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1. Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

Author

Hélène Péré, Raphael Vernet, Simon Pernot, Juliette Pavie, Nicolas Robillard, Julien Puech, Sonia Lameiras, Marie-Laure Lucas, Alain Nicolas, Cécile Badoual, Bastien Rance, Laurent Bélec, Laurence Weiss, Maxime Wack, and David Veyer

Subjects
Medicine, Science
Abstract

Abstract Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

Published
2021
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2. Fusogenicity and neutralization sensitivity of the SARS-CoV-2 Delta sublineage AY.4.2

Author

Nell Saunders, Delphine Planas, William H. Bolland, Christophe Rodriguez, Slim Fourati, Julian Buchrieser, Cyril Planchais, Matthieu Prot, Isabelle Staropoli, Florence Guivel-Benhassine, Françoise Porrot, David Veyer, Hélène Péré, Nicolas Robillard, Madelina Saliba, Artem Baidaliuk, Aymeric Seve, Laurent Hocqueloux, Thierry Prazuck, Felix A. Rey, Hugo Mouquet, Etienne Simon-Lorière, Timothée Bruel, Jean-Michel Pawlotsky, and Olivier Schwartz

Subjects
SARS-CoV-2, Delta, AY.4.2, Vaccines, Fusogenicity, Neutralization, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: SARS-CoV-2 lineages are continuously evolving. As of December 2021, the AY.4.2 Delta sub-lineage represented 20 % of sequenced strains in the UK and had been detected in dozens of countries. It has since then been supplanted by Omicron. The AY.4.2 spike displays three additional mutations (T95I, Y145H and A222V) in the N-terminal domain when compared to the original Delta variant (B.1.617.2) and remains poorly characterized. Methods: We compared the Delta and the AY.4.2 spikes, by assessing their binding to antibodies and ACE2 and their fusogenicity. We studied the sensitivity of an authentic AY.4.2 viral isolate to neutralizing antibodies. Findings: The AY.4.2 spike exhibited similar binding to all the antibodies and sera tested, and similar fusogenicity and binding to ACE2 than the ancestral Delta spike. The AY.4.2 virus was slightly less sensitive than Delta to neutralization by a panel of monoclonal antibodies; noticeably, the anti-RBD Imdevimab showed incomplete neutralization. Sensitivity of AY.4.2 to sera from vaccinated individuals was reduced by 1.3 to 3-fold, when compared to Delta. Interpretation: Our results suggest that mutations in the NTD remotely impair the efficacy of anti-RBD antibodies. The spread of AY.4.2 was not due to major changes in spike fusogenicity or ACE2 binding, but more likely to a partially reduced neutralization sensitivity. Funding: The work was funded by Institut Pasteur, Fondation pour la Recherche Médicale, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute, Labex IBEID, ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR.

Published
2022
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3. Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

Author

Blandine Monel, Delphine Planas, Ludivine Grzelak, Nikaïa Smith, Nicolas Robillard, Isabelle Staropoli, Pedro Goncalves, Françoise Porrot, Florence Guivel-Benhassine, Nathalie Demory Guinet, Julien Rodary, Julien Puech, Victor Euzen, Laurent Bélec, Galdric Orvoen, Léa Nunes, Véronique Moulin, Jacques Fourgeaud, Maxime Wack, Sandrine Imbeaud, Pascal Campagne, Darragh Duffy, James P. Di Santo, Timothée Bruel, Hélène Péré, David Veyer, and Olivier Schwartz

Subjects
COVID-19, SARS-CoV-2, Nasal swabs, variants, infectious particles, Medicine, Medicine (General), R5-920
Abstract

Background: The dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised. Methods: We measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants. Findings: With both lineages, viral titers were variable, ranging from 0 to >106 infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10). Interpretation: The alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection. Funding: This retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale.

Published
2021
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4. 2022-RA-1480-ESGO TRANSLACOL project: digital-PCR human papilloma virus (HPV) detection for recurrence prediction in early cervical cancer patients without pelvic lymph node invasion

Author

Rosa Montero Macías, Nicolas Robillard, Thomas Bruneau, Coronado Pluvio, Mélanie Boulhic, Marie-Aude Le Frére-Belda, Ivana Stankovic, Martina Aida Angeles, Eliane Mery, Pascal Rigolet, Cecile Badoual, Patrice Mathevet, Anne-Sophie Bats, Valérie Taly, David Veyer, Fabrice Lecuru, and Helene Pere

Published
2022

5. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Author

Najiby Kassis-Chikhani, Samira Fafi-Kremer, Olivier Schwartz, Laurent Bélec, Matthieu Prot, Cyril Planchais, Timothée Bruel, Laura Courtellemont, Florence Guivel-Benhassine, Artem Baidaliuk, Isabelle Staropoli, Julien Le Guen, Etienne Simon-Loriere, Laurent Hocqueloux, Delphine Planas, David Veyer, Pierre Gantner, Maaran Michael Rajah, Aurélie Velay, Thierry Prazuck, Dhiaeddine Edriss, Félix A. Rey, Françoise Porrot, Hélène Péré, Floriane Gallais, Aymeric Sève, Nicolas Robillard, Julien Puech, Hugo Mouquet, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, The Opera system was co-funded by the Institut Pasteur and the Région Île de France (DIM1Health). Work in the O.S. laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Work in UPBI is funded by grant ANR-10-INSB-04-01 and the Région Île-de-France program DIM1-Health. D.P. is supported by the Vaccine Research Institute. The H.M. laboratory is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The S.F.K. laboratory is funded by Strasbourg University Hospitals (SeroCoV-HUS, PRI 7782), the Programme Hospitalier de Recherche Clinique (PHRC N 2017–HUS no. 6997), the Agence Nationale de la Recherche (ANR-18-CE17-0028), Laboratoire d’Excellence TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) and the Institut National de la Santé et de la Recherche Médicale (UMR_S 1109). The E.S.-L. laboratory is funded by the Institut Pasteur and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID)., We thank N. Casartelli for critical reading of the manuscript, P. Guardado Calvo for discussion, the individuals who participated in the study, members of the Virus and Immunity Unit for discussions and help, N. Aulner and the UTechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis, and the DRCI, CIC, Médecine du Travail and Pôle de Biologie teams (CHU de Strasbourg) for the management of the Strasbourg cohort and serology testing., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), 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), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), and Université Paris Cité (UPC)

Subjects
Male, Delta, COVID-19 Vaccines, medicine.drug_class, India, Alpha (ethology), Biology, Antibodies, Monoclonal, Humanized, Antibodies, Viral, Monoclonal antibody, Neutralization, Epitope, Epitopes, Immune system, Neutralization Tests, medicine, Humans, Immune Evasion, Multidisciplinary, COVID-19, Convalescence, Middle Aged, Antibodies, Neutralizing, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Spike Glycoprotein, Coronavirus, Monoclonal, biology.protein, France, Antibody
Abstract

The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1–5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2—also termed the Delta variant—is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein. The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.

Published
2021

6. TRANSLACOL project: Nodal human papillomavirus tumoral DNA detection by ddPCR for survival prediction in early cervical cancer patients without pelvic lymph node invasion

Author

Rosa Montero-Macías, David Veyer, Thomas Bruneau, Nicolas Robillard, Marie-Aude Le Frère-Belda, Pascal Rigolet, Mélanie Boulhic, Ivana Stankovic, Laurent Bélec, Martina Aida Angeles, Eliane Mery, Cécile Badoual, Pluvio J Coronado, Anne-Sophie Bats, Patrice Mathevet, Valérie Taly, Fabrice Lécuru, and Hélène Péré

Subjects
Infectious Diseases, Virology
Published
2023

7. Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

Author

Julien Puech, Marie-Laure Lucas, Simon Pernot, Raphael Vernet, David Veyer, Laurence Weiss, Cécile Badoual, Bastien Rance, Nicolas Robillard, Hélène Péré, Laurent Bélec, Sonia Lameiras, Alain Nicolas, Maxime Wack, Juliette Pavie, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Bergonié [Bordeaux], UNICANCER, Hôtel-Dieu, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Curie [Paris], Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Gestionnaire, Hal Sorbonne Université, 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 National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Science, Context (language use), Virus, Article, Metastasis, Tumour biomarkers, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Carcinoma, Medicine, Humans, Tumour virus infections, Neoplasm Metastasis, Prospective cohort study, Retrospective Studies, Whole genome sequencing, Human papillomavirus 16, Multidisciplinary, medicine.diagnostic_test, business.industry, Papillomavirus Infections, Anal Squamous Cell Carcinoma, virus diseases, Translational research, medicine.disease, Anus Neoplasms, female genital diseases and pregnancy complications, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Carcinoma, Squamous Cell, business, Biomarkers
Abstract

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

Published
2021

8. Persistent Coronavirus Disease 2019 (COVID-19) in an Immunocompromised Host Treated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific Monoclonal Antibodies

Author

Anne Laure Clairet, Ana Berceanu, Laurie Spehner, Etienne Daguindau, Solène Marty-Quinternet, Karine Lacombe, Benoit Bailly, Kevin Bouiller, Jean-Laurent Casanova, Julien Puech, Sandrine Imbeaud, Quentin Lepiller, Marie Kroemer, Pauline Roux, Brigitte Autran, Catherine Chirouze, Xavier de Lamballerie, David Veyer, Paul Bastard, Fanny Angelot Delettre, Olivier Hermine, Hélène Péré, Nicolas Robillard, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service d'Hématologie [CHRU Besançon], Hôpital JeanMinjoz, LITTORAL (LITTORAL), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier Lons le Saunier, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), and Howard Hughes Medical Institute (HHMI)

Subjects
Microbiology (medical), 0303 health sciences, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), 030306 microbiology, business.industry, Host (biology), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Monoclonal antibody, Virology, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Medicine, 030212 general & internal medicine, business
Abstract

International audience; No abstract available

Published
2022

9. Severe relapse of SARS‐CoV‐2 infection in a kidney transplant recipient with negative nasopharyngeal SARS‐CoV‐2 RT‐PCR after rituximab

Author

Antoine Morel, Sandrine Imbeaud, Anne Scemla, Hélène Péré, Jacques Fourgeaud, Lucile Amrouche, Nicolas Robillard, Delphine Planas, Julien Puech, Sylvie Simon, Fanny Lanternier, Laurent Bélec, Julien Zuber, Olivier Schwartz, Dany Anglicheau, Nathalie Chavarot, David Veyer, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), 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), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), 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 (UPC), The authors would like to thank AcaciaTools for their proofreading services, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Saclay, Service Néphrologie et transplantation rénale Adultes [CHU Necker], Université Sorbonne Paris Cité (USPC), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Vaccine Research Institute [Créteil, France] (VRI), Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Transplantation, MESH: Humans, infection and infectious agents-viral, translational research/science, [SDV]Life Sciences [q-bio], infectious disease, MESH: COVID-19 Testing, kidney transplantation/nephrology, clinical research/practice, MESH: Kidney Transplantation, MESH: Recurrence, lung disease: infectious, MESH: Reverse Transcriptase Polymerase Chain Reaction, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology and Allergy, MESH: COVID-19, Pharmacology (medical), MESH: SARS-CoV-2, MESH: Rituximab
Abstract

International audience; Immunocompromised patients may experience prolonged viral shedding after their initial SARS-CoV-2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID-19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID-19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho-alveolar lavage specimen (BAL) by RT-PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3-amino-acids at position 143-145. These mutations located within the N-terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID-19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso-pharyngeal SARS-CoV-2 PCR.

Published
2022

10. Circulating Ubiquitous RNA, A Highly Predictive and Prognostic Biomarker in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients

Author

Thomas Bruneau, Maxime Wack, Geoffroy Poulet, Nicolas Robillard, Aurélien Philippe, Pierre Laurent Puig, Laurent Bélec, Jérôme Hadjadj, Wenjin Xiao, Julia Linnea Kallberg, Solen Kernéis, Jean Luc Diehl, Benjamin Terrier, David M Smadja, Valerie Taly, David Veyer, Hélène Péré, TALY, Valerie, 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), Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AP-HP CUP Paris, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ddPCR, tissue/cell lysis biomarker, hospitalized COVID-19 patient, predictive and prognostic biomarkers, SARS-CoV-2 and RNAseP RNAemia
Abstract

Background Approximately 15–30% of hospitalized coronavirus disease 2019 (COVID-19) patients develop acute respiratory distress syndrome, systemic tissue injury, and/or multi-organ failure leading to death in around 45% of cases. There is a clear need for biomarkers that quantify tissue injury, predict clinical outcomes, and guide the clinical management of hospitalized COVID-19 patients. Methods We herein report the quantification by droplet-based digital polymerase chain reaction (ddPCR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and the plasmatic release of a ubiquitous human intracellular marker, the ribonuclease P (RNase P) in order to evaluate tissue injury and cell lysis in the plasma of 139 COVID-19 hospitalized patients at admission. Results We confirmed that SARS-CoV-2 RNAemia was associated with clinical severity of COVID-19 patients. In addition, we showed that plasmatic RNase P RNAemia at admission was also highly correlated with disease severity (P Conclusions Viral and ubiquitous blood biomarkers monitored by ddPCR could be useful for the clinical monitoring and the management of hospitalized COVID-19 patients. Moreover, these results could pave the way for new and more personalized circulating biomarkers in COVID-19, and more generally in infectious diseases, specific from each patient organ injury profile.

Published
2022

11. HPV Molecular Genotyping as a Differential Diagnosis Tool in Cervical Cancer Metastasis

Author

Rosa Montero-Macías, Pluvio J. Coronado, Nicolas Robillard, David Veyer, Vincent Villefranque, Marie-Aude Le Frére-Belda, Elisabeth Auberger, Pauline Bitolog, Ivana Stankovic, Laurent Bélec, Anne-Sophie Bats, Fabrice Lécuru, and Hélène Péré

Subjects
Medicine (miscellaneous)
Abstract

Background: Differentiating metastatic cervical cancer from another primary tumor can be difficult in patients with a history of cervical cancer and a distant lesion. The use of routine HPV molecular detection and genotyping tests could help in these cases. The objective of this study was to identify if an easy-to-use HPV molecular genotyping assay would allow differentiating between HPV tumor metastasis and a new independent primary non-HPV-induced tumor. Materials and Methods: Between 2010 and 2020, we identified patients with a primary cervical carcinoma who also had another secondary lesion. This identification included a clinical and histologic differential diagnosis of metastatic cervical cancer versus a new primary cancer or metastatic cancer from another site. We used a routine multiplex real-time PCR (rt-PCR) AnyplexTM II HPV28 (Seegene, Seoul, Republic of Korea) to detect the high-risk (HR)-HPV genome in the distant lesions in these patients. Results: Eight cases of cervical cancer with a new secondary lesion were identified. In seven, HR-HPV DNA was detected in the biopsy of the distant lesion, which confirmed the diagnosis of cervical cancer metastasis. In the remaining case, no HPV was detected in the secondary lung biopsy, confirming the diagnosis of new primary lung cancer. Conclusion: Our results pave the way for HPV molecular genotyping use in cases of newly diagnosed distant lesions in patients with a history of HPV cervical neoplasia by using a routine diagnosis process to complete the clinical and histologic differential diagnosis when confronted with ambiguous situations.

Published
2023

12. Transmission of SARS-CoV-2 Alpha Variant (B.1.1.7) From a BNT162b2-Vaccinated Individual

Author

Timothée Bruel, Olivier Schwartz, Delphine Planas, Julien Puech, Hélène Péré, Sandrine Imbeaud, David Veyer, Solen Kernéis, Nicolas Robillard, Laurent Bélec, Thomas Vieillard, Julien Rodary, Isabelle Staropoli, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Laboratoire Biosmose-idf [Rueil-Malmaison], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), D.P. is supported by the Vaccine Research Institute. D.V. and H.P. are funded by IDEX AAP EMERGENCE-Université de Paris (EMER-VEYER project) and Mécénat COVID APHP-CUP., Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), École Pratique des Hautes Études (EPHE), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine [Santé] (UPC UFR Médecine), and Université Paris Cité (UPC)

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Transmission (medicine), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, transmission, Alpha (ethology), virus diseases, vaccination, Virology, Vaccination, Infectious Diseases, AcademicSubjects/MED00290, Oncology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Brief Reports, BNT162b2, Seroconversion, business
Abstract

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition after vaccination with BNT162b2 have been described, but the risk of secondary transmission from fully vaccinated individuals remains ill defined. Herein we report a confirmed transmission of SARS-CoV-2 alpha variant (B.1.1.7) from a symptomatic immunocompetent woman 4 weeks after her second dose of BNT162b2, despite antispike seroconversion.

Published
2021

13. Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

Author

Olivier Schwartz, Cyril Planchais, Aurélie Velay, Françoise Porrot, Thierry Prazuck, Laura Courtellemenont, Matthieu Prot, Julien Le Guen, Maaran Michael Rajah, Julien Puech, Hugo Mouquet, Floriane Gallais, Aymeric Sève, Florence Guivel-Benhassine, Laurent Hocqueloux, Samira Fafi-Kremer, Etienne Simon-Loriere, Dhiaeddine Edriss, Hélène Péré, Artem Baidaliuk, Félix A. Rey, Delphine Planas, David Veyer, Nicolas Robillard, Timothée Bruel, Najibi Kassis-Chikhani, Laurent Bélec, Isabelle Staropoli, and Pierre Gantner

Subjects
Lineage (genetic), Immune system, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, biology.protein, Biology, Antibody, Monoclonal antibody, Virology, Epitope, Neutralization
Abstract

The SARS-CoV-2 B.1.617 lineage emerged in October 2020 in India1–6. It has since then become dominant in some indian regions and further spread to many countries. The lineage includes three main subtypes (B1.617.1, B.1617.2 and B.1.617.3), which harbour diverse Spike mutations in the N-terminal domain (NTD) and the receptor binding domain (RBD) which may increase their immune evasion potential. B.1.617.2 is believed to spread faster than the other versions. Here, we isolated infectious B.1.617.2 from a traveller returning from India. We examined its sensitivity to monoclonal antibodies (mAbs) and to antibodies present in sera from COVID-19 convalescent individuals or vaccine recipients, in comparison to other viral lineages. B.1.617.2 was resistant to neutralization by some anti-NTD and anti-RBD mAbs, including Bamlanivimab, which were impaired in binding to the B.1.617.2 Spike. Sera from convalescent patients collected up to 12 months post symptoms and from Pfizer Comirnaty vaccine recipients were 3 to 6 fold less potent against B.1.617.2, relative to B.1.1.7. Sera from individuals having received one dose of AstraZeneca Vaxzevria barely inhibited B.1.617.2. Thus, B.1.617.2 spread is associated with an escape to antibodies targeting non-RBD and RBD Spike epitopes.

Published
2021

14. Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-B.1.1.7 or B.1.1.7 SARS-CoV-2 variants

Author

Nathalie Demory, Pascal Campagne, David Veyer, Jacques Fourgeaud, Julien Puech, Laurent Bélec, Isabelle Staropoli, Galdric Orvoen, Florence Guivel-Benhassine, Julien Rodary, Veronique Moulin, Darragh Duffy, Blandine Monel, Ludivine Grzelak, Victor Euzen, Hélène Péré, Nikaïa Smith, Maxime Wack, Timothée Bruel, Lea Nunes, Delphine Planas, Pedro Gonçalves, Sandrine Imbeaud, Françoise Porrot, Olivier Schwartz, James P. Di Santo, and Nicolas Robillard

Subjects
Infectivity, Titer, Cytokine, Antigen, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, medicine, biology.protein, Biology, Antibody, Virology, Virus, Infectious virus
Abstract

The mechanisms that allowed for the SARS-CoV-2 B.1.1.7 variant to rapidly outcompete pre-existing variants in many countries remain poorly characterized. Here, we analyzed viral release, anti-SARS-CoV-2 antibodies and cytokine production in a retrospective series of 427 RT–qPCR+ nasopharyngeal swabs collected in COVID-19 patients harbouring either non-B.1.1.7 or B.1.17 variants. We utilized a novel rapid assay, based on S-Fuse-T reporter cells, to quantify infectious SARS-CoV-2. With both non-B.1.1.7 and B.1.1.7 variants, viral titers were highly variable, ranging from 0 to >106 infectious units, and correlated with viral RNA levels. Lateral flow antigenic rapid diagnostic tests (RDTs) were positive in 96% of the samples harbouring infectious virus. About 67 % of individuals carried detectable infectious virus within the first two days after onset of symptoms. This proportion decreased overtime, and viable virus was detected up to 14 days. Samples containing anti-SARS-CoV-2 IgG or IgA did not generally harbour infectious virus. The proportion of individuals displaying viable virus or being RDT-positive was not higher with B.1.1.7 than with non-B.1.1.7 variants. Ct values were slightly but not significantly lower with B.1.1.7. The variant was characterized by a fast decrease of infectivity overtime and a marked release of 17 cytokines (including IFN-β, IP-10, IL-10 and TRAIL). Our results highlight differences between non-B.1.1.7 and B.1.1.7 variants. B.1.1.7 is associated with modified viral decays and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection.

Published
2021

15. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19

Author

Blandine Monel, David Veyer, Benoit Visseaux, Anne Blanchard, Antoine Fayol, David Lebeaux, Benoit Vedie, Maureen Betton, Hélène Péré, Jade Ghosn, Delphine Planas, Timothée Bruel, Marine Livrozet, Jean-Sébastien Hulot, Jean-Claude Manuguerra, Olivier Schwartz, Nicolas Robillard, Eric Tartour, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 biochimie [AP-HP Hôpital Européen Georges Pompidou], 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), Laboratoire d’immunologie [Hôpital Européen Georges Pompidou - APHP], Service de Microbiologie [CHU GeorgesPompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris]-Institut Pasteur [Paris], Services de Maladies Infectieuses et Tropicales [CHU Bichat], 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), 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 Bichat], 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), The French COVID cohort is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424). Work in OS lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 and IDISCOVR. Outside the submitted work, JSH is supported by AP-HP, INSERM, the French National Research Agency (NADHeart ANR-17-CE17-0015-02, PACIFIC ANR-18-CE14-0032-01, CORRECT_LMNA ANR-19-CE17-0013-02), the ERA-Net-CVD (ANR-16-ECVD-0011-03, Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation (18CVD05), and is coordinating a French PIA Project (2018-PSPC-07, PACIFIC-preserved, BPIFrance) and a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure)., The French COVID cohort study group : Laurent ABEL (Inserm UMR 1163, Paris, France), Claire ANDREJAK (CHU Amiens, France), François ANGOULVANT (Hôpital Necker, Paris, France), Delphine BACHELET, Krishna BHAVSAR, Lila BOUADMA, Anissa CHAIR, Camille COUFFIGNAL, Charlene DA SILVEIRA, Marie-Pierre DEBRAY, Diane DESCAMPS, Xavier DUVAL, Philippine ELOY, Marina ESPOSITO-FARESE, Nadia ETTALHAOUI, Nathalie GAULT, Jade GHOSN, Isabelle GORENNE, Isabelle HOFFMANN, Ouifiya KAFIF, Sabrina KALI, Antoine KHALIL, Cédric LAOUÉNAN, Samira LARIBI, Minh LE, Quentin LE HINGRAT, François-Xavier LESCURE, Jean Christophe LUCET, France MENTRÉ, Jimmy Mullaert, Nathan PEIFFER-SMADJA, Gilles PEYTAVIN, Carine ROY, Marion SCHNEIDER, Nassima SI MOHAMMED, Lysa TAGHERSET, Coralie TARDIVON, Marie-Capucine TELLIER, Jean-François TIMSIT, Théo TRIOUX, Sarah TUBIANA, Benoit VISSEAUX, Yazdan YAZDANPANAH (Hôpital Bichat, Paris, France), Romain BASMACI, Olivier PICONE (Hôpital Louis Mourier, Colombes, France), Sylvie BEHILILL, Sylvie VAN DER WERF, Vincent ENOUF, Hugo MOUQUET (Pasteur Institute, Paris, France), Marine BELUZE (F-CRIN Partners Platform, Paris, France), Dehbia BENKERROU, Céline DORIVAL, François TÉOULÉ, Amina MEZIANE (Inserm UMR 1136, Paris, France), François BOMPART (Drugs for Neglected Diseases initiative, Geneva, Switzerland), Maude BOUSCAMBERT (Inserm UMR 1111, Lyon, France), Minerva CERVANTES-GONZALEZ, Eric d’ORTENZIO, Oriane PUÉCHAL, Caroline SEMAILLE (REACTing, Paris, France), Catherine CHIROUZE (CHRU Jean Minjoz, Besançon, France), Alexandra COELHO (Inserm UMR 1018, Paris, France), Sandrine COUFFIN-CADIERGUES, Hélène ESPEROU, Ikram HOUAS, Salma JAAFOURA, Aurélie PAPADOPOULOS (Inserm sponsor, Paris, France), Dominique DEPLANQUE (Hôpital Calmette, Lille, France), Mathilde DESVALLÉE, Coralie KHAN (Inserm UMR 1219, Bordeaux, France), Alpha DIALLO, Marie BARTOLI, Soizic LE MESTRE, Noémie MERCIER, Christelle PAUL, Ventzislava PETROV-SANCHEZ (ANRS, Paris, France), Alphonsine DIOUF, Alexandre HOCTIN, Marina MAMBERT (Inserm UMR 1018, Paris, France), François DUBOS (CHU Lille, France), Manuel ETIENNE (CHU Rouen, France), Alexandre GAYMARD (Inserm UMR 1111, Lyon, France), Tristan GIGANTE, Morgane GILG, Bénédicte ROSSIGNOL (F-CRIN INI-CRCT, Nancy, France), Jérémie GUEDJ, Hervé LE NAGARD, Guillaume LINGAS, Nadège NEANT (Inserm UMR 1137, Paris, France), Jean-Sébastien HULOT (Hôpital Européen Georges Pompidou, Paris, France), Florentia KAGUELIDOU, Justine PAGES (Hôpital Robert Debré, Paris, France), Yves LEVY, Aurélie WIEDEMANN (Vaccine Research Insitute (VRI), Inserm UMR 955, Créteil, France), Claire LEVY-MARCHAL (F-CRIN INI-CRCT, Paris, France), Bruno LINA, Manuel ROSA-CALATRAVA, Olivier TERRIER (Inserm UMR 1111, Lyon, France), Denis MALVY (CHU Bordeaux, France), Marion NORET (RENARCI, Annecy, France), Patrick ROSSIGNOL (CHU Nancy, France), Christelle TUAL, Aurélie VEISLINGER (Inserm CIC-1414, Rennes, France), Noémie VANEL (Hôpital la Timone, Marseille, France), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE17-0015,NAD-HEART,Supplémentation en précurseur du NAD+ pour le traitement de l'insuffisance cardiaque(2017), ANR-18-CE14-0032,PACIFIC,Cellules PW1+ dans la fibrose cardiaque(2018), ANR-19-CE17-0013,Correct-LMNA,Édition génomique par CRISPR/Cas9 pour traiter les cardiomyopathies liées aux mutations du gène LMNA(2019), ANR-16-ECVD-0011,CLARIFY,Communication between cardiomyocytes and innate immune cells in failing hearts(2016), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, and French COVID cohort study group

Subjects
0301 basic medicine, Microbiology (medical), [SDV]Life Sciences [q-bio], 030106 microbiology, Antibodies, Viral, medicine.disease_cause, Severity of Illness Index, Immunoglobulin G, Neutralization, law.invention, Serology, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Major Article, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pandemics, Coronavirus, biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Intensive care unit, 3. Good health, Hospitalization, Editorial Commentary, AcademicSubjects/MED00290, Infectious Diseases, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Antibody, business
Abstract

Background Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.

Published
2021

16. Usefulness of Plasma SARS-CoV-2 RNA Quantification by Droplet-based Digital PCR to Monitor Treatment Against COVID-19 in a B-cell Lymphoma Patient

Author

Valérie Taly, Laure Izquierdo, Laurent Bélec, Hélène Péré, Solen Kernéis, Celia Azoulay, Thomas Serrano, Nicolas Robillard, Pierre Laurent-Puig, Karine Lacombe, Benjamin Terrier, Deborah Eshagh, Adrien Contejean, Marguerite Vignon, David Veyer, Tali Anne Szwebel, Thomas Hueso, Flore Rozenberg, Etienne Canouï, Thomas Bruneau, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Equipe Mobile d'Infectiologie [APHP Centre, Paris], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Labex OncoImmunology, Equipe labellisée Ligue Contre le Cancer, Université Paris Descartes - Paris 5 (UPD5), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], This work was supported by the Assistance Publique Hôpitaux de Paris (AP-HP), Ministère de l’Enseignement Supérieur et de la Recherche, the Université de Paris, the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Collecte Crise COVID/APHP Centre-Université de Paris., Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [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), École pratique des hautes études (EPHE), TALY, Valerie, 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), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, medicine.drug_class, business.industry, [SDV]Life Sciences [q-bio], RNA, medicine.disease, Monoclonal antibody, Article, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Biomarker (medicine), Digital polymerase chain reaction, Stem cell, business, B-cell lymphoma, Viral load
Abstract

International audience; We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.

Published
2021

17. Persistence of Sera Neutralizing Activity Six Month after Hospitalization for COVID-19

Author

Maureen Betton, Marine Livrozet, Antoine Fayol, Delphine Planas, Blandine Monel, Benoit Vedie, Timothée Bruel, Eric Tartour, Nicolas Robillard, Anne Blanchard, Jade Ghosn, Benoit Visseaux, Hélène Péré, David Lebeaux, Olivier Schwartz, David Veyer, Jean-Sébastien Hulot, and French COVID Cohort Study Group

Subjects
Coronavirus disease 2019 (COVID-19), business.industry, Immunology, Medicine, business, Persistence (computer science)
Published
2021

18. Highly sensitive quantification of plasma SARS-CoV-2 RNA shelds light on its potential clinical value

Author

Benjamin Terrier, Hélène Péré, Nicolas Robillard, Laurent Bélec, Flore Rozenberg, Jérôme Hadjadj, Solen Kernéis, Valérie Taly, Maxime Wack, Pierre Laurent-Puig, Anne-Sophie L’Honneur, David Veyer, Geoffroy Poulet, 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), 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, Eurofins Biomnis, Institut Pasteur [Paris], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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 National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and TALY, Valerie

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Critical Illness, [SDV]Life Sciences [q-bio], Severity of Illness Index, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Severity of illness, medicine, Major Article, Humans, Digital polymerase chain reaction, 030212 general & internal medicine, Respiratory system, Polymerase chain reaction, Liver injury, business.industry, Diagnostic Tests, Routine, SARS-CoV-2, COVID-19, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Editorial Commentary, Pneumonia, 030104 developmental biology, Infectious Diseases, AcademicSubjects/MED00290, RNA, Viral, Biomarker (medicine), RNA, business, Viral load
Abstract

Background Coronavirus disease 2019 (COVID-19) is a global public health problem that has already caused more than 662 000 deaths worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, some patients present other severe damage such as cardiovascular, renal and liver injury, and/or multiple organ failure, suggesting a spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood. Recent ultrasensitive polymerase chain reaction (PCR) technology now allows absolute quantification of nucleic acids in plasma. We intend to use the droplet-based digital PCR technology to obtain sensitive detection and precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia) in hospitalized COVID-19 patients. Methods Fifty-eight consecutive COVID-19 patients with pneumonia 8 to 12 days after onset of symptoms and 12 healthy controls were analyzed. Disease severity was categorized as mild to moderate in 17 patients, severe in 16, and critical in 26. Plasma SARS-CoV-2 RNAemia was quantified by droplet digital Crystal Digital PCR next-generation technology (Stilla Technologies, Villejuif, France). Results Overall, SARS-CoV-2 RNAemia was detected in 43 (74.1%) patients. Prevalence of positive SARS-CoV-2 RNAemia correlated with disease severity, ranging from 53% in mild-to-moderate patients to 88% in critically ill patients (P = .036). Levels of SARS-CoV-2 RNAemia were associated with severity (P = .035). Among 9 patients who experienced clinical deterioration during follow-up, 8 had positive SARS-CoV-2 RNAemia at baseline, whereas only 1 critical patient with undetectable SARS-CoV-2 RNAemia at the time of analysis died at day 27. Conclusion SARS-CoV-2 RNAemia measured by droplet-based digital PCR constitutes a promising prognosis biomarker in COVID-19 patients.

Published
2020

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