Washington, November 21st
An Indian-American scientist has discovered a potential strategy to prevent life-threatening inflammation, lung damage and organ failure in patients diagnosed with Covid-19.
Published online in the journal Cell, the research that comes from the laboratory of Dr. Thirumala-Devi Kanneganti, an Indian-born researcher working at St Jude Children’s Research Hospital in Tennessee, identified the drugs after discovering that the hyperinflammatory immune response associated with Covid -19 leads to tissue damage and multiorgan failure in mice by triggering inflammatory cell death pathways.
The researchers detailed how the signaling pathway for inflammatory cell death worked, leading to potential therapies to disrupt the process.
“Understanding the pathways and mechanism that drive this inflammation is essential to developing effective treatment strategies,”
Kanneganti was born and raised in Telangana. She received her bachelor’s degree from Kakatiya University in Warangal, where she studied chemistry, zoology and botany. She then received her master’s degree and Ph.D. from Osmania University in India. She joined St Jude in Memphis, Tennessee, USA, in 2007.
“This research provides that understanding. We also identified the specific cytokines that activate inflammatory cell death pathways and have significant potential for the treatment of Covid and other highly deadly diseases, including sepsis,” she said.
The other researchers were Shraddha Tuladhar, Parimal Samir, Min Zheng, Balamurugan Sundaram, Balaji Banoth, RK Subbarao Malireddi, Patrick Schreiner, Geoffrey Neale, Peter Vogel and Richard Webby from St. Jude; and Evan Peter Williams, Lillian Zalduondo and Colleen Beth Jonsson, of the University of Tennessee Health Science Center.
Covid is caused by the SARS-CoV-2 virus. The infection has killed more than 1.2 million people in less than a year and sickened millions more.
The infection is characterized by increased blood levels of several cytokines. These small proteins are secreted primarily by immune cells to ensure a rapid response to limit the virus. Some cytokines also trigger inflammation.
The term cytokine storm has been used to describe the dramatically elevated cytokine levels in the blood and other immune changes that have also been observed in Covid-19, sepsis and inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH), said St. Judes in a statement.
However, the specific pathways that trigger the cytokine storm and subsequent inflammation, lung damage, and organ failure in Covid-19 and the other disorders were unclear.
The cellular and molecular mechanisms that extensively define cytokine storms were also lacking. Kanneganti’s team focused on a selection of the most elevated cytokines in Covid-19 patients. The researchers showed that no single cytokine induced cell death in congenital immune cells, it said.
“The results link inflammatory cell death induced by TNF-alpha and IFN-gamma to COVID-19,” Kanneganti said.
“The results also suggest that therapies targeted at this cytokine combination are candidates for rapid clinical trials to treat not only Covid-19, but several other often fatal disorders associated with cytokine storm,” she said.
“We were pleased to connect these dots to understand how TNF-alpha and IFN-gamma trigger PANoptosis,” said co-first author Rajendra Karki, a scientist at Kanneganti Laboratory.
“In fact, understanding how PANoptosis contributes to disease and mortality is crucial to identifying therapies,” added co-author Bhesh Raj Sharma, a scientist at Kanneganti Laboratory. PTI