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

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

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.