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

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 widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show 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 previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave 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. 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: A population-based study.

Background: More than two years into the COVID-19 pandemic, 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. Here, we estimated 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 and June 9, 2022, recruiting children and adults of all ages from age-stratified random samples of the general population of Geneva, Switzerland. We tested for anti-SARS-CoV-2 antibodies using commercial immunoassays targeting either the spike (S) or nucleocapsid (N) protein, and for antibody neutralization capacity against different SARS-CoV-2 variants using a cell-free Spike trimer-ACE2 binding-based surrogate neutralization assay. We estimated seroprevalence and neutralization capacity using a Bayesian modeling framework accounting for the demographics, vaccination, and infection statuses of the Geneva population. Findings: Among the 2521 individuals included in the analysis, the estimated total antibodies seroprevalence was 93.8% (95% CrI 93.1-94.5), including 72.4% (70.0-74.7) for infection-induced antibodies. Estimates of neutralizing antibodies in a representative subsample (N = 1160) 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. Overall, vaccination was associated with higher neutralizing activity against pre-Omicron variants. Vaccine booster alongside recent infection was associated with higher neutralizing activity against Omicron subvariants. Interpretation: While most of the Geneva population has developed anti-SARS-CoV-2 antibodies through vaccination and/or infection, less than half has neutralizing activity against the currently circulating Omicron BA.5 subvariant. Hybrid immunity obtained through booster vaccination and infection confers the greatest neutralization capacity, including against Omicron. Funding: General Directorate of Health in Geneva canton, Private Foundation of the Geneva University Hospitals, European Commission ("CoVICIS" grant), and a private foundation advised by CARIGEST SA.

Implementing a Multifaceted Intervention among Internal Medicine Residents with Audit and Educative Data Feedback Significantly Reduces Low-Value Care in Hospitalized Patients

Background: The dissemination of recommendations on low-value care alone may not lead to physicians’ behavioral changes. The aim of this study was to evaluate whether a multifaceted behavioral intervention among internal medicine residents could reduce low-value care in hospitalized patients. Methods: A pre–post quality improvement intervention was conducted at the Internal Medicine Division of La Tour hospital (Geneva, Switzerland) from May 2020 to October 2021. The intervention period (3 months) consisted of a multifaceted informational intervention with audits and educative feedback about low-value care. The pre- and post-intervention periods including the same six calendar months were compared in terms of number of blood samples per patient day, prescription rates of benzodiazepines (BZDs) and proton pump inhibitors (PPIs), as well as safety indicators including potentially avoidable readmissions, premature deaths and complications. results: A total of 3400 patients were included in this study;1095 (32.2%) and 1155 (34.0%) were, respectively, hospitalized during the pre- and post-intervention periods. Patient characteristics were comparable between the two periods. Only the number of blood tests per patient day and the BZD prescription rate at discharge were significantly reduced in the post-intervention phase (pre: 0.54 ± 0.43 vs. post: 0.49 ± 0.60, p ≤ 0.001;pre: 4.2% vs. post: 1.7%, p = 0.003, respectively). PPI prescription rates remained comparable. Safety indicators analyses revealed no significant differences between the two periods of interest. Conclusions: Our results demonstrate a modest but statistically significant effect of a multifaceted educative intervention in reducing the number of blood tests and the BZD prescription rate at discharge in hospitalized patients. Limiting low-value services is very challenging and additional long-term interventions are necessary for wider implementation.

A new screening tool for SARS-CoV-2 infection based on self-reported patient clinical characteristics: the COV19-ID score.

BACKGROUND: While several studies aimed to identify risk factors for severe COVID-19 cases to better anticipate intensive care unit admissions, very few have been conducted on self-reported patient symptoms and characteristics, predictive of RT-PCR test positivity. We therefore aimed to identify those predictive factors and construct a predictive score for the screening of patients at admission. METHODS: This was a monocentric retrospective analysis of clinical data from 9081 patients tested for SARS-CoV-2 infection from August 1 to November 30 2020. A multivariable logistic regression using least absolute shrinkage and selection operator (LASSO) was performed on a training dataset (60% of the data) to determine associations between self-reported patient characteristics and COVID-19 diagnosis. Regression coefficients were used to construct the Coronavirus 2019 Identification score (COV19-ID) and the optimal threshold calculated on the validation dataset (20%). Its predictive performance was finally evaluated on a test dataset (20%). RESULTS: A total of 2084 (22.9%) patients were tested positive to SARS-CoV-2 infection. Using the LASSO model, COVID-19 was independently associated with loss of smell (Odds Ratio, 6.4), fever (OR, 2.7), history of contact with an infected person (OR, 1.7), loss of taste (OR, 1.5), muscle stiffness (OR, 1.5), cough (OR, 1.5), back pain (OR, 1.4), loss of appetite (OR, 1.3), as well as male sex (OR, 1.05). Conversely, COVID-19 was less likely associated with smoking (OR, 0.5), sore throat (OR, 0.9) and ear pain (OR, 0.9). All aforementioned variables were included in the COV19-ID score, which demonstrated on the test dataset an area under the receiver-operating characteristic curve of 82.9% (95% CI 80.6%-84.9%), and an accuracy of 74.2% (95% CI 74.1%-74.3%) with a high sensitivity (80.4%, 95% CI [80.3%-80.6%]) and specificity (72.2%, 95% CI [72.2%-72.4%]). CONCLUSIONS: The COV19-ID score could be useful in early triage of patients needing RT-PCR testing thus alleviating the burden on laboratories, emergency rooms, and wards.

Specchio-COVID19 cohort study: a longitudinal follow-up of SARS-CoV-2 serosurvey participants in the canton of Geneva, Switzerland.

INTRODUCTION: 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 COVID-19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. The 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. This follow-up aims at monitoring COVID-19 related symptoms and SARS-CoV-2 seroconversion, as well as the overall impact of the pandemic on several dimensions of health and on socioeconomic factors over a period of at least 2 years. METHODS AND ANALYSIS: Serosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/). On registration, an initial questionnaire assessed sociodemographic 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, hospitalisations). 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, healthcare consumption and changes in health behaviours. 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, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the Specchio-COVID-19 platform, social media posts, press releases and through regular scientific dissemination methods (open-access articles, conferences).

Association between SARS-CoV-2 Seroprevalence in Nursing Home Staff and Resident COVID-19 Cases and Mortality: A Cross-Sectional Study.

The burden of COVID-19 has disproportionately impacted the elderly, who are at increased risk of severe disease, hospitalization, and death. This cross-sectional study aimed to assess the association between SARS-CoV-2 seroprevalence among nursing home staff, and cumulative incidence rates of COVID-19 cases, hospitalizations, and deaths among residents. Staff seroprevalence was estimated within the SEROCoV-WORK+ study between May and September 2020 across 29 nursing homes in Geneva, Switzerland. Data on nursing home residents were obtained from the canton of Geneva for the period between March and August 2020. Associations were assessed using Spearman's correlation coefficient and quasi-Poisson regression models. Overall, seroprevalence among staff ranged between 0 and 31.4%, with a median of 8.3%. A positive association was found between staff seroprevalence and resident cumulative incidence of COVID-19 cases (correlation coefficient R = 0.72, 95%CI 0.45-0.87; incidence rate ratio [IRR] = 1.10, 95%CI 1.07-1.17), hospitalizations (R = 0.59, 95%CI 0.25-0.80; IRR = 1.09, 95%CI 1.05-1.13), and deaths (R = 0.71, 95%CI 0.44-0.86; IRR = 1.12, 95%CI 1.07-1.18). Our results suggest that SARS-CoV-2 transmission between staff and residents may contribute to the spread of the virus within nursing homes. Awareness among nursing home professionals of their likely role in the spread of SARS-CoV-2 has the potential to increase vaccination coverage and prevent unnecessary deaths due to COVID-19.

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

OBJECTIVES: This cohort study including essential workers, assessed the risk and incidence of SARS-CoV-2 infection during the second surge of COVID-19 according to baseline serostatus and occupational sector. METHODS: Essential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralised registry compiling SARS-CoV-2 infections. Primary outcome was the incidence of virologically confirmed infections from serological assessment (between May and September 2020) to 25 January 2021, according to baseline antibody status and stratified by three predefined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others). RESULTS: 10 457 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 the follow-up with no significant between-occupational group difference. CONCLUSIONS: A 10-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 6 months after infection.

Seroprevalence of anti-SARS-CoV-2 antibodies 6 months into the vaccination campaign in Geneva, Switzerland, 1 June to 7 July 2021.

BackgroundUp-to-date seroprevalence estimates are critical to describe the SARS-CoV-2 immune landscape and to guide public health decisions.AimWe estimate seroprevalence of anti-SARS-CoV-2 antibodies 15 months into the COVID-19 pandemic and 6 months into the vaccination campaign.MethodsWe conducted a population-based cross-sectional serosurvey between 1 June and 7 July 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 using the 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).ResultsAmong 3,355 individuals (54.1% women; 20.8% aged < 18 years and 13.4% aged ≥ 65 years), 2,161 (64.4%) had anti-S antibodies and 906 (27.0%) had anti-N antibodies. The total seroprevalence was 66.1% (95% credible interval (CrI): 64.1-68.0). We estimated that 29.9% (95% Crl: 28.0-31.9) of the population developed antibodies after infection; the rest having developed antibodies via vaccination. Seroprevalence estimates differed markedly across age groups, being lowest among children aged 0-5 years (20.8%; 95% Crl: 15.5-26.7) and highest among older adults aged ≥ 75 years (93.1%; 95% Crl: 89.6-96.0). Seroprevalence of antibodies developed via infection and/or vaccination was higher among participants with higher educational level.ConclusionMost of the population has developed anti-SARS-CoV-2 antibodies, despite most teenagers and children remaining 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 to minimise spread among children.

Persistence of anti-SARS-CoV-2 antibodies: immunoassay heterogeneity and implications for serosurveillance.

OBJECTIVES: Serological studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-CoV-2 infections as a function of time since infection for three commercially available SARS-CoV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence. METHODS: We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n = 354) at least 8 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays: Roche-N, Roche-RBD and EuroImmun-S1. We developed a latent class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates. RESULTS: Antibodies were detected at follow-up in 74-100% of participants, depending on immunoassays. Both Roche assays maintain high sensitivity, with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. DISCUSSION: Antibodies persist for at least 8 months after infection in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay performance adjustment is important for the interpretation of serological studies in the case of diminishing sensitivity after infection.

Large variation in anti-SARS-CoV-2 antibody prevalence among essential workers in Geneva, Switzerland.

Limited data exist on SARS-CoV-2 infection rates across sectors and occupations, hindering our ability to make rational policy, including vaccination prioritization, to protect workers and limit SARS-CoV-2 spread. Here, we present results from our SEROCoV-WORK + study, a serosurvey of workers recruited after the first wave of the COVID-19 pandemic in Geneva, Switzerland. We tested workers (May 18-September 18, 2020) from 16 sectors and 32 occupations for anti-SARS-CoV-2 IgG antibodies. Of 10,513 participants, 1026 (9.8%) tested positive. The seropositivity rate ranged from 4.2% in the media sector to 14.3% in the nursing home sector. We found considerable within-sector variability: nursing home (0%-31.4%), homecare (3.9%-12.6%), healthcare (0%-23.5%), public administration (2.6%-24.6%), and public security (0%-16.7%). Seropositivity rates also varied across occupations, from 15.0% among kitchen staff and 14.4% among nurses, to 5.4% among domestic care workers and 2.8% among journalists. Our findings show that seropositivity rates varied widely across sectors, between facilities within sectors, and across occupations, reflecting a higher exposure in certain sectors and occupations.

Unenhanced computed tomography (CT) utility for triage at the emergency department during COVID-19 pandemic.

BACKGROUND: Unenhanced chest computed tomography (CT) can assist in the diagnosis and classification of coronavirus disease 2019 (COVID-19), complementing to the reverse-transcription polymerase chain reaction (RT-PCR) tests; the performance of which has yet to be validated in emergency department (ED) setting. The study sought to evaluate the diagnostic performance of chest CT in the diagnosis and management of COVID-19 in ED. METHODS: This retrospective single-center study included 155 patients in ED who underwent both RT-PCR and chest CT for suspected COVID-19 from March 1st to April 1st, 2020. The clinical information, CT images and laboratory reports were reviewed and the performance of CT was assessed, using the RT-PCR as standard reference. Moreover, an adjudication committee retrospectively rated the probability of COVID-19 before and after the CT calculating the net reclassification improvement (NRI). Their final diagnosis was considered as reference. The proportion of patients with negative RT-PCR test that was directed to the referent hospital based on positive CT findings was also assessed. RESULTS: Among 155 patients, 42% had positive RT-PCR results, and 46% had positive CT findings. Chest CT showed a sensitivity of 84.6%, a specificity of 80.0% and a diagnostic accuracy of 81.9% in suggesting COVID-19 with RT-PCR as reference. Concurrently, corresponding values of 89.4%, 84.3% and 86.5% were retrieved with the adjudication committee diagnosis as reference. For the subgroup of patients with age > 65, specificity and sensitivity were 50% and 80.8%, respectively. In patients with negative RT-PCR results, 20% (18/90) had positive chest CT finding and 22% (4/18) of those were eventually considered as COVID-19 positive according to the adjudication committee. After CT, the estimated probability of COVID-19 changed in 10/104 (11%) patients with available data: 4 (4%) were downgraded, 6 (6%) upgraded. The NRI was 1.92% (NRI event -2.08% + NRI non-event 5.36%). No patient with negative RT-PCR but positive CT was eventually directed to hospital. CONCLUSION: Chest CT showed promising sensitivity for diagnosing COVID-19 across all patients' subgroups. However, CT did not modify the estimated probability of COVID-19 infection in a substantial proportion of patients and its utility as an emergency department triage tool warrants further analyses.

Computed tomography (CT) utility for diagnosis and triage during COVID-19 pandemic / Utilite du CT-scan thoracique pour le diagnostic et le triage des patients suspects de COVID-19

The nasopharyngeal smear with PCR analysis is the first diagnostic test proposed to confirm infection with COVID-19 SARS-CoV-2. However, its usefulness in emergency centers is limited due to its imperfect sensitivity (56-83 %), limited availability and the time required to obtain results. For this reason, the chest CT-scan has been proposed as a rapid triage tool for diagnosis in these suspect Covid-19 patients. However, its specificity is limited, exposing to the risk of over-diagnosis, and further data are needed to confirm its usefulness, and to highlight the possible prognostic value of the CT, in detecting early lesions associated with poor outcome, indicating the need for admission to intensive care. Le frottis nasopharynge avec analyse par PCR est le premier test diagnostique propose pour confirmer une infection a SARS-CoV-2, virus de la maladie COVID-19. Son utilite dans les centres durgence est cependant limitee du fait de sa sensibilite imparfaite (56 a 83 %), de sa disponibilite restreinte et du delai pour lobtention des resultats. Aussi, le CT-scan thoracique a ete propose comme outil de triage rapide pour poser le diagnostic chez ces patients suspects de COVID-19. Toutefois, sa specificite est limitee, exposant au risque de surdiagnostic. Des donnees complementaires sont necessaires pour confirmer son utilite et lui attribuer une eventuelle valeur pronostique, capable de deceler des lesions associees a une mauvaise evolution, indiquant la necessite dune admission aux soins intensifs.