4. Therapeutic intervention thromboinflammation resolution
Understanding neutrophil and platelet responses in the context thromboinflammation in COVID-19 has resulted in promising pre-clinical studies demonstrating that e.g. immune regulatory properties are being lost in patients with COVID-19, with the virus seemingly to ‘suppress’ or ‘silence’ the immune system.(Bost et al. 2021) Drugs that can ‘stimulate’ or ‘reawaken’ the immune system may be the way forward, as seen with dexamethasone.(Group et al. 2021; Bost et al. 2021) Other therapies may lie in targeting the cytokine storm with anti-inflammatory agents such as IL-6 and IL-1β antagonists.
Accumulating data linking inflammation and thrombosis supports the hypothesis that anti-inflammatory therapies may limit thrombosis and that anti-thrombotic therapies may reduce vascular inflammation.(Vital et al. 2016) Furthermore, there is a growing evidence of the importance of resolution biology in vascular inflammation to develop innovative approaches for the treatment of diseases, which may include COVID-19. Inflammation resolution, is an active process involving specific endogenous mediators (e.g. Annexin A1 [AnxA1], aspirin triggered lipoxin A4), and pathways (e.g. formyl peptide receptor 2 [Fpr2/ALX] pathway).(Senchenkova, Ansari, et al. 2019) FPR2 agonists are being developed and currently tested in man. In the context of thromobinflammation and the possible insights for therapeutic strategies for COVID-19 treatments, we recently discovered targeting the AnxA1/Fpr2/ALX pathway promotes thromboinflammation resolution by altering both the platelet phenotype (from pro-pathogenic to regulatory)(Senchenkova, Ansari, et al. 2019) and the pathological neutrophil phenotype (from a pro-NETotic to pro-apoptotic).(Ansari et al. 2021)