induced antibody response.