Pharmacological Immunomodulation by Collagen-Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19, Through a Similar Mechanism of Action Involving the JAK-STAT Signaling Pathway. Pilot Study

The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen-polyvinylpyrrolidone (collagen-PVP) and pirfenidone have the ability to control the cytokine storms observed in rheumatic and fibrotic disorders. Here, we explore separately their therapeutic effects on the early treatment of 26 patients with severe COVID-19, compared to 10 controls treated with dexamethasone alone. Our results showed that hospital stay, quick COVID-19 severity index (qCSI) and admission to the ICU were statistically significantly lower (P<0.02) in treated patients with collagen-PVP or pirfenidone; only collagen-PVP normalised serum glucose at discharge. Since the intracellular mechanism of action of pirfenidone is partially known, we performed a human genome microarray assay with total RNA isolated from fibroblast and monocyte cultures treated with collagen-PVP. Ingenuity Pathway Analysis showed that cell cycle, inflammation, and cell surface-extracellular matrix interactions could be regulated by collagen-PVP by downregulation of proinflammatory cytokines, while Th2 anti-inflammatory response signaling could be upregulated. Furthermore, downregulation of some of the genes involved in nitric oxide production 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.