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Juntao Luo, PhD, an associate professor of pharmacology, in his lab.

Upstate researchers publish work on new technology to treat severe sepsis that could be used for COVID-19 patients

A team of Upstate Medical University researchers recently published a paper in a prominent scientific journal about a new type of sepsis treatment that could bolster survival rates and be used to treat severe cases of COVID-19.

The team was led by Juntao Luo, PhD, an associate professor of pharmacology who has been studying this new therapy to neutralize severe inflammation during sepsis for the last three years. His work, “A nanotrap improves survival in severe sepsis by attenuating hyperinflammation,” was published in Nature Communications on July 7. 

Severe sepsis or septic shock, describes the detrimental effects of a life-threatening infection and hyperinflammation, which causes different organs (lungs, kidneys) to lose function and/or fail. Sepsis affects 1.7 million adults in the United States each year and contributes to more than 270,000 deaths. Doctors at Upstate have been pooling their expertise on the topic through the Sepsis Interdisciplinary Research Center (SIRC) since last summer. Luo’s work is one of the center’s primary projects.  

“We are targeting the cytokine storm and inflammatory mediators,” Luo said. The cytokine storm is when the body releases too many cytokines too quickly, which causes severe inflammation, organ failure and if uninterrupted can lead to death. Cytokine storm and hyperinflammation have been documented in many severe COVID-19 cases. Sepsis often contributes to organ failure, which is the leading cause of death among ICU patients.

According to a summary of the project: “Patients with severe infections and sepsis are at increased risk for developing organ failure (decreased function of lungs or kidney, requiring mechanical ventilation or dialysis) due to excessive release of inflammatory mediators, so-called ‘cytokine storm,’ which is also seen in current pandemic COVID-19 patients. While multiple organ failure is a leading cause of death in ICU patients, the underlying mechanisms are poorly understood and effective treatments are still limited. The current treatment for sepsis includes antibiotic administration to treat the infection and supportive measures like intravenous fluids, medications to support blood pressure and mechanical ventilation or dialysis to support injured lungs or kidneys.”

Luo, with Professor and Chair of Surgery Robert Cooney, MD, have developed new technology to adsorb the excessive inflammatory mediators in blood and improve survival in experimental sepsis. “The novel nanotrap technology uses a combination of molecular charge and size characteristics to selectively capture inflammatory mediators in an experimental model of sepsis called cecal-ligation and puncture. In addition to reducing the inflammatory effects of infection, the nanotrap technology decreased injury to lung, kidney and liver and also improved survival,” according to the summary.

“Inflammation is a double-bladed sword as it is meant to control infection naturally but can cause tissue damage if unchecked,” Luo said. “Inflammation in a sepsis patient is really hard to control and for many patients they cannot overcome that and may die.”

Luo and Cooney’s new nanotrap technology, when used in conjunction with antibiotics – a standard and integral method of treating sepsis – dramatically increased survival rates in experimental models.

“With antibiotics alone to control infection we get a 50 to 60 percent survival rate,” Luo said. “Our new approach to control inflammation also gives us a 50 to 60 percent rate. But when they are combined together the survival rate is 100 percent. This technology can be used as a blood-cleaning therapy and is promising to improve the survival rate of severe sepsis.”

Luo said the conventional kind of blood-cleaning technology has already been approved by the FDA for emergency use in treating severe COVID-19 patients.

Cooney said Upstate physicians and researchers involved in SIRC are working to combine their interests and efforts into studying sepsis, infection and organ failure. The group meets regularly to share research and collaborate on projects such as this one to develop integrative therapies for sepsis and critical illness.

“Sepsis is a critically important public health problem and it’s one of the diseases that the New York State Department of Health and the U.S. Department of Health and Human Services is devoting a lot of time and energy to,” Cooney said. “Upstate is trying to combine our energies and expertise to improve outcomes.”

Luo’s research is supported by several grants from the National Institutes of Health. Other Upstate contributors to the project are: Changying Shi, Xiaojing Wang, Lili Wang, Qinghe Meng, Dandan Guo and Guirong Wang.

Li Chen from Baylor Scott and White Medical Center in Temple, Texas and Matthew Dai, formerly of Upstate and now from Brown University, also contributed.

For more information about SIRC and Upstate sepsis research, visit www.upstate.edu/pharm/sirc.

Caption: Juntao Luo, PhD, an associate professor of pharmacology, in his lab.