Type I interferon: From innate response to treatment for COVID-19

Effective prophylactic and therapeutic interventions are urgently needed to address the coronavirus disease 2019 (COVID-19) pandemic. Various antiviral drugs have recently been tested. Type I interferon (IFN) is a regulatory protein involved in the innate immune response, with broad-spectrum antiviral activities and the ability to directly block viral replication and support the immune response to eliminate virus infection. Insufficient virus-induced type I IFN production is characteristic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, because SARS-CoV-2 suppresses the IFN response by interacting with essential IFN signaling pathways. Exogenous type I IFN is recommended for treating COVID-19. Unexpectedly however, angiotensin converting enzyme-2 (ACE2) receptor, which acts as a SARS-CoV-2 receptor, was shown to be stimulated by IFN, raising doubts about the suitability of IFN use. However, further studies have excluded concerns regarding IFN administration. Type I IFNs, including IFN-α1b, have been used clinically as antiviral drugs for many years and have shown strong antiviral activity against SARS-CoV-2 in vitro. Preliminary clinical studies of type I IFNs, especially when delivered via aerosol inhalation, have demonstrated efficacy for the treatment and prevention of COVID-19. Randomized controlled trials of IFN for COVID-19 treatment are ongoing.