Publications by authors named "Laurent Kaiser"

227 Publications

SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1.

Eur J Clin Invest 2021 Jul 29:e13661. Epub 2021 Jul 29.

Division of Laboratory Medicine, Department of Diagnostics and of Medical Specialties, Geneva University Hospitals and Geneva University, Geneva, Switzerland.

Objectives: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining i) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response, and ii) the degree of linear homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes.

Methods: Bio-informatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126), and a general population cohort (n=663) with available samples in the pre and post-pandemic period.

Results: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2, and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than non-exposed ones (34% vs 16.8%; p=0.004).

Conclusion: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
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http://dx.doi.org/10.1111/eci.13661DOI Listing
July 2021

Persistence of anti-sars-cov-2 antibodies: immunoassay heterogeneity and implications for serosurveillance.

Clin Microbiol Infect 2021 Jul 7. Epub 2021 Jul 7.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA; Unit of Population Epidemiology, Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland; Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

Objectives: Serologic 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 3 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) through 9 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 persisted at follow-up in 74% to 100% of participants, depending on immunoassays. Model estimates indicate that 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.

Conclusions: Antibodies persist after 9 months in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay-performance-adjustment are important for the interpretation of serologic studies in the case of decaying sensitivity after infection.
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http://dx.doi.org/10.1016/j.cmi.2021.06.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261139PMC
July 2021

SARS-CoV-2 rapid diagnostic tests for emerging variants.

Lancet Microbe 2021 Jun 29. Epub 2021 Jun 29.

Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1016/S2666-5247(21)00147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241290PMC
June 2021

Identifying adults with acute rhinosinusitis in primary care that benefit most from antibiotics: protocol of an individual patient data meta-analysis using multivariable risk prediction modelling.

BMJ Open 2021 Jul 1;11(7):e047186. Epub 2021 Jul 1.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: Acute rhinosinusitis (ARS) is a prime reason for doctor visits and among the conditions with highest antibiotic overprescribing rates in adults. To reduce inappropriate prescribing, we aim to predict the absolute benefit of antibiotic treatment for individual adult patients with ARS by applying multivariable risk prediction methods to individual patient data (IPD) of multiple randomised placebo-controlled trials.

Methods And Analysis: This is an update and re-analysis of a 2008 IPD meta-analysis on antibiotics for adults with clinically diagnosed ARS. First, the reference list of the 2018 Cochrane review on antibiotics for ARS will be reviewed for relevant studies published since 2008. Next, the systematic searches of CENTRAL, MEDLINE and Embase of the Cochrane review will be updated to 1 September 2020. Methodological quality of eligible studies will be assessed using the Cochrane Risk of Bias 2 tool. The primary outcome is cure at 8-15 days. Regression-based methods will be used to model the risk of being cured based on relevant predictors and treatment, while accounting for clustering. Such model allows for risk predictions as a function of treatment and individual patient characteristics and hence gives insight into individualised absolute benefit. Candidate predictors will be based on literature, clinical reasoning and availability. Calibration and discrimination will be evaluated to assess model performance. Resampling techniques will be used to assess internal validation. In addition, internal-external cross-validation procedures will be used to inform on between-study differences and estimate out-of-sample model performance. Secondarily, we will study possible heterogeneity of treatment effect as a function of outcome risk.

Ethics And Dissemination: In this study, no identifiable patient data will be used. As such, the Medical Research Involving Humans Subject Act (WMO) does not apply and official ethical approval is not required. Results will be submitted for publication in international peer-reviewed journals.

Prospero Registration Number: CRD42020220108.
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http://dx.doi.org/10.1136/bmjopen-2020-047186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252877PMC
July 2021

Diagnostic accuracy of SARS-CoV-2 rapid antigen detection testing in symptomatic and asymptomatic children in the clinical setting.

J Clin Microbiol 2021 Jun 30:JCM0099121. Epub 2021 Jun 30.

Pediatric Emergency Department, Child and Adolescent Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.

Antigen-based rapid diagnostic tests (RDTs) are used in children despite the lack of data. We evaluated the diagnostic performance of the Panbio-COVID-19 Ag Rapid Test Device (P-RDT) in children. Symptomatic and asymptomatic participants 0-16yo had two NPS for both RT-PCR and P-RDT 822 participants completed the study, of which 533 (64.9%) were symptomatic. Among the 119 (14.5%) RT-PCR-positive patients, the P-RDT sensitivity was 0.66 (95%CI 0.57-0.74). Mean viral load (VL) was higher among P-RDT-positive than negative ones (p<0.001). Sensitivity was 0.91 in specimens with VL>1.0E6 IU/mL (95%CI 0.83-0.99), and decreased to 0.75 (95%CI 0.66-0.83) for specimens >1.0E3 IU/mL. Among symptomatic participants, the P-RDT displayed a sensitivity of 0.73 (95%CI 0.64-0.82), which peaked at 1.00 at 2 days post-onset of symptoms (DPOS; 95%CI 1.00-1.00), then decreased to 0.56 (95%CI 0.23-0.88) at 5 DPOS. There was a trend towards lower P-RDT sensitivity in symptomatic children <12 years (0.62 [95%CI 0.45-0.78]) versus ≥12 years (0.80 [95%CI 0.69-0.91]; p=0.09). In asymptomatic participants, the P-RDT displayed a sensitivity of 0.43 (95%CI 0.26-0.61). Specificity was 1.00 in symptomatic and asymptomatic children (95%CI 0.99-1.00). . The overall respective 73% and 43% sensitivities of P-RDT in symptomatic and asymptomatic children was below the 80% cut-off recommended by the WHO. We observed a correlation between VL and P-RDT sensitivity as well as variation of sensitivity according to DPOS, a major determinant of VL. These data highlight the limitations of RDTs in children, with the potential exception in early symptomatic children ≥12yrs.
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http://dx.doi.org/10.1128/JCM.00991-21DOI Listing
June 2021

Diagnostic accuracy of Panbio rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2.

PLoS One 2021 24;16(6):e0253321. Epub 2021 Jun 24.

Infectious Disease Division, Geneva University Hospitals, Geneva, Switzerland.

Background: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients.

Methods: We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland.

Results: 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS.

Interpretation: Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224876PMC
July 2021

Development and validation of the OUTCoV score to predict the risk of hospitalisation among patients with SARS-CoV-2 infection in ambulatory settings: a prospective cohort study.

BMJ Open 2021 06 18;11(6):e044242. Epub 2021 Jun 18.

Division of Primary Care, Geneva University Hospitals, Geneva, Switzerland.

Objectives: To develop and validate a rule-out prediction model for the risk of hospitalisation among patients with SARS-CoV-2 infection in the ambulatory setting to derive a simple score to determine outpatient follow-up.

Design: Prospective cohort study.

Setting: Swiss university hospital.

Participants: 1459 individuals with a positive result for SARS-CoV-2 infection between 2 March and 23 April 2020.

Methods: We applied the rule of 10 events per variable to construct our multivariable model and included a maximum of eight covariates. We assessed the model performance in terms of discrimination and calibration and performed internal validation to estimate the statistical optimism of the final model. The final prediction model included age, fever, dyspnoea, hypertension and chronic respiratory disease. To develop the OUTCoV score, we assigned points for each predictor that were proportional to the coefficients of the regression equation. Sensitivity, specificity, positive and negative likelihood ratios were estimated, including positive and negative predictive values in different thresholds.

Main Outcome Measure: The primary outcome was COVID-19-related hospitalisation.

Results: The OUTCoV score ranged from 0 to 7.5 points. The two threshold parameters with optimal rule-out and rule-in characteristics for the risk of hospitalisation were 3 and 5.5, respectively. Outpatients with a score <3 (997/1459; 68.3%) had no follow-up as at low risk of hospitalisation (1.8%; 95% CI 1.1 to 2.8). For a score ≥5.5 (20/1459; 1.4%), the hospitalisation risk was higher (30%; 95% CI 11.9 to 54.3).

Conclusions: The OUTCoV score allows to rule out two-thirds of outpatients with SARS-CoV-2 infection presenting a low hospitalisation risk and to identify those at high risk that require careful follow-up to assess the need for hospitalisation. The model provides a simple decision-making tool for an effective allocation of resources to maintain quality care for outpatient populations.
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http://dx.doi.org/10.1136/bmjopen-2020-044242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214986PMC
June 2021

Insights into household transmission of SARS-CoV-2 from a population-based serological survey.

Nat Commun 2021 06 15;12(1):3643. Epub 2021 Jun 15.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Understanding the risk of infection from household- and community-exposures and the transmissibility of asymptomatic infections is critical to SARS-CoV-2 control. Limited previous evidence is based primarily on virologic testing, which disproportionately misses mild and asymptomatic infections. Serologic measures are more likely to capture all previously infected individuals. We apply household transmission models to data from a cross-sectional, household-based population serosurvey of 4,534 people ≥5 years from 2,267 households enrolled April-June 2020 in Geneva, Switzerland. We found that the risk of infection from exposure to a single infected household member aged ≥5 years (17.3%,13.7-21.7) was more than three-times that of extra-household exposures over the first pandemic wave (5.1%,4.5-5.8). Young children had a lower risk of infection from household members. Working-age adults had the highest extra-household infection risk. Seropositive asymptomatic household members had 69.4% lower odds (95%CrI,31.8-88.8%) of infecting another household member compared to those reporting symptoms, accounting for 14.5% (95%CrI, 7.2-22.7%) of all household infections.
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http://dx.doi.org/10.1038/s41467-021-23733-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206123PMC
June 2021

Feasibility and safety of rVSV-ZEBOV vaccination of humanitarian health workers against Ebola virus disease: an observational study.

J Travel Med 2021 Jun 15. Epub 2021 Jun 15.

Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 6, Geneva 1205, Switzerland.

Background And Rationale: Geneva University Hospitals were granted a temporary authorization to administer the recombinant live vesicular stomatitis virus rVSV-ZEBOV (Ervebo®) vaccine to expatriate humanitarian frontline workers (FLWs) prior to mission deployment.

Objectives: Our aims were to assess the feasibility of FLW vaccination before deployment and to report adverse events (AEs).

Methods: FLWs received a single injection of rVSV-ZEBOV (>7.2E7 plaque forming unit) during their pre-deployment medical check-up at the Travel Medicine Clinic of the Geneva University Hospitals (Day 0). A safety questionnaire regarding potential AEs was emailed to FLWs on Days 3 and 21. Early and delayed AEs were those starting within 3 or 21 days of vaccination, respectively.

Results: Between 1 August 2019 and 30 June 2020, 124 FLWs received the rVSV-ZEBOV vaccine. Eighty-six volunteers (86/124; 69%) received a concomitant vaccine. The response rate to the follow-up questionnaire was 88 and 55% at Days 3 and 21, respectively. Most respondents (105/109; 96.3%), experienced at least one AE, with a mean of three (±SD 1.75) AEs per person. The most common AE was injection site pain, followed by fever (53/109; 48.6%), fatigue (51/109; 46.7%) and myalgia (49/109; 44.9%). Most early AEs (360/377; 95.4%) resolved within 3 days, reflecting vaccine reactogenicity. Delayed AEs were reported by 6/69 (7.2%) subjects, the median time to symptom onset was 11 days (range: 5-14); half of them were joint-related AEs (3/6). Four serious adverse events (SAE) were observed: two cases of high grade fever, one rash and one case of arthritis. Two suspected unexpected serious adverse reactions were observed: one case of continuing recurrent transient dizziness and fatigue considered related to the vaccine; and one case of presbyopia that was deemed unrelated.

Conclusion: AEs to rVSV-ZEBOV were common but in general transient and were well tolerated, pre-deployment rVSV-ZEBOV vaccination in FLW is feasible and can be included with pre-mission check-up.
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http://dx.doi.org/10.1093/jtm/taab086DOI Listing
June 2021

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

Nat Commun 2021 06 8;12(1):3455. Epub 2021 Jun 8.

Department of Health and Community Medicine, Faculty of Medicine, University of Geneva, 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.
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http://dx.doi.org/10.1038/s41467-021-23796-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187639PMC
June 2021

Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study.

Clin Infect Dis 2021 May 27. Epub 2021 May 27.

Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland.

Background: Serological assays detecting anti-SARS-CoV-2 antibodies are being widely deployed in studies and clinical practice. However, the duration and effectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals as compared to seronegative controls we conducted a retrospective longitudinal matched study.

Methods: A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland between April and June 2020, immediately after the first pandemic wave. Seropositive participants were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, BMI, smoking status and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confirmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021).

Results: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (SD 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of whom 5 (1.0%) were classified as reinfections. In contrast, the infection rate was higher in seronegative individuals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95%CI 86% to 98%, P<0.001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives.

Conclusions: Seroconversion after SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.
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http://dx.doi.org/10.1093/cid/ciab495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241483PMC
May 2021

Novel SARS-CoV-2 variants: the pandemics within the pandemic.

Clin Microbiol Infect 2021 May 17. Epub 2021 May 17.

Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, 1205 Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals & Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.

Background: Many new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been termed variants of concern/interest (VOC/I) because of the greater risk they pose due to possible enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy.

Aims: We sought to review the current knowledge of emerging SARS-CoV-2 variants, particularly those deemed VOC/Is: B.1.351, B.1.1.7, and P.1.

Sources: MEDLINE and BioRxiv databases, as well as the grey literature, were searched for reports of SARS-CoV-2 variants since November 2020. Relevant articles and their references were screened.

Content: Mutations on the spike protein in particular may affect both affinity for the SARS-CoV-2 cell receptor ACEII and antibody binding. These VOC/Is often share similar mutation sets. The N501Y mutation is shared by the three main VOCs: B.1.1.7, first identified in the United Kingdom, P.1, originating from Brazil, and B.1.351, first described in South Africa. This mutation likely increases transmissibility by increasing affinity for ACEII. The B.1.351 and P.1 variants also display the E484K mutation which decreases binding of neutralizing antibodies, leading to partial immune escape; this favours reinfections, and decreases the in vitro efficacy of some antibody therapies or vaccines. Those mutations may also have phenotypical repercussions of greater severity. Furthermore, the accumulation of mutations poses a diagnostic risk (lowered when using multiplex assays), as seen for some assays targeting the S gene. With ongoing surveillance, many new VOC/Is have been identified. The emergence of the E484K mutation independently in different parts of the globe may reflect the adaptation of SARS-CoV-2 to humans against a background of increasing immunity.

Implications: These VOC/Is are increasing in frequency globally and pose challenges to any herd immunity approach to managing the pandemic. While vaccination is ongoing, vaccine updates may be prudent. The virus continues to adapt to transmission in humans, and further divergence from the initial Wuhan sequences is expected.
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http://dx.doi.org/10.1016/j.cmi.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127517PMC
May 2021

SARS-CoV-2 viral load kinetics in symptomatic children, adolescents and adults.

Clin Infect Dis 2021 May 5. Epub 2021 May 5.

Department of Molecular Medicine and Microbiology, Faculty of Medicine, Université de Genève, Geneva, Switzerland.

SARS-CoV-2 viral load (VL) can serve as a correlate for infectious virus presence and transmission. Viral shedding kinetics over the first week of illness for symptomatic children (n=279), adolescents (n=639) and adults (n=7109) show VLs compatible with infectious virus presence, with slightly lower VL in children than adults.
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http://dx.doi.org/10.1093/cid/ciab396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135785PMC
May 2021

Analytical Evaluation of Visby Medical RT-PCR Portable Device for Rapid Detection of SARS-CoV-2.

Diagnostics (Basel) 2021 Apr 29;11(5). Epub 2021 Apr 29.

Laboratory of Virology, Laboratory Medicine Division, Diagnostic Department, Geneva University Hospitals, CH-1211 Geneva, Switzerland.

Extended community testing constitutes one of the main strategic pillars in controlling the COVID-19 pandemic. Reverse transcription PCR (RT-PCR) targeting the SARS-CoV-2 genome on nasopharyngeal swab samples is currently the reference test. While displaying excellent analytical sensitivity and specificity, this test is costly, often requires a substantial turnaround time, and, more importantly, is subject to reagent and other material shortages. To complement this technology, rapid antigen tests have been developed and made available worldwide, allowing cheap, quick, and decentralized SARS-CoV-2 testing. The main drawback of these tests is the reduced sensitivity when RT-PCR is the gold standard. In this study, we evaluate Visby an innovative, portable, easy-to-use RT-PCR point-of-care (POC) diagnostic device. Our retrospective analysis shows that overall, compared to the Cobas 6800 RT-qPCR assay (Roche), this RT-PCR POC technology detects SARS-CoV-2 RNA with 95% sensitivity (95%CI = 86.3-99%) and 100% specificity (95% CI = 80.5-100%). For samples with cycle-threshold values below 31, we observed 100% sensitivity (95% CI = 66.4-100%). While showing an analytical sensitivity slightly below that of a standard RT-qPCR system, the evaluated Visby RT-PCR POC device may prove to be an interesting diagnostic alternative in the COVID-19 pandemic, potentially combining the practical advantages of rapid antigen tests and the robust analytical performances of nucleic acid detection systems.
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http://dx.doi.org/10.3390/diagnostics11050813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146445PMC
April 2021

A high-throughput microfluidic nanoimmunoassay for detecting anti-SARS-CoV-2 antibodies in serum or ultralow-volume blood samples.

Proc Natl Acad Sci U S A 2021 05;118(18)

Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland;

Novel technologies are needed to facilitate large-scale detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies in human blood samples. Such technologies are essential to support seroprevalence studies and vaccine clinical trials, and to monitor quality and duration of immunity. We developed a microfluidic nanoimmunoassay (NIA) for the detection of anti-SARS-CoV-2 IgG antibodies in 1,024 samples per device. The method achieved a specificity of 100% and a sensitivity of 98% based on the analysis of 289 human serum samples. To eliminate the need for venipuncture, we developed low-cost, ultralow-volume whole blood sampling methods based on two commercial devices and repurposed a blood glucose test strip. The glucose test strip permits the collection, shipment, and analysis of 0.6 μL of whole blood easily obtainable from a simple finger prick. The NIA platform achieves high throughput, high sensitivity, and specificity based on the analysis of 289 human serum samples, and negligible reagent consumption. We furthermore demonstrate the possibility to combine NIA with decentralized and simple approaches to blood sample collection. We expect this technology to be applicable to current and future SARS-CoV-2 related serological studies and to protein biomarker analysis in general.
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http://dx.doi.org/10.1073/pnas.2025289118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106336PMC
May 2021

Blood virosphere in febrile Tanzanian children.

Emerg Microbes Infect 2021 Dec;10(1):982-993

Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half of the patients (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% rotaviruses, 11% human herpesvirus type 6). Additionally, we report the detection of a large number of viruses (related to arthropod, vertebrate or mammalian viral species) not yet known to cause human infection/disease, highlighting those who should be on the radar, deserve specific attention in the febrile paediatric population and, more broadly, for surveillance of emerging pathogens. ClinicalTrials.gov identifier: NCT02225769.
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http://dx.doi.org/10.1080/22221751.2021.1925161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171259PMC
December 2021

Head-to-Head Evaluation of Five Automated SARS-CoV-2 Serology Immunoassays in Various Prevalence Settings.

J Clin Med 2021 Apr 10;10(8). Epub 2021 Apr 10.

Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and Geneva University, 1211 Geneva, Switzerland.

Purpose: To assess the diagnostic performances of five automated anti-SARS-CoV-2 immunoassays, Epitope (N), Diasorin (S1/S2), Euroimmun (S1), Roche N (N), and Roche S (S-RBD), and to provide a testing strategy based on pre-test probability.

Methods: We assessed the receiver operating characteristic (ROC) areas under the curve (AUC) values, along with the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), of each assay using a validation sample set of 172 COVID-19 sera and 185 negative controls against a validated S1-immunofluorescence as a reference method. The three assays displaying the highest AUCs were selected for further serodetection of 2033 sera of a large population-based cohort.

Results: In the validation analysis (pre-test probability: 48.1%), Roche N, Roche S and Euroimmun showed the highest discriminant accuracy (AUCs: 0.99, 0.98, and 0.98) with PPVs and NPVs above 96% and 94%, respectively. In the population-based cohort (pre-test probability: 6.2%) these three assays displayed AUCs above 0.97 and PPVs and NPVs above 90.5% and 99.4%, respectively. A sequential strategy using an anti-S assay as screening test and an anti-N as confirmatory assays resulted in a 96.7% PPV and 99.5% NPV, respectively.

Conclusions: Euroimmun and both Roche assays performed equally well in high pre-test probability settings. At a lower prevalence, sequentially combining anti-S and anti-N assays resulted in the optimal trade-off between diagnostic performances and operational considerations.
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http://dx.doi.org/10.3390/jcm10081605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069412PMC
April 2021

SARS-CoV-2 testing strategy: A comparison of restricted and extended strategies in a Swiss outpatient cohort from the community and hospital employees.

PLoS One 2021 22;16(4):e0250021. Epub 2021 Apr 22.

Division of Primary Care, Geneva University Hospitals, Geneva, Switzerland.

Background: Testing is a key measure to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we empirically compared two SARS-CoV-2 testing strategies.

Methods: We used data from a Swiss single-centre, outpatient cohort study (n = 6,331 test results). A "restricted" strategy was applied to individuals with respiratory symptoms and/or fever and selected risk factors, or an epidemiological link and an "extended" strategy included any clinical symptoms without restriction, irrespective of risk factors and exposure. Data on infection, symptoms, viral load were collected during the first wave (March 11-April 21, 2020) and patients were followed up for clinical complications and hospitalisations until August 31, 2020.

Findings: Infection, clinical complications, and hospitalisation rates were lower for those in the extended strategy compared with the restricted strategy (17.2% vs. 25.0%, 12.3% vs. 20.8%, and 0.7% vs. 2.3%). In the whole cohort, participants included in the extended strategy had a lower number of symptoms (3.51 vs. 4.57; p < .001) and visits occurred earlier after symptom onset (0-3 days: 59.2% vs. 44.2%; p < .001). Among positive cases, the viral load was higher for the extended strategy (p < .001).

Conclusions: These findings highlighted the crucial importance to implement a widespread testing strategy to achieve a better understanding of the infection, to mount an effective control response, by capturing people when their viral load is highest. A widespread test strategy should be available without barriers to help break the chains of transmission.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250021PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061911PMC
May 2021

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

Microorganisms 2021 Mar 25;9(4). Epub 2021 Mar 25.

Applied Microbiology Research, Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.
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http://dx.doi.org/10.3390/microorganisms9040677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064472PMC
March 2021

Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study.

PLoS Med 2021 Apr 1;18(4):e1003587. Epub 2021 Apr 1.

Médecins Sans Frontières, Amsterdam, the Netherlands.

Background: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population.

Methods And Findings: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown.

Conclusions: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.
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http://dx.doi.org/10.1371/journal.pmed.1003587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059831PMC
April 2021

Diagnostic accuracy of two commercial SARS-CoV-2 antigen-detecting rapid tests at the point of care in community-based testing centers.

PLoS One 2021 31;16(3):e0248921. Epub 2021 Mar 31.

Division of Infectious Disease, Geneva University Hospitals, Geneva, Switzerland.

Objectives: Determine the diagnostic accuracy of two antigen-detecting rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 at the point of care and define individuals' characteristics providing best performance.

Methods: We performed a prospective, single-center, point of care validation of two Ag-RDT in comparison to RT-PCR on nasopharyngeal swabs.

Results: Between October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioTM Covid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0-91.2). Specificity was 100.0% (95% CI: 99.1-100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7-93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4-100). For individuals presenting with fever 1-5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. Lower sensitivity of 88.2% was seen on the same day of symptom development (day 0).

Conclusions: We provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248921PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011749PMC
April 2021

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroconversion and occupational exposure of employees at a Swiss university hospital: A large longitudinal cohort study.

Infect Control Hosp Epidemiol 2021 Mar 19:1-8. Epub 2021 Mar 19.

Infection Control Program and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.

Background: The dynamics of coronavirus disease 2019 (COVID-19) seroconversion of hospital employees are understudied. We measured the proportion of seroconverted employees and evaluated risk factors for seroconversion during the first pandemic wave.

Methods: In this prospective cohort study, we recruited Geneva University Hospitals employees and sampled them 3 times, every 3 weeks from March 30 to June 12, 2020. We measured the proportion of seroconverted employees and determined prevalence ratios of risk factors for seroconversion using multivariate mixed-effects Poisson regression models.

Results: Overall, 3,421 participants (29% of all employees) were included, with 92% follow-up. The proportion of seroconverted employees increased from 4.4% (95% confidence interval [CI], 3.7%-5.1%) at baseline to 8.5% [(95% CI, 7.6%-9.5%) at the last visit. The proportions of seroconverted employees working in COVID-19 geriatrics and rehabilitation (G&R) wards (32.3%) and non-COVID-19 G&R wards (12.3%) were higher compared to office workers (4.9%) at the last visit. Only nursing assistants had a significantly higher risk of seroconversion compared to office workers (11.7% vs 4.9%; P = .006). Significant risk factors for seroconversion included the use of public transportation (adjusted prevalence ratio, 1.59; 95% CI, 1.25-2.03), known community exposure to severe acute respiratory coronavirus virus 2 (2.80; 95% CI, 2.22-3.54), working in a ward with a nosocomial COVID outbreak (2.93; 95% CI, 2.27-3.79), and working in a COVID-19 G&R ward (3.47; 95% CI, 2.45-4.91) or a non-COVID-19 G&R ward (1.96; 95% CI, 1.46-2.63). We observed an association between reported use of respirators and lower risk of seroconversion (0.73; 95% CI, 0.55-0.96).

Conclusion: Additional preventive measures should be implemented to protect employees in G&R wards. Randomized trials on the protective effect of respirators are urgently needed.
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http://dx.doi.org/10.1017/ice.2021.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082127PMC
March 2021

Clinical, virologic and immunologic features of a mild case of SARS-CoV-2 reinfection.

Clin Microbiol Infect 2021 Feb 20. Epub 2021 Feb 20.

Geneva Centre for Emerging Viral Diseases, Geneva, Switzerland; Laboratory of Virology, Division of Laboratory Medicine, Geneva, Switzerland.

Objectives: To report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection 6 months after the first infection in a young healthy female physician. Both episodes led to mild coronavirus disease 2019 (COVID-19).

Methods: SARS-CoV-2 infections were detected by real-time reverse transcriptase PCR (RT-PCR) on nasopharyngeal specimens. Reinfection was confirmed by whole-genome sequencing. Kinetics of total anti-S receptor binding domain immunoglobulins (Ig anti-S RBD), anti-nucleoprotein (anti-N) and neutralizing antibodies were determined in serial serum samples retrieved during both infection episodes. Memory B-cell responses were assessed at day 12 after reinfection.

Results: Whole-genome sequencing identified two different SARS-CoV-2 genomes both belonging to clade 20A, with only one nonsynonymous mutation in the spike protein and clustered with viruses circulating in Geneva (Switzerland) at the time of each of the corresponding episodes. Seroconversion was documented with low levels of total Ig anti-S RBD and anti-N antibodies at 1 month after the first infection, whereas neutralizing antibodies quickly declined after the first episode and then were boosted by the reinfection, with high titres detectable 4 days after symptom onset. A strong memory B-cell response was detected at day 12 after onset of symptoms during reinfection, indicating that the first episode elicited cellular memory responses.

Conclusions: Rapid decline of neutralizing antibodies may put medical personnel at risk of reinfection, as shown in this case. However, reinfection leads to a significant boosting of previous immune responses. Larger cohorts of reinfected subjects with detailed descriptions of their immune responses are needed to define correlates of protection and their duration after infection.
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http://dx.doi.org/10.1016/j.cmi.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896115PMC
February 2021

Socioeconomically Disadvantaged Neighborhoods Face Increased Persistence of SARS-CoV-2 Clusters.

Front Public Health 2020;8:626090. Epub 2021 Jan 27.

Geneva University Hospitals, Geneva, Switzerland.

To investigate the association between socioeconomic deprivation and the persistence of SARS-CoV-2 clusters. We analyzed 3,355 SARS-CoV-2 positive test results in the state of Geneva (Switzerland) from February 26 to April 30, 2020. We used a spatiotemporal cluster detection algorithm to monitor SARS-CoV-2 transmission dynamics and defined spatial cluster persistence as the time in days from emergence to disappearance. Using spatial cluster persistence measured outcome and a deprivation index based on neighborhood-level census socioeconomic data, stratified survival functions were estimated using the Kaplan-Meier estimator. Population density adjusted Cox proportional hazards (PH) regression models were then used to examine the association between neighborhood socioeconomic deprivation and persistence of SARS-CoV-2 clusters. SARS-CoV-2 clusters persisted significantly longer in socioeconomically disadvantaged neighborhoods. In the Cox PH model, the standardized deprivation index was associated with an increased spatial cluster persistence (hazard ratio [HR], 1.43 [95% CI, 1.28-1.59]). The adjusted tercile-specific deprivation index HR was 1.82 [95% CI, 1.56-2.17]. The increased risk of infection of disadvantaged individuals may also be due to the persistence of community transmission. These findings further highlight the need for interventions mitigating inequalities in the risk of SARS-CoV-2 infection and thus, of serious illness and mortality.
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http://dx.doi.org/10.3389/fpubh.2020.626090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894360PMC
March 2021

Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo.

Adv Sci (Weinh) 2021 Feb 14;8(3):2001012. Epub 2020 Dec 14.

Insitute of Materials École Polytechnique Fédérale de Lausanne Station 12 Lausanne 1015 Switzerland.

Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is high. It is important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, that is, irreversibly inhibit viral infectivity. Here, a new class of broad-spectrum anti-influenza macromolecules is described that meets these criteria and display exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated either in 6'sialyl--acetyllactosamine (6'SLN) or in 3'SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, it is shown that, in mice, one of the compounds provides therapeutic efficacy when administered 24 h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir.
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http://dx.doi.org/10.1002/advs.202001012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856883PMC
February 2021

Viral co-infections among SARS-CoV-2-infected children and infected adult household contacts.

Eur J Pediatr 2021 Jun 27;180(6):1991-1995. Epub 2021 Jan 27.

Laboratory of Virology, Geneva University Hospitals and Faculty of Medicine, 1211, Geneva, Switzerland.

We evaluated the rates of viral respiratory co-infections among SARS-CoV-2-infected children. Twelve percent of SARS-CoV-2-infected children had viral co-infection with one or more common respiratory viruses. This was significantly more frequent than among their SARS-CoV-2-infected adult household contacts (0%; p=0.028). Compared to the same period the previous year, common respiratory viruses were less frequently detected (12% vs 73%, p<0.001).Conclusion: Despite partial lockdown with school and daycare closure, and consequently similar exposure to common viruses between children and adults, SARS-CoV-2-infected children had more frequent viral respiratory co-infections than their SARS-CoV-2-infected adult household contacts. Circulation of common respiratory viruses was less frequent during the SARS-CoV-2 outbreak when compared to the same period last year, showing the impact of partial lockdown on the circulation of common viruses. What is Known: • Viral respiratory co-infections are frequent in children. • SARS-CoV-2 can be identified alongside other respiratory viruses, but data comparing children and adults are lacking. What is New: • Children infected with SARS-CoV-2 are more likely to have viral respiratory co-infections than their SARS-CoV-2-infected adult household contacts, which is surprising in the context of partial lockdown with schools and daycare closed. • When compared to data collected during the same period last year, our study also showed that partial lockdown reduced circulation of common respiratory viruses.
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http://dx.doi.org/10.1007/s00431-021-03947-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838463PMC
June 2021

Puumala Virus Infection in Family, Switzerland.

Emerg Infect Dis 2021 02;27(2):658-660

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.
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http://dx.doi.org/10.3201/eid2702.203770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853570PMC
February 2021

Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study.

Clin Microbiol Infect 2021 Jan 20. Epub 2021 Jan 20.

Laboratory of Virology, Department of Diagnostics, Geneva University Hospitals and Faculty of Medicine, 4 rue Gabrielle-Perret-Gentil, 1211 Geneve 4, Switzerland; Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Faculty of Medicine, 4 rue Gabrielle-Perret-Gentil, 1211 Geneve 4, Geneva Switzerland; Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals and Faculty of Medicine, 4 rue Gabrielle-Perret-Gentil, 1211 Geneve 4, Switzerland.

Objectives: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19).

Methods: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay.

Results: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2; p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0; p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6; p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4; p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics.

Conclusions: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.
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http://dx.doi.org/10.1016/j.cmi.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816882PMC
January 2021

RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions.

Viruses 2021 Jan 19;13(1). Epub 2021 Jan 19.

Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. A better understanding of their pathogenesis is still needed as there are no approved efficient anti-viral nor vaccine against pneumoviruses. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. Our investigation showed that HMPV is less pathogenic than RSV in this model. Compared to RSV, HMPV replicated less efficiently, induced a lower immune response, did not block cilia beating, and was more sensitive to IFNs. In dual infections, RSV-infected epithelia were less permissive to HMPV. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue. This suggests that interference in dual infection would be at least partly mediated by the host immune response. In summary, this work provides new insight regarding virus-host and virus-virus interactions of pneumoviruses in the airway epithelium. This could be helpful for the proper handling of at-risk patients.
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http://dx.doi.org/10.3390/v13010139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835908PMC
January 2021
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