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1. 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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2. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

Author

Delphine Planas, Nell Saunders, Piet Maes, Florence Guivel-Benhassine, Cyril Planchais, Julian Buchrieser, William-Henry Bolland, Françoise Porrot, Isabelle Staropoli, Frederic Lemoine, Hélène Péré, David Veyer, Julien Puech, Julien Rodary, Guy Baele, Simon Dellicour, Joren Raymenants, Sarah Gorissen, Caspar Geenen, Bert Vanmechelen, Tony Wawina-Bokalanga, Joan Martí-Carreras, Lize Cuypers, Aymeric Sève, Laurent Hocqueloux, Thierry Prazuck, Félix A. Rey, Etienne Simon-Loriere, Timothée Bruel, Hugo Mouquet, Emmanuel André, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-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 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), Université libre de Bruxelles (ULB), University Hospitals Leuven [Leuven], Centre Hospitalier Régional d'Orléans (CHRO), Virologie Structurale - Structural Virology, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, The Opera system was co-funded by Institut Pasteur and the Région ile de France (DIM1Health). Work in the O.S. laboratory 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. Work in the UPBI is funded by grant ANR-10-INSB-04-01 and Région Ile-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), the INSERM, REACTing, EU (RECOVER) and Fondation de France (00106077) grants. The E.S.-L. laboratory is funded by Institut Pasteur, the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005) 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). G.B. acknowledges support from the Internal Funds KU Leuven under grant agreement C14/18/094, and the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G0E1420N, G098321N). P.M. acknowledges support from a COVID-19 research grant of ‘Fonds Wetenschappelijk Onderzoek’/Research Foundation–Flanders (grant no. G0H4420N). S.D. is supported by the Fonds National de la Recherche Scientifique (FNRS, Belgium) and also acknowledges support from the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G098321N) and from the European Union Horizon 2020 project MOOD (grant no. 874850)., 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-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 874850,H2020-SC1-2019-Single-Stage-RTD,MOOD(2020), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-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)-École pratique des hautes études (EPHE), and European Project: 874850,MOOD

Subjects
MESH: Humans, MESH: Mutation, Multidisciplinary, MESH: ChAdOx1 nCoV-19, MESH: Neutralization Tests, MESH: Adult, MESH: Convalescence, MESH: Male, MESH: Antibodies, Monoclonal, MESH: Antibodies, Neutralizing, MESH: Belgium, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: COVID-19, MESH: Immunization, Secondary, MESH: SARS-CoV-2, MESH: Immune Evasion, MESH: BNT162 Vaccine, MESH: Phylogeny, MESH: Travel, MESH: Female, MESH: Antibodies, Viral
Abstract

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose. ispartof: NATURE vol:602 issue:7898 pages:671-+ ispartof: location:England status: published

Published
2021

3. Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization

Author

Delphine Planas, Nell Saunders, Piet Maes, Florence Guivel-Benhassine, Cyril Planchais, Julian Buchrieser, William-Henry Bolland, Françoise Porrot, Isabelle Staropoli, Frederic Lemoine, Hélène Péré, David Veyer, Julien Puech, Julien Rodary, Guy Baela, Simon Dellicour, Joren Raymenants, Sarah Gorissen, Caspar Geenen, Bert Vanmechelen, Tony Wawina-Bokalanga, Joan Martí-Carrerasi, Lize Cuypers, Aymeric Sève, Laurent Hocqueloux, Thierry Prazuck, Félix Rey, Etienne Simon-Lorrière, Timothée Bruel, Hugo Mouquet, Emmanuel André, and Olivier Schwartz

Abstract

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1,2. It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development3, and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.

Published
2021

4. 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

5. 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

6. Nasal Swab Sampling for SARS-CoV-2: a Convenient Alternative in Times of Nasopharyngeal Swab Shortage

Author

Eric Caudron, Edouard Flamarion, Caroline Hauw-Berlemont, Laurent Bélec, Sophie Carrabin, Tristan Mirault, David Veyer, Guillaume Goudot, Julien Rodary, Isabelle Podglajen, Hélène Péré, Tatiana Ribeyre, Maxime Wack, and Laetitia Le

Subjects
0301 basic medicine, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Pneumonia, Viral, RT-PCR, Economic shortage, World health, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, COVID-19 Testing, Nasopharynx, molecular diagnosis, Medicine, Humans, 030212 general & internal medicine, Letter to the Editor, Pandemics, nasal swab, business.industry, SARS-CoV-2, Clinical Laboratory Techniques, COVID-19, Virology, nasopharyngeal swab, Equipment and Supplies, Nasal Swab, business, Coronavirus Infections
Abstract

Nasopharyngeal swab is the reference sampling method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as recommended by the World Health Organization (WHO) ([1][1]). However, nasal specimens may have a slightly lower sensitivity than nasopharyngeal specimens ([2][2], [3][3]).

Published
2020
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7. Comparative practicability and analytical performances of Credo VitaPCR™ Flu A&B and Cepheid Xpert® Xpress Flu/RSV platforms

Author

Laurent Bélec, Ralph Sydney Mboumba Bouassa, Serge Tonen-Wolyec, and Julien Rodary

Subjects
0301 basic medicine, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Hospital setting, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Nasopharynx, Influenza, Human, Humans, Medicine, 030212 general & internal medicine, business.industry, Reproducibility of Results, virus diseases, Influenza a, General Medicine, Virology, Infectious Diseases, Molecular Diagnostic Techniques, Influenza A virus, Point-of-Care Testing, Viruses, Reagent Kits, Diagnostic, business
Abstract

To compare the practicability (usability and satisfaction) and analytical performances of VitaPCR™ Flu AB Assay (Credo Diagnostics Biomedical Pte. Ltd., Singapore, Republic of Singapore) and Xpert® Xpress Flu/RSV kit (Cepheid, Sunnyvale, USA), two rapid point-of-care (POC) nucleic acid amplification tests (NAATs) by reference to multiplex RT-PCR for respiratory viruses. Nasopharyngeal swabs (n=117) were collected from patients with influenza-like illness in Paris, France. Thawed specimens were further analyzed with both NAATs. The usability was comparable for both NAATs. Satisfaction questionnaire was better for the VitaPCR™ platform for the short time of test result in 20 minutes. Both NAATs showed comparable sensitivities (VitaPCR

Published
2021

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