Viral infections pose a major threat to human health. Vaccines protect from specificinfections, yet newly emerging or pandemic viral strains that exhibit genetic drift or reassortmentof genes preclude immediate responses using a vaccine strategy. Moreover, for SARS CoV-2,although current vaccines reduce severity of disease, they do not protect from re-infection,resulting in persistent community transmission and outbreaks. The emergence of drug resistancealso mitigates against pathogen-specific antiviral drugs. A complementary strategy focusing onthe host not the pathogen is the basis for development of broad-spectrum antivirals.Our immediate response to any and all virus infections is the immediate production of interferon(IFN). Data reveal that the robustness of an IFN response to respiratory infections, determinesthe outcome – an aggressive or mild infection. We provide evidence that an IFN response to viralinfection, and/or IFN treatment, induces an activated phenotype in target cells that results in anantiviral state and an optimized innate immune response, regardless of the virus. We extendedthese findings to examine the therapeutic potential of IFN treatment in hospitalized individualsinfected with SARS and showed that IFN treatment accelerated viral clearance and reduced lungabnormalities. Similarly, using human lung explants, IFN treatment cleared infection againstH5N1 avian and pandemic H1N1 influenza strains. During the Ebola virus outbreak in WestAfrica, we conducted a clinical study in Guinea and provided evidence of increased survivalassociated with IFN treatment. At the start of the COVID-19 pandemic we undertook a clinicalstudy in Wuhan, China, providing evidence that early treatment with an inhaled IFN acceleratedviral clearance, reduced inflammation and also reduced lung abnormalities. Given that limitingtransmission is the solution to shutting down any outbreak, we next conducted a clinical trial todetermine whether IFN treatment of SARS CoV-2 exposed, but uninfected individuals, wouldprotect from infection. We provide evidence that prophylactic treatment with IFN limitshousehold transmission, being most effective when the infected case in the household has a highviral burden.
