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)