Serveur d'exploration COVID et hydrochloroquine

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Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.

Identifieur interne : 001078 ( Main/Corpus ); précédent : 001077; suivant : 001079

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.

Auteurs : Pauline Maisonnasse ; Jérémie Guedj ; Vanessa Contreras ; Sylvie Behillil ; Caroline Solas ; Romain Marlin ; Thibaut Naninck ; Andres Pizzorno ; Julien Lemaitre ; Antonio Gonçalves ; Nidhal Kahlaoui ; Olivier Terrier ; Raphael Ho Tsong Fang ; Vincent Enouf ; Nathalie Dereuddre-Bosquet ; Angela Brisebarre ; Franck Touret ; Catherine Chapon ; Bruno Hoen ; Bruno Lina ; Manuel Rosa Calatrava ; Sylvie Van Der Werf ; Xavier De Lamballerie ; Roger Le Grand

Source :

RBID : pubmed:32698191

English descriptors

Abstract

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.

DOI: 10.1038/s41586-020-2558-4
PubMed: 32698191

Links to Exploration step

pubmed:32698191

Le document en format XML

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<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
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<name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name>
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<name sortKey="Marlin, Romain" sort="Marlin, Romain" uniqKey="Marlin R" first="Romain" last="Marlin">Romain Marlin</name>
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<name sortKey="Naninck, Thibaut" sort="Naninck, Thibaut" uniqKey="Naninck T" first="Thibaut" last="Naninck">Thibaut Naninck</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
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<name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
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<name sortKey="Lemaitre, Julien" sort="Lemaitre, Julien" uniqKey="Lemaitre J" first="Julien" last="Lemaitre">Julien Lemaitre</name>
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<name sortKey="Goncalves, Antonio" sort="Goncalves, Antonio" uniqKey="Goncalves A" first="Antonio" last="Gonçalves">Antonio Gonçalves</name>
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<nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation>
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<name sortKey="Kahlaoui, Nidhal" sort="Kahlaoui, Nidhal" uniqKey="Kahlaoui N" first="Nidhal" last="Kahlaoui">Nidhal Kahlaoui</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
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<name sortKey="Fang, Raphael Ho Tsong" sort="Fang, Raphael Ho Tsong" uniqKey="Fang R" first="Raphael Ho Tsong" last="Fang">Raphael Ho Tsong Fang</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
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<name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name>
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<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
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<affiliation>
<nlm:affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Dereuddre Bosquet, Nathalie" sort="Dereuddre Bosquet, Nathalie" uniqKey="Dereuddre Bosquet N" first="Nathalie" last="Dereuddre-Bosquet">Nathalie Dereuddre-Bosquet</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name>
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<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
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<name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name>
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<nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Chapon, Catherine" sort="Chapon, Catherine" uniqKey="Chapon C" first="Catherine" last="Chapon">Catherine Chapon</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Hoen, Bruno" sort="Hoen, Bruno" uniqKey="Hoen B" first="Bruno" last="Hoen">Bruno Hoen</name>
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<nlm:affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</nlm:affiliation>
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<name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name>
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<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Calatrava, Manuel Rosa" sort="Calatrava, Manuel Rosa" uniqKey="Calatrava M" first="Manuel Rosa" last="Calatrava">Manuel Rosa Calatrava</name>
<affiliation>
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name>
<affiliation>
<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name>
<affiliation>
<nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name>
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<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</nlm:affiliation>
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<title xml:lang="en">Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.</title>
<author>
<name sortKey="Maisonnasse, Pauline" sort="Maisonnasse, Pauline" uniqKey="Maisonnasse P" first="Pauline" last="Maisonnasse">Pauline Maisonnasse</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
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<name sortKey="Guedj, Jeremie" sort="Guedj, Jeremie" uniqKey="Guedj J" first="Jérémie" last="Guedj">Jérémie Guedj</name>
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<nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Contreras, Vanessa" sort="Contreras, Vanessa" uniqKey="Contreras V" first="Vanessa" last="Contreras">Vanessa Contreras</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Behillil, Sylvie" sort="Behillil, Sylvie" uniqKey="Behillil S" first="Sylvie" last="Behillil">Sylvie Behillil</name>
<affiliation>
<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Solas, Caroline" sort="Solas, Caroline" uniqKey="Solas C" first="Caroline" last="Solas">Caroline Solas</name>
<affiliation>
<nlm:affiliation>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, Marseille, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Marlin, Romain" sort="Marlin, Romain" uniqKey="Marlin R" first="Romain" last="Marlin">Romain Marlin</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Naninck, Thibaut" sort="Naninck, Thibaut" uniqKey="Naninck T" first="Thibaut" last="Naninck">Thibaut Naninck</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name>
<affiliation>
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Lemaitre, Julien" sort="Lemaitre, Julien" uniqKey="Lemaitre J" first="Julien" last="Lemaitre">Julien Lemaitre</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Goncalves, Antonio" sort="Goncalves, Antonio" uniqKey="Goncalves A" first="Antonio" last="Gonçalves">Antonio Gonçalves</name>
<affiliation>
<nlm:affiliation>Université de Paris, IAME, Inserm, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kahlaoui, Nidhal" sort="Kahlaoui, Nidhal" uniqKey="Kahlaoui N" first="Nidhal" last="Kahlaoui">Nidhal Kahlaoui</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Terrier, Olivier" sort="Terrier, Olivier" uniqKey="Terrier O" first="Olivier" last="Terrier">Olivier Terrier</name>
<affiliation>
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Fang, Raphael Ho Tsong" sort="Fang, Raphael Ho Tsong" uniqKey="Fang R" first="Raphael Ho Tsong" last="Fang">Raphael Ho Tsong Fang</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name>
<affiliation>
<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Dereuddre Bosquet, Nathalie" sort="Dereuddre Bosquet, Nathalie" uniqKey="Dereuddre Bosquet N" first="Nathalie" last="Dereuddre-Bosquet">Nathalie Dereuddre-Bosquet</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Brisebarre, Angela" sort="Brisebarre, Angela" uniqKey="Brisebarre A" first="Angela" last="Brisebarre">Angela Brisebarre</name>
<affiliation>
<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Touret, Franck" sort="Touret, Franck" uniqKey="Touret F" first="Franck" last="Touret">Franck Touret</name>
<affiliation>
<nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Chapon, Catherine" sort="Chapon, Catherine" uniqKey="Chapon C" first="Catherine" last="Chapon">Catherine Chapon</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hoen, Bruno" sort="Hoen, Bruno" uniqKey="Hoen B" first="Bruno" last="Hoen">Bruno Hoen</name>
<affiliation>
<nlm:affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name>
<affiliation>
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Calatrava, Manuel Rosa" sort="Calatrava, Manuel Rosa" uniqKey="Calatrava M" first="Manuel Rosa" last="Calatrava">Manuel Rosa Calatrava</name>
<affiliation>
<nlm:affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name>
<affiliation>
<nlm:affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</nlm:affiliation>
</affiliation>
<affiliation>
<nlm:affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="De Lamballerie, Xavier" sort="De Lamballerie, Xavier" uniqKey="De Lamballerie X" first="Xavier" last="De Lamballerie">Xavier De Lamballerie</name>
<affiliation>
<nlm:affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Le Grand, Roger" sort="Le Grand, Roger" uniqKey="Le Grand R" first="Roger" last="Le Grand">Roger Le Grand</name>
<affiliation>
<nlm:affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</nlm:affiliation>
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<title level="j">Nature</title>
<idno type="eISSN">1476-4687</idno>
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<date when="2020" type="published">2020</date>
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<term>Animals (MeSH)</term>
<term>Azithromycin (pharmacology)</term>
<term>Azithromycin (therapeutic use)</term>
<term>Betacoronavirus (drug effects)</term>
<term>COVID-19 (MeSH)</term>
<term>Chlorocebus aethiops (MeSH)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (physiopathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cytokines (blood)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (pharmacokinetics)</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Hydroxychloroquine (therapeutic use)</term>
<term>In Vitro Techniques (MeSH)</term>
<term>Kinetics (MeSH)</term>
<term>Macaca fascicularis (MeSH)</term>
<term>Male (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (drug therapy)</term>
<term>Pneumonia, Viral (pathology)</term>
<term>Pneumonia, Viral (physiopathology)</term>
<term>Pneumonia, Viral (virology)</term>
<term>Pre-Exposure Prophylaxis (MeSH)</term>
<term>Respiratory Mucosa (cytology)</term>
<term>Respiratory Mucosa (drug effects)</term>
<term>Respiratory Mucosa (virology)</term>
<term>SARS-CoV-2 (MeSH)</term>
<term>Time Factors (MeSH)</term>
<term>Treatment Failure (MeSH)</term>
<term>Vero Cells (MeSH)</term>
<term>Viral Load (drug effects)</term>
</keywords>
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<term>Cytokines</term>
</keywords>
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<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Azithromycin</term>
<term>Hydroxychloroquine</term>
</keywords>
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<term>Azithromycin</term>
<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Respiratory Mucosa</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Betacoronavirus</term>
<term>Respiratory Mucosa</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
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<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
</keywords>
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<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>Respiratory Mucosa</term>
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<term>Animals</term>
<term>COVID-19</term>
<term>Chlorocebus aethiops</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Kinetics</term>
<term>Macaca fascicularis</term>
<term>Male</term>
<term>Pandemics</term>
<term>Pre-Exposure Prophylaxis</term>
<term>SARS-CoV-2</term>
<term>Time Factors</term>
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<div type="abstract" xml:lang="en">Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease
<sup>1-3</sup>
. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19
<sup>4-7</sup>
. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.</div>
</front>
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<DateCompleted>
<Year>2020</Year>
<Month>10</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised>
<Year>2021</Year>
<Month>01</Month>
<Day>28</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1476-4687</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>585</Volume>
<Issue>7826</Issue>
<PubDate>
<Year>2020</Year>
<Month>09</Month>
</PubDate>
</JournalIssue>
<Title>Nature</Title>
<ISOAbbreviation>Nature</ISOAbbreviation>
</Journal>
<ArticleTitle>Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.</ArticleTitle>
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<MedlinePgn>584-587</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s41586-020-2558-4</ELocationID>
<Abstract>
<AbstractText>Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease
<sup>1-3</sup>
. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19
<sup>4-7</sup>
. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.</AbstractText>
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<LastName>Maisonnasse</LastName>
<ForeName>Pauline</ForeName>
<Initials>P</Initials>
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<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
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<LastName>Guedj</LastName>
<ForeName>Jérémie</ForeName>
<Initials>J</Initials>
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<AffiliationInfo>
<Affiliation>Université de Paris, IAME, Inserm, Paris, France.</Affiliation>
</AffiliationInfo>
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<LastName>Contreras</LastName>
<ForeName>Vanessa</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Behillil</LastName>
<ForeName>Sylvie</ForeName>
<Initials>S</Initials>
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<Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
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<LastName>Solas</LastName>
<ForeName>Caroline</ForeName>
<Initials>C</Initials>
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<Affiliation>Laboratoire de Pharmacocinétique et Toxicologie, Aix-Marseille Université, APHM, Unité des Virus Emergents (UVE) IRD 190, INSERM 1207, Hôpital La Timone, Marseille, France.</Affiliation>
</AffiliationInfo>
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<LastName>Marlin</LastName>
<ForeName>Romain</ForeName>
<Initials>R</Initials>
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<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Naninck</LastName>
<ForeName>Thibaut</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Pizzorno</LastName>
<ForeName>Andres</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lemaitre</LastName>
<ForeName>Julien</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
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<LastName>Gonçalves</LastName>
<ForeName>Antonio</ForeName>
<Initials>A</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-8759-2429</Identifier>
<AffiliationInfo>
<Affiliation>Université de Paris, IAME, Inserm, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kahlaoui</LastName>
<ForeName>Nidhal</ForeName>
<Initials>N</Initials>
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<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
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<LastName>Terrier</LastName>
<ForeName>Olivier</ForeName>
<Initials>O</Initials>
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<AffiliationInfo>
<Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fang</LastName>
<ForeName>Raphael Ho Tsong</ForeName>
<Initials>RHT</Initials>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Enouf</LastName>
<ForeName>Vincent</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Plate-forme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dereuddre-Bosquet</LastName>
<ForeName>Nathalie</ForeName>
<Initials>N</Initials>
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<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Brisebarre</LastName>
<ForeName>Angela</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Touret</LastName>
<ForeName>Franck</ForeName>
<Initials>F</Initials>
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<AffiliationInfo>
<Affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chapon</LastName>
<ForeName>Catherine</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hoen</LastName>
<ForeName>Bruno</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lina</LastName>
<ForeName>Bruno</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Laboratoire de Virologie, Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
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<LastName>Calatrava</LastName>
<ForeName>Manuel Rosa</ForeName>
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<AffiliationInfo>
<Affiliation>CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.</Affiliation>
</AffiliationInfo>
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<LastName>van der Werf</LastName>
<ForeName>Sylvie</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-1148-4456</Identifier>
<AffiliationInfo>
<Affiliation>Unité de Génétique Moléculaire des Virus à ARN, GMVR, Institut Pasteur, UMR CNRS 3569, Université de Paris, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Centre National de Référence des Virus des infections respiratoires (dont la grippe), Institut Pasteur, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>de Lamballerie</LastName>
<ForeName>Xavier</ForeName>
<Initials>X</Initials>
<AffiliationInfo>
<Affiliation>Unité des Virus Emergents (UVE), Aix-Marseille Université, IRD 190, INSERM 1207, IHU Méditerranée Infection, Marseille, France.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Le Grand</LastName>
<ForeName>Roger</ForeName>
<Initials>R</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-4928-4484</Identifier>
<AffiliationInfo>
<Affiliation>Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France. roger.le-grand@cea.fr.</Affiliation>
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<Month>07</Month>
<Day>22</Day>
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<DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName>
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<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
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<Month>04</Month>
<Day>30</Day>
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<Year>2020</Year>
<Month>07</Month>
<Day>10</Day>
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<Year>2020</Year>
<Month>7</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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