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1. Anti-SARS-CoV-2 Neutralizing Responses in Various Populations: Use of a Rapid Surrogate Lateral Flow Assay and Correlations with Anti-RBD Antibody Levels

Author

Joël Gozlan, Audrey Baron, Anders Boyd, Maud Salmona, Djeneba Fofana, Marine Minier, Audrey Gabassi, Laurence Morand-Joubert, Constance Delaugerre, and Sarah Maylin

Subjects
SARS-CoV-2, neutralizing antibodies, neutralization surrogate assays, Science
Abstract

Background: After the global COVID-19 crisis, understanding post-infectious immunity and vaccine efficacy remains crucial. This study aims to assess anti-SARS-CoV-2 immunity through a quantitative analysis of anti-receptor-binding domain (RBD) antibodies and rapid functional testing of the neutralizing humoral response. Methods: A retrospective analysis was conducted on samples from various cohorts, including partially vaccinated, fully vaccinated, post-COVID/no-vaccination, and post-COVID/vaccination individuals with various immune-competency statuses. The anti-RBD antibodies were measured using an automated chemiluminescence assay, while the neutralizing antibodies’ (NAbs’) activity was assessed through the lateral flow ichroma COVID-19 nAb test (LFT), a surrogate neutralization assay. Results: The analysis revealed various levels of anti-RBD antibodies and seroneutralization responses across cohorts, with the post-COVID/vaccination group demonstrating the most robust protection. A correlation between anti-RBD antibodies and seroneutralization was observed, albeit with varying strength depending on the subgroup analyzed. Longitudinal assessment following natural infection showed an initial surge followed by a decline in both measures. A cutoff of 3.0 log10 BAU/mL was established to predict significant seroneutralization. Conclusions: The ichroma™ COVID-19 nAb test displayed high specificity and emerged as a valuable tool for monitoring anti-SARS-CoV-2 immunity. These findings contribute to understand the antibody response dynamics and underscore the potential of rapid tests in predicting protection against SARS-CoV-2 infection.

Published
2024
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2. Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations

Author

Aurélie Schnuriger, Sophie Vimont, Alexandre Godmer, Joël Gozlan, Salah Gallah, Muriel Macé, Valérie Lalande, Kenda Saloum, Marine Perrier, Nicolas Veziris, and Laurence Morand-Joubert

Subjects
meningitis/encephalitis, pediatric/adult population, performance, sensitivity/specificity, syndromic assay, Microbiology, QR1-502
Abstract

ABSTRACT Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.

Published
2022
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3. Stepwise release of biologically active HMGB1 during HSV-2 infection.

Author

Chloé Borde, Stéphanie Barnay-Verdier, Claire Gaillard, Hakim Hocini, Vincent Maréchal, and Joël Gozlan

Subjects
Medicine, Science
Abstract

BACKGROUND: High mobility group box 1 protein (HMGB1) is a major endogenous danger signal that triggers inflammation and immunity during septic and aseptic stresses. HMGB1 recently emerged as a key soluble factor in the pathogenesis of various infectious diseases, but nothing is known of its behaviour during herpesvirus infection. We therefore investigated the dynamics and biological effects of HMGB1 during HSV-2 infection of epithelial HEC-1 cells. METHODOLOGY/PRINCIPAL FINDINGS: Despite a transcriptional shutdown of HMGB1 gene expression during infection, the intracellular pool of HMGB1 protein remained unaffected, indicating its remarkable stability. However, the dynamics of HMGB1 was deeply modified in infected cells. Whereas viral multiplication was concomitant with apoptosis and HMGB1 retention on chromatin, a subsequent release of HMGB1 was observed in response to HSV-2 mediated necrosis. Importantly, extracellular HMGB1 was biologically active. Indeed, HMGB1-containing supernatants from HSV-2 infected cells induced the migration of fibroblasts from murine or human origin, and reactivated HIV-1 from latently infected T lymphocytes. These effects were specifically linked to HMGB1 since they were blocked by glycyrrhizin or by a neutralizing anti-HMGB1 antibody, and were mediated through TLR2 and the receptor for Advanced Glycation End-products (RAGE). Finally, we show that genital HSV-2 active infections also promote HMGB1 release in vivo, strengthening the clinical relevance of our experimental data. CONCLUSIONS: These observations target HMGB1 as an important actor during HSV-2 genital infection, notably in the setting of HSV-HIV co-infection.

Published
2011
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4. A high-sensitivity method for detection and measurement of HMGB1 protein concentration by high-affinity binding to DNA hemicatenanes.

Author

Claire Gaillard, Chloé Borde, Joël Gozlan, Vincent Maréchal, and François Strauss

Subjects
Medicine, Science
Abstract

BACKGROUND: Protein HMGB1, an abundant nuclear non-histone protein that interacts with DNA and has an architectural function in chromatin, was strikingly shown some years ago to also possess an extracellular function as an alarmin and a mediator of inflammation. This extracellular function has since been actively studied, both from a fundamental point of view and in relation to the involvement of HMGB1 in inflammatory diseases. A prerequisite for such studies is the ability to detect HMGB1 in blood or other biological fluids and to accurately measure its concentration. METHODOLOGY/PRINCIPAL FINDINGS: In addition to classical techniques (western blot, ELISA) that make use of specific anti-HMGB1 antibodies, we present here a new, extremely sensitive technique that is based on the fact that hemicatenated DNA loops (hcDNA) bind HMGB1 with extremely high affinity, higher than the affinity of specific antibodies, similar in that respect to DNA aptamers. DNA-protein complexes formed between HMGB1 and radiolabeled hcDNA are analyzed by electrophoresis on nondenaturing polyacrylamide gels using the band-shift assay method. In addition, using a simple and fast protocol to purify HMGB1 on the basis of its solubility in perchloric acid allowed us to increase the sensitivity by suppressing any nonspecific background. The technique can reliably detect HMGB1 at a concentration of 1 pg per microliter in complex fluids such as serum, and at much lower concentrations in less complex samples. It compares favorably with ELISA in terms of sensitivity and background, and is less prone to interference from masking proteins in serum. CONCLUSION: The new technique, which illustrates the potential of DNA nanoobjects and aptamers to form high-affinity complexes with selected proteins, should provide a valuable tool to further investigate the extracellular functions of HMGB1 and its involvement in inflammatory pathologies.

Published
2008
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5. Mpox Hepatic and Pulmonary Lesions in HIV/Hepatitis B Virus Co-Infected Patient, France

Author

Ruxandra Calin, Claire Périllaud-Dubois, Stéphane Marot, Khaldoun Kerrou, Gilles Peytavin, Marwa Bachir, Anne Laure Kirch, Ludovic Lassel, Vincent Fallet, Joel Gozlan, Jean Baptiste Pain, Patricia Senet, Olivier Ferraris, Sébastien Bine, Mathieu Hubert, Olivier Schwartz, Laurence Morand-Joubert, and Gilles Pialoux

Subjects
mpox, monkeypox virus, HIV, HIV/AIDS and other retroviruses, hepatitis B virus, HBV, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report a case of persistent disseminated mpox evolving over >6 months in an HIV/hepatitis B virus co-infected patient in France who had

Published
2024
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6. Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial)

Author

Karine Lacombe, Raoul Moh, Corine Chazallon, Maud Lemoine, Babacar Sylla, Fatoumata Fadiga, Jerôme Le Carrou, Fabienne Marcellin, Charles Kouanfack, Laura Ciaffi, Michelle Tagni Sartre, Magloire Biwole Sida, Alpha Diallo, Joel Gozlan, Moussa Seydi, Viviane Cissé, Christine Danel, Pierre Marie Girard, Thomas d’Aquin Toni, Albert Minga, Sylvie Boyer, Patrizia Carrieri, Alain Attia, and The TAC ANRS12311 Study Group

Subjects
Hepatitis C, HIV, Africa, Sofosvubir, Clinical trial, Viral resistance, Medicine, Science
Abstract

Abstract Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Published
2024
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7. Caution in interpretation of SARS-CoV-2 quantification based on RT-PCR cycle threshold value

Author

Kenda Saloum, Aurélie Schnuriger, Yanne Michel, Corinne Amiel, D. B. Fofana, Marine Perrier, Narjis Boukli, Joël Gozlan, Laurence Morand-Joubert, Valérie Marinho, Sidonie Lambert-Niclot, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Microbiology (medical), Oncology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Datasets as Topic, Genome, Viral, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Nasopharynx, medicine, Humans, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, Cycle threshold, business.industry, Diagnostic Tests, Routine, SARS-CoV-2, COVID-19, General Medicine, Viral Load, Infectious Diseases, Real-time polymerase chain reaction, COVID-19 Nucleic Acid Testing, RNA, Viral, Original Article, business, Viral load
Abstract

International audience; RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.

Published
2021

8. Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients

Author

Agnès Carol, Narjis Boukli, Elyanne Gault, Juliette Villemonteix, Tiffany Guilleminot, Héloïse Petit, Guislaine Carcelain, Dominique Challine, Diane Descamps, Sarah Maylin, Jean-François Meritet, Claire Périllaud-Dubois, Laurence Morand-Joubert, Sonia Burrel, Marie-Anne Rameix-Welti, Frédérique Moreau, Charlotte Charpentier, Jérôme LeGoff, Jean-Michel Pawlotsky, Anne-Geneviève Marcelin, Emmanuel Gordien, Christelle Vauloup-Fellous, Samuel Lepape, Isabelle Podglajen, Slim Fourati, Sepideh Akhavan, Nadhira Houhou-Fidouh, Ana-Maria Roque-Afonso, Marianne Leruez-Ville, Vincent Mackiewicz, Florence Damond, Véronique Avettand-Fenoel, Jacques Fourgeaud, Jean-Baptiste Ronat, Chakib Alloui, Ségolène Brichler, Joël Gozlan, Thierry Naas, Elise Gardiennet, Marie-Laure Chaix, Stéphane Bonacorsi, Constance Delaugerre, Flore Rozenberg, Laurent Dortet, Stéphane Marot, Service de Virologie [Hôpital Paul-Brousse - APHP] (World Health Organization Rubella National Reference Laboratory), Hôpital Paul Brousse, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Microbiologie Clinique [Hôpital Avicenne - APHP], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service de Microbiologie et Hygiène [AP-HP Hôpital Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Microbiologie [Hôpital Robert Debré - APHP], Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Comets, Emmanuelle, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], and Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Microbiology (medical), 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Antibodies, Viral, Sensitivity and Specificity, COVID-19 Serological Testing, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Immunoassay, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], business.industry, SARS-CoV-2, Brief Report, COVID-19, General Medicine, Report evaluation, Serum samples, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Immunoglobulin M, Reagent Kits, Diagnostic, business
Abstract

We report evaluation of 30 assays’ (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04232-3.

Published
2021

9. Pre-emptive rituximab treatment for Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes

Author

Corinne Amiel, Myriam Labopin, Federica Giannotti, Béatrice Gaugler, Joël Gozlan, Florent Malard, Nicolas Stocker, Olivier Paccoud, Giorgia Battipaglia, Annalisa Ruggeri, Eolia Brissot, Remy Dulery, Inès Boussen, Mohamad Mohty, Agnès Bonnin, Stocker, N., Labopin, M., Boussen, I., Paccoud, O., Bonnin, A., Malard, F., Amiel, C., Gozlan, J., Battipaglia, G., Dulery, R., Giannotti, F., Ruggeri, A., Gaugler, B., Mohty, M., and Brissot, E.

Subjects
Oncology, Epstein-Barr Virus Infections, medicine.medical_specialty, Herpesvirus 4, Human, medicine.medical_treatment, Hematopoietic stem cell transplantation, Neutropenia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Humans, Cumulative incidence, Epstein-Barr Virus Infections / drug therapy, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Bone marrow failure, Hematopoietic Stem Cell Transplantation / adverse effects, Retrospective cohort study, Hematology, Rituximab / therapeutic use, medicine.disease, Lymphoproliferative Disorders, 030220 oncology & carcinogenesis, Rituximab, Neoplasm Recurrence, Local, business, 030215 immunology, medicine.drug
Abstract

This retrospective study evaluated the impact of a pre-emptive rituximab (RTX) strategy for Epstein-Barr virus (EBV) reactivation on immune recovery and outcomes of 219 high-risk recipients undergoing allogeneic stem cell transplantation (allo-SCT) for hematological malignancies or bone marrow failure. One-hundred and seven patients received pre-emptive RTX for EBV reactivation (RTX group) and 112 did not (control group). The median onset time of EBV reactivation was 49 days (range, 14-561), including five patients who developed post-transplant lymphoproliferative disorder (EBV-PTLD). RTX and control groups were pair-matched to assess the impact of RTX on all endpoints. In RTX patients, CD19 + B cells were significantly decreased until 1-year post-transplant, so were immunoglobulin levels. Twenty-one patients (17%) developed RTX-related neutropenia. There was, in the RTX group, a trend towards a lower cumulative incidence of chronic GvHD (P = 0.059). Overall survival, progression-free survival, non-relapse mortality, relapse incidence, and incidence of overall infections at 2 years following allo-SCT were comparable in the two groups. We conclude that pre-emptive RTX, despite inducing a delayed B-cell reconstitution and a high risk of RTX-related neutropenia, may be considered as a worthwhile treatment, given the absence of negative impact on post allo-SCT outcomes and a low incidence of EBV-PTLD.

Published
2020

10. Prévalence des infections à virus respiratoires en période épidémique de SARS-CoV-2 : comment une épidémie en chasse une autre

Author

Aurélie Schnuriger, Nadia Valin, Karine Lacombe, J. Jullien, Patrick Ingiliz, K. Boussaid, Joël Gozlan, M. Sukach, Laurence Morand-Joubert, and T. Chiarabini

Subjects
Gynecology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Infectious Diseases, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, business, Article
Abstract

Introduction Le 10 mars 2020, l’OMS a déclaré pandémique la diffusion du SARS-CoV2 en recommandant de pratiquer de façon massive le dépistage du virus. Cette épidémie s’est installée alors que les épidémies hivernales de virus respiratoires n’étaient pas encore achevées. Afin de mieux comprendre les étiologies des syndromes grippaux en période COVID-19, nous avons analysé les prélèvements effectués dans un centre de dépistage hospitalier Francilien au tout début de l’épidémie. Matériels et méthodes La période d’étude s’est étendue du 28 février au 27 mars 2020. Tout patient consultant pour une recherche de SARS-CoV2 par RT-PCR dans le cadre d’un syndrome grippal a bénéficié d’une PCR multiplex pour les autres virus respiratoires. Les caractéristiques démographiques, cliniques et virologiques des consultants ont été analysées et les variables associées aux prélèvements positifs pour le SARS-CoV ou les autres virus ont été recherchées par régression logistique. Résultats Au total 707 patients ont consulté pendant la période d’étude et 468 patients ont bénéficié de la recherche de SARS-CoV2 et autres virus respiratoires. L’âge médian (IQR) était de 37 ans (29–50) avec 139 hommes (29,7 %). La prévalence du SARS-CoV2 était de 37,4 % (IQR : 33,01–41,8), et 37 sujets (7,9 %) étaient positifs pour d’autres pathogènes : Influenza A – 6 (1,3 %), Influenza B – 7 (1,5 %), Metapneumovirus – 5 (1,1 %), Rhinovirus – 4 (0,9 %), Coronavirus (229E, HKU1) – 3 (0,6 %), Adenovirus – 2 (0,4 %), Enterovirus – 4 (0,9 %), M. pneumoniae – 1 (0,2 %), Virus Respiratoire syncytial – 1 (0,2 %), infection mixte hors SARS-CoV-2 – 4 (0,9 %). À noter qu’aucun agent pathogène n’a été retrouvé chez 256 consultants. Les symptômes d’anosmie, fièvre et céphalées étaient plus fréquemment présents chez les sujets avec SARS-CoV2 comparés aux autres pathogènes (respectivement 26,3 % vs 2,7 %, p

Published
2020

11. Usefulness of Dried Blood Spots (DBS) to Perform Hepatitis C Virus Genotyping in Drug Users in Senegal: DBS for HCV Genotyping

Author

Coumba Toure Kane, Moussa Thiam, Gora Lo, A. Leprêtre, Halimatou Diop-Ndiaye, Joël Gozlan, S. Chapelain, Pierre-Marie Girard, M. Maynart, Ousseynou Ndiaye, Souleymane Mboup, I. Ba, A.S. Sall, Mamour Gueye, Karine Lacombe, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Hospitalier National et Universitaire de Fann-Dakar, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Hepatitis C virus, Hepacivirus, [SDV]Life Sciences [q-bio], Population, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Virology, Genotype, medicine, 030212 general & internal medicine, education, Genotyping Techniques, Genotyping, education.field_of_study, biology, business.industry, virus diseases, Hepatitis C, medicine.disease, biology.organism_classification, digestive system diseases, Infectious Diseases, Immunology, 030211 gastroenterology & hepatology, business, Viral load
Abstract

The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti-HCV antibodies, using a rapid immune-chromatographic test. HCV RNA was quantified on anti-HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti-HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484-488, 2017. © 2015 Wiley Periodicals, Inc.

Published
2017

12. Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients

Author

Laurent Fonquernie, Anders Boyd, Patrick Miailhes, Karine Lacombe, Laetitia Canini, Pierre-Marie Girard, Joël Gozlan, Caroline Lascoux-Combe, HAL-UPMC, Gestionnaire, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Edinburgh, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [Lyon], Hospices Civils de Lyon (HCL), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Male, HBsAg, Logistic growth model, HIV Infections, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Hepatitis B e Antigens, 030212 general & internal medicine, Anti-HBs antibodies, education.field_of_study, biology, Coinfection, HBsAg-seroconversion, virus diseases, Middle Aged, Viral Load, Hepatitis B, 3. Good health, Antiretroviral therapy, Infectious Diseases, Seroconversion, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, 030211 gastroenterology & hepatology, Antibody, Viral load, Adult, Population, 03 medical and health sciences, Hepatitis B, Chronic, Virology, Humans, Serologic Tests, Hepatitis B Antibodies, education, Hepatitis B virus, Hepatitis B Surface Antigens, business.industry, medicine.disease, digestive system diseases, Kinetics, DNA, Viral, Immunology, biology.protein, business
Abstract

Background Hepatitis B surface antigen (HBsAg)-seroconversion, or loss of HBsAg and acquisition of anti-hepatitis B surface (HBs) antibodies, defines functional cure of chronic hepatitis B virus (HBV) infection. After HBsAg-loss, little is known regarding the development of anti-HBs antibodies and even less so in individuals co-infected with HIV. Objectives To determine anti-HBs antibody kinetics after HBsAg-loss and explore determinants of HBsAg-seroconversion in HIV-HBV co-infected patients. Study design Patients enrolled in the French HIV-HBV cohort were included if they had >1 study visit after HBsAg-loss. Individual patient kinetics of anti-HBs antibody levels were modeled over time using mixed-effect non-linear regression, whereby maximum specific growth rate and maximal level of antibody production were estimated from a Gompertz growth equation. Results Fourteen (4.6%) of 308 co-infected patients followed in the cohort exhibited HBsAg-loss, all of whom were undergoing antiretroviral therapy. Nine (64.3%) of these patients achieved HBsAg-seroconversion during a median 3.0 years (IQR = 1.1–5.1) after HBsAg-loss. Across individuals with HBsAg-seroconversion, the fastest rates of antibody growth ranged between 0.57–1.93 year−1 (population maximum growth rate = 1.02) and antibody production plateaued between 2.09–3.66 log10 mIU/mL at the end of follow-up (population maximal antibody levels = 2.66). Patients with HBsAg-seroconversion had substantial decreases in HBV DNA viral loads (P = 0.03) and proportion with elevated ALT levels (P = 0.02) and HBeAg-positive serology (P = 0.08). No such differences were observed in those without HBsAg-seroconversion. Conclusions Most co-infected patients with HBsAg-seroconversion produced and maintained stable antibody levels, yet kinetics of anti-HBs production were much slower compared to those observed post-vaccination or after clearance of acute HBV-infection.

Published
2017

13. Testing for Hepatitis B Virus Alone Does Not Increase Vaccine Coverage in Non-Immunized Persons

Author

Anders Boyd, Fabrice Carrat, Julie Bottero, Joël Gozlan, Pierre-Marie Girard, Karine Lacombe, Hayette Rougier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Infectious diseases

Subjects
Adult, Male, Vaccine coverage, Hepatitis B virus, medicine.medical_specialty, Testing intervention, animal diseases, viruses, [SDV]Life Sciences [q-bio], chemical and pharmacologic phenomena, medicine.disease_cause, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Mass Screening, Hepatitis B Vaccines, 030212 general & internal medicine, Young adult, Mass screening, Public health, Hepatitis B virus vaccination, business.industry, Vaccination, Gastroenterology, General Medicine, Middle Aged, biochemical phenomena, metabolism, and nutrition, Hepatitis B, medicine.disease, Virology, [SDV] Life Sciences [q-bio], Health service organization, Prospective Study, bacteria, Female, 030211 gastroenterology & hepatology, Vaccine covera, business
Abstract

AIM: To determine whether hepatitis B virus (HBV)-testing could serve as a gateway to vaccinate non-immunized individuals in a low-prevalent country. METHODS: Non-immunized subjects participating in a multi-center, HBV-testing campaign in Paris, France were identified and contacted via telephone 3-9 mo after testing in order to determine vaccination status. Vaccination coverage was evaluated in per-protocol (for all respondents) and intent-to-treat analysis (assuming all non-responders did not vaccinate). RESULTS: In total, 1215/4924 (24.7%) enrolled subjects with complete HBV serology were identified as nonimmunized and eligible for analysis. There were 99/902 successfully contacted subjects who had initiated HBV vaccination after screening: per-protocol, 11.0% (95%CI: 9.0-13.2); intent-to-treat, 8.2% (95%CI: 6.7-9.8). In multivariable analysis, vaccination was more likely to be initiated in individuals originating from moderate or high HBV-endemic countries (P < 0.001), patients with limited healthcare coverage (P = 0.01) and men who have sex with men (P = 0.02). When asked about the reasons for not initiating HBV vaccination, the most frequent response was "will be vaccinated later" (33.4%), followed by "did not want to vaccinate" (29.8%), and "vaccination was not proposed by the physician" (21.5%). Sub-group analysis indicated a stark contrast in vaccination coverage across centers, ranging from 0%-56%. CONCLUSION: HBV-vaccination after HBV screening was very low in this study, which appeared largely attributed to physician-patient motivation towards vaccination. Increased vaccination coverage might be achieved by emphasizing its need at the organizational level.

Published
2017

14. Effectiveness of hepatitis B rapid tests toward linkage-to-care: results of a randomized, multicenter study

Author

Anne Collignon, Philippe Dhotte, Karine Lacombe, Cécile Charlois-Ou, Pauline Campa, Maud Lemoine, N. Boo, Julie Bottero, Fabrice Carrat, Hayette Rougier, O. Cha, Pierre-Marie Girard, Anders Boyd, Joël Gozlan, B. Varsat, Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département des Examens Périodiques de Santé de l’Adulte (DEPSA), Caisse primaire d'assurance maladie (CPAM), Direction de l'Action Sociale de l'Enfance et de la Santé (DASES), Mairie de Paris, Centre de dépistage anonyme et gratuit de Belleville (CDAG), Laboratoire St Marcel, Centre de dépistage anonyme et gratuit du Figuier (CDAG), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie [CHU Saint-Antoine], and HAL-UPMC, Gestionnaire

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, HBsAg, Paris, Time Factors, medicine.disease_cause, Serology, law.invention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Randomized controlled trial, law, medicine, Clinical endpoint, Humans, Mass Screening, Hepatitis B Vaccines, 030212 general & internal medicine, Young adult, Hepatitis B Antibodies, Referral and Consultation, Mass screening, Hepatitis B virus, Hepatitis B Surface Antigens, Hepatology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis B, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, 030211 gastroenterology & hepatology, Female, business
Abstract

International audience; Objectives: Worldwide, many infected individuals are unaware of their hepatitis B virus (HBV) status. We evaluated the effectiveness of HBV rapid testing in promoting linkage-to-care.Methods: In 2012, volunteers were recruited from five Parisian centers. Participants were randomized 1 : 1 to receive standard serology (S) or rapid testing (VIKIA-HBsAg/Quick Profile anti-HBsAb) with confirmatory serology (R+S). The primary endpoint was percentage of individuals with appropriate linkage-to-care (nonimmunized individuals starting vaccination or HBsAg-positive individuals receiving medical evaluation). The secondary outcomes were percentage receiving HBV-test results and performance of HBV rapid tests.Results: In total, 995 individuals were screened. Among the HBV-infection groups included in the primary endpoint (n=409), 20 (4.9%) received appropriate linkage-to-care, with no difference between S and R+S groups (5.7 vs. 4.1%, P=0.5). Two of eight HBsAg-positive participants had a medical visit (1/6 and 1/2 in the S and R+S groups, respectively) and 18/401 (4.5%) nonimmunized participants initiated HBV-vaccination (11/205 and 7/196). Factors that tended to be associated with linkage-to-care were female sex, birth country of high HBV prevalence, and extended medical stay. Test results were not obtained in 4.7% of participants, which was significantly higher in the S arm (P=0.02). Both sensitivity and specificity were 100% for the VIKIA-HBsAg rapid test and 94.4 and 80.8%, respectively, for the anti-HBsAb Quick Profile rapid test.Conclusion: Despite a higher proportion of participants obtaining their results in the R+S arm and better performance of anti-HBsAb rapid tests than described previously, we found no evidence that HBV screening based initially on rapid tests leads to increased HBV-vaccination rates or medical evaluation. This strategy should be evaluated in more hard-to-reach populations

Published
2016

15. Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping

Author

Evelyne Schvoerer, Elisabeth André-Garnier, Joël Gozlan, Etienne Brochot, Sylvie Larrat, Sébastien Hantz, Catherine Gaudy-Graffin, Hélène Le Guillou-Guillemette, Nelly Magnat, Vincent Mackiewicz, Syria Laperche, Jean-Christophe Plantier, Philippe Colson, Françoise Lunel-Fabiani, Patrick Soussan, Gisèle Lagathu, Christopher Payan, Jacques Izopet, Sylvain Rosec, S. Gouriou, Anne-Marie Roque-Afonso, Patrice Morand, Caroline Scholtes, Adeline Pivert, Sophie Vallet, Florence Legrand-Abravanel, Vincent Thibault, Sarah Maylin, Audrey Mirand, Stéphane Chevaliez, Jean-Michel Pawlotsky, Charlotte Charpentier, Valérie Giordanengo, Cécile Henquell, Françoise Bouchardeau, Lina Aguilera, Pascale Trimoulet, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de virologie moléculaire et structurale (LVMS), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de virologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Laboratoire de Virologie, CHU Strasbourg, Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours-EA3856, CHU Bordeaux [Bordeaux], Laboratoire de Virologie [CHU Amiens], CHU Amiens-Picardie, Unité de Virologie clinique et fondamentale (UVCF), CHU Amiens-Picardie-Université de Picardie Jules Verne (UPJV), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], 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)-Hôpital Paul Brousse, Carcinogenèse Hépatique et Virologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Tours (UT)-EA3856, Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service de virologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Université Nice Sophia Antipolis (1965 - 2019) (UNS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Microbiology (medical), Quality Control, MESH: Antiviral Agents, MESH: Sequence Analysis, DNA, MESH: Mutation, Genotype, Hepatitis C virus, Hepacivirus, [SDV]Life Sciences [q-bio], MESH: Quality Control, MESH: Amino Acid Sequence, Viral Nonstructural Proteins, MESH: Base Sequence, medicine.disease_cause, Antiviral Agents, MESH: Genotype, 03 medical and health sciences, 0302 clinical medicine, Virology, Drug Resistance, Viral, medicine, Protease inhibitor (pharmacology), Protease Inhibitors, MESH: Hepacivirus, Amino Acid Sequence, Genotyping, 0303 health sciences, NS3, MESH: Drug Resistance, Viral, MESH: Protease Inhibitors, biology, Base Sequence, 030306 microbiology, Inhibitor resistance, virus diseases, Sequence Analysis, DNA, biology.organism_classification, 3. Good health, Hcv protease, Mutation, MESH: Viral Nonstructural Proteins, 030211 gastroenterology & hepatology
Abstract

Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

Published
2013

16. Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

Author

Florent Malard, Béatrice Gaugler, Joel Gozlan, Lucie Bouquet, Djeneba Fofana, Lama Siblany, Deborah Eshagh, Olivier Adotevi, Caroline Laheurte, Laure Ricard, Rémy Dulery, Nicolas Stocker, Zoe van de Wyngaert, Alexis Genthon, Anne Banet, Mara Memoli, Souhila Ikhlef, Simona Sestilli, Anne Vekhof, Eolia Brissot, Zora Marjanovic, Yannick Chantran, Nancy Cuervo, Eric Ballot, Laurence Morand-Joubert, and Mohamad Mohty

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p

Published
2021
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17. Drug-resistant and immune-escape HBV mutants in HIV-infected hosts

Author

Joël Gozlan, Fabien Zoulim, Fabien Lavocat, Pierre-Marie Girard, Anders Boyd, Karine Lacombe, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie moléculaire et nouveaux traitements des hépatites virales, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu, Lacombe, Karine, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Hepatitis B virus, Genotype, HIV Infections, Gene mutation, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Orthohepadnavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Viral, medicine, Animals, Humans, Pharmacology (medical), Hepatitis B Vaccines, Gene, 030304 developmental biology, Pharmacology, Genetics, 0303 health sciences, Mutation, Hepatitis B Surface Antigens, biology, Genetic Variation, Hepatitis B, medicine.disease, biology.organism_classification, Virology, 3. Good health, Infectious Diseases, Viral replication, Hepadnaviridae, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology
Abstract

International audience; HIV-HBV-coinfected patients require optimal control of viral replication in order to prevent the development of severe comorbidities, such as liver cirrhosis and hepatocellular carcinoma. The genetic diversity of HBV is a poorly investigated factor of such viral replication in HIV-infected hosts. HBV genome diversity can be differentiated into two major aspects: genotypic and phenotypic. Genotypic diversity is more related to the natural history of HBV infection and genotypes are mostly determined by geographical origin of the hosts. Phenotypic diversity arises from attempts to escape from host immune surveillance (that is, precore, core and basal core promoter mutants), selection resulting from the use of treatments with weak genetic barrier (that is, pol mutants), exposure to hepatitis B immunoglobulin (that is, 'immune-escape' S gene mutants) or treatment-induced mutations from overlapping genes (that is, pol mutants inducing 'vaccine-escape' S gene mutants). pol mutations typically lead to uncontrolled viral replication, whereas S gene mutations can significantly alter hepatitis B surface antigen synthesis and reduce binding to antibodies, which renders individuals who are vaccinated or cured of HBV infection susceptible to infection. For patients coinfected with HIV, hepatitis B treatment options that aim to reduce the risk of HBV mutations from emerging must be seriously considered, not only from clinical but also public health perspectives.

Published
2010

18. A high-sensitivity method for detection and measurement of HMGB1 protein concentration by high-affinity binding to DNA hemicatenanes

Author

François Strauss, Vincent Maréchal, Joël Gozlan, Chloé Borde, and Claire Gaillard

Subjects
Gel electrophoresis of nucleic acids, Herpesvirus 2, Human, Aptamer, Immunology, lcsh:Medicine, Enzyme-Linked Immunosorbent Assay, chemical and pharmacologic phenomena, Cell Biology/Cell Signaling, chemistry.chemical_compound, Critical Care and Emergency Medicine/Sepsis and Multiple Organ Failure, Western blot, medicine, Humans, HMGB1 Protein, Binding site, lcsh:Science, Biochemistry/Biomacromolecule-Ligand Interactions, Inflammation, Gel electrophoresis, Binding Sites, Multidisciplinary, medicine.diagnostic_test, Chemistry, lcsh:R, Epithelial Cells, DNA, Blood proteins, Chromatin, DNA-Binding Proteins, Kinetics, Biochemistry, Nucleic Acid Conformation, lcsh:Q, Cell Biology/Nuclear Structure and Function, Research Article
Abstract

Background Protein HMGB1, an abundant nuclear non-histone protein that interacts with DNA and has an architectural function in chromatin, was strikingly shown some years ago to also possess an extracellular function as an alarmin and a mediator of inflammation. This extracellular function has since been actively studied, both from a fundamental point of view and in relation to the involvement of HMGB1 in inflammatory diseases. A prerequisite for such studies is the ability to detect HMGB1 in blood or other biological fluids and to accurately measure its concentration. Methodology/Principal Findings In addition to classical techniques (western blot, ELISA) that make use of specific anti-HMGB1 antibodies, we present here a new, extremely sensitive technique that is based on the fact that hemicatenated DNA loops (hcDNA) bind HMGB1 with extremely high affinity, higher than the affinity of specific antibodies, similar in that respect to DNA aptamers. DNA-protein complexes formed between HMGB1 and radiolabeled hcDNA are analyzed by electrophoresis on nondenaturing polyacrylamide gels using the band-shift assay method. In addition, using a simple and fast protocol to purify HMGB1 on the basis of its solubility in perchloric acid allowed us to increase the sensitivity by suppressing any nonspecific background. The technique can reliably detect HMGB1 at a concentration of 1 pg per microliter in complex fluids such as serum, and at much lower concentrations in less complex samples. It compares favorably with ELISA in terms of sensitivity and background, and is less prone to interference from masking proteins in serum. Conclusion The new technique, which illustrates the potential of DNA nanoobjects and aptamers to form high-affinity complexes with selected proteins, should provide a valuable tool to further investigate the extracellular functions of HMGB1 and its involvement in inflammatory pathologies.

Published
2008

19. Cell Cycle Arrest in G2 Induces Human Immunodeficiency Virus Type 1 Transcriptional Activation through Histone Acetylation and Recruitment of CBP, NF-κB, and c-Jun to the Long Terminal Repeat Promoter

Author

Jean-Claude Nicolas, Sylvain Thierry, Joël Gozlan, Vincent Maréchal, Michèle Sabbah, Gérard Redeuilh, and Michelle Rosenzwajg

Subjects
G2 Phase, Transcriptional Activation, Proto-Oncogene Proteins c-jun, TATA box, viruses, Immunology, Microbiology, Cell Line, Histones, Virology, Nucleosome, Gene silencing, Humans, Promoter Regions, Genetic, Transcription factor, biology, NF-kappa B, Terminal Repeat Sequences, Promoter, Acetylation, Histone acetyltransferase, Molecular biology, Long terminal repeat, Virus-Cell Interactions, Histone, Insect Science, biology.protein, HIV-1, Virus Activation, Carrier Proteins, Corticosterone
Abstract

In human immunodeficiency virus type 1 (HIV-1)-infected cells, a cell cycle arrest in G 2 increases viral expression and may represent a strategy for the virus to optimize its expression. In latently infected cells, balance between viral silencing and reactivation relies on the nucleosomal organization of the integrated long terminal repeat (LTR). It is shown here that nucleosome nuc-1, which is located downstream of the TATA box, is specifically modified when latently infected cells are arrested in G 2 by chemical inducers. Notably, histones H3 and H4 are hyperacetylated, and this modification is associated with an increased LTR-driven transcription. nuc-1 hyperacetylation is also associated with the recruitment of histone acetyltransferase CBP and transcription factors NF-κB and c-Jun. NF-κB and/or c-Jun binding to the LTR in G 2 -arrested cells appears to be required for CBP recruitment as well as for nuc-1 remodeling and viral reactivation.

Published
2004

20. SARS-CoV-2 Neutralizing Responses in Various Populations, at the Time of SARS-CoV-2 Variant Virus Emergence: Evaluation of Two Surrogate Neutralization Assays in Front of Whole Virus Neutralization Test

Author

Stephane Marot, Djeneba Bocar Fofana, Philippe Flandre, Isabelle Malet, Karen Zafilaza, Valentin Leducq, Diane Vivien, Sarah Mrabet, Corentin Poignon, Vincent Calvez, Laurence Morand-Joubert, Anne-Geneviève Marcelin, and Joel Gozlan

Subjects
SARS-CoV-2, COVID-19, neutralizing antibodies, neutralization surrogate assays, SARS-CoV-2 variants, Science
Abstract

The SARS-CoV-2 neutralizing antibodies response is the best indicator of effective protection after infection and/or vaccination, but its evaluation requires tedious cell-based experiments using an infectious virus. We analyzed, in 105 patients with various histories of SARS-CoV-2 infection and/or vaccination, the neutralizing response using a virus neutralization test (VNT) against B.1, Alpha, Beta and Omicron variants, and compared the results with two surrogate assays based on antibody-mediated blockage of the ACE2-RBD interaction (Lateral Flow Boditech and ELISA Genscript). The strongest response was observed for recovered COVID-19 patients receiving one vaccine dose. Naïve patients receiving 2 doses of mRNA vaccine also demonstrate high neutralization titers against B.1, Alpha and Beta variants, but only 34.3% displayed a neutralization activity against the Omicron variant. On the other hand, non-infected patients with half vaccination schedules displayed a weak and inconstant activity against all isolates. Non-vaccinated COVID-19 patients kept a neutralizing activity against B.1 and Alpha up to 12 months after recovery but a decreased activity against Beta and Omicron. Both surrogate assays displayed a good correlation with the VNT. However, an adaptation of the cut-off positivity was necessary, especially for the most resistant Beta and Omicron variants. We validated two simple and reliable surrogate neutralization assays, which may favorably replace cell-based methods, allowing functional analysis on a larger scale.

Published
2022
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21. Human Immunodeficiency Virus Type 1 Induction Mediated by Genistein Is Linked to Cell Cycle Arrest in G2

Author

Janet L. Lathey, Stephen A. Spector, and Joël Gozlan

Subjects
G2 Phase, Cell cycle checkpoint, Cell division, Cellular differentiation, Immunology, Genistein, Biology, Phosphatidylinositols, Virus Replication, Microbiology, Cell Line, chemistry.chemical_compound, Virology, Topoisomerase II Inhibitors, Enzyme Inhibitors, Cell cycle, Protein-Tyrosine Kinases, Cell biology, Virus-Cell Interactions, Viral replication, chemistry, Cell culture, Insect Science, HIV-1, Tyrosine kinase, Cell Division
Abstract

Protein tyrosine kinase (PTK) phosphorylation is involved in cellular proliferation and differentiation processes that are key factors for human immunodeficiency virus type 1 (HIV-1) regulation in infected monocytic cells. Short-term exposure of the chronically infected promyelocytic OM10 cell line with the PTK inhibitor genistein induced a dose-dependent increase in p24 antigen production in culture supernatants. This induction persisted in the presence of the reverse transcriptase inhibitor, zidovudine, and was associated with an increased transcription of HIV-1 multiply spliced and unspliced RNAs, suggesting a transcriptional mechanism targeting the integrated provirus. Genistein induced cell differentiation, apoptosis, and a G 2 arrest in the OM10 cells. Cell differentiation and apoptosis were not directly involved in the observed increase in HIV-1 replication that was closely linked to genistein-induced G 2 arrest. Alleviation of the G 2 arrest by pentoxyfylline resulted in a concomitant reduction of HIV-1 to baseline replication. Additionally, by flow cytometry, a significant increase in the number of p24 antigen-expressing cells was observed in cells arrested in G 2 compared to those located in G 1 or S. Tyrosine kinase inhibition was found not to be essential for enhanced viral replication, which seemed to be related to two other properties of genistein, inhibition of topoisomerase II activity and inhibition of phosphotidylinositol turnover. These findings are consistent with the recent observation that HIV-1 Vpr induces viral replication through preventing proliferation of cells by arresting them in G 2 of the cell cycle and strongly suggest that manipulation of the cell cycle plays an important role in HIV-1 pathogenesis.

Published
1998

22. Human cytomegalovirus (HCMV) late-mRNA detection in peripheral blood of AIDS patients: diagnostic value for HCMV disease compared with those of viral culture and HCMV DNA detection

Author

J M Salord, Christos Chouaid, Marie-Caroline Meyohas, C Duvivier, Jean-Claude Petit, O Picard, Joël Gozlan, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gozlan J, JM Salord, C Chouaïd, Duvivier C, O Picard, Meyohas MC, JC Petit ., and Annesi-Maesano, Isabella

Subjects
Male, Human cytomegalovirus, viruses, Cytomegalovirus, MESH: Base Sequence, medicine.disease_cause, Polymerase Chain Reaction, law.invention, law, Polymerase chain reaction, Viral culture, MESH: AIDS-Related Opportunistic Infections, Evaluation Studies as Topic, MESH: RNA, Viral, Cytomegalovirus Infections, MESH: Evaluation Studies as Topic, RNA, Viral, Female, Viral disease, Research Article, Adult, Microbiology (medical), MESH: Cytomegalovirus, Virus Cultivation, Molecular Sequence Data, Biology, Sensitivity and Specificity, Virus, Herpesviridae, MESH: Virus Cultivation, medicine, Humans, RNA, Messenger, Viremia, MESH: Viremia, MESH: RNA, Messenger, MESH: Molecular Sequence Data, MESH: Humans, AIDS-Related Opportunistic Infections, Base Sequence, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Cytomegalovirus Infections, medicine.disease, Virology, Reverse transcriptase, MESH: Sensitivity and Specificity, MESH: Male, MESH: DNA, Viral, Viral replication, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, DNA, Viral, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract

International audience; A reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect a human cytomegalovirus (HCMV) late mRNA in peripheral blood leukocytes (PBL) of 102 human immunodeficiency virus-infected individuals. The clinical value of this new technique for the diagnosis of acute HCMV disease was evaluated in comparison with viral culture and direct amplification of viral DNA (PCR). The sensitivity of the RT-PCR was slightly lower than that of the two other methods, but its specificity was 94%, compared to 55 and 32% for culture and PCR, respectively. Transcription of this late mRNA is linked to viral replication, and its detection in PBL confirms that these cells can support a complete viral cycle. The relationship between complete replicative cycles and HCMV disease makes RT-PCR a useful clinical tool.

Published
1993

23. Current state of and needs for hepatitis B screening: results of a large screening study in a low-prevalent, metropolitan region.

Author

Julie Bottero, Anders Boyd, Maud Lemoine, Fabrice Carrat, Joel Gozlan, Anne Collignon, Nicolas Boo, Philippe Dhotte, Brigitte Varsat, Gerard Muller, Olivier Cha, Nadia Valin, Jean Nau, Pauline Campa, Benjamin Silbermann, Marc Bary, Pierre-Marie Girard, and Karine Lacombe

Subjects
Medicine, Science
Abstract

BackgroundIn low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing.MethodsDuring a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals.Results85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (pConclusionsMissed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.

Published
2014
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