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

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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 treatments are beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease. One Sentence Summary The timing of type I interferon treatment is a critical determinant of its efficacy against SARS-CoV-2 infection.

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