Publications by authors named "Nicolas Vuilleumier"

129 Publications

SARS-CoV-2 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.

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

Design: Bioinformatics 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 < .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-day 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 nonexposed ones (34% vs 16.8%; P = .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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420318PMC
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; Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Unit of Population Epidemiology, Division of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland. Electronic address:

Objectives: Serological studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-CoV-2 infections as a function of time since infection for three commercially available SARS-CoV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence.

Methods: We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n = 354) at least 8 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays: Roche-N, Roche-RBD and EuroImmun-S1. We developed a latent class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates.

Results: Antibodies were detected at follow-up in 74-100% of participants, depending on immunoassays. Both Roche assays maintain high sensitivity, with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates.

Discussion: Antibodies persist for at least 8 months after infection in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay performance adjustment is important for the interpretation of serological studies in the case of diminishing sensitivity after infection.
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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

Performance of Fully Automated Antimicrobial Disk Diffusion Susceptibility Testing Using Copan WASP Colibri Coupled to the Radian In-Line Carousel and Expert System.

J Clin Microbiol 2021 Aug 18;59(9):e0077721. Epub 2021 Aug 18.

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

The purpose of the present study was to assess the agreement at the categorical level between the Vitek 2 system and the Colibri coupled to the Radian under real routine laboratory conditions. The 675 nonduplicate clinical strains included in this study (249 isolates, 198 Pseudomonas aeruginosa, 107 Staphylococcus aureus, 78 coagulase-negative staphylococci, 38 Enterococcus faecalis, and 5 Enterococcus faecium) were isolated from nonconsecutive clinical samples referred to our laboratory between June and November 2020. In addition, 43 carbapenemase-producing (CPE) formerly identified and stored in our laboratory were added to the panel, for a total of 718 strains. The overall categorical agreements between the two compared methods were 99.3% (4,350/4,380; 95% CI 99% to 99.5%); 98.6% (2,147/2,178; 95% CI 98.0% to 99.0%); 99.4% (1,839/1,850; 95% CI 98.9% to 99.7%); and 99.4% (342/344; 95% CI 97.9% to 99.8%) for , P. aeruginosa, Staphylococcus spp., and spp., respectively. The most important cause of the very major errors encountered on the Vitek 2 for P. aeruginosa (62%, 13/21) was related to the presence of heteroresistant populations. Among the 43 CPE included in this study, one OXA-48-like, and one OXA-181-like were missed by the Vitek 2, even by rigorously applying the CPE screening cutoffs defined by EUCAST. The Colibri coupled to the Radian provide a fully automated solution for antimicrobial disk diffusion susceptibility testing with an accuracy that is equal to or better than that of the Vitek 2 system.
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http://dx.doi.org/10.1128/JCM.00777-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373016PMC
August 2021

Interleukin 8, a Biomarker to Differentiate Guillain-Barré Syndrome From CIDP.

Neurol Neuroimmunol Neuroinflamm 2021 07 17;8(5). Epub 2021 Jun 17.

From the Department of Neurosciences (G.B., A.M.L., P.H.L.), Division of Neurology, Geneva University Hospitals and University of Geneva, Faculty of Medicine, Switzerland; Department of Diagnostic, Division of Laboratory Medicine (P.R.-L., N.V.), Geneva University Hospitals, Switzerland; Department of Medicine (P.R.-L., P.H.L.), Division of Immunology and Allergy (P.R.-L.), Geneva University Hospitals, Switzerland; and Department of Pathology and Immunology (P.H.L.), Faculty of Medicine, University of Geneva, Switzerland.

Objective: To determine whether CSF interleukin 8 (IL-8) concentration can help to distinguish Guillain-Barré syndrome (GBS) from chronic inflammatory demyelinating polyneuropathy (CIDP) at the initial stage of the disease.

Methods: We performed retrospective immunoassay of IL-8 in CSF, collected at the University Hospitals of Geneva between 2010 and 2018, from patients diagnosed with GBS (n = 45) and with CIDP (n = 30) according to the Brighton and European Federation of Neurological Societies/Peripheral Nerve Society criteria by a physician blinded to biological results.

Results: CSF IL-8 was higher in GBS (median: 83.9 pg/mL) than in CIDP (41.0 pg/mL) ( < 0.001). Receiver operating characteristic analyses indicated that the optimal IL-8 cutoff was 70 pg/mL. Above this value, patients were more likely to present GBS than CIDP (specificity 96.7%, sensitivity 64.4%, positive predictive value [PPV] 96.7%, and negative predictive value [NPV] 64.4%). Among GBS subcategories, IL-8 was higher in acute inflammatory demyelinating polyneuropathy (AIDP, median: 101.8 pg/mL) than in other GBS variants (median: 53.7 pg/mL). In addition, with CSF IL-8 above 70 pg/mL, patients were more likely to present AIDP than acute-onset CIDP ( < 0.001; specificity 100%, sensitivity 78.8%, PPV 100%, and NPV 46.2%) or other CIDP with nonacute presentation ( < 0.0001; specificity 95.8%, sensitivity 78.8%, PPV 96.3%, and NPV 76.7%).

Conclusion: CSF IL-8 levels can help to differentiate AIDP variant of GBS from CIDP, including acute-onset CIDP, with high specificity and PPV. This may improve early and appropriate treatment.

Classification Of Evidence: This study provides Class II evidence that CSF IL-8 levels accurately distinguish patients with GBS from those with CIDP.
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http://dx.doi.org/10.1212/NXI.0000000000001031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216426PMC
July 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

Anti-SARS-CoV-2 mRNA vaccine in patients with rheumatoid arthritis.

Lancet Rheumatol 2021 Jul 8;3(7):e470-e472. Epub 2021 Jun 8.

Division of Rheumatology, Kantonsspital St Gallen, St Gallen, Switzerland.

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http://dx.doi.org/10.1016/S2665-9913(21)00186-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186851PMC
July 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

Performances of automated digital imaging of Gram-stained slides with on-screen reading against manual microscopy.

Eur J Clin Microbiol Infect Dis 2021 Oct 8;40(10):2171-2176. Epub 2021 May 8.

Bacteriology Laboratory, Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1205, Geneva, Switzerland.

The objective of this study was to evaluate the performances of the automated digital imaging of Gram-stained slides against manual microscopy. Four hundred forty-three identified Gram-stained slides were included in this study. When both methods agreed, we considered the results as correct, and no further examination was carried out. Whenever the methods gave discrepant results, we reviewed the digital images and the glass slides by manual microscopy to avoid incorrectly read smears. The final result was a consensus of multiple independent reader interpretations. Among the 443 slides analyzed in this study, 101 (22.8%) showed discrepant results between the compared methods. The rates of discrepant results according to the specimen types were 5.7% (9/157) for positive blood cultures, 42% (60/142) for respiratory tract specimens, and 22% (32/144) for sterile site specimens. After a subsequent review of the discrepant slides, the final rate of discrepancies dropped to 7.0% (31/443). The overall agreement between the compared methods and the culture results reached 78% (345/443) and 79% (349/443) for manual microscopy and automated digital imaging, respectively. According to culture results, the specificity for automated digital imaging and manual microscopy were 90.8% and 87.7% respectively. In contrast, sensitivity was 84.1% for the two compared methods. The discrepant results were mostly encountered with microorganism morphologies of rare occurrence. The results reported in this study emphasize that on-screen reading is challenging, since the recognition of morphologies on-screen can appear different as compared to routine manual microscopy. Monitoring of Gram stain errors, which is facilitated by automated digital imaging, remains crucial for the quality control of reported Gram stain results.
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http://dx.doi.org/10.1007/s10096-021-04233-2DOI Listing
October 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

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

Prognostic value of total testosterone levels in patients with acute coronary syndromes.

Eur J Prev Cardiol 2021 04;28(2):235–242

Cardiology Division, Geneva University Hospitals, Switzerland.

Background: Endogenous testosterone levels decrease in men with aging. Controversies persist regarding the screening and treatment of low testosterone levels in patients with acute coronary syndromes (ACS).

Methods And Results: Total serum testosterone levels were measured in 1054 men hospitalized for ACS that were part of a Swiss prospective cohort. Total testosterone levels were classified first in tertiles and using the cut-off of 300 ng/dL. Primary endpoint was all-cause mortality at one year. Cox regression models adjusting for the GRACE score (composite of age, heart rate systolic blood pressure, creatinine, cardiac arrest at admission, ST segment deviation, abnormal troponin enzyme and Killip classification), preexisting diabetes and inflammation (high-sensitivity C-reactive protein). A total of 430 men (40.8%) had total testosterone levels ≤300 ng/dL. Low total testosterone levels were correlated with lower high-density lipoprotein cholesterol and higher triglycerides, high-sensitivity C-reactive protein, high-sensitivity troponin T, N-terminal-pro B-type natriuretic peptide and glucose levels (all p < 0.01). Patients in the lowest testosterone tertile had a mortality rate at one-year of 5.4% compared with 2.9% in the highest tertile with an unadjusted hazard ratio of 1.92 (95% confidence interval 0.96-1.90, p = 0.095) and adjusted hazard ratio of 1.26 (95% confidence interval 0.57-2.78, p = 0.565). In an exploratory analysis, the highest mortality rate (10.3%) was observed in men aged >65 years old belonging to the lowest testosterone tertile.

Conclusion: In this large population of men with ACS, we found a prevalence of low total endogenous testosterone levels of almost 40%. However, low testosterone levels were not significantly associated with mortality after adjustment for high-risk confounders.
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http://dx.doi.org/10.1177/2047487319853343DOI Listing
April 2021

Sphingosine-1-phosphate as a key player of insulin secretion induced by high-density lipoprotein treatment.

Physiol Rep 2021 03;9(6):e14786

Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.

Beta cell failure is one of the most important features of type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) has been proposed to improve β-cell function. However, the mechanisms involved in this process are still poorly understood. The aim of this study was to investigate the contribution of sphingosine-1-phosphate (S1P) in the impact of HDL treatment on insulin secretion by pancreatic β-cells and to determine its mechanisms. Primary cultures of β-cells isolated from rat were treated with or without HDL in the presence or absence of S1P pathway inhibitors and insulin secretion response was analyzed. The S1P content of HDL (HDL-S1P) isolated from T2DM patients was analyzed and correlated to the HDL-induced insulin secretion. The expression of genes involved in the biosynthesis of the insulin was also evaluated. HDL as well as S1P treatment enhanced glucose-stimulated insulin secretion (GSIS). In HDL isolated from T2DM patients, while HDL-S1P was strongly correlated to its pro-secretory capacity (r = 0.633, p = 0.005), HDL-cholesterol and apolipoprotein AI levels were not. HDL-induced GSIS was blocked by the S1P1/3 antagonist but not by the S1P2 antagonist, and was also accompanied by increased intracellular S1P in β-cells. We also observed that HDL improved GSIS without significant changes in expression levels of insulin biosynthesis genes. Our present study highlights the importance HDL-S1P in GSIS in T2DM patients and demonstrates that HDL induces insulin secretion by a process involving both intra- and extra-cellular sources of S1P independently of an effect on insulin biosynthesis genes.
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http://dx.doi.org/10.14814/phy2.14786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995544PMC
March 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

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

Sci Rep 2021 Feb 4;11(1):3100. Epub 2021 Feb 4.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
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http://dx.doi.org/10.1038/s41598-021-82714-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862626PMC
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

Prognostic and therapeutic considerations of antibodies against c-ter apolipoprotein A-1 in the general population.

Clin Transl Immunology 2020 14;9(12):e1220. Epub 2020 Dec 14.

Department of Internal Medicine Lausanne University Hospital Lausanne Switzerland.

Objectives: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgGs) and its C-terminal region (cter apoA1) have emerged as an independent biomarker for cardiovascular disease. Cter apoA1 mimetic peptides were shown to reverse the deleterious anti-apoA1 IgG effects . We evaluated the association of anti-cter apoA1 IgGs with overall mortality in the general population and tested the ability of a cter apoA1 mimetic peptide to reverse the anti-apoA1 IgG-induced inflammatory response and mortality and , respectively.

Methods: Anti-cter apoA1 IgGs were measured in serum samples of 6386 participants of the CoLaus study of which 5220 were followed for a median duration of 5.6 years. The primary outcome was overall mortality. The peptide inhibitory concentration 50% (IC) was determined on HEK-Blue-4 and RAW cells. ApoE mice were exposed to 16 weeks of anti-apoA1IgG passive immunisation with and without peptide co-incubation.

Results: Anti-cter apoA1 IgGs were associated with higher interleukin 6 levels and independently predicted overall mortality; an increase of one standard deviation of anti-cter apoA1 IgG level was associated with an 18% increase in mortality risk (hazard ratio: 1.18, 95% confidence interval: 1.04-1.33;  = 0.009). The cterApoA1 analogue reversed the antibody-mediated inflammatory response with an IC of 1 µm but did not rescue the significant anti-apoA1 IgG-induced mortality rate (69% vs. 23%, LogRank  = 0.02).

Conclusion: Anti-cter apoA1 IgG independently predicts overall mortality in the general population. Despite being effective , our cter apoA1 analogue did not reverse the anti-apoA1 IgG-induced mortality in mice. Our data suggest that these autoantibodies are not readily treatable through cognate peptide immunomodulation.
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http://dx.doi.org/10.1002/cti2.1220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734471PMC
December 2020

Geospatial digital monitoring of COVID-19 cases at high spatiotemporal resolution.

Lancet Digit Health 2020 08 16;2(8):e393-e394. Epub 2020 Jun 16.

Geneva University Hospitals, 1205 Geneva, Switzerland; Laboratory of Geographic Information Systems, School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/S2589-7500(20)30139-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832151PMC
August 2020

Impact of restricting procalcitonin measurements in a Swiss tertiary-care hospital on antibiotic use, clinical outcomes, and costs: An interrupted time-series analysis.

Infect Control Hosp Epidemiol 2021 07 2;42(7):890-892. Epub 2020 Dec 2.

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

We evaluated the impact of a restriction of procalcitonin measurements on antibiotic use, length of stay, mortality, and cost in a Swiss tertiary-care hospital using interrupted time-series analysis. There was no significant change in level or slope for rates of antibiotic consumption, and costs decreased considerably, by ~54,488 CHF (US$55,714) per month.
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http://dx.doi.org/10.1017/ice.2020.1314DOI Listing
July 2021

Auto-antibodies against apolipoprotein A-1 block cancer cells proliferation and induce apoptosis.

Oncotarget 2020 Nov 17;11(46):4266-4280. Epub 2020 Nov 17.

Division of Laboratory Medicine, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland.

Auto-antibodies against apoA-1 (anti-apoA-1 IgGs) have been identified as important actors of atherosclerosis development through pro-inflammatory and pro-atherogenic properties and to also induce apoptosis in tumoral neuronal and lymphocyte derived cell lines through unknown mechanisms. The purpose of this study was to explore the cellular pathways involved in tumoral cell survival modulated by anti-apoA-1 antibodies. We observed that anti-apoA-1 antibodies induce growth arrest (in G2/M phase) and cell apoptosis through caspase 3 activation, accompanied by a selective p53 phosphorylation on serine 15. RNA sequencing indicated that anti-apoA-1 IgGs affect the expression of more than 950 genes belonging to five major groups of genes and respectively involved in i) cell proliferation inhibition, ii) p53 stabilisation and regulation, iii) apoptosis regulation, iv) inflammation regulation, and v) oxidative stress. In conclusion, anti-apoA-1 antibodies seem to have a role in blocking tumoral cell proliferation and survival, by activating a major tumor suppressor protein and by modulating the inflammatory and oxidative stress response. Further investigations are needed to explore a possible anti-cancer therapeutic approach of these antibodies in very specific and circumscribed conditions.
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http://dx.doi.org/10.18632/oncotarget.27814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679029PMC
November 2020

Impact of Total Laboratory Automation on Turnaround Times for Urine Cultures and Screening Specimens for MRSA, ESBL, and VRE Carriage: Retrospective Comparison With Manual Workflow.

Front Cell Infect Microbiol 2020 28;10:552122. Epub 2020 Oct 28.

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

Using computerized time-stamps, we compared the turnaround-times (TAT) for urine samples and screening ESwabs of MRSA, VRE, and ESBL carriage in the bacteriology laboratory of Geneva University Hospitals between January and December 2017 (period preceding the implementation of the WASPLab) with the same specimen types analyzed between January and December 2019 (period after the implementation of the automation). During both 1-year periods, a total of 98'380 specimens were analyzed (48'158 in 2017 vs. 50'222 in 2019). On the WASPLab, all culture plates were imaged at defined intervals each day of incubation, but the processing of the cultures (i.e., pathogen identification and antimicrobial susceptibility testing) was only performed during day shift hours (~8:00 A.M. to 4:30 P.M.). The median TAT for negative reports decreased by almost half for urine samples from 52.1 (2017) to 28.3 h (2019) ( < 0.001), and for MRSA screening specimens from 50.7 to 26.3 h ( < 0.001). The difference in median TAT for negative reports was less pronounced for screening of ESBL (50.2 vs. 43.0 h) ( < 0.001) and VRE (50.6 vs. 45.7 h) ( < 0.001). Despite a trend toward shorter result delivery for positive samples, there was no significant change in the median TAT. These results suggest that TAT for negative samples immediately benefit from automation, whereas TAT for positive samples also depend on the laboratory hours of operation and daily human resource management.
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http://dx.doi.org/10.3389/fcimb.2020.552122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664309PMC
June 2021

Prevalence of Immunoglobulin G (IgG) Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Evaluation of a Rapid MEDsan IgG Test in Children Seeking Medical Care.

Clin Infect Dis 2021 04;72(7):e192-e195

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

In 208 children seeking medical care, the seropositivity rate of anti-SARS-CoV-2 IgG antibodies was 8.7%, suggesting an infection rate similar to that observed in adults but >100-fold the incidence of RT-PCR-confirmed pediatric cases. Compared with the gold-standard combined ELISA + immunofluorescence, the MEDsan IgG rapid diagnostic test performed accurately.
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http://dx.doi.org/10.1093/cid/ciaa1702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717220PMC
April 2021

Atherosclerotic plaque vulnerability is increased in mouse model of lupus.

Sci Rep 2020 10 27;10(1):18324. Epub 2020 Oct 27.

Division of Cardiology, Foundation for Medical Researches, Department of Medicine Specialties, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, 1211, Geneva 4, Switzerland.

Anti-apolipoprotein A-1 (anti-apoA-1 IgG) and anti-double stranded DNA (anti-dsDNA IgG) autoantibodies have been described as mediators of atherogenesis in mice and humans. In the present study, we aim to investigate the association between atherosclerotic parameters, autoantibodies and plaque vulnerability in the context of systemic lupus erythematosus (SLE). We therefore bred a lupus prone-mouse model (Nba2.Yaa mice) with Apoe mice resulting in ApoeNba2.Yaa mice spontaneously producing anti-apoA-1 IgG antibodies. Although ApoeNba2.Yaa and Apoe mice subject to a high cholesterol diet displayed similar atherosclerosis lesions size in aortic roots and abdominal aorta, the levels of macrophage and neutrophil infiltration, collagen, MMP-8 and MMP-9 and pro-MMP-9 expression in ApoeNba2.Yaa mice indicated features of atherosclerotic plaque vulnerability. Even though ApoeNba2.Yaa mice and Apoe mice had similar lipid levels, ApoeNba2.Yaa mice showed higher anti-apoA-1 and anti-dsDNA IgG levels. ApoeNba2.Yaa mice displayed a reduction of the size of the kidney, splenomegaly and lymph nodes (LN) hypertrophy. In addition, anti-apoA-1 and anti-dsDNA IgG increased also in relation with mRNA levels of GATA3, IL-4, Bcl-6 and CD20 in the spleen and aortic arch of ApoeNba2.Yaa mice. Our data show that although atherosclerosis-lupus-prone ApoeNba2.Yaa mice did not exhibit exacerbated atherosclerotic lesion size, they did show features of atherosclerotic plaque destabilization in correlation with the increase of pro-atherogenic autoantibodies.
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http://dx.doi.org/10.1038/s41598-020-74579-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591560PMC
October 2020

Anti-Apolipoprotein A-1 IgG Influences Neutrophil Extracellular Trap Content at Distinct Regions of Human Carotid Plaques.

Int J Mol Sci 2020 10 19;21(20). Epub 2020 Oct 19.

Division of Cardiology, Foundation for Medical Researches, Department of Medicine Specialties, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, 1211 Geneva, Switzerland.

Background: Neutrophils accumulate in atherosclerotic plaques. Neutrophil extracellular traps (NET) were recently identified in experimental atherosclerosis and in complex human lesions. However, not much is known about the NET marker citrullinated histone-3 (H3Cit) expression and functionality in human carotid plaques. Moreover, the association between the proatherosclerotic autoantibody anti-apolipoprotein A-1 (anti-ApoA-1 IgG) and NET has never been investigated.

Methods: Atherosclerotic plaques have been obtained from 36 patients with severe carotid stenosis that underwent carotid endarterectomy for severe carotid stenosis. Samples were sectioned into upstream and downstream regions from the same artery segment. Plaque composition and expression of NET markers neutrophil elastase (NE) and H3Cit were quantified by immunohistochemistry. H3Cit expression and function was evaluated by immunofluorescence and confocal analysis in a subset of patients.

Results: Pathological features of vulnerable phenotypes were exacerbated in plaques developed at downstream regions, including higher accumulation of neutrophils and enhanced expression of NE and H3Cit, as compared to plaques from upstream regions. The H3Cit signal was also more intense in downstream regions, with significant extracellular distribution in spaces outside of neutrophils. The percentage of H3Cit colocalization with CD66b (neutrophils) was markedly lower in downstream portions of carotid plaques, confirming the extrusion of NET in this region. In agreement, the maximum distance of the H3Cit signal from neutrophils, extrapolated from vortex distance calculation in all possible directions, was also higher in downstream plaques. The serum anti-ApoA-1index positively correlated with the expression of H3Cit in downstream segments of plaques. Expression of the H3Cit signal outside of neutrophils and H3Cit maximal distance from CD66b-positive cells increased in plaques from serum positive anti-ApoA-1 patients compared with serum negative patients.

Conclusion: NET elements are differentially expressed in upstream versus downstream regions of human carotid plaques and may be influenced by circulating levels of anti-ApoA-1 IgG. These findings could warrant the investigation of NET elements as potential markers of vulnerability.
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http://dx.doi.org/10.3390/ijms21207721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588926PMC
October 2020

Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT).

Emerg Microbes Infect 2020 Dec;9(1):2394-2403

Centre for Infectious Disease Control, WHO COVID-19 reference laboratory, RIVM, Bilthoven, Netherlands.

To understand SARS-CoV-2 immunity after natural infection or vaccination, functional assays such as virus neutralising assays are needed. So far, assays to detect SARS-CoV-2 neutralising antibodies rely on cell-culture based infection assays either using wild type SARS-CoV-2 or pseudotyped viruses. Such assays are labour-intensive, require appropriate biosafety facilities and are difficult to standardize. Recently, a new surrogate virus neutralisation test (sVNT) was described that uses the principle of an ELISA to measure the neutralisation capacity of anti-SARS-CoV-2 antibodies directed against the receptor binding domain. Here, we performed an independent evaluation of the robustness, specificity and sensitivity on an extensive panel of sera from 269 PCR-confirmed COVID-19 cases and 259 unmatched samples collected before 2020 and compared it to cell-based neutralisation assays. We found a high specificity of 99.2 (95%CI: 96.9-99.9) and overall sensitivity of 80.3 (95%CI: 74.9-84.8) for the sVNT. Clinical sensitivity increased between early (<14 days post symptom onset or post diagnosis, dpos/dpd) and late sera (>14 dpos/dpd) from 75.0 (64.7-83.2) to 83.1 (76.5-88.1). Also, higher severity was associated with an increase in clinical sensitivity. Upon comparison with cell-based neutralisation assays we determined an analytical sensitivity of 74.3 (56.4-86.9) and 98.2 (89.4-99.9) for titres ≥10 to <40 and ≥40 to <160, respectively. Only samples with a titre ≥160 were always positive in the sVNT. In conclusion, the sVNT can be used as an additional assay to determine the immune status of COVID-19 infected of vaccinated individuals but its value needs to be assessed for each specific context.
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http://dx.doi.org/10.1080/22221751.2020.1835448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605318PMC
December 2020

Accuracy of C-reactive protein, procalcitonin, serum amyloid A and neopterin for low-dose CT-scan confirmed pneumonia in elderly patients: A prospective cohort study.

PLoS One 2020 30;15(9):e0239606. Epub 2020 Sep 30.

Medical Faculty, Geneva, Switzerland.

Objective: The diagnosis of pneumonia based on semiology and chest X-rays is frequently inaccurate, particularly in elderly patients. Older (C-reactive protein (CRP); procalcitonin (PCT)) or newer (Serum amyloid A (SAA); neopterin (NP)) biomarkers may increase the accuracy of pneumonia diagnosis, but data are scarce and conflicting. We assessed the accuracy of CRP, PCT, SAA, NP and the ratios CRP/NP and SAA/NP in a prospective observational cohort of elderly patients with suspected pneumonia.

Methods: We included consecutive patients more than 65 years old, with at least one respiratory symptom and one symptom or laboratory finding suggestive of infection, and a working diagnosis of pneumonia. Low-dose CT scan and comprehensive microbiological testing were done in all patients. The index tests, CRP, PCT, SAA and NP, were obtained within 24 hours. The reference diagnosis was assessed a posteriori by a panel of experts considering all available data, including patients' outcome. We used area under the curve (AUROC) and Youden index to assess the accuracy and obtain optimal cut-off of the index tests.

Results: 200 patients (median age 84 years) were included; 133 (67%) had pneumonia. AUROCs for the diagnosis of pneumonia was 0.64 (95% CI: 0.56-0.72) for CRP; 0.59 (95% CI: 0.51-0.68) for PCT; 0.60 (95% CI: 0.52-0.69) for SAA; 0.41 (95% CI: 0.32-0.49) for NP; 0.63 (95% CI: 0.55-0.71) for CRP/NP; and 0.61 (95% CI: 0.53-0.70) for SAA/NP. No cut-off resulted in satisfactory sensitivity or specificity.

Conclusions: Accuracy of traditional (CRP, PCT) and newly proposed biomarkers (SAA, NP) and ratios of CRP/NP and SAA/NP was too low to help diagnosing pneumonia in the elderly. CRP had the highest AUROC.

Clinical Trial Registration: NCT02467092.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239606PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526885PMC
November 2020

Anti-ApoA-1 IgGs predict resistance to waist circumference reduction after Mediterranean diet.

Eur J Clin Invest 2021 Mar 27;51(3):e13410. Epub 2020 Sep 27.

Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy.

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http://dx.doi.org/10.1111/eci.13410DOI Listing
March 2021

Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma.

PLoS One 2020 9;15(9):e0238089. Epub 2020 Sep 9.

Department of Organic Chemistry, NCCR Chemical Biology, Faculty of Science, University of Geneva, Geneva, Switzerland.

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients (12) and heathy patients (6), we identified three immunodominant linear epitopes, two of which correspond to key proteolytic sites on the spike protein (S1/S2 and S2') known to be critical for cellular entry. We show biochemical evidence that plasma positive for the epitope adjacent to the S1/S2 cleavage site inhibits furin-mediated proteolysis of spike.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238089PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480855PMC
September 2020

Head-to-Head Accuracy Comparison of Three Commercial COVID-19 IgM/IgG Serology Rapid Tests.

J Clin Med 2020 Jul 24;9(8). Epub 2020 Jul 24.

Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals and Geneva University, 1205 Geneva, Switzerland.

Background: Comparative data of SARS-CoV-2 IgM/IgG serology rapid diagnostic tests (RDTs) is scarce. We thus performed a head-to-head comparison of three RDTs.

Methods: In this unmatched case-control study, blood samples from 41 RT-PCR-confirmed COVID-19 cases and 50 negative controls were studied. The diagnostic accuracy of three commercially available COVID-19 RDTs: NTBIO (RDT-A), Orient-Gene (RDT-B), and MEDsan (RDT-C), against both a recombinant spike-expressing immunofluorescence assay (rIFA) and Euroimmun IgG ELISA, was assessed. RDT results concordant with the reference methods, and between whole blood and plasma, were established by the Kendall coefficient.

Results: COVID-19 cases' median time from RT-PCR to serology was 22 days (interquartile range (IQR) 13-31 days). Whole-blood IgG detection with RDT-A, -B, and -C showed 0.93, 0.83, and 0.98 concordance with rIFA. Against rIFA, RDT-A sensitivity (SN) was 92% (95% CI: 78-98) and specificity (SP) 100% (95% CI: 91-100), RDT-B showed 87% SN (95% CI: 72-95) and 98% SP (95% CI: 88-100), and RDT-C 100% SN (95% CI: 88-100) and 98% SP (95% CI: 88-100). Against ELISA, SN and SP were above 90% for all three RDTs.

Conclusions: RDT-A and RDT-C displayed IgG detection SN and SP above 90% in whole blood. These RDTs could be considered in the absence of routine diagnostic serology facilities.
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http://dx.doi.org/10.3390/jcm9082369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463984PMC
July 2020
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