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.