11. Conclusion
Reducing the patient’s risk of COVID-19 progression is assumed to be
biologically linked with suppression of neutrophilic component that
predisposes to increased systemic inflammation and coagulopathy
associated with COVID-19 infection. Therefore, management of COVID-19
should focus on modulating neutrophils function and their response.
According to the underlying guidelines, recommended anti-inflammatory
therapies for COVID-19 do not provide treatment satisfaction and
effectiveness until now.
As the search continues, PDE4i has
been suggested to offer an intriguing new class of COVID-19 treatment,
since inhibiting PDE4 is thought to exhibit effective anti-inflammatory
and anti-platelets activities. Among the clinically used PDE4i,
roflumilast has been reported to be the most selective and potent drug
submitted for treating many neutrophils-mediated airway inflammatory
disorders. Furthermore, roflumilast has been recently reported to behave
as a potential inhibitor of 3CLpro, which is a proteolytic enzyme
required for viral replication within the host cells.
Considering COVID-19 treatment, roflumilast may also have additive
advantages to the concurrent protocol, since it had been reported to be
used safely in combination with either corticosteroids, azithromycin and
recommended vitamins (C, E and Zinc) without showing any dangerous
adverse effects up till now. As well, via attenuating the airway
neutrophilic inflammation, roflumilast can enhance the compromised
anti-inflammatory properties of corticosteroids and improve their
resistance effect.
Additionally, as a result of increasing cAMP level,
we suppose that roflumilast can
prolong its anti-inflammatory effect and display other therapeutic
properties via enhancing NEP activity, which is proposed to be an
important target for managing COVID-19.
Therefore, taken into our consideration that this review is the first
one to discuss the NEP-mediated therapeutic properties of roflumilast
and its role in facing the inflammatory, coagulopathy and fibrotic
cascades driven by COVID-19, we hope that our hypothesis will serve as a
stimulus for further confirmation about the therapeutic impact of
roflumilast in COVID-19 management and consequently, may provide
physicians with a novel repurposed treatment option against COVID-19.