The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the "cytokine storm" in COVID-19 patients: a hypothesis.
Acute lung injury
Acute respiratory distress syndrome
Barrier function
COVID-19
Cytokine storm
LMWF5A
SARS-CoV-2
Journal
Patient safety in surgery
ISSN: 1754-9493
Titre abrégé: Patient Saf Surg
Pays: England
ID NLM: 101319176
Informations de publication
Date de publication:
2020
2020
Historique:
received:
27
04
2020
accepted:
06
05
2020
entrez:
21
5
2020
pubmed:
21
5
2020
medline:
21
5
2020
Statut:
epublish
Résumé
A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a "cytokine storm". While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm. A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures. A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration. If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit. In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.
Sections du résumé
BACKGROUND
BACKGROUND
A common complication of viral pulmonary infections, such as in the ongoing COVID-19 pandemic, is a phenomenon described as a "cytokine storm". While poorly defined, this hyperinflammatory response results in diffuse alveolar damage. The low molecular weight fraction of commercial human serum albumin (LMWF5A), a novel biologic in development for osteoarthritis, demonstrates beneficial in vitro immunomodulatory effects complimentary to addressing inflammation, thus, we hypothesize that LMWF5A could improve the clinical outcomes of COVID-19 by attenuating hyperinflammation and the potential development of a cytokine storm.
PRESENTATION OF THE HYPOTHESIS
OBJECTIVE
A variety of human in vitro immune models indicate that LMWF5A reduces the production of pro-inflammatory cytokines implicated in cytokine storm associated with COVID-19. Furthermore, evidence suggests LMWF5A also promotes the production of mediators required for resolving inflammation and enhances the barrier function of endothelial cultures.
TESTING THE HYPOTHESIS
METHODS
A randomized controlled trial, to evaluate the safety and efficacy of nebulized LMWF5A in adults with Acute Respiratory Distress Syndrome (ARDS) secondary to COVID-19 infection, was developed and is currently under review by the Food and Drug Administration.
IMPLICATIONS OF HYPOTHESIS
UNASSIGNED
If successful, this therapy may attenuate the cytokine storm observed in these patients and potentially reduce mortality, increase ventilation free days, improve oxygenation parameters and consequently lessen the burden on patients and the intensive care unit.
CONCLUSIONS
CONCLUSIONS
In conclusion, in vitro findings suggest that the immunomodulatory effects of LMWF5A make it a viable candidate for treating cytokine storm and restoring homeostasis to the immune response in COVID-19.
Identifiants
pubmed: 32431755
doi: 10.1186/s13037-020-00248-4
pii: 248
pmc: PMC7220573
doi:
Types de publication
Journal Article
Langues
eng
Pagination
21Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsG.T and M. Hoke are employees, shareholders, and have been granted stock options at Ampio Pharmaceuticals. E.F. and L.G. are employees and have been granted stock options at Ampio Pharmaceuticals. M. Hausburg is a shareholder at Ampio Pharmaceuticals. D.B-O is a Director and shareholder at Ampio Pharmaceuticals. All other authors have nothing to declare.
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