3.Interferons role in COVID-19 Infection:
Interferons are one of the key mediators in limiting viral invasion to
the cells, but activation of inhibitory responses like CD200:CD200R1
signaling pathway by specific viral pathogens such as COVID-19 limit
their antiviral activity(17). As
mentioned before, using novel agents such as CD200 inhibitors might not
yet be optimized for this situation. So, how about taking one step
further in the signaling pathway and trying interferons for supporting
the virus clearance system?
Intrinsic viral resistance of the cells is highly dependent on IFN I &
IFN III. One of the cellular attack strategies by coronavirus is to
suppress the IFN response (18). As
expected, a serum analysis study of COVID-19 patients revealed
suppressed levels of type I & type III interferon and elevated
inflammatory and proinflammatory cytokines and chemokines
(19). However, some researchers suggest
that the virus induce a late interferon response rather than a complete
absence (20). An animal study on a mouse
model of SARS-CoV infection also showed that IFN-1 was detectable in the
lung until several hours after the viral load
peak(21). A small COVID-19 patients
cohort revealed surprising results. In this study, a strong association
between IFN-α and viral load, as well as disease severity, was
discovered. This study concluded that high interferon levels in the late
stages of the infection could not successfully bring down the viral
load, and interferon probably acts optimally in the early stages of the
disease (22).
So, according to all these details, can IFN be a therapeutic strategy in
COVID-19 infection?
Actually, the efficacy of the interferons as a therapeutic option for
COVID-19 is a subject of debate. Numerous in vitro and in vivo studies
candidate IFN-I as a promising therapeutic option for SARS and MERS
infections (23). The knowledge from
SARS-CoV and MERS-CoV studies on interferon efficacy can be a valuable
guide for determining interferons’ position in COVID-19 treatment
guidelines. Several randomized clinical trials are registered to test
this. These studies include the DisCoVeRy trial (NCT04315948, the first
clinical trial by the WHO Solidarity consortium) that is aimed to
evaluate the therapeutical efficacy of subcutaneous injection of IFN-b1a
in combination with lopinavir-ritonavir, lopinavir-ritonavir alone,
hydroxychloroquine, or remdesivir. Another phase II clinical trial on
inhaled IFN-b1a as a single agent is ongoing in the UK (NCT04385095)
(24). A retrospective study of 77
COVID-19 patients in Wuhan, China compared nebulized IFN-a2b with
arbidol or a combination of the two and claimed that nebulized IFN-a2b
significantly reduced the level of inflammatory markers, interleukin-6
and C-reactive protein (CRP) as well as the duration of the detectable
virus (25). A case series in Hubei
Province evaluated the efficacy of recombinant IFN-a nasal drops in
preventing COVID-19 incidence. In this study, 2944 healthcare workers
received the IFN-a nasal drop. After 28 days, the rate of COVID-19
infection among them was zero (26).
Fortunately, the primary results of ongoing clinical studies on
interferons are encouraging. However, studies on different animal models
and larger sample sizes are required to obtain more precise details on
the safety and efficacy of IFN-I as a therapy in COVID-19.