Posted at 12:15 p.m. on Monday, November 23, 2020
The Brillion News
MEMPHIS, Tenn. – Researchers at St. Jude Children’s Research Hospital say existing drugs may offer a valid treatment for serious complications associated with the COVID-19 virus.
The drugs address the inflammatory problems produced by the virus which often cause its most serious consequences.
Immunologists at St. Jude have determined that the process driving life-threatening inflammation, lung damage and organ failure in patients with COVID-19, sepsis and other inflammatory disorders could likely be treated using existing drugs.
The COVID-19 pandemic continues to cause significant illness and death while treatment options remain limited.
St. Jude Children’s Research Hospital scientists have discovered a potential strategy to prevent life-threatening inflammation, lung damage and organ failure in patients with COVID-19. The research appeared online in the journal Cell.
The scientists identified the drugs after discovering that the hyperinflammatory immune response associated with 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 worked, which led to potential therapies to disrupt the process.
“Understanding the pathways and mechanism driving this inflammation is critical to develop effective treatment strategies,” said corresponding author Thirumala-Devi Kanneganti, Ph.D., vice chair of the St. Jude Department of Immunology. “This research provides that understanding. We also identified the specific cytokines that activate inflammatory cell death pathways and have considerable potential for treatment of COVID-19 and other highly fatal diseases, including sepsis.”
COVID-19 is caused by the SARS-CoV-2 virus. The infection has killed more than 1.2 million people in less than one year and sickened millions more.
The infection is marked by increased blood levels of multiple cytokines. These small proteins are secreted primarily by immune cells to ensure a rapid response to restrict the virus. Some cytokines also trigger inflammation.
The phrase 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 other inflammatory disorders.
But the specific pathways that initiate the cytokine storm and the subsequent inflammation, lung damage and organ failure in COVID-19 and the other disorders was unclear. The cellular and molecular mechanisms that comprehensively define cytokine storm was also lacking.
Kanneganti’s team focused on a select set of the most elevated cytokines in COVID-19 patients. The scientists showed that no single cytokine induced cell death in innate immune cells.
“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 cytokine combination are candidates for rapid clinical trials for treatment of not only COVID-19, but several other often fatal disorders associated with cytokine storm.”
Added co-first author Rajendra Karki, Ph.D., a scientist in the Kanneganti laboratory: “We were excited to connect these dots to understand how TNF-alpha and IFN-gamma trigger PANoptosis.” Co-first author Bhesh Raj Sharma, Ph.D., a scientist in the Kanneganti laboratory, added: “Indeed, understanding how PANoptosis contributes to disease and mortality is critical for identifying therapies.”
In their research. scientists identified how the virus activates inflammatory cell death pathways. Based on this discovery, they found that drugs already used to treat some inflammatory diseases could be repurposed for use in COVID-19.
The drugs protected against death in mice with COVID-19 as well as sepsis and other inflammatory disorders that every year kill millions worldwide.
“The understanding that we gained in this study of how SARS-CoV-2 causes COVID-19 and inflammation helped us identify a promising therapy that relies on available drugs,” Kanneganti said.
~ Ed Byrne/BN from St. Jude Children’s Research Hospital reports and the original research paper in the medical journal Cell.