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.