Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Pierre Bessière; Marine Wasniewski; Evelyne Picard-Meyer; Alexandre Servat; Thomas Figueroa; Charlotte Foret-Lucas; Amelia Coggon; Sandrine Lesellier; Frank Boué; Nathan Cebron; Blandine Gausserès; Catherine Trumel; Gilles Foucras; Francisco J. Salguero; Elodie Monchatre-Leroy; Romain Volmer

doi:10.1371/journal.ppat.1009427

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Pierre Bessière, Marine Wasniewski, Evelyne Picard-Meyer, Alexandre Servat, Thomas Figueroa, Charlotte Foret-Lucas, Amelia Coggon, Sandrine Lesellier, Frank Boué, Nathan Cebron, Blandine Gausserès, Catherine Trumel, Gilles Foucras, Francisco J. Salguero, Elodie Monchatre-Leroy, Romain Volmer^*

^*Corresponding author for this work

Research & Development Institute Scientific Leaders

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Abstract

Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.

Original language	English
Article number	1009427
Number of pages	17
Journal	PLoS Pathogens
Volume	17
Issue number	8
DOIs	https://doi.org/10.1371/journal.ppat.1009427
Publication status	Published - 9 Aug 2021

Bibliographical note

Funding Information: This work was funded by a grant from the Agence Nationale de la Recherche (ANR-20-COV5-0004) to RV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Open Access: This is an open access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher Copyright: © 2021 Bessière et al.

Citation: Bessière P, Wasniewski M, Picard-Meyer E, Servat A, Figueroa T, Foret-Lucas C, et al. (2021) Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model. PLoS Pathog 17(8): e1009427.

DOI: https://doi.org/10.1371/journal. ppat.1009427

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Bessiere2021IntranasalTypeIInterfereonTreatmentIsBeneficialPLoSPathogFinal published version, 2.39 MBLicence: CC BY

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Bessière, P., Wasniewski, M., Picard-Meyer, E., Servat, A., Figueroa, T., Foret-Lucas, C., Coggon, A., Lesellier, S., Boué, F., Cebron, N., Gausserès, B., Trumel, C., Foucras, G., Salguero, F. J., Monchatre-Leroy, E., & Volmer, R. (2021). Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model. PLoS Pathogens, 17(8), [1009427]. https://doi.org/10.1371/journal.ppat.1009427

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title = "Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model",

abstract = "Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.",

author = "Pierre Bessi{\`e}re and Marine Wasniewski and Evelyne Picard-Meyer and Alexandre Servat and Thomas Figueroa and Charlotte Foret-Lucas and Amelia Coggon and Sandrine Lesellier and Frank Bou{\'e} and Nathan Cebron and Blandine Gausser{\`e}s and Catherine Trumel and Gilles Foucras and Salguero, {Francisco J.} and Elodie Monchatre-Leroy and Romain Volmer",

note = "Funding Information: This work was funded by a grant from the Agence Nationale de la Recherche (ANR-20-COV5-0004) to RV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Publisher Copyright: {\textcopyright} 2021 Bessi{\`e}re et al. Citation: Bessi{\`e}re P, Wasniewski M, Picard-Meyer E, Servat A, Figueroa T, Foret-Lucas C, et al. (2021) Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model. PLoS Pathog 17(8): e1009427. DOI: https://doi.org/10.1371/journal. ppat.1009427",

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Bessière, P, Wasniewski, M, Picard-Meyer, E, Servat, A, Figueroa, T, Foret-Lucas, C, Coggon, A, Lesellier, S, Boué, F, Cebron, N, Gausserès, B, Trumel, C, Foucras, G, Salguero, FJ, Monchatre-Leroy, E & Volmer, R 2021, 'Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model', PLoS Pathogens, vol. 17, no. 8, 1009427. https://doi.org/10.1371/journal.ppat.1009427

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T1 - Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

AU - Bessière, Pierre

AU - Wasniewski, Marine

AU - Picard-Meyer, Evelyne

AU - Servat, Alexandre

AU - Figueroa, Thomas

AU - Foret-Lucas, Charlotte

AU - Coggon, Amelia

AU - Lesellier, Sandrine

AU - Boué, Frank

AU - Cebron, Nathan

AU - Gausserès, Blandine

AU - Trumel, Catherine

AU - Foucras, Gilles

AU - Salguero, Francisco J.

AU - Monchatre-Leroy, Elodie

AU - Volmer, Romain

N1 - Funding Information: This work was funded by a grant from the Agence Nationale de la Recherche (ANR-20-COV5-0004) to RV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Publisher Copyright: © 2021 Bessière et al. Citation: Bessière P, Wasniewski M, Picard-Meyer E, Servat A, Figueroa T, Foret-Lucas C, et al. (2021) Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model. PLoS Pathog 17(8): e1009427. DOI: https://doi.org/10.1371/journal. ppat.1009427

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N2 - Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.

AB - Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.

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DO - 10.1371/journal.ppat.1009427

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JO - PLoS Pathogens

JF - PLoS Pathogens

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M1 - 1009427

ER -

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

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