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

Lin, Fuyu; Shen, Kunling

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.