U-M Research Lab Opens to Explore New Treatment Targets for Patients with COVID-19

Yogendra Kanthi, MD
Yogendra Kanthi, MD
Jason Knight, MD, PhD
Jason Knight, MD, PhD
April 10, 2020

Yogendra Kanthi, MD, from the Division of Cardiovascular Medicine, and Jason Knight, MD, PhD, from the Division of Rheumatology, were selected as recipients of the Frankel Cardiovascular Center (FCVC) “COVID-19: CV Impact Research Ignitor Grant”, a grant specifically designed to promote the initiation of a promising project targeting the COVID-19 virus’s impact on cardiovascular health.  

Their project, “Neutrophil Extracellular Traps (NETs) in COVID-19 Inflammatory Storm”, will look at how certain products of neutrophil cell death may drive inflammatory responses in patients with COVID-19.

“In light of the COVID-19 pandemic, there is an urgent need to better understand what causes the inflammatory storm triggered by SARS-CoV-2 infection. It’s this storm that seems to lead to respiratory failure and the requirement for mechanical ventilation in many patients,” says Dr. Knight.

Ray Zuo, MD, a rheumatologist and member of Dr. Knight’s lab, also played an instrumental role in launching the study. “Our project is pursuing the hypothesis that levels of circulating NETs will predict COVID-19 patients at risk for severe disease, and we hope will also identify new actionable treatment targets,” explains Dr. Zuo.

Dr. Kanthi’s and Dr. Knight’s team consists of cardiologists and rheumatologists who study natural checkpoints in the immune system that, when not properly regulated, lead to hyperactivity of white blood cells such as neutrophils and monocytes. Their group and others have recently revealed a critical role for neutrophils - and especially structures called neutrophil extracellular traps (NETs) - in various diseases including sepsis, blood clots, and respiratory failure. NETs are spiderweb-like tangles of DNA, proteins, and enzymes that are released by neutrophils to corral infections, but which, when not properly regulated, have potential to amplify inflammation and blood clotting.

Dr. Kanthi and Dr. Knight hope to achieve an immediate and direct impact on patient care decisions during the pandemic. Their goals are to:

  • Develop a neutrophil-based biomarker on admission testing to predict progression and severity of COVID-19
  • Define the natural neutrophil and cytokine signatures associated with COVID-19 to better inform timing of personalized treatment interventions

“We want to find a blood biomarker that will precisely tell us which patients with COVID-19 will suffer the worst complications. Then we can direct more resources to these vulnerable patients early, and perhaps help people recover better,” says Dr. Kanthi.

In addition to Dr. Kanthi’s and Dr. Knight's research, U-M researchers have launched a wide range of efforts to study and address coronavirus pandemic – learn more.