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.
Highlights
Type I interferons (IFNs) are major antiviral cytokines and their finely tuned production is critical for host protection against viruses [1]
Delayed or impaired type I IFN signalling response has been shown to correlate with severe COVID-19
These observations provided further impetus to test the administration of exogenous type I IFN as a treatment against SARS-CoV-2 infection in patients
Summary
Type I interferons (IFNs) are major antiviral cytokines and their finely tuned production is critical for host protection against viruses [1]. Development of severe COVID-19 was shown to correlate with decreased type I IFNs production or impaired type I IFN signaling [5,6,7,8,9] In agreement with these observations, recombinant type I IFNs are being tested in a number of clinical trials to treat COVID-19 patients [10,11,12]. The design and interpretation of these clinical trials need to consider that the timing of type I IFN treatment may be critical for its efficacy and safety against SARS-CoV-2 [13,14]. How the timing of type I IFN treatment modulates clinical efficacy against SARS-CoV-2 is currently unknown and needs to be tested in an animal model
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