Factors Associated With COVID-19 Non-Vaccination in Switzerland: A Nationwide Study.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness.

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.

Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

BACKGROUND: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. AIM: To explore the factors associated with the overruling of initial procalcitonin guidance. DESIGN AND SETTING: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. METHOD: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. RESULTS: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03-3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32-9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34-23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18-4.37); and the GP's number of years of experience (aOR per year 1.05, 1.01-1.09). CONCLUSIONS: Overruling of procalcitonin guidance was associated with GPs' socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.

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.

Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

BACKGROUND: Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. METHODS: In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. RESULTS: Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. CONCLUSIONS: RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

SARS-COV-2 SEROPREVALENCE IN EMPLOYEES OF FOUR ESSENTIAL NON-HEALTHCARE SECTORS AT MODERATE/HIGH RISK OF EXPOSURE TO CORONAVIRUS INFECTION: DATA FROM THE "FIRST WAVE".

OBJECTIVE: to evaluate SARS-CoV-2 seroprevalence in Swiss non-healthcare employees at a moderate to high risk of exposure: bus drivers; 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 IgG and IgA targeting the spike protein were measured between May and July 2020. RESULTS: The overall crude seroprevalence estimate (15.9%, 95% CI = 12.6-19.7) among essential workers was not significantly higher than that of the general working-age population (11.2%, 95% CI = 7.1-15.2). Seroprevalence ranged from 11.9% (95% CI = 6.3-19.8) among bus drivers to 22.0% (95% CI = 12.6-19.7) 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.

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.

Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic cluster randomised trial.

OBJECTIVE: To assess whether point-of care procalcitonin and lung ultrasonography can safely reduce unnecessary antibiotic treatment in patients with lower respiratory tract infections in primary care. DESIGN: Three group, pragmatic cluster randomised controlled trial from September 2018 to March 2020. SETTING: 60 Swiss general practices. PARTICIPANTS: One general practitioner per practice was included. General practitioners screen all patients with acute cough; patients with clinical pneumonia were included. INTERVENTIONS: Randomisation in a 1:1:1 of general practitioners to either antibiotics guided by sequential procalcitonin and lung ultrasonography point-of-care tests (UltraPro; n=152), procalcitonin guided antibiotics (n=195), or usual care (n=122). MAIN OUTCOMES: Primary outcome was proportion of patients in each group prescribed an antibiotic by day 28. Secondary outcomes included duration of restricted activities due to lower respiratory tract infection within 14 days. RESULTS: 60 general practitioners included 469 patients (median age 53 years (interquartile range 38-66); 278 (59%) were female). Probability of antibiotic prescription at day 28 was lower in the procalcitonin group than in the usual care group (0.40 v 0.70, cluster corrected difference -0.26 (95% confidence interval -0.41 to -0.10)). No significant difference was seen between UltraPro and procalcitonin groups (0.41 v 0.40, -0.03 (-0.17 to 0.12)). The median number of days with restricted activities by day 14 was 4 days in the procalcitonin group and 3 days in the usual care group (difference 1 day (95% confidence interval -0.23 to 2.32); hazard ratio 0.75 (95% confidence interval 0.58 to 0.97)), which did not prove non-inferiority. CONCLUSIONS: Compared with usual care, point-of-care procalcitonin led to a 26% absolute reduction in the probability of 28 day antibiotic prescription without affecting patients' safety. Point-of-care lung ultrasonography did not further reduce antibiotic prescription, although a potential added value cannot be excluded, owing to the wide confidence intervals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03191071.

[Covid-19 crisis: testing and vaccination in the light of diminishing returns]. / Crise du Covid-19 : le testing et la vaccination à l'aune des rendements décroissants.

At the time of the assessment of the sanitary measures taken to fight the crisis, we have analysed the testing and vaccination following the grid well known in health economics: the law of diminishing returns. In the first phase, the returns are positive and increasing, the increase in benefits being faster than the increase in costs. In the second phase, returns are still positive but decreasing, with costs increasing faster than benefits. In the third and last phase, the returns become negative, with benefits decreasing despite an increase in costs. Both testing and vaccination, which were very beneficial at the beginning of the crisis, progressively followed a trajectory of diminishing returns with the extension of the measures to wider populations (asymptomatic or young persons), or for example with the emergence of the Omicron variant.

À l'heure du bilan des mesures sanitaires prises pour juguler la crise, nous avons soumis le testing et la vaccination à la grille d'analyse connue en économie de la santé : la loi des rendements décroissants. Dans une première phase, les rendements sont positifs et croissants, l'augmentation des bénéfices étant plus rapide que celle des coûts. Dans une deuxième phase, les rendements sont toujours positifs mais décroissants, l'augmentation des coûts étant plus rapide que celle des bénéfices. Dans une troisième et dernière phase, les rendements deviennent négatifs, les bénéfices diminuant malgré une augmentation des coûts. Tant le testing que la vaccination, très bénéfiques au début de la crise, ont progressivement suivi une trajectoire de rendements décroissants avec l'extension des mesures à des populations plus larges (asymptomatiques ou jeunes), ou par exemple avec l'apparition du variant Omicron.

The Corona Immunitas Digital Follow-Up eCohort to Monitor Impacts of the SARS-CoV-2 Pandemic in Switzerland: Study Protocol and First Results

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance.

Expert guidance for COVID-19 vaccine deployment in Switzerland: a Delphi process.

BACKGROUND AND AIM: Vaccines providing protection against COVID-19 are a core tool for ending the pandemic. Though international organisations created guidance in 2020 for vaccine deployment, this had to be adapted for each country's situation and values. We aimed to assist public health decision makers by identifying areas of consensus among Swiss experts for the deployment of one or more novel COVID-19 vaccines. METHODS: An electronic, modified Delphi process between September and November 2020. We recruited a convenience sample of experts working in Switzerland from a variety of specialities, who completed two anonymous questionnaires. They voted on clarification questions and guidance statements from 0 (complete disagreement) to 10 (complete agreement). Responses for guidance statements with a median ≥8 and a lower inter-quartile range bound ≥7 were considered as reaching consensus. RESULTS: Sixty-five experts accepted (66% response rate), with 47 completing the first questionnaire (72%), and 48 the second (74%). Statements reaching consensus included: in the first phase we should vaccinate front-line healthcare professionals and people ≥65 years with risk factors; widespread vaccination of children and adolescents should not be an early priority; and vaccines should be provided free of charge in the setting of national or cantonal vaccination campaigns. Statements not reaching consensus included: early vaccination of people living with someone with risk factors who are not themselves at risk; vaccination of people with previous confirmed or suspected COVID-19; and whether vaccination should be mandatory for individuals with certain activities, such as front-line healthcare professionals. CONCLUSIONS: Experts reached consensus on several statements that were available for decision-makers when making key decisions for COVID-19 vaccine deployment in Switzerland. Statements without consensus highlighted areas requiring expert and public dialogue. The modified Delphi process allowed us to rapidly synthesise views from a broad panel of experts on sensitive topics, and could be considered for a broad range of issues during public health crises.

Caring During COVID-19: Reconfigurations of Gender and Family Relations During the Pandemic in Switzerland.

COVID-19 caused major changes in private and public arenas. Individuals were forced to reorganise their daily lives in response to the restrictive measures imposed by governments. The redistribution of gender roles and the responsibility for care provides an example of the reconfigurations that took place during the pandemic. This article sheds light on the implications of the pandemic for gender inequalities by exploring how care work was reconfigured as women and men sought to protect family members and navigated risks of infection. The study is based on qualitative data - interviews and observations - gathered in an interdisciplinary medical anthropology project. In the article, the authors focus on seven cases selected from a larger corpus to illustrate how reconfigurations of the gendered division of care work within families shifted during the pandemic as men assumed greater moral responsibility for safeguarding family members, without infringing the norms of masculinity. The first part of the article explores the intensification of care activities during lockdown for women living in the Canton de Vaud in Switzerland. The second part centres on the moral responsibility and duty for women and men to protect family members from viral exposure. The results from the study confirm not only that most care activities continued to be delegated to female family members, but also that men's roles evolved. While their safeguarding role can be understood as a new form of caring for men, the findings suggest that it was essentially crisis specific and did not challenge masculinity norms. The extent to which this reconfiguration of gender roles might have a longer-term impact on gender inequalities remains to be seen. Meanwhile, these observations could have important implications for policies aimed at mitigating the medium and long-term effects of the pandemic on gender inequality.

Scoping future outbreaks: a scoping review on the outbreak prediction of the WHO Blueprint list of priority diseases.

BACKGROUND: The WHO's Research and Development Blueprint priority list designates emerging diseases with the potential to generate public health emergencies for which insufficient preventive solutions exist. The list aims to reduce the time to the availability of resources that can avert public health crises. The current SARS-CoV-2 pandemic illustrates that an effective method of mitigating such crises is the pre-emptive prediction of outbreaks. This scoping review thus aimed to map and identify the evidence available to predict future outbreaks of the Blueprint diseases. METHODS: We conducted a scoping review of PubMed, Embase and Web of Science related to the evidence predicting future outbreaks of Ebola and Marburg virus, Zika virus, Lassa fever, Nipah and Henipaviral disease, Rift Valley fever, Crimean-Congo haemorrhagic fever, Severe acute respiratory syndrome, Middle East respiratory syndrome and Disease X. Prediction methods, outbreak features predicted and implementation of predictions were evaluated. We conducted a narrative and quantitative evidence synthesis to highlight prediction methods that could be further investigated for the prevention of Blueprint diseases and COVID-19 outbreaks. RESULTS: Out of 3959 articles identified, we included 58 articles based on inclusion criteria. 5 major prediction methods emerged; the most frequent being spatio-temporal risk maps predicting outbreak risk periods and locations through vector and climate data. Stochastic models were predominant. Rift Valley fever was the most predicted disease. Diseases with complex sociocultural factors such as Ebola were often predicted through multifactorial risk-based estimations. 10% of models were implemented by health authorities. No article predicted Disease X outbreaks. CONCLUSIONS: Spatiotemporal models for diseases with strong climatic and vectorial components, as in River Valley fever prediction, may currently best reduce the time to the availability of resources. A wide literature gap exists in the prediction of zoonoses with complex sociocultural and ecological dynamics such as Ebola, COVID-19 and especially Disease X.

Aetiology of fever in returning travellers and migrants: a systematic review and meta-analysis.

BACKGROUND: Numerous publications focus on fever in returning travellers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines. OBJECTIVES: Primary objectives of this review were (i) to determine the aetiology of fever in travellers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and (ii) to assess the predictors for specific tropical diseases. METHOD: Embase, MEDLINE and Cochrane Library were searched with terms combining fever and travel/migrants. All studies focusing on causes of fever in returning travellers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses. RESULTS: 10 064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5-14, 3-11 and 5-7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants' characteristics, setting, laboratory investigations performed and diseases included. CONCLUSION: Malaria accounted for one-fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travellers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-centre studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.

Corona Immunitas: study protocol of a nationwide program of SARS-CoV-2 seroprevalence and seroepidemiologic studies in Switzerland.

OBJECTIVES: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community. METHODS: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic. RESULTS: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far. CONCLUSIONS: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .

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.

A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma.

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates previous infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific immunoglobulin G titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the ß (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.

Performance of RT-PCR on Saliva Specimens Compared With Nasopharyngeal Swabs for the Detection of SARS-CoV-2 in Children: A Prospective Comparative Clinical Trial.

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.