Figure 1 : COVID-19 progression and proposed
pharmacological actions of immunomodulatory tetracyclines. Upon initial
infection, SARS-CoV2 spreads to the lower respiratory track, infecting
type II pneumocytes as well as other cell populations, such as alveolar
macrophages and the endothelium. Viral infection and its cytopathic
effects lead to an exacerbated immune activation, which may result in
increased tissue damage and fibrosis. Alterations in lung tissue
architecture (defined as Diffuse Alveolar Damage) progress into ARDS,
characterised by the reduction in lung compliance and impaired blood
oxygenation. Additionally, complications such as thrombosis and
secondary infections are frequently observed. Tetracyclines can target
this pathological process at multiple levels: A) Prevention of secondary
bacterial infection. B) Reduce viral entry and replication. C) Reduce
immune recruitment and activation. D) Inhibition of exacerbated
inflammatory reaction via immunomodulatory effects and inhibition of
oxidative stress and MMP, thus reducing tissue damage and fibrosis. E)
Inhibition of enzymes involved in platelet function and coagulation. F)
Inhibition of altered epithelial response.