The dual sides of interferon induction in COVID-19 treatment

Document Type: Review Article


1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.


Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a pandemic with an immense impact on different aspects of human life globally.
Generally, type I and II interferons are essential cytokines to combat viral infections including COVID-19. However, SARS-CoV-2 adopts evasion mechanisms to overcome interferon-mediated antiviral responses and neutralizes a key human defensive strategy.
Indication of interferon-α2b or interferon β-1a has shown benefit at the disease’s early stages in some clinical trials. Though, interferon administration could help in the incubation period or before the peak viral load. The incubation period and the duration from the symptom onset till the peak viral load has been estimated 5-6 and 2-3 days, respectively.
On the other hand, an increase of interferon level in the disease’s late stages could lead to delayed recovery and increased mortality rates due to the upregulation of ACE-2 expression in human airway epithelial cells, leading to the facilitation of virus entry into host cells. Besides, it promotes the overactivation of inflammatory responses, which often happens in the disease’s pulmonary phase causing the cytokine storm. In this stage, antiviral agents might not work, and anti-inflammatory drugs are beneficial, such as corticosteroids (dexamethasone or prednisolone), tocilizumab (an IL-6 inhibitor), or anakinra (a recombinant IL-1 receptor antagonist). Hydroxychloroquine has been the subject of controversy and was announced ineffective by WHO recently. Some other proposed drugs such as TNF-α inhibitors, JAK inhibitors, and colchicine need further investigations in future studies.