The dual sides of interferon induction in COVID-19 treatment

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a pandemic with immense impacts 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. The aim of this mini-review is to survey both beneficial and non-beneficial effects of interferon during COVID-19 disease course. The indication of interferon-α2b or interferon β-1a has shown benefit at the early stages of COVID-19 in some clinical trials; though, interferon administration could only 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 leads to delayed recovery and probably increased mortality rates due to the upregulation of ACE-2 expression in human airway epithelial cells, leading to the facilitation of virus entry into the 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, including corticosteroids (dexamethasone or prednisolone), tocilizumab (an IL-6 inhibitor), or anakinra (a recombinant IL-1 receptor antagonist), are beneficial. Some other proposed drugs such as TNF-α inhibitors and JAK inhibitors need further investigations in future studies.