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1. Editorial: Therapeutic management of COVID-19 in immunocompromised patients and interaction with the immune response: from preventive to curative strategies

Author: Ilies Benotmane and Morgane Solis
Subjects: COVID-19, SARS-CoV-2, immunocompromised patients, solid organ transplantation, HIV, vaccine, Immunologic diseases. Allergy, RC581-607
Published: 2024
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2. Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe

Author: Kamil Demircan, Thilo Samson Chillon, Tommy Bracken, Ilaria Bulgarelli, Irene Campi, Gijs Du Laing, Samira Fafi-Kremer, Laura Fugazzola, Alejandro Abner Garcia, Raban Heller, David J. Hughes, Louis Ide, Georg Jochen Klingenberg, Pawel Komarnicki, Zbigniew Krasinski, Alain Lescure, Patrick Mallon, Arash Moghaddam, Luca Persani, Mirko Petrovic, Marek Ruchala, Morgane Solis, Linos Vandekerckhove, and Lutz Schomburg
Subjects: trace elements, SARS-CoV-2, mortality, biomarker, nutrition, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionCertain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe.MethodsSerum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory.ResultsMedian levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769).DiscussionThe data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.
Published: 2022
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3. Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality

Author: Francis Schneider, Pierrick Le Borgne, Jean-Etienne Herbrecht, François Danion, Morgane Solis, Sophie Hellé, Cosette Betscha, Raphaël Clere-Jehl, François Lefebvre, Vincent Castelain, Yannick Goumon, and Marie-Hélène Metz-Boutigue
Subjects: Innate immunity, COVID, Catestatin, Chromogranin A, hypoxia, critically ill, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionNeuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity.Patients & MethodsAdmission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves).ResultsAmong COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or (COVID-ICU+, patients n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p
Published: 2022
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4. Case Report: Evolution of Humoral and Cellular Immunity in Two COVID-19 Breakthrough Infections After BNT162b2 Vaccine

Author: Floriane Gallais, Pierre Gantner, Delphine Planas, Morgane Solis, Timothée Bruel, Florian Pierre, Eric Soulier, Paola Rossolillo, Slim Fourati, Jean Sibilia, Olivier Schwartz, and Samira Fafi-Kremer
Subjects: SARS-CoV-2, variant of concern, vaccine, immune evasion, breakthrough infection, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.
Published: 2022
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5. Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Author: Floriane Gallais, Pierre Gantner, Timothée Bruel, Aurélie Velay, Delphine Planas, Marie-Josée Wendling, Sophie Bayer, Morgane Solis, Elodie Laugel, Nathalie Reix, Anne Schneider, Ludovic Glady, Baptiste Panaget, Nicolas Collongues, Marialuisa Partisani, Jean-Marc Lessinger, Arnaud Fontanet, David Rey, Yves Hansmann, Laurence Kling-Pillitteri, Olivier Schwartz, Jérome De Sèze, Nicolas Meyer, Maria Gonzalez, Catherine Schmidt-Mutter, and Samira Fafi-Kremer
Subjects: SARS-CoV-2, COVID-19, Immunity, Neutralizing antibodies, Reinfection, Medicine, Medicine (General), R5-920
Abstract: Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. Fun1ding: None.
Published: 2021
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6. Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors

Author: Morgane Solis, Aurélien Guffroy, François Lersy, Eric Soulier, Floriane Gallais, Mathilde Renaud, Nawal Douiri, Xavier Argemi, Yves Hansmann, Jérôme De Sèze, Stéphane Kremer, and Samira Fafi-Kremer
Subjects: immunology, viral infection, predictive marker, Microbiology, QR1-502
Abstract: JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.
Published: 2020
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7. An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides.

Author: Pilar Domingo-Calap, Benjamin Schubert, Mélanie Joly, Morgane Solis, Meiggie Untrau, Raphael Carapito, Philippe Georgel, Sophie Caillard, Samira Fafi-Kremer, Nicodème Paul, Oliver Kohlbacher, Fernando González-Candelas, and Seiamak Bahram
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(-3)-10(-5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.
Published: 2018
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8. In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

Author: Heidi Barth, Morgane Solis, Wallys Kack-Kack, Eric Soulier, Aurélie Velay, and Samira Fafi-Kremer
Subjects: polyomavirus, in vitro models, animal models, tropism, entry, pathogenesis, Microbiology, QR1-502
Abstract: Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned.
Published: 2016
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9. Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients

Author: Floriane Gallais, Benjamin Renaud-Picard, Morgane Solis, Elodie Laugel, Eric Soulier, Sophie Caillard, Romain Kessler, and Samira Fafi-Kremer
Subjects: Torque teno virus, Pulmonary and Respiratory Medicine, Vaccines, Synthetic, Transplantation, COVID-19 Vaccines, SARS-CoV-2, COVID-19, Antibodies, Viral, Antibodies, Neutralizing, Transplant Recipients, Immunoglobulin G, Antibody Formation, DNA, Viral, Humans, Surgery, RNA, Messenger, mRNA Vaccines, Cardiology and Cardiovascular Medicine, Lung, BNT162 Vaccine, Biomarkers, Retrospective Studies
Abstract: Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors.A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression.After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 logCOVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.
Published: 2022

10. Acute‐onset delirium in intensive care COVID patients: association of imperfect brain repair with foodborne micro‐pollutants

Author: Dimitri Heintz, Francis Schneider, Thierry Artzner, Mathieu Alemann, Julie Helms, Arnaud Agin, Mathieu Baldacini, Morgane Solis, Loïc Maurer, Stéphane Kremer, Claire Villette, Maleka Schenck, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Critical Care, Short Communication, brain, Encephalopathy, Clinical Neurology, Context (language use), Gastroenterology, White matter, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Intensive care, medicine, Humans, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Sciences du Vivant [q-bio]/Biologie végétale, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), COVID, medicine.diagnostic_test, SARS-CoV-2, hypoxia, Lumbar puncture, business.industry, COVID-19, Delirium, medicine.disease, metabolomics, 3. Good health, medicine.anatomical_structure, Neurology, Environmental Pollutants, erythropoietin, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background and purpose COVID‐19 affects the brain in various ways, amongst which delirium is worrying. An assessment was made of whether a specific, long‐lasting, COVID‐19‐related brain injury develops in acute respiratory distress syndrome patients after life‐saving re‐oxygenation. Methods Ten COVID+ patients (COVID+) with unusual delirium associated with neuroimaging suggestive of diffuse brain injury and seven controls with non‐COVID encephalopathy were studied. The assessment took place when the intractable delirium started at weaning off ventilation support. Brain magnetic resonance imaging (MRI) was performed followed by standard cerebrospinal fluid (CSF) analyses and assessment of CSF erythropoietin concentrations (as a marker for the assessment of tissue repair), and of non‐targeted CSF metabolomics using liquid chromatography high resolution mass spectrometry. Results Patients were similar as regards severity scores, but COVID+ were hospitalized longer (25 [11.75; 25] vs. 9 [4.5; 12.5] days, p = 0.03). On admission, but not at MRI and lumbar puncture performance, COVID+ were more hypoxic (p = 0.002). On MRI, there were leptomeningeal enhancement and diffuse white matter haemorrhages only in COVID+. In the latter, CSF erythropoietin concentration was lower (1.73 [1.6; 2.06] vs. 3.04 [2.9; 3.91] mIU/ml, p = 0.01), and CSF metabolomics indicated (a) increased compounds such as foodborne molecules (sesquiterpenes), molecules from industrialized beverages and micro‐pollutants (diethanolamine); and (b) decreased molecules such as incomplete breakdown products of protein catabolism and foodborne molecules (glabridin). At 3‐month discharge, fatigue, anxiety and depression as well as MRI lesions persisted in COVID+. Conclusions Some COVID+ are at risk of a specific delirium. Imperfect brain repair after re‐oxygenation and lifestyle factors might influence long‐lasting brain injuries in a context of foodborne micro‐pollutants., This explorative cohort study suggests that life‐saving re‐oxygenation of COVID+ patients is possibly followed by an incomplete brain repair as indicated by magnetic resonance imaging and low cerebrospinal fluid erythropoietin (CSF EPO) concentrations. In addition, non‐targeted metabolomics analysis identified the presence of many perturbed metabolites during COVID‐induced delirium, including biomarkers for the consumption of specific food and intermediate factors that have tangible impact on inflammatory pathways.
Published: 2021

11. Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

Author: Caroline Papeix, Elisabeth Maillart, Morgane Solis, Caroline Houillier, Philippe Kerschen, Manel Alleg, Jerome Tamburini Bonnefoy, Xavier Roussel, Bertrand Bourre, Céline Kennel, Stéphane Kremer, Jean-Pierre Marolleau, Philippe Agape, Guido Ahle, Adrien Chauchet, François Cotton, Alexis Caulier, Xavier Leclerc, Patrick Vermersch, Cécile Chabrot, Béatrice Claise, Guillaume Martin-Blondel, Sandra Malak, Samira Fafi-Kremer, Seyyid Baloglu, Jérôme De Seze, Fabrice Bonneville, Jean-Pierre Pruvo, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Virologie [Strasbourg], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), CHU Rouen, Normandie Université (NU), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Neuroradiologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Clermont-Ferrand, Institut Curie - Saint Cloud (ICSC), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Limoges, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de neurologie 2 [CHU Pitié-Salpêtrière], Institut Curie [Saint-Cloud], Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neuroradiologie [CHU Toulouse], CHU Toulouse [Toulouse], Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Service de Radiologie (Hôpitaux Universitaires de Strasbourg), Laboratoire de Virologie Médicale [Strasbourg], CHU Strasbourg, Université de Lyon, Centre Hospitalier Universitaire de Rouen, University of Rouen, Rouen, France, University of Lille, Univ. Lille, Inserm, CHU Lille, U1172 - Lille Neurosciences & Cognition, F-59000 Lille, France, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de Clermont-Ferrand, université Clermont-Auvergne, Service des maladies infectieuses et tropicales[Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service d'Hématologie Clinique [CHU Amiens], Centre Hospitalier Universitaire de Besançon (CHU Besançon), Service of Neurologie - Centres Mémoire de Ressources et de Recherche (Hôpitaux Universitaires de Strasbourg ) (CMRR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Leukoencephalopathy, Progressive Multifocal* / diagnostic imaging, medicine.medical_specialty, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], viruses, MESH: Natalizumab / adverse effects, HIV Infections, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Progressive multifocal leukoencephalopathy, medicine, MESH: HIV Infections* / complications, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, Retrospective Studies, Chemotherapy, MESH: Humans, business.industry, Leukoencephalopathy, Progressive Multifocal, virus diseases, Brain, Immunosuppression, MESH: Retrospective Studies, General Medicine, MESH: HIV Infections* / drug therapy, medicine.disease, Magnetic Resonance Imaging, MESH: Rituximab / adverse effects, 3. Good health, 030220 oncology & carcinogenesis, MESH: Leukoencephalopathy, Progressive Multifocal* / chemically induced, Rituximab, MESH: Brain / diagnostic imaging, Radiology, medicine.symptom, Neuro, Complication, business, medicine.drug
Abstract: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
Published: 2020

12. Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study

Author: François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Cancérologie de Strasbourg Europe (ICANS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Coinfections, Computed tomography, Aspergillosis, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Invasive fungal infections, Internal medicine, medicine, Humans, Leukaemia, 030212 general & internal medicine, Mortality, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, Aspergillus species, Aged, 80 and over, medicine.diagnostic_test, business.industry, Coinfection, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Transplantation, Infectious Diseases, Fungal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Child, Preschool, Hematologic Neoplasms, business
Abstract: Objectives To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. Patients and methods We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. Results Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8–43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2–4.4)), other haematological malignancies (OR 2.1 (1.2–3.8)), other underlying diseases (OR 4.3 (1.4–13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2–3.0)), fever (OR 2.4 (1.5–4.1)), tracheal intubation (OR 2.6 (1.5–4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1–6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3–3.7) and OR 2.2 (1.2–4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1–1.9), p Conclusions Coinfections are frequent in IA patients and are associated with higher mortality.
Published: 2021

13. Combining predictive markers for severe COVID-19: Torquetenovirus DNA load and SARS-CoV-2 RNAemia

Author: Morgane Solis, Floriane Gallais, Sabrina Garnier-Kepka, Nicolas Lefebvre, Ilies Benotmane, Pierre-Olivier Ludes, Vincent Castelain, Ferhat Meziani, Sophie Caillard, Olivier Collange, and Samira Fafi-Kremer
Subjects: Infectious Diseases, COVID-19 Testing, SARS-CoV-2, Virology, COVID-19, Humans, RNA, Viral, DNA, Antibodies, Viral
Abstract: SARS-CoV-2 is the cause of worldwide COVID-19, which severity has been linked to the immune and inflammatory response. Here, we investigate Torquetenovirus (TTV) DNA load - a marker reflecting the intensity of the overall immune response - as well as SARS-CoV-2 RNAemia and IgM/IgG antibodies in COVID-19-positive patients.Two hundred and fifteen COVID-19-positive patients were enrolled, including 87 severe cases and 128 mild-moderate cases. SARS-CoV-2 RNAemia and IgM/IgG antibodies, as well as TTV DNA loads, were measured on longitudinal plasma samples.The rate of severe cases was higher in patients with low TTV DNA load in plasma considering a threshold of 700 copies/mL. In severe patients, SARS-CoV-2 RNAemia positivity rates were higher than those in mild-moderate cases at any timepoint. When combined, TTV DNA load and SARS-CoV-2 RNAemia allowed to predict the outcome of COVID-19 infection, with a higher risk (HR=12.4) of ICU admission in patients with low TTV DNA load and positive SARS-CoV-2 RNAemia.TTV DNA load and SARS-CoV-2 RNAemia may be effective, non-invasive markers reflecting disease severity and poor outcome that could be conveniently measured in a clinical laboratory setting, as soon as COVID-19 diagnosis is made.
Published: 2021

14. Le BK virus en greffe rénale

Author: Floriane Gallais, Aurélie Velay, Morgane Solis, Ilies Benotmane, and Samira Fafi-Kremer
Subjects: 03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract: Resume Le BK virus (BKV), polyomavirus decou- vert dans les annees 1970, est responsable de pathologies majeures chez le greffe renal depuis l’utilisation de molecules immuno- suppressives puissantes, comme les anticalci- neurines. Pres de la moitie des transplantes renaux developpe une replication du BKV et jusqu’a 10 % d’entre eux peuvent progresser jusqu’a la nephropathie (BKVN), potentielle- ment responsable de la perte du greffon. Ces patients sont particulierement concernes car le BKV persiste dans le tractus renal et peut donc etre transmis du rein du donneur vers l’organisme du receveur. En l’absence de trai- tement antiviral specifique efficace, la prise en charge actuelle de l’infection a BKV repose sur un suivi regulier de la replication et sur la diminution de l’immunosuppression, mais n’est pas satisfaisante en raison de l’exposition a un risque de rejet. Cet article presente les connaissances actuelles sur la physiopatho- logie de l’infection et la reponse immunitaire anti-BKV ainsi que les perspectives qui en decoulent en termes de diagnostic, de pronos- tic et de strategies preventives de l’infection. Download : Download high-res image (487KB) Download : Download full-size image
Published: 2019

15. Tick-borne encephalitis virus: molecular determinants of neuropathogenesis of an emerging pathogen

Author: Morgane Solis, Marlène Cesbron, Samira Fafi-Kremer, Eric Soulier, Yves Hansmann, Magali Paz, Aurélie Velay, Martin Martinot, Xavier Argemi, and Pierre Gantner
Subjects: 0301 basic medicine, Virulence Factors, viruses, 030106 microbiology, Applied Microbiology and Biotechnology, Microbiology, Virus, Encephalitis Viruses, Tick-Borne, 03 medical and health sciences, Emerging pathogen, medicine, Animals, Humans, biology, Transmission cycle, General Medicine, medicine.disease, biology.organism_classification, Tick vector, Virology, Disease Models, Animal, Tick-borne encephalitis virus, 030104 developmental biology, Host-Pathogen Interactions, Ixodes, Neuropathogenesis, Encephalitis, Tick-Borne, Encephalitis
Abstract: Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. The transmission cycle involves the virus, the Ixodes tick vector, and a vertebrate reservoir, such as ...
Published: 2019

16. Situation épidémique en juin 2022, évolution du SARS-CoV-2 et des variants, intérêt du suivi sérologique et de l’immunité

Author: Morgane Solis
Subjects: Public Health, Environmental and Occupational Health
Published: 2022

17. Anti-SARS-CoV-2 Antibodies Persist for up to 13 Months and Reduce Risk of Reinfection

Author: Arnaud Fontanet, Timothée Bruel, Yves Hansmann, Jérôme De Seze, Catherine Schmidt-Mutter, Samira Fafi-Kremer, Nathalie Reix, Delphine Planas, Aurélie Velay, Jean-Marc Lessinger, Anne Schneider, Baptiste Panaget, Laurence Kling-Pillitteri, Marialuisa Partisani, Olivier Schwartz, Morgane Solis, Floriane Gallais, Ludovic Glady, David Rey, Elodie Laugel, Nicolas Collongues, Nicolas Meyer, Pierre Gantner, Maria Candelaria Martin Gonzalez, Marie-Josée Wendling, and Sophie Bayer
Subjects: biology, business.industry, Incidence (epidemiology), Arbitrary unit, Antibody titer, Virology, Neutralization, Persistence (computer science), Vaccination, Interquartile range, biology.protein, Medicine, Antibody, business
Abstract: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCWs), including 916 COVID-19 negative HCWs and 393 convalescent COVID-19 for up to 422 days post-symptom. From month (M)1 to M7-9 post-infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCWs in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N dramatically decreased (half-life: 283 days) while anti-S stabilized (half-life: 725 days) at a median of 2.39 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.10 -2.75). Overall, 69 SARS-CoV-2 infections developed in the COVID-19 negative group (incidence of 12.22 per 100 person-years) versus one in the COVID-19 positive group (incidence of 0.40 per 100 person-years), indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7% (p
Published: 2021

18. Protracted SARS‐CoV‐2 pneumonia with rituximab treatment: About two cases

Author: Axel Ursenbach, Louis Boehn, Yves Hansmann, Morgane Solis, Aurélie Velay, Charlotte Kaeuffer, François Danion, Estelle Rougier, Nicolas Lefebvre, Victor Gerber, and Yvon Ruch
Subjects: 2019-20 coronavirus outbreak, Immunologic Factors, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Virology, Medicine, Humans, 030212 general & internal medicine, Letter to the Editor, business.industry, SARS-CoV-2, COVID-19, Immunosuppression, Pneumonia, medicine.disease, respiratory tract diseases, Infectious Diseases, Immunology, 030211 gastroenterology & hepatology, Rituximab, Immunization, Previously treated, business, Viral load, medicine.drug
Abstract: Here, we describe two patients, previously treated with rituximab, who presented with a protracted SARS-CoV-2 infection with an atypical course. We hypothesized an incomplete viral clearance with persistent pneumonia due to an impaired or delayed humoral response. This article is protected by copyright. All rights reserved.
Published: 2021

19. Is COVID‐19 infection more severe in kidney transplant recipients?

Author: Nathalie Chavarot, Bruno Moulin, Valérie Moal, Olivier Thaunat, Marc Hazzan, Jamal Bamoulid, Antoine Durrbach, Christiane Mousson, Nassim Kamar, Yannick Lemeur, Charlotte Kaeuffer, Clarisse Greze, Philippe Grimbert, Ilies Benotmane, Dominique Bertrand, Antoine Thierry, Tristan Legris, Gilles Blancho, Pierre François Westeel, Mariam Jdidou, Hélène François, Sophie Caillard, Marie Matignon, Yvon Ruch, Morgane Solis, Antoine Sicard, Dany Anglicheau, Philippe Gatault, Valentin Goutaudier, François Danion, Lionel Couzi, Charlotte Colosio, Renaud Snanoudj, Christophe Masset, Agnès Duveau, Jonathan M. Chemouny, Luc Frimat, CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours (UT), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Aix Marseille Université (AMU), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Hôpital Pasteur [Nice] (CHU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Bourgogne (UB), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Poitiers, Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU de Bordeaux Pellegrin [Bordeaux], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), University of Lille, This study was supported by the Strasbourg University Hospital (COVIS-HUS Study- HUS number 7760), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AP-HP Hôpital Tenon [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University Hospital of Montpellier, Hôpital Bicêtre, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), PINIER, CHRISTINE, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Registries, Aucun, MESH: Comorbidity, 030230 surgery, law.invention, chemistry.chemical_compound, 0302 clinical medicine, law, cardiovascular disease, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, clinical research / practice, Immunology and Allergy, Cumulative incidence, Pharmacology (medical), kidney transplantation / nephrology, MESH: Incidence, MESH: Aged, Univariate analysis, MESH: France / epidemiology, MESH: Middle Aged, MESH: Transplant Recipients / statistics & numerical data, Acute kidney injury, Intensive care unit, 3. Good health, MESH: COVID-19 / epidemiology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, glomerular filtration rate (GFR), kidney failure / injury, medicine.medical_specialty, infection and infectious agents - viral, infectious disease, Brief Communication, MESH: Graft Rejection / prevention & control, 03 medical and health sciences, Internal medicine, Diabetes mellitus, MESH: Severity of Illness Index, MESH: COVID-19 / diagnosis, medicine, Humans, MESH: SARS-CoV-2, Mechanical ventilation, Creatinine, Transplantation, MESH: Humans, business.industry, SARS-CoV-2, MESH: Graft Rejection / epidemiology, COVID-19, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, Transplant Recipients, MESH: Male, immunosuppressive regimens, MESH: Immunosuppressive Agents / therapeutic use, MESH: Pandemics, MESH: Propensity Score, chemistry, Reinfection, MESH: Immunosuppression / methods, MESH: Intensive Care Units, business, MESH: Female, MESH: Kidney Transplantation
Abstract: International audience; There are no studies which have compared the risk of severe Covid-19 and related mortality between transplant recipients and non-transplant patients. We enrolled two groups of patients hospitalized for Covid-19, i.e., kidney transplant recipients from the French Registry of Solid Organ Transplant (n=306) and a single-center cohort of non-transplant patients (n=795). An analysis was performed among subgroups matched for age and risk factors for severe Covid-19 or mortality. Severe Covid-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death.Transplant recipients were younger and had more comorbidities compared to non-transplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe Covid-19 did not differ between KTR and non-transplant patients; however, 30-day Covid-19-related mortality was significantly higher in KTR (17.9% versus 11.4%, respectively, p=0.038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe Covid-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR=1.55), and creatinine level >115 µmol/L (HR=2.32) were associated with Covid-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. Kidney transplant recipients had a higher Covid-19-related mortality compared to non-transplant hospitalized patients.
Published: 2021

20. SARS‐CoV‐2 viral load in nasopharyngeal swabs in the emergency department does not predict COVID‐19 severity and mortality

Author: Ferhat Meziani, Samira Fafi-Kremer, Yves Hansmann, Pascal Bilbault, Karine Alamé Intern, Eric Bayle, Hamid Merdji, Yvon Ruch, François Severac, Pierrick Le Borgne, Morgane Solis, Les Hôpitaux Universitaires de Strasbourg (HUS), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, CHU Strasbourg, Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis), and univOAK, Archive ouverte
Subjects: medicine.medical_specialty, Original Contributions, severity, law.invention, 03 medical and health sciences, 0302 clinical medicine, nasopharyngeal swabs, Interquartile range, law, COVID‐19, Internal medicine, medicine, Humans, Pandemics, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, Odds ratio, Emergency department, Original Contribution, General Medicine, Viral Load, medicine.disease, Intensive care unit, mortality, Europe, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Viral pneumonia, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Cohort, Emergency Medicine, France, business, Emergency Service, Hospital, Viral load
Abstract: International audience; Introduction The ongoing COVID-19 pandemic has led to devastating repercussions on health care systems worldwide. This viral infection has a broad clinical spectrum (ranging from influenza-like disease, viral pneumonia, and hypoxemia to acute respiratory distress syndrome requiring prolonged intensive care unit stays). The prognostic impact of measuring viral load on nasopharyngeal swab specimens (by reverse transcriptase polymerase chain reaction [RT-PCR]) is yet to be elucidated. Methods Between March 3 and April 5, 2020, we conducted a retrospective study on a cohort of COVID-19 patients (mild or severe disease) who were hospitalized after presenting to the emergency department (ED) and had at least one positive nasopharyngeal swab during their hospital stay. We led our study at the University Hospitals of Strasbourg in the Greater East region of France, one of the pandemic's epicenters in Europe. Results We have collected samples from a cohort of 287 patients with a confirmed diagnosis of COVID-19 who were included in our study. Nearly half of them (50.5%) presented a mild form of the disease, while the other half (49.5%) presented a severe form, requiring mechanical ventilation. Median (interquartile range) viral load on the initial upper respiratory swab at admission was 4.76 (3.29–6.06) log10 copies/reaction. When comparing survivors and nonsurvivors, this viral load measurement did not differ according to subgroups (p = 0.332). Additionally, we have found that respiratory viral load measurement was predictive of neither in-hospital mortality (adjusted odds ratio [AOR] = 1.05, 95% confidence interval [CI] = 0.85 to 1.31, p = 0.637) nor disease severity (AOR = 0.88, 95% CI = 0.73 to 1.06, p = 0.167). Conclusion Respiratory viral load measurement on the first nasopharyngeal swab (by RT-PCR) during initial ED management is neither a predictor of severity nor a predictor of mortality in SARS-CoV-2 infection. Host response to this viral infection along with the extent of preexisting comorbidities might be more foretelling of disease severity than the virus itself.
Published: 2021
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21. Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection

Author: Anne Schneider, Aurélie Velay, David Rey, Arnaud Fontanet, Timothée Bruel, Baptiste Panaget, Nicolas Meyer, Yves Hansmann, Laurence Kling-Pillitteri, Olivier Schwartz, Floriane Gallais, Samira Fafi-Kremer, Elodie Laugel, Pierre Gantner, María González, Nathalie Reix, Catherine Schmidt-Mutter, Jean-Marc Lessinger, Jérôme De Seze, Ludovic Glady, Marialuisa Partisani, Nicolas Collongues, Morgane Solis, Marie-Josée Wendling, Sophie Bayer, Delphine Planas, Bertram, Marie-Liesse, APPEL À PROJETS GÉNÉRIQUE 2018 - Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées - - HuMABK2018 - ANR-18-CE17-0028 - AAPG2018 - VALID, Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Laboratoire de Génétique Moléculaire [CHRU Strasbourg], CHRU Strasbourg, CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), Service des Maladies Infectieuses et Tropicales [CHU Strasbourg], Service de Santé Publique [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), This work was supported by Strasbourg University Hospital (SeroCoV-HUS, PRI 7782), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d'Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX), Strasbourg University and Institut National de la Santé et de la Recherche Médicale (UMR_S 1109)., ANR-18-CE17-0028,HuMABK,Les anticorps monoclonaux humains : une Nouvelle approche thérapeutique contre l'infection par le virus BK et les maladies associées(2018), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, Medicine (General), Time Factors, Antibodies, Viral, Neutralization, Immunoglobulin G, 0302 clinical medicine, Medicine, Longitudinal Studies, Prospective Studies, Prospective cohort study, 0303 health sciences, biology, Incidence (epidemiology), Antibody titer, General Medicine, Middle Aged, 3. Good health, Vaccination, Titer, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Antibody, Research Paper, Adult, COVID-19 Vaccines, Neutralizing antibodies, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Coronavirus Nucleocapsid Proteins, Humans, 030304 developmental biology, business.industry, SARS-CoV-2, Immunity, COVID-19, Phosphoproteins, Antibodies, Neutralizing, Immunity, Humoral, Kinetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Reinfection, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants., Graphical abstract Image, graphical abstract
Published: 2021

22. In‐depth virological assessment of kidney transplant recipients with COVID‐19

Author: Aurélie Velay, Clement Baldacini, Noëlle Cognard, Ilies Benotmane, Louise Gontard, Margaux Della-Chiesa, Samira Fafi-Kremer, Dogan Firat Bozman, Floriane Gallais, Marie Josée Wendling, Heloise Delagreverie, Dimitri Bedo, Sophie Caillard, Gabriela Gautier-Vargas, Bruno Moulin, Francoise Heibel, Laura Braun-Parvez, Morgane Solis, Mylene Sagnard, Jérôme Olagne, David Marx, Xavier Bassand, Baptiste Panaget, and Peggy Perrin
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Enzyme-Linked Immunosorbent Assay, Comorbidity, 030230 surgery, Brief Communication, Antibodies, Viral, Gastroenterology, Kidney transplant, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Nasopharynx, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Viral shedding, Pandemics, Aged, Transplantation, biology, business.industry, SARS-CoV-2, COVID-19, Middle Aged, Viral Load, Kidney Transplantation, Survival Rate, medicine.anatomical_structure, biology.protein, Female, France, Antibody, business, Viral load, Respiratory tract
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.
Published: 2020

23. In-depth virological assessment of kidney transplant recipients with COVID-19

Author: Morgane Solis, Baptiste Panaget, Clement Baldacini, Mylene Sagnard, Ilies Benotmane, Dogan-Firat Bozman, Francoise Heibel, Gabriela Gautier Vargas, Samira Fafi-Kremer, Louise Gontard, Noëlle Cognard, Laura Braun, B. Moulin, Heloise Delagreverie, Dimitri Bedo, Margaux Della Chiesa, Aurélie Velay, Jérôme Olagne, David Marx, Peggy Perrin, Floriane Gallais, Xavier Bassand, Marie-Josée Wendling, and Sophie Caillard
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), biology, business.industry, viruses, Kidney transplant, Gastroenterology, Serology, medicine.anatomical_structure, Disease severity, Internal medicine, medicine, biology.protein, Viral shedding, Antibody, business, Viral load, Respiratory tract
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.
Published: 2020

24. CT lung lesions as predictors of early death or ICU admission in COVID-19 patients

Author: Yves Hansmann, François Danion, Nicolas Lefebvre, Morgane Solis, Valentin Greigert, Sabrina Kepka, Charlotte Kaeuffer, Yvon Ruch, Mickaël Ohana, Aissam Labani, Pascal Bilbault, Thibaut Fabacher, and Centre Hospitalier Régional Universitaire de Strasbourg (CHRU de Strasbourg)
Subjects: 0301 basic medicine, Male, Severity of Illness Index, law.invention, 0302 clinical medicine, COVID-19 Testing, law, Clinical endpoint, 030212 general & internal medicine, Lung, Computed tomography, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Reverse Transcriptase Polymerase Chain Reaction, General Medicine, Middle Aged, Prognosis, Intensive care unit, 3. Good health, Intensive Care Units, Infectious Diseases, medicine.anatomical_structure, Female, Radiology, Coronavirus Infections, Microbiology (medical), Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 030106 microbiology, Pneumonia, Viral, Article, 03 medical and health sciences, Betacoronavirus, Severity of illness, medicine, Humans, Visual quantification, Pandemics, Survival analysis, Aged, Retrospective Studies, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, COVID-19, Retrospective cohort study, Survival Analysis, Confidence interval, Coronavirus, Ground-glass opacities, business, Tomography, X-Ray Computed, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective The main objective of this study was to investigate the prognostic value of early systematic chest computed tomography (CT) with quantification of lung lesions in coronavirus disease 2019 (COVID-19) patients. Methods We studied 572 patients diagnosed with COVID-19 (confirmed using polymerase chain reaction) for whom a chest CT was performed at hospital admission. Visual quantification was used to classify patients as per the percentage of lung parenchyma affected by COVID-19 lesions: normal CT, 0–10%, 11–25%, 26–50%, 51–75% and >75%. The primary endpoint was severe disease, defined by death or admission to the intensive care unit in the 7 days following first admission. Results The mean patient age was 66.0 ± 16.0 years, and 343/572 (60.0%) were men. The primary endpoint occurred in 206/572 patients (36.0%). The extent of lesions on initial CT was independently associated with prognosis (odds ratio = 2.35, 95% confidence interval 1.24–4.46; p 50% (66/95, 69.5%) developed severe disease compared to patients with lung involvement of 26–50% (70/171, 40.9%) and ≤25% (70/306, 22.9%) (p, Graphical abstract Image 1
Published: 2020

25. Coronavirus Disease 2019: Associated Multiple Organ Damage

Author: Seyyid Baloglu, Olivier Collange, Arnaud Sauer, Mathieu Anheim, Charlotte Kaeuffer, Xavier Delabranche, Charles Tacquard, Patrick Pessaux, Mickaël Ohana, Walid Oulehri, Stéphane Kremer, Patrick Ohlmann, Ian Leonard-Lorant, Paul-Michel Mertes, Morgane Solis, Mihaela Onea, univOAK, Archive ouverte, Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Stress vasculaire et tissulaire en transplantation : microparticules et environnement, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des interactions hôte pathogène (DIHP), Hôpital de Hautepierre [Strasbourg], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Biotechnologie et signalisation cellulaire (BSC), and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Coronavirus disease 2019 (COVID-19), COVID19, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pulmonary infection, severe acute respiratory syndrome, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Kidney, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Lung, microthrombi, business.industry, SARS-CoV-2, Brief Report, COVID-19, medicine.disease, Pathophysiology, Pulmonary embolism, Organ damage, medicine.anatomical_structure, AcademicSubjects/MED00290, Infectious Diseases, Oncology, Immunology, brain magnetic resonance imaging, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, 030217 neurology & neurosurgery
Abstract: A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2., This patient with severe COVID-19 presented damage to five different organs: lungs, kidneys, brain, eyes and gut were injured. The multiplicity of injured organs argues for a systemic response to SARS-CoV-2 infection. “
Published: 2020

26. Neurol-Neuroimmunol

Author: Cornelia Kuhnert, Vincent Poindron, Morgane Solis, Thierry Martin, Sandrine Hirschi, Aurélien Guffroy, Laurent Kremer, Anne Molitor, Raphael Carapito, Yves Hansmann, Vincent Gies, Anne-Sophie Korganow, Yannick Dieudonné, and Cédric Lenormand
Subjects: Autoimmune disease, 0303 health sciences, Systemic lupus erythematosus, business.industry, medicine.medical_treatment, Progressive multifocal leukoencephalopathy, Interleukin, Immunosuppression, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Neurology, Immune reconstitution inflammatory syndrome, Immunology, medicine, Primary immunodeficiency, Neurology (clinical), Sarcoidosis, business, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: ObjectiveTo report the association of JC virus infection of the brain (progressive multifocal encephalopathy [PML]) during the course of sarcoidosis and the challenging balance between immune reconstitution under targeted cytokine interleukin 7 (IL7) therapy for PML and immunosuppression for sarcoidosis.MethodsOriginal case report including deep sequencing (whole-exome sequencing) to exclude a primary immunodeficiency (PID) and review of the literature of cases of PML and sarcoidosis.ResultsWe report and discuss here a challenging case of immune reconstitution with IL7 therapy for PML in sarcoidosis in a patient without evidence for underling PID or previous immunosuppressive therapy.ConclusionsNew targeted therapies in immunology and infectiology open the doors of more specific and more specialized therapies for patients with immunodeficiencies, autoimmune diseases, or cancers. However, before instauration of these treatments, the risk of immune reconstitution inflammatory syndrome and potential exacerbation of an underlying disease must be considered. It is particularly true in case of autoimmune disease such as sarcoidosis or lupus.
Published: 2020

27. Neutralizing Antibody–Mediated Response and Risk of BK Virus–Associated Nephropathy

Author: Wallys Kack-Kack, Aurélie Velay, Samira Fafi-Kremer, Siamak Bahram, Françoise Stoll-Keller, Eric Soulier, Sophie Caillard, Mélanie Joly, Bruno Moulin, Mariam Meddeb, Pilar Domingo-Calap, Morgane Solis, Heidi Barth, and Raphaël Porcher
Subjects: 0301 basic medicine, business.industry, viruses, medicine.medical_treatment, virus diseases, Immunosuppression, Viremia, General Medicine, 030230 surgery, medicine.disease_cause, medicine.disease, Lower risk, BK virus, Nephropathy, 03 medical and health sciences, Titer, 030104 developmental biology, 0302 clinical medicine, Clinical Research, Nephrology, Immunology, medicine, business, Viral load, Kidney transplantation
Abstract: BK virus–associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype–specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients’ neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against the donor’s strain
Published: 2017

28. Letter to the Editor concerning 'Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy'

Author: Bruno Moulin, Ilies Benotmane, Morgane Solis, Samira Fafi-Kremer, and Sophie Caillard
Subjects: Transplantation, Letter to the editor, Infectious disease (medical specialty), business.industry, medicine, Immunology and Allergy, Pharmacology (medical), Viremia, medicine.disease, business, Virology, Nephropathy
Published: 2019

29. Intravenous Immunoglobulin Administration Significantly Increases BKPyV Genotype-Specific Neutralizing Antibody Titers in Kidney Transplant Recipients

Author: Bruno Moulin, Aurélie Velay, Sophie Caillard, Ilies Benotmane, Eric Soulier, Samira Fafi-Kremer, Pierre Gantner, and Morgane Solis
Subjects: Adult, Male, Adolescent, Genotype, 030230 surgery, medicine.disease_cause, Antiviral Agents, Nephropathy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Neutralizing antibody, Kidney transplantation, Aged, 030304 developmental biology, Pharmacology, Polyomavirus Infections, 0303 health sciences, biology, business.industry, Immunologic Deficiency Syndromes, Immunoglobulins, Intravenous, Middle Aged, medicine.disease, Antibodies, Neutralizing, Kidney Transplantation, BK virus, Titer, Infectious Diseases, BK Virus, Immunology, biology.protein, Female, Antibody, business
Abstract: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the major causes of kidney graft dysfunction, and there are no BKPyV-specific antiviral therapies available. BKPyV neutralizing antibodies (NAbs) play key roles in protecting against BKPyV replication and represent a potential therapeutic or preventive strategy. In this study, we evaluated NAb titers in intravenous immunoglobulin (i.v. Ig) preparations and in kidney transplant recipients (KTR) before and after i.v. Ig administration. NAb titers directed against major BKPyV genotypes were measured using a BKPyV pseudovirion system. Thirty-three KTR receiving high (1 g/kg of body weight/day; n = 17) or low (0.4 g/kg/day; n = 16) i.v. Ig doses were included. Median NAb titers in i.v. Ig preparations ranged from 5.9 log(10) 50% inhibitory concentration (IC(50)) for genotype I to 4.1 log(10) IC(50) for genotype IV. A mean of 90% of patients (range, 88% to 100%) displaying low or negative BKPyV NAb titers against genotype I reached 4 log(10) IC(50) after the first i.v. Ig administration. This value was reached by a mean of 44% (range, 13% to 83%) and 19% (range, 0% to 38%) of patients against genotype II and genotype IV, respectively. The benefit of i.v. Ig administration persisted until the following course of treatment (day 22 ± 7 days) for genotypes I and II, and no cumulative effect was observed through the three doses. Our findings demonstrate that i.v. Ig administration results in a significant increase in BKPyV NAb titers in KTR. These in vitro and in vivo pharmacokinetic data provide the rationale for a proof-of-concept study investigating the efficacy of i.v. Ig for the prevention of BKPyV infection in KTR.
Published: 2019

30. [BK-virus and pathophysiology of associated diseases]

Author: Morgane, Solis, Floriane, Gallais, Aurélie, Velay, and Samira, Fafi-Kremer
Subjects: Immunocompromised Host, Polyomavirus Infections, Tumor Virus Infections, BK Virus, Cystitis, Humans, Nephritis, Interstitial, Cell Transformation, Viral, Kidney Transplantation, Bone Marrow Transplantation
Abstract: BK virus (BKV) is a widely distributed polyomavirus in the world population. It is the causative agent of BKV-associated nephropathy in kidney transplant recipients and hemorrhagic cystitis in bone marrow transplant patients. To date, there is no specific antiviral treatment against BKV. A better understanding of the pathophysiology of BKV-associated diseases, especially in immunocompromised patients, may contribute to the development of novel preventive and therapeutic strategies. After a detailed description of the genomic characteristics of the virus, its replication cycle and available model systems, the pathophysiological and immune mechanisms involved in BKV infection are developed and discussed in this review.
Published: 2019

31. Inadequate Immune Humoral Response against JC Virus in Progressive Multifocal Leukoencephalopathy Non-Survivors

Author: Stéphane Kremer, Samira Fafi-Kremer, Jérôme De Seze, François Lersy, Yves Hansmann, Xavier Argemi, Morgane Solis, N. Douiri, Mathilde Renaud, Floriane Gallais, Aurélien Guffroy, Eric Soulier, univOAK, Archive ouverte, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Genotype, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, viruses, lcsh:QR1-502, JC virus, Antibodies, Viral, medicine.disease_cause, lcsh:Microbiology, immunology, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Neutralization Tests, Virology, Humans, Medicine, 030212 general & internal medicine, Neutralizing antibody, biology, business.industry, Communication, Progressive multifocal leukoencephalopathy, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Leukoencephalopathy, Progressive Multifocal, Viral Load, medicine.disease, Antibodies, Neutralizing, JC Virus, Pathophysiology, Immunity, Humoral, Titer, 030104 developmental biology, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Host-Pathogen Interactions, Mutation, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, viral infection, business, predictive marker, Viral load
Abstract: International audience; JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization “blind spot” was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients’ humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.
Published: 2020

32. Sequence Variation in Amplification Target Genes and Standards Influences Interlaboratory Comparison of BK Virus DNA Load Measurement

Author: Pilar Domingo-Calap, Bruno MOULIN, Valerie Giordanengo, Seiamak Bahram, Véronique Avettand-Fenoel, Sébastien Hantz, Samira Fafi-Kremer, Jerome LeGoff, ALEXANDRA DUCANCELLE, Bruno POZZETTO, Sophie Caillard, ERIC SOULIER, Peggy Perrin, Sylvie Pillet, Morgane Solis, Astrid VABRET, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), French BKV Study Group, Laboratoire de Virologie [Hôpitaux universitaires de Strasbourg], Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Virulence bactérienne précoce, Université de Strasbourg (EA7290), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Service de Néphrologie et Transplantation, Interaction virus-hôte et maladies du foie, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and BRICHEUX, Genevieve
Subjects: Microbiology (medical), Laboratory Proficiency Testing, viruses, 030230 surgery, Biology, medicine.disease_cause, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Sensitivity and Specificity, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, isolation & purification, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Genetic variation, Genotype, medicine, Humans, Sequence variation, methods, standards, Gene, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, Sciences du Vivant [q-bio]/Ingénierie biomédicale, Polyomavirus Infections, 0303 health sciences, diagnosis, virology, 030306 microbiology, genetics, Genetic Variation, virus diseases, Viral Load, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, DNA extraction, Hospitals, 3. Good health, BK virus, BK Virus, DNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, Primer (molecular biology), Viral load
Abstract: International guidelines define a BK virus (BKV) load of ≥4 log 10 copies/ml as presumptive of BKV-associated nephropathy (BKVN) and a cutoff for therapeutic intervention. To investigate whether BKV DNA loads (BKVL) are comparable between laboratories, 2 panels of 15 and 8 clinical specimens (urine, whole blood, and plasma) harboring different BKV genotypes were distributed to 20 and 27 French hospital centers in 2013 and 2014, respectively. Although 68% of the reported results fell within the acceptable range of the expected result ±0.5 log 10 , the interlaboratory variation ranged from 1.32 to 5.55 log 10 . Polymorphisms specific to BKV genotypes II and IV, namely, the number and position of mutations in amplification target genes and/or deletion in standards, arose as major sources of interlaboratory disagreements. The diversity of DNA purification methods also contributed to the interlaboratory variability, in particular for urine samples. Our data strongly suggest that (i) commercial external quality controls for BKVL assessment should include all major BKV genotypes to allow a correct evaluation of BKV assays, and (ii) the BKV sequence of commercial standards should be provided to users to verify the absence of mismatches with the primers and probes of their BKV assays. Finally, the optimization of primer and probe design and standardization of DNA extraction methods may substantially decrease interlaboratory variability and allow interinstitutional studies to define a universal cutoff for presumptive BKVN and, ultimately, ensure adequate patient care.
Published: 2015

33. Towards a pharmacochemical hypothesis of the prophylaxis of SARS-CoV-2 by psychoactive substances

Author: Morgane Solis, Wissam El-Hage, Coraline Hingray, Julien Petrignet, Luisa Weiner, Jeanne Briet, Frédéric Addiego, Hervé Javelot, Laboratoire de pharmacologie et de toxicologie neurocardiovasculaire (LPTNC), Université de Strasbourg (UNISTRA), Synthèse et isolement de molécules bio-actives EA 7502 (SIMBA), Université de Tours, Luxembourg Institute of Science and Technology (LIST), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Psychologie des Cognitions (LPC), Université de Tours (UT), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Nicotine, medicine.medical_specialty, Middle East respiratory syndrome coronavirus, viruses, Aucun, Context (language use), Infectious bronchitis virus, Comorbidity, Disease, Severe Acute Respiratory Syndrome, Virus Replication, medicine.disease_cause, Antiviral Agents, Chemoprevention, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diabetes mellitus, Internal medicine, Humans, Medicine, Polypharmacy, Neurotransmitter Agents, Psychotropic Drugs, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, Mental Disorders, COVID-19, virus diseases, General Medicine, Models, Theoretical, medicine.disease, Obesity, COVID-19 Drug Treatment, 3. Good health, 030104 developmental biology, Caregivers, Sciences de l'Homme et Société/Psychologie, Immune System, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Coronavirus Infections, business, 030217 neurology & neurosurgery
Abstract: SJR 2019 Q3; An increasing body of evidence suggests a protective effect of some psychoactive substances against SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus type 2). Recent findings suggest that patients with psychiatric disorders are less affected by SARS-CoV-2 than their caregivers, which may seem surprising given some of the frequent risk factors for an unfavorable course of the disease (e.g., obesity, diabetes, cardiovascular and pulmonary diseases). We propose here a mixed pharmacoepidemiological and pharmacochemical hypothesis to explain these findings. A number of psychotropic drugs exhibit activities against coronaviruses (Middle East Respiratory Syndrome coronavirus (MERS-CoV), the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and the Infectious Bronchitis Virus (IBV)) and have been put forward as potentially anti-SARS-CoV-2. These treatments include numerous mee-too drugs (chemically and pharmacologically linked to those which have demonstrated anti-SARS-CoV-2 efficacy) which are frequently prescribed in psychiatric settings. Taken alone or in polypharmacy, these drugs could have a prophylactic anti-SARS-CoV-2 effect, explaining the unexpectedly low proportion of patients with psychiatric disorders and COVID-19. Associated factors such as nicotine can also be considered in the context of a broad chemoprophylactic hypothesis in patients with psychiatric disorders taking different psychoactive substances.
Published: 2020

34. Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation

Author: B. Moulin, Pierre Gantner, R. Freitag, J. Bausson, Sophie Caillard, Aurélie Velay, Samira Fafi-Kremer, A. Filipputtu, Morgane Solis, Immuno-Rhumatologie Moléculaire, and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Graft Rejection, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030106 microbiology, Viremia, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Clinical Decision Rules, medicine, BK Virus Infection, Humans, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Kidney transplantation, Aged, Torque teno virus, Polyomavirus Infections, business.industry, Hazard ratio, Immunosuppression, Middle Aged, medicine.disease, Kidney Transplantation, DNA Virus Infections, 3. Good health, BK virus, Transplantation, surgical procedures, operative, Infectious Diseases, BK Virus, Female, business, CD8, Biomarkers
Abstract: Summary Objectives New biomarkers reflecting the degree of immunosuppression in transplant recipients are needed to provide an optimal personalized balance between rejection and infection risks. Methods For this purpose, we investigated TTV viremia dynamics in 66 kidney transplant recipients followed up for two years after transplantation, in relation to BK virus infection and graft rejection. Results After transplantation, TTV viremia rose by ≥2 log10 copies/mL from baseline to month 3, then declined by ≥1 log10 copies/mL thereafter. Higher TTV viremia was associated with recipients of a deceased donor, a lower count of CD8+ T cells and a higher BKV viremia. Importantly, TTV loads were significantly lower in KTR who would later display graft rejection; indeed, patients with TTV viremia lower than 3.4 log10 copies/mL at transplantation or lower than 4.2 log10 copies/mL at month 1 had a higher risk of developing graft rejection in the two following years (hazard ratio (HR) at D0 = 7.30, p = 0.0007 and HR at M1 = 6.16, p = 0.001). Conclusions TTV viremia measurement at early times post transplantation predicts graft rejection and would represent a useful tool to improve kidney transplant monitoring.
Published: 2018

35. Herpes simplex virus 2 hepatitis in a lung transplant recipient: a diagnostic challenge

Author: Sandrine Hirschi, V. Rosner, Ronald C. Kessler, D. Biondini, Morgane Solis, A. D'Urso, and Mickaël Ohana
Subjects: Adult, Hepatitis, Viral, Human, Herpesvirus 2, Human, viruses, medicine.medical_treatment, Acyclovir, Immunoglobulins, Herpes simplex virus, medicine.disease_cause, Antiviral Agents, Cystic fibrosis, Hepatitis, Immunocompromised Host, Quantitative polymerase chain reaction, medicine, Humans, Lung transplantation, Viral, Transplantation, business.industry, Herpesvirus 2, Immunoglobulins, Intravenous, Immunosuppression, medicine.disease, Infectious Diseases, Real-time polymerase chain reaction, Immunology, Female, Cholecystectomy, Lung Transplantation, Intravenous, business, Complication, Human
Abstract: Herpes simplex virus (HSV) hepatitis is a rare and serious complication in immunocompromised patients. We report the case of an HSV hepatitis occurring 4 years after lung transplantation in a cystic fibrosis patient. The presentation was nonspecific, mimicking acute cholecystitis; orogenital signs were absent. The diagnosis was made based on viral cultures performed during cholecystectomy and confirmed by blood quantitative polymerase chain reaction. Although the diagnosis and treatment were delayed, the patient fully recovered with acyclovir, reduced immunosuppression, and intravenous immunoglobulins. The diagnostic difficulties, prognostic factors, and treatments of this infection are discussed.
Published: 2015

36. Clinical relevance of herpes simplex virus viremia in Intensive Care Unit patients

Author: Morgane Solis, F. Stoll-Keller, Charlotte Sueur, Francis Schneider, H. Barth, L. Glady, Samira Fafi-Kremer, François Lefebvre, Quentin Lepiller, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Laboratoire de Virologie [Strasbourg], Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Lissalde, Claire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)
Subjects: Adult, Male, Microbiology (medical), Herpes simplex, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, viruses, medicine.medical_treatment, Viremia, medicine.disease_cause, Polymerase Chain Reaction, law.invention, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, Prevalence, medicine, Humans, Simplexvirus, Aged, Retrospective Studies, Aged, 80 and over, Mechanical ventilation, Hepatitis, business.industry, Mortality rate, Middle Aged, medicine.disease, Survival Analysis, Intensive care unit, 3. Good health, Intensive Care Units, Pneumonia, Blood, Infectious Diseases, Herpes simplex virus, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load
Abstract: Summary Objectives To determine the clinical relevance of herpes simplex virus (HSV) viremia episodes in critically ill adult patients. Methods 1556 blood samples obtained for HSV PCR analysis in Intensive Care Unit (ICU) patients over 4 years were retrospectively analyzed, focusing on the comprehensive analysis of 88 HSV-viremic patients. Results HSV DNA was detected in 11.8% of samples from the ICU. HSV viral loads remained below 5×10 2 copies/ml in 68.2% of patients and exceeded 10 4 copies/ml in 7.9%. Episodes of HSV-viremia correlated with immunosuppressed status and mechanical ventilation in 79.5% and 65.9% of patients, respectively. Only a subset of patients exhibited HSV-related organ damage, including pneumonia and hepatitis (10.2% and 2.3%, respectively). The mortality rate in HSV-viremic patients was not significantly increased compared to the overall mortality rate in the ICU (27.3% vs. 22.9%, p = 0.33). Only patients with high HSV viral loads tended to have a higher, though non-significant, death rate (57.1%, p = 0.14). Conclusions Our results suggest HSV viremia is common in ICU patients, potentially favored by immunocompromised status and mechanical ventilation. The global impact of HSV-viremia on mortality in the ICU was low. Quantifying HSV DNA may help identifying patients at-risk of severe HSV-induced symptoms.
Published: 2015

37. Toward Standardization of BK Virus Monitoring: Evaluation of the BK Virus R-gene Kit for Quantification of BK Viral Load in Urine, Whole-Blood, and Plasma Specimens

Author: Morgane Solis, Pilar Domingo-Calap, Heidi Barth, Françoise Stoll-Keller, Samira Fafi-Kremer, Charlotte Sueur, Quentin Lepiller, Mariam Meddeb, Seiamak Bahram, Rachel Freitag, Sophie Caillard, and Eric Soulier
Subjects: Microbiology (medical), Urine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Biology, medicine.disease_cause, Virology, Genotype, medicine, Humans, methods, standards, Whole blood, Polyomavirus Infections, Reproducibility of Results, R gene, Viral Load, Molecular diagnostics, virology, BK virus, Tumor Virus Infections, Blood, BK Virus, Reagent Kits, Diagnostic, Viral load
Abstract: Screening of BK virus (BKV) replication is recommended to identify patients at increased risk of BKV-associated diseases. However, the heterogeneity of molecular techniques hinders the establishment of universal guidelines for BKV monitoring. Here we aimed to compare the performance of the CE-marked BK virus R-gene kit (R-gene) to the performance of our in-house assay for quantification of BKV DNA loads (BKVL). A 12-specimen panel from the Quality Control for Molecular Diagnostics (QCMD) organization, 163 urine samples, and 88 paired specimens of plasma and whole blood (WB) from transplant recipients were tested. Both the R-gene and in-house assays showed a good correlation within the QCMD panel ( r = 0.995 and r = 0.989, respectively). BKVL were highly correlated between assays, although positive biases were observed with the in-house assay in analysis of urine (0.72 ± 0.83 log 10 copies/ml), plasma (1.17 ± 0.63 log 10 copies/ml), and WB (1.28 ± 0.37 log 10 copies/ml). Recalibration with a common calibrator significantly reduced the bias in comparisons between assays. In contrast, BKVL was underestimated with the in-house PCR in eight samples containing BKV genotype II, presenting point mutations at primer-annealing sites. Using the R-gene assay, plasma and WB specimens were found to be equally suitable for quantification of BKVL, as indicated by the high correlation coefficient ( r = 0.965, P < 0.0001). In conclusion, the R-gene assay demonstrated reliable performance and higher accuracy than the in-house assay for quantification of BKVL in urine and blood specimens. Screening of BKV replication by a well-validated commercial kit may enable clinical laboratories to assess viral loads with greater reproducibility and precision.
Published: 2014

38. A new hot spot for tick-borne encephalitis (TBE): A marked increase of TBE cases in France in 2016

Author: Aurélie Velay, Emmanuelle Cart-Tanneur, Olivier Augereau, P. Kieffer, Caroline Lohmann, Xavier Argemi, Marianne Maquart, Wallys Kack-Kack, Yves Hansmann, Martin Martinot, Samira Fafi-Kremer, Jean Dominique Poveda, Pierre Gantner, Marie-Josée Wendling, Morgane Solis, Sylvie De Martino, Dominique De Briel, Benoît Jaulhac, Sophie Raguet, Isabelle Leparc-Goffart, Laboratoire de Virologie [Strasbourg], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Centre National de Référence (CNR) des Arbovirus - Laboratoire coordonnateur : Equipe Résidente de Recherche d'Infectiologie Tropicale (ERRIT), Institut de Recherche Biomédicale des Armées Hôpital d’Instruction des Armées Laveran, Service de Médecine Interne et de Rhumatologie [Colmar], Hôpitaux Civils Colmar, Laboratoire de Microbiologie [Colmar], Hospices civils Colmar, Médecine interne [CH Emile Muller, Mulhouse], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Laboratoire de Microbiologie [GHR Mulhouse Sud-Alsace, Mulhouse], Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Département de Génétique et de Biologie Spécialisée [Saint-Ouen-L'aumône] (Laboratoire CERBA), Laboratoire CERBA [Saint Ouen l'Aumône], Département Immunologie [Lyon] (Les Laboratoires Eurofins Biomnis), Eurofins Biomnis, Service des Maladies Infectieuses et Tropicales [CHU Strasbourg], CHU Strasbourg, Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Santé publique France - French National Public Health Agency [Saint-Maurice, France], BUISINE, Soline, Eurofins Biomnis [Lyon, France], and Santé publique France
Subjects: 0301 basic medicine, Male, Pediatrics, Pathology, Health agency, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Tick-borne encephalitis, Tick-borne diseases, Prospective Studies, Child, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Tick-borne disease, Incidence, Zoonotic infection, Middle Aged, Antibodies, Bacterial, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Seasons, Encephalitis, Encephalitis, Tick-Borne, Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, 030231 tropical medicine, Enzyme-Linked Immunosorbent Assay, Biology, Microbiology, Encephalitis Viruses, Tick-Borne, 03 medical and health sciences, Young Adult, medicine, Humans, Aged, Retrospective Studies, medicine.disease, Lyme Neuroborreliosis, Immunoglobulin M, Insect Science, Immunoglobulin G, Parasitology, Neurological impairment
Abstract: Objectives Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. In 2016, in Northeastern France, we faced a TBEV infection increase, leading to a warning from the Regional Health Agency. Here, we report the confirmed TBE cases diagnosed between January 2013 and December 2016, with particular emphasis on the year 2016. Methods A total of 1643 blood and cerebrospinal fluid (CSF) samples from everywhere in France, corresponding to 1460 patients, were prospectively tested for anti-TBEV-specific IgM and IgG antibodies by ELISA. Additional 39 blood and CSF samples from patients with suspected Lyme neuroborreliosis were retrospectively investigated. Results The TBEV seropositivity rate was estimated to 5.89% and 54 patients were diagnosed as TBE-confirmed cases. A significant increase in TBE cases was observed during the year 2016 with 29 confirmed cases, instead of a mean of eight cases during the three previous years (p = 0.0006). Six imported cases and 48 autochthonous cases, located in the Alsace region (n = 43) and in the Alpine region (n = 5) were reported. Forty-six patients experienced neurological impairment. Nine patients showed an incomplete recovery at last follow-up (from 15 days to eight months post-infection). TBE diagnosis was performed earlier for patients taken in charge in the Alsace region than those hospitalized elsewhere in France (p = 0.0087). Among the 39 patients with suspected Lyme neuroborreliosis retrospectively investigated, one showed a TBEV recent infection. Conclusion The TBE increase that occurred in France in 2016 highlights the need to improve our knowledge about the true burden of TBEV infection and subsequent long-term outcomes.
Published: 2017

39. Comparison of six commercial tick-borne encephalitis IgM and IgG ELISA kits and the molecular characterization of their antigenic design

Author: Véronique Sohn, Samira Fafi-Kremer, Aurélie Velay, Marie-Josée Wendling, Morgane Solis, Heidi Barth, Anne Moncollin, and Amandine Neeb
Subjects: 0301 basic medicine, Microbiology (medical), 030106 microbiology, Enzyme-Linked Immunosorbent Assay, Antibodies, Viral, Sensitivity and Specificity, Immunoglobulin G, Virus, Serology, 03 medical and health sciences, medicine, Humans, Serologic Tests, biology, Tick-borne encephalitis, Reproducibility of Results, General Medicine, medicine.disease, biology.organism_classification, Virology, Tick-borne encephalitis virus, 030104 developmental biology, Infectious Diseases, Immunoglobulin M, biology.protein, Reagent Kits, Diagnostic, Antibody, Encephalitis, Encephalitis, Tick-Borne
Abstract: Tick-borne encephalitis virus (TBEV) diagnosis is mainly based on the detection of viral-specific antibodies in serum. Several commercial assays are available, but published data on their performance remain unclear. We assessed six IgM and six IgG commercial enzyme-linked immunosorbent assay (ELISA) kits (ELISA-1 through ELISA-6) using 94 samples, including precharacterized TBEV-positive samples (n=50) and -negative samples (n=44). The six manufacturers showed satisfactory sensitivity and specificity and high overall agreement for both IgM and IgG. Three manufacturers showed better reproducibility and were the most sensitive (100%) and specific (95.5-98.1%) for both IgM and IgG. Two of them were also in agreement with the clinical interpretation in more than 90% of the cases. All the assays use inactivated virus as antigen, with strains showing approximately 94% homology at the amino acid level. The antigenic format of the assays was discussed to further improve this TBEV diagnostic tool.
Published: 2017

40. Problem-based learning in laboratory medicine resident education: a satisfaction survey

Author: Morgane Solis, Aurélie Velay, Françoise Stoll-Keller, Pierre Gantner, Quentin Lepiller, Charlotte Sueur, Heidi Barth, and Samira Fafi-Kremer
Subjects: Students, Medical, education, Pharmacy Residencies, Medical laboratory, Personal Satisfaction, Formative assessment, 03 medical and health sciences, 0302 clinical medicine, Internship, Surveys and Questionnaires, Virology, Medical Laboratory Science, Humans, Medical education, business.industry, 05 social sciences, 050301 education, Internship and Residency, Resident education, General Medicine, Problem-Based Learning, University hospital, Problem-based learning, Students, Pharmacy, Situational interest, Clinical Competence, France, business, 0503 education, Educational program, 030217 neurology & neurosurgery
Abstract: Theoretical knowledge in biology and medicine plays a substantial role in laboratory medicine resident education. In this study, we assessed the contribution of problem-based learning (PBL) to improve the training of laboratory medicine residents during their internship in the department of virology, Strasbourg University Hospital, France. We compared the residents' satisfaction regarding an educational program based on PBL and a program based on lectures and presentations. PBL induced a high level of satisfaction (100%) among residents compared to lectures and presentations (53%). The main advantages of this technique were to create a situational interest regarding virological problems, to boost the residents' motivation and to help them identify the most relevant learning objectives in virology. However, it appears pertinent to educate the residents in appropriate bibliographic research techniques prior to PBL use and to monitor their learning by regular formative assessment sessions.
Published: 2017

41. RBCs inclusions after splenectomy: not only Howell-Jolly bodies!

Author: Jean-François Lesesve, Jean-Claude Guédenet, Julien Perrin, and Morgane Solis
Subjects: Male, Pathology, medicine.medical_specialty, Basophilic stippling, Multiple Organ Failure, medicine.medical_treatment, Splenectomy, Erythrocytes, Abnormal, Context (language use), Fatal Outcome, Postoperative Complications, Humans, Medicine, Postoperative Period, Kidney, business.industry, Pappenheimer bodies, General Medicine, Middle Aged, medicine.disease, Liver Insufficiency, Erythrocyte Inclusions, Blood smear, medicine.anatomical_structure, Anisocytosis, business
Abstract: We report on several abnormalities of the red blood cells, in particular erythrocytic inclusions, in a 49 year old man. The blood smear presented with marked anisocytosis, target cells, acanthocytes and Howell-Jolly bodies, as well as Pappenheimer bodies and basophilic stippling. These abnormalities can be explained by the clinical context which associated splenectomy, iron overload and severe denutrition. The patient died a few weeks after from kidney and liver insufficiency. We comment on the different features of erythrocytic inclusions and the clinical situations in which they can be found.
Published: 2013

42. 45 years after the discovery of human polyomaviruses BK and JC: Time to speed up the understanding of associated diseases and treatment approaches

Author: Sophie Caillard, Samira Fafi-Kremer, Quentin Lepiller, Charlotte Sueur, Françoise Stoll-Keller, Eric Soulier, Morgane Solis, and Heidi Barth
Subjects: 0301 basic medicine, Polyomavirus Infections, Biomedical Research, Progressive multifocal leukoencephalopathy, Anti viral immunity, General Medicine, Computational biology, Biology, History, 20th Century, medicine.disease, Applied Microbiology and Biotechnology, Microbiology, Polyomavirus associated nephropathy, History, 21st Century, JC Virus, 03 medical and health sciences, 030104 developmental biology, BK Virus, Virology, Immunology, Host-Pathogen Interactions, medicine, Humans, Viral persistence
Abstract: Nearly 45 years after the discovery of the first two human polyomaviruses BK and JC, their life-long persistence and mechanisms of pathogenesis remain poorly understood and efficient antiviral treatments are severely lacking. In this review, we sought to provide an update on recent advances in understanding the life cycle of these two viruses, particularly focusing on their interaction with the host immune system and pathogenesis. We have also discussed novel treatment approaches and highlighted areas of future research.
Published: 2016

43. The Authors Reply

Author: Bruno MOULIN, Samira Fafi-Kremer, Sophie Caillard, Morgane Solis, and Aurélie Velay
Subjects: Polyomavirus Infections, Nephrology, BK Virus, Humans, General Medicine, Polyomavirus, Letters to the Editor, Antibodies, Neutralizing
Published: 2018

44. In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

Author: Aurélie Velay, Morgane Solis, Samira Fafi-Kremer, Heidi Barth, Wallys Kack-Kack, and Eric Soulier
Subjects: 0301 basic medicine, 030106 microbiology, lcsh:QR1-502, polyomavirus, Review, Genome amplification, Biology, lcsh:Microbiology, Pathogenesis, 03 medical and health sciences, In vivo, Virology, medicine, Animals, Humans, In patient, Tropism, in vitro models, Polyomavirus Infections, Merkel cell carcinoma, tropism, pathogenesis, Progressive multifocal leukoencephalopathy, Models, Theoretical, biochemical phenomena, metabolism, and nutrition, medicine.disease, animal models, In vitro, Disease Models, Animal, 030104 developmental biology, Infectious Diseases, Host-Pathogen Interactions, Immunology, entry
Abstract: Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned.
Published: 2016

45. Interlaboratory comparison of BK virus DNA load assays

Author: Françoise Stoll-Keller, Seiamak Bahram, Sophie Caillard, Samira Fafi-Kremer, Peggy Perrin, A. Chabaud, Eric Soulier, Mariam Meddeb, Charlotte Sueur, B. Moulin, Morgane Solis, and Pilar Domingo-Calap
Subjects: Dna load, Infectious Diseases, Chemistry, Virology, medicine, medicine.disease_cause, BK virus
Published: 2015

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