Collagen-polyvinylpyrrolidone (collagen-PVP) and pirfenidone have the ability to controlcytokine storms. This work explores the therapeutic effects of both, on the earlytreatment of patients with severe COVID-19. The hospital stay, quick COVID-19 severityindex (qCSI) and admission to the ICU were statistically significantly lower when thepatients were treated with collagen-PVP or pirfenidone, compared to the controls treatedwith dexamethasone alone.
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.
Drug: Collagen-polyvinylpyrrolidone
2 ml intramuscular q24 h
Drug: Pirfenidone 1200 mg
1,200 mg of oral q12 h
Inclusion Criteria:
- patients infected with SARS-CoV-2, hospitalized, with total bilirubin ≤1.5
Exclusion Criteria:
- if the patient underwent treatment with biological antirheumatic drugs, disease
modifiers (DMARDs) or other immunosuppressive agents, patients who required
continuous therapy with systemic corticosteroids in a dose greater than 10 mg of
prednisone per day or equivalent; pregnant women, calculated creatinine clearance
(or estimated glomerular filtration rate less than 10 ml/min or patients requiring
renal replacement therapy
Monica Pretelini Saenz Maternal Perinatal Hospital
Toluca 3515302, State of Mexico 3523272, Mexico
Hugo Mendieta Zerón, PhD, Principal Investigator
Mónica Pretelini Sáenz Maternal Perinatal Hospital