The Impact of Non-pharmaceutical Interventions on COVID-19 in Workers and Residents of Nursing Homes in Geneva: A Mixed-Methods Study (preprint)

Non-pharmaceutical interventions (NPIs), including social distancing, wearing personal protective equipment, and lockdown measures, have been at the forefront of outbreak control in nursing homes. We used a mixed methodology to assess which NPIs nursing homes in the canton of Geneva, Switzerland, followed for their staff and residents during the first wave of the pandemic, between March 1, 2020 and June 1, 2020. For the qualitative component, we interviewed the attending physicians and/or director of each nursing home. Based on in-vivo codes, NPIs for nursing home workers and residents in each nursing home were thematically classified as: maximally restrictive, moderately restrictive, and minimally restrictive. In the quantitative component, we calculated incident rate ratios (IRR) for infection between the three levels of COVID-19-related measures taken in these nursing homes. We found an equal distribution of maximally (n=4), moderately (n=4), and minimally (n=4) restrictive NPIs. The extent of restriction did not show to be significantly associated with the cumulative incidence of COVID-19 cases among residents (maximally restrictive IRR = 3.90, 95%CI 0.82-45.54, p = 0.184; moderately restrictive IRR = 3.55, 95%CI 0.75-41.42, p = 0.212 ; minimally restrictive IRR = reference). Variabilities in NPIs adopted by nursing homes, and the number of COVID-19 cases appear to be randomly affected.

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

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 1'083 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 show 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 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. Taken together these results indicate 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 with a history of previous SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will come next, 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 (preprint)

ABSTRACT Background More 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. Methods We conducted a population-based serosurvey between April 29 th and June 9 th , 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. Results Among 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. Conclusion More 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.

Seroprevalence of anti-SARS-CoV-2 antibodies six months into the vaccination campaign in Geneva, Switzerland (preprint)

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.

Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study. (preprint)

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.

The Specchio-COVID19 cohort study: a longitudinal follow-up of SARS-CoV-2 serosurvey participants in the canton of Geneva, Switzerland (Study protocol) (preprint)

Background The 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. Objective The objective 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. Methods Serosurvey 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), 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 dissemination The study was approved by the Cantonal Research Ethics Commission of Geneva (CCER Project ID 2020-00881). Results will be disseminated via the Specchio-COVID19 platform and scientific articles.

Persistence and detection of anti-SARS-CoV-2 antibodies: immunoassay heterogeneity and implications for serosurveillance (preprint)

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.