Pirfenidone LP or Collagen-polyvinylpyrrolidone in COVID-19

The therapeutic target of COVID-19 is focused on the control of inflammation and the prevention of fibrosis. Collagen-polyvinylpyrrolidone (collagen-PVP) and pirfenidone have the ability to control cytokine storms observed in rheumatic and fibrotic disorders. In this work, the investigators explored the therapeutic effects of both, in addition to dexamethasone, on the early treatment of patients with severe COVID-19. The hospital stay, quick COVID-19 severity index (qCSI) and admission to the ICU were statistically significantly lower when the patients were treated with collagen-PVP or pirfenidone, compared to the controls treated with dexamethasone alone. Furthermore, only collagen-PVP normalized serum glucose at discharge. Since the intracellular mechanism of action of pirfenidone is partially known, it was performed a whole human genome microarray assay with total RNA isolated from fibroblast and macrophage cultures treated with collagen-PVP. Ingenuity Pathway Analysis showed that cell cycle, inflammation, and cell surface-extracellular matrix interaction could be regulated by the collagen-PVP copolymer, by down-regulation of pro-inflammatory cytokines, such as IL-6 and -8, while Th2 anti-inflammatory response signaling could be up-regulated. Additionally, down-regulation of some of the genes involved in nitric oxide production by inducible nitric oxide synthase showed a possible control for JAK, in the IFN-γ pathway, allowing the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib. In summary, once again, collagen-PVP and pirfenidone have demonstrated to favor inflammatory control and stand out as a possible therapy for inflammatory disorders derived from viral or microorganism infections.