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Interferon (IFN) therapies are used to treat a variety of infections and diseases and could be used to treat SARS-CoV-2. However, optimal use and timing of IFN therapy to treat SARS-CoV-2 is not well documented. We aimed to synthesize available evidence to understand whether interferon therapy should be recommended for treatment compared to a placebo or standard of care in adult patients. We reviewed literature comparing outcomes of randomized control trials that used IFN therapy for adults diagnosed with SARS-CoV-2 between 2019 and 2021. Data were extracted from 11 of 669 screened studies. Evidence of IFN effectiveness was mixed. Five studies reported that IFN was a better therapy than the control, four found no or minimal difference between IFN and the control, and two concluded that IFN led to worse patient outcomes than the control. Evidence was difficult to compare because of high variability in outcome measures, intervention types and administration, subtypes of IFNs used and timing of interventions. We recommend standardized indicators and reporting for IFN therapy for SARS-CoV-2 to improve evidence synthesis and generation. While IFN therapy has the potential to be a viable treatment for SARS-CoV-2, especially when combined with antivirals and early administration, the lack of comparable of study outcomes prevents evidence synthesis and uptake.