The researchers found a specific immune response pathway that results in severe sickness and death in SARS-CoV-2 virus-infected patients.
It is previously known that once the COVID-19 virus infects the lungs, it can cause a “cytokine storm,” or an excessive immune response that leads to severe pulmonary inflammation.
The researchers looked at the impact of SARS-CoV-2 infection in mice with a human immune system, led by postdoctoral colleague Esen Sefik, who works in the lab of senior author Dr Richard Flavell.
Surprisingly, the findings of the study revealed that the virus can be carried by immune cells as well as epithelial cells lining the lungs.
When the body identifies the virus in these cells, inflammasomes, which are part of the immune system’s early warning system, generate and release cytokines, causing these immune cells to commit suicide in an attempt to stop the infection. The cytokines, on the other hand, attract even more inflammatory cells from the bloodstream to the lungs, resulting in a vicious cycle that leads to pneumonia.
“It’s like a broadcast system, but in this case the message is lethal,” says professor Dr. Richard Flavell.
Importantly, the study team was able to save infected animals from pneumonia in a mouse model of COVID-19 by blocking the NLPR3 inflammasome pathway. Immune system cells were still infected even when the inflammasome pathway was stopped. The researchers discovered that they were no longer inflammatory and so could not contribute to harmful levels of inflammation.
However, one side effect of this rescue is that the cells no longer die, and as a result, more virus is released.
However, the researchers believe that blocking the inflammasome pathway in combination with antiviral therapy could be used to treat COVID-19 pneumonia and avoid severe cases of COVID-19.
Despite the fact that no medications to block the NLPR3 pathway have been approved, multiple pharmaceutical and biotech companies are working on them, according to Dr. Flavell.
Melatonin, a cheap and widely available supplement, has been shown to suppress the activation of the NLPR3 inflammasome in one research. Melatonin inhibits NF-κB signaling via RORα and silent information regulator 1 (SIRT1)-dependent deacetylation of NF-κB, which prevents the NLRP3 inflammasome from being activated. The NLRP3 inflammasome is activated by reactive oxygen species (ROS).
Melatonin was also discovered to inhibit NLRP3 Inflammasome activation by boosting α7 nAChR-mediated autophagic flux.
Melatonin reduces NLRP3 Inflammasome activation and is useful in the treatment of COVID-19, according to numerous previous research.
Image Credit: Getty
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