The National Institute of Health (NIH) guidelines state that there is insufficient evidence to recommend for or against use of interferon-β (IFN- β) in early (<7 days from symptom onset), mild to moderate COVID-19; however, they recommend against using interferons in severe and critical COVID-19, except in clinical trial settings. An open-label study showed that IFN- β -1b (8 million units subcutaneously every other day up to 7 days) with or without ribavirin may be associated with positive outcomes in patients presenting within seven days of onset of symptoms. However, its efficacy in those presenting ≥7 days after onset of symptoms remains unknown. 
According to the Infectious Disease Society of America (IDSA) guidelines, IFN- β-1b has shown to reduce viral load of middle east respiratory syndrome coronavirus (MERS-CoV), and use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is being evaluated in clinical trials. 
The Society of Critical Care Medicine (SCCM) guidelines provide no recommendation on the use of any recombinant interferon (rIFN) preparations alone or in combination with other antivirals in critically ill adults with COVID-19 due to lack of evidence. Most available evidence evaluates use of rIFN in MERS-CoV. Additionally, a trial of critically ill patients with MERS showed that rIFN preparations (rIFN-α2a, rIFN-α2b, rIFN-β1a and rIFN-β1b) with ribavirin is not associated with lower mortality (odds ratio 1.03; 95% CI 0.73-1.44) or reduced viral clearance. Among the various rIFN preparations, rIFN-β has shown to have the strongest MERS-CoV inhibition. Regarding its use in SARS-CoV2, unpublished in-vitro data suggest rIFN may inhibit SARS-CoV2; however, its clinical efficacy is unknown. 
It is stated that route of administration of IFN-β in COVID-19 may impact outcomes because of the difference in bioavailability. Although studies show that there is no difference in pharmacological effect between subcutaneous (S.C) and intravenous (I.V) IFN-β-1a, intravenous administration results in significantly higher total exposure compared to S.C injection (p= 0.0001). Subcutaneous IFN- β has demonstrated efficacy in a clinical trial; however, it should be noted that the patients had mild to moderate COVID-19 and presented within seven days of symptom onset. The efficacy in severe disease or in those presenting ≥7 days of onset of symptoms remains unclear. Additionally, the consideration of difference in bioavailability may be of a greater importance, especially in critically ill patients with compromised circulation.