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An Indo-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, research from the lab of Dr. Thirumala-Devi Kanneganti, an Indian-born researcher working at St. Jude Children’s Research Hospital in Tennessee, identified the drugs after finding that the associated hyperinflammatory immune response to Covid-19 leads to tissue damage and multi-organ failure in mice by triggering inflammatory cell death pathways.
The researchers detailed how the inflammatory cell death signaling pathway works, which has led to potential therapies to disrupt the process.
“Understanding the pathways and mechanism behind this inflammation is essential for developing effective treatment strategies,” said Kanneganti, vice president of St Jude’s Department of Immunology.
Kanneganti was born and raised in Telangana. She received her undergraduate degree from Kakatiya University in Warangal, where she majored in chemistry, zoology and botany. She then received her M.Sc. and Ph.D from Osmania University in India. She joined St. Jude, in Memphis, Tennessee, USA, in 2007.
“This research provides that understanding. We have also identified specific cytokines that activate inflammatory cell death pathways and have tremendous potential for the treatment of Covid-19 and other highly fatal 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, of St. Jude; and Evan Peter Williams, Lillian Zalduondo and Colleen Beth Jonsson from the University of Tennessee Health Sciences Center.
Covid-19 is caused by the SARS-CoV-2 virus. The infection killed more than 1.2 million people in less than a year and sickened millions more.
The infection is marked by an increase in the blood levels of several cytokines. These small proteins are mainly secreted by immune cells to ensure a rapid response to restrict the virus. Certain cytokines also trigger inflammation.
The term cytokine storm has been used to describe dramatically elevated levels of cytokines in the blood and other immune changes that have also been seen in Covid-19, sepsis, and inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH) St Jude said in a statement.
But the specific pathways that trigger the cytokine storm and the resulting inflammation, lung damage and organ failure in Covid-19 and other disorders were not clear.
The cellular and molecular mechanisms that globally define the cytokine storm were also lacking. Kanneganti’s team focused on a selected set of the highest cytokines in Covid-19 patients. Scientists have shown that no cytokine induces cell death in innate immune cells, he said.
“The findings link inflammatory cell death induced by TNF-alpha and IFN-gamma to Covid-19,” Kanneganti said.
“The results also suggest that therapies that target this combination of cytokines are candidates for rapid clinical trials for the treatment of not only Covid-19, but also several other often fatal disorders associated with the cytokine storm,” a- she declared.
“We were excited to connect these dots to understand how TNF-alpha and IFN-gamma trigger PANoptosis,” said co-first author Rajendra Karki, a scientist at the Kanneganti lab.
“Indeed, understanding how PANoptosis contributes to disease and mortality is key to identifying therapies,” added co-first author Bhesh Raj Sharma, a scientist at Kanneganti’s lab.
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