T. Ronald Theodore

Integrated Biologics, LLC

HEPES is a true biological response modifier (BRM). The effects of HEPES as broad immune stimulant and its effects on cytokines has been demonstrated. Effects are dose dependent. HEPES anti-viral effect has been noted. HEPES has also been shown to inhibit the conversion of prion protein. HEPES has been shown to improve O2 saturation in COPD. HEPES primary action is in the mitochondria and increases the rate of oxidative phosphorylation.

https://www.liebertpub.com/doi/10.1089/cbr.1997.12.345

http://www.freepatentsonline.com/6071919.html

https://www.ncbi.nlm.nih.gov/pubmed/21289158

The effect of viral infections on mitochondrial dynamics has been described.

https://www.ncbi.nlm.nih.gov/pubmed/25595529

HEPES has the potential to reduce the “cytokine storm” in Corvid19 infection. Corvid19 is a virus that disrupts the normal production of cytokines. A cytokine storm in Corvid19 is an excessive immune response to the virus. The result is severe mitochondrial dysfunction which increases pro-inflammatory cytokine production. This has been reported to impair repair and corticosteroid responsiveness in lung epithelium. Scientific Reports

https://www.nature.com/articles/s41598-019-51517-x

Cytokine storm is a major cause of respiratory distress syndrome (ARDS). The cytokine storm results in pneumonia and serious lung damage in Corvid19. The pathophysiology is a complex derangement at the cellular level. It can manifest severe intra-alveolar hemorrhaging with atelectasis. The patient is essentially asphyxiated. There are often cardiac complications (both viral cardiomyopathy and hemodynamic failure).

https://www.sciencedirect.com/science/article/pii/S0163445320301651

HEPES has demonstrated safety for use in humans. It has been approved for a Physician IND by the FDA. The Canadian Health Protection Branch has allowed HEPES for use under the Emergency Health Protection Act.

https://www.liebertpub.com/doi/abs/10.1089/cbr.1997.12.351

https://www.liebertpub.com/doi/10.1089/cbr.1997.12.345

The pathophysiology of Corvid19 is reasonably understood and various treatments for the pulmonary complications have been implemented. However the morbidity and high mortality rate of patients with ARDS with Covid19 requires better treatment results. I believe that the use of HEPES in severe ARDS has a reasonable probability of improved recovery from cytokine storm and reduce alveolar/epithelial injury. (Note: HEPES does treat bacterial infection but lowers MICs of antibiotics). There are several other benefits that may occur including amelioration of cardiomyopathy (including arrhythmias). It may allow other drugs to be safely administered.

Using HEPES in treating pulmonary complications of Corvid19 should be promptly implemented with appropriate compliance of emergency drug treatment requirements. There should be no delay.