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Cédric Hartard
Laboratoire de Virologie, CHRU de Nancy Brabois, 54500 Vandoeuvre-lès-Nancy, France

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Review
Published: 18 June 2021 in Viruses
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has accumulated around two mutations per genome each month. The first relevant event in this context was the occurrence of the mutant D614G in the Spike gene. Moreover, several variants have emerged, including the well-characterized 20I/501Y.V1, 20H/501Y.V2, and 20J/501Y.V3 strains, in addition to those that have been detected within clusters, such as 19B/501Y or 20C/655Y in France. Mutants have also emerged in animals, including a variant transmitted to humans, namely, the Mink variant detected in Denmark. The emergence of these variants has affected the transmissibility of the virus (for example, 20I/501Y.V1, which was up to 82% more transmissible than other preexisting variants), its severity, and its ability to escape natural, adaptive, vaccine, and therapeutic immunity. In this respect, we review the literature on variants that have currently emerged, and their effect on vaccines and therapies, and, in particular, monoclonal antibodies (mAbs). The emergence of SARS-CoV-2 variants must be examined to allow effective preventive and curative control strategies to be developed.

ACS Style

Ahlam Chaqroun; Cédric Hartard; Evelyne Schvoerer. Anti-SARS-CoV-2 Vaccines and Monoclonal Antibodies Facing Viral Variants. Viruses 2021, 13, 1171 .

AMA Style

Ahlam Chaqroun, Cédric Hartard, Evelyne Schvoerer. Anti-SARS-CoV-2 Vaccines and Monoclonal Antibodies Facing Viral Variants. Viruses. 2021; 13 (6):1171.

Chicago/Turabian Style

Ahlam Chaqroun; Cédric Hartard; Evelyne Schvoerer. 2021. "Anti-SARS-CoV-2 Vaccines and Monoclonal Antibodies Facing Viral Variants." Viruses 13, no. 6: 1171.

Original article
Published: 20 April 2021 in Journal of Viral Hepatitis
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Hepatitis E virus (HEV) usually causes self‐limited liver diseases but can also result in severe cases. Genotypes 1 (G1) and 2 circulate in developing countries are human‐restricted and waterborne, while zoonotic G3 and G4 circulating in industrialized countries preferentially infect human through consumption of contaminated meat. Our aims were to identify amino acid patterns in HEV variants that could be involved in pathogenicity or in transmission modes, related to their impact on antigenicity and viral surface hydrophobicity. HEV sequences from human (n = 37) and environmental origins (wild boar [n = 3], pig slaughterhouse effluent [n = 6] and urban wastewater [n = 2]) were collected for the characterization of quasispecies using ultra‐deep sequencing (ORF2/ORF3 overlap). Predictive and functional assays were carried out to investigate viral particle antigenicity and hydrophobicity. Most quasispecies showed a major variant while a mixture was observed in urban wastewater and in one chronically infected patient. Amino acid signatures were identified, as a rabbit‐linked HEV pattern in two infected patients, or the S68L (ORF2) / H81C (ORF3) residue mostly identified in wild boars. By comparison with environmental strains, molecular patterns less likely represented in humans were identified. Patterns impacting viral hydrophobicity and/or antigenicity were also observed, and the higher hydrophobicity of HEV naked particles compared with the enveloped forms was demonstrated. HEV variants isolated from human and environment present molecular patterns that could impact their surface properties as well as their transmission. These molecular patterns may concern only one minor variant of a quasispecies and could emerge under selective pressure.

ACS Style

Cédric Hartard; Honorine Fenaux; Alexis Gentilhomme; John M. Murray; Elma Akand; Elodie Laugel; Sibel Berger; Armand Maul; Alexis de Rougemont; Hélène Jeulin; Thomas Remen; Mouni Bensenane; Jean‐Pierre Bronowicki; Christophe Gantzer; Isabelle Bertrand; Evelyne Schvoerer. Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission. Journal of Viral Hepatitis 2021, 28, 1078 -1090.

AMA Style

Cédric Hartard, Honorine Fenaux, Alexis Gentilhomme, John M. Murray, Elma Akand, Elodie Laugel, Sibel Berger, Armand Maul, Alexis de Rougemont, Hélène Jeulin, Thomas Remen, Mouni Bensenane, Jean‐Pierre Bronowicki, Christophe Gantzer, Isabelle Bertrand, Evelyne Schvoerer. Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission. Journal of Viral Hepatitis. 2021; 28 (7):1078-1090.

Chicago/Turabian Style

Cédric Hartard; Honorine Fenaux; Alexis Gentilhomme; John M. Murray; Elma Akand; Elodie Laugel; Sibel Berger; Armand Maul; Alexis de Rougemont; Hélène Jeulin; Thomas Remen; Mouni Bensenane; Jean‐Pierre Bronowicki; Christophe Gantzer; Isabelle Bertrand; Evelyne Schvoerer. 2021. "Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission." Journal of Viral Hepatitis 28, no. 7: 1078-1090.

Journal article
Published: 03 February 2021 in Proceedings of the National Academy of Sciences
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The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

ACS Style

Nadège Néant; Guillaume Lingas; Quentin Le Hingrat; Jade Ghosn; Ilka Engelmann; Quentin Lepiller; Alexandre Gaymard; Virginie Ferré; Cédric Hartard; Jean-Christophe Plantier; Vincent Thibault; Julien Marlet; Brigitte Montes; Kevin Bouiller; François-Xavier Lescure; Jean-François Timsit; Emmanuel Faure; Julien Poissy; Christian Chidiac; François Raffi; Antoine Kimmoun; Manuel Etienne; Jean-Christophe Richard; Pierre Tattevin; Denis Garot; Vincent Le Moing; Delphine Bachelet; Coralie Tardivon; Xavier Duval; Yazdan Yazdanpanah; France Mentré; Cédric Laouénan; Benoit Visseaux; Jérémie Guedj; for the French COVID Cohort Investigators and French Cohort Study groups. Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Nadège Néant, Guillaume Lingas, Quentin Le Hingrat, Jade Ghosn, Ilka Engelmann, Quentin Lepiller, Alexandre Gaymard, Virginie Ferré, Cédric Hartard, Jean-Christophe Plantier, Vincent Thibault, Julien Marlet, Brigitte Montes, Kevin Bouiller, François-Xavier Lescure, Jean-François Timsit, Emmanuel Faure, Julien Poissy, Christian Chidiac, François Raffi, Antoine Kimmoun, Manuel Etienne, Jean-Christophe Richard, Pierre Tattevin, Denis Garot, Vincent Le Moing, Delphine Bachelet, Coralie Tardivon, Xavier Duval, Yazdan Yazdanpanah, France Mentré, Cédric Laouénan, Benoit Visseaux, Jérémie Guedj, for the French COVID Cohort Investigators and French Cohort Study groups. Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort. Proceedings of the National Academy of Sciences. 2021; 118 (8):1.

Chicago/Turabian Style

Nadège Néant; Guillaume Lingas; Quentin Le Hingrat; Jade Ghosn; Ilka Engelmann; Quentin Lepiller; Alexandre Gaymard; Virginie Ferré; Cédric Hartard; Jean-Christophe Plantier; Vincent Thibault; Julien Marlet; Brigitte Montes; Kevin Bouiller; François-Xavier Lescure; Jean-François Timsit; Emmanuel Faure; Julien Poissy; Christian Chidiac; François Raffi; Antoine Kimmoun; Manuel Etienne; Jean-Christophe Richard; Pierre Tattevin; Denis Garot; Vincent Le Moing; Delphine Bachelet; Coralie Tardivon; Xavier Duval; Yazdan Yazdanpanah; France Mentré; Cédric Laouénan; Benoit Visseaux; Jérémie Guedj; for the French COVID Cohort Investigators and French Cohort Study groups. 2021. "Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort." Proceedings of the National Academy of Sciences 118, no. 8: 1.

Review
Published: 22 November 2020 in Reviews in Medical Virology
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Among the five main viruses responsible for human hepatitis, hepatitis C virus (HCV) and hepatitis E virus (HEV) are different while sharing similarities. Both viruses can be transmitted by blood or derivatives whereas HEV can also follow environmental or zoonotic routes. These highly variable RNA viruses can cause chronic hepatitis potentially leading to hepatocarcinoma. HCV and HEV can develop new structures and functions under selective pressure to adapt to host immunity, human tissues, treatments or even various animal reservoirs. Elsewhere, with directly acting antiviral treatments, HCV can be eradicated whereas HEV is an emerging pathogen against which specific treatments have to be improved. As a unique molecular tool able to explore viral genomic plasticity, full-length genome (FLG) sequencing has become easier, faster and cheaper. The present review will show how FLG sequencing can explore these RNA viruses with the aim to investigate key genomics data to improve basic knowledge, patients' healthcare and preventive tools.

ACS Style

Elodie Laugel; Cédric Hartard; Hélène Jeulin; Sibel Berger; Véronique Venard; Jean‐Pierre Bronowicki; Evelyne Schvoerer. Full‐length genome sequencing of RNA viruses—How the approach can enlighten us on hepatitis C and hepatitis E viruses. Reviews in Medical Virology 2020, 31, e2197 .

AMA Style

Elodie Laugel, Cédric Hartard, Hélène Jeulin, Sibel Berger, Véronique Venard, Jean‐Pierre Bronowicki, Evelyne Schvoerer. Full‐length genome sequencing of RNA viruses—How the approach can enlighten us on hepatitis C and hepatitis E viruses. Reviews in Medical Virology. 2020; 31 (4):e2197.

Chicago/Turabian Style

Elodie Laugel; Cédric Hartard; Hélène Jeulin; Sibel Berger; Véronique Venard; Jean‐Pierre Bronowicki; Evelyne Schvoerer. 2020. "Full‐length genome sequencing of RNA viruses—How the approach can enlighten us on hepatitis C and hepatitis E viruses." Reviews in Medical Virology 31, no. 4: e2197.

Review
Published: 27 August 2019 in Reviews in Medical Virology
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Hepatitis A (HAV) and E (HEV) viruses are able to cause liver disease in humans. Among the five classical hepatotropic viruses, they are mainly transmitted via the fecal‐oral route. Historically, many similarities have thus been described between them according to their incidence and their pathogenicity, especially in countries with poor sanitary conditions. However, recent advances have provided new insights, and the gap is widening between them. Indeed, while HAV infection incidence tends to decrease in developed countries along with public health improvement, HEV is currently considered as an underdiagnosed emerging pathogen. HEV autochthonous infections are increasingly observed and are mainly associated with zoonotic transmissions. Extra hepatic signs resulting in neurological or renal impairments have also been reported for HEV, as well as a chronic carrier state in immunocompromised patients, arguing in favor of differential pathogenesis between those two viruses. Recent molecular tools have allowed studies of viral genome variability and investigation of links between viral plasticity and clinical evolution. The identification of key functional mutations in viral genomes may improve the knowledge of their clinical impact and is analyzed in depth in the present review.

ACS Style

Cédric Hartard; Christophe Gantzer; Jean‐Pierre Bronowicki; Evelyne Schvoerer. Emerging hepatitis E virus compared with hepatitis A virus: A new sanitary challenge. Reviews in Medical Virology 2019, 29, e2078 .

AMA Style

Cédric Hartard, Christophe Gantzer, Jean‐Pierre Bronowicki, Evelyne Schvoerer. Emerging hepatitis E virus compared with hepatitis A virus: A new sanitary challenge. Reviews in Medical Virology. 2019; 29 (6):e2078.

Chicago/Turabian Style

Cédric Hartard; Christophe Gantzer; Jean‐Pierre Bronowicki; Evelyne Schvoerer. 2019. "Emerging hepatitis E virus compared with hepatitis A virus: A new sanitary challenge." Reviews in Medical Virology 29, no. 6: e2078.