<p>Viral infections pose a major threat to human health. Vaccines protect from specific</p><p>infections, yet newly emerging or pandemic viral strains that exhibit genetic drift or reassortment</p><p>of genes preclude immediate responses using a vaccine strategy. Moreover, for SARS CoV-2,</p><p>although current vaccines reduce severity of disease, they do not protect from re-infection,</p><p>resulting in persistent community transmission and outbreaks. The emergence of drug resistance</p><p>also mitigates against pathogen-specific antiviral drugs. A complementary strategy focusing on</p><p>the host not the pathogen is the basis for development of broad-spectrum antivirals.</p><p>Our immediate response to any and all virus infections is the immediate production of interferon</p><p>(IFN). Data reveal that the robustness of an IFN response to respiratory infections, determines</p><p>the outcome – an aggressive or mild infection. We provide evidence that an IFN response to viral</p><p>infection, and/or IFN treatment, induces an activated phenotype in target cells that results in an</p><p>antiviral state and an optimized innate immune response, regardless of the virus. We extended</p><p>these findings to examine the therapeutic potential of IFN treatment in hospitalized individuals</p><p>infected with SARS and showed that IFN treatment accelerated viral clearance and reduced lung</p><p>abnormalities. Similarly, using human lung explants, IFN treatment cleared infection against</p><p>H5N1 avian and pandemic H1N1 influenza strains. During the Ebola virus outbreak in West</p><p>Africa, we conducted a clinical study in Guinea and provided evidence of increased survival</p><p>associated with IFN treatment. At the start of the COVID-19 pandemic we undertook a clinical</p><p>study in Wuhan, China, providing evidence that early treatment with an inhaled IFN accelerated</p><p>viral clearance, reduced inflammation and also reduced lung abnormalities. Given that limiting</p><p>transmission is the solution to shutting down any outbreak, we next conducted a clinical trial to</p><p>determine whether IFN treatment of SARS CoV-2 exposed, but uninfected individuals, would</p><p>protect from infection. We provide evidence that prophylactic treatment with IFN limits</p><p>household transmission, being most effective when the infected case in the household has a high</p><p>viral burden.</p>
