Recent reports have been describing how some of the worst outcomes from Covid-19 in humans is caused by an inflammatory immune response. Research published in the journal Frontiers in Immunology has revealed that pangolins, which can carry coronaviruses, may be protected from the disease as they lack two virus-sensing genes that are known to elicit the kind of extreme immune response seen in humans.
Pangolins are scaly animals that resemble anteaters and are the most trafficked animal in the world. It’s been suggested they could potentially be the intermediary animal that enabled Covid-19 from bats to humans, though there is no conclusive evidence for this theory. As such, the team from the Medical University of Vienna in Austria decided to study their genome to see if here lay an explanation as to how these animals can tolerate having a virus in their systems that is so devastating to other animals.
They analyzed the genome sequence of pangolins and compared it to other mammals, including humans, cats, dogs, and cattle. Their findings revealed that the two key genes that signal an immune response in other mammals are missing from pangolins, which could potentially provide some explanation as to why this disease is tolerated by these animals.
"Our work shows that pangolins have survived through millions of years of evolution without a type of antiviral defense that is used by all other mammals," says co-author Dr Leopold Eckhart in a statement. "Further studies of pangolins will uncover how they manage to survive viral infections, and this might help to devise new treatment strategies for people with viral infections."
The discovery is significant as it could suggest that gene suppression is a potential route for treatment. As the pandemic has developed, physicians across the globe have been reporting that the inflammatory immune response triggered by these key genes in some patients causes what’s known as a cytokine storm. Cytokines are proteins in the body that activate immune cells. In Covid-19, these have been found to flock to the lungs, causing hyperinflammation that can kill the patient rather than helping them.
As the response by the immune system is sometimes what’s killing infected patients, it’s possible that pharmaceutical suppression of gene signaling could be a route of treatment for severe cases of Covid-19. However, Eckhart cautions that reducing the body’s immune response could also make the symptoms of the disease worse.
"The main challenge is to reduce the response to the pathogen while maintaining sufficient control of the virus,” he suggested. He noted that this could be achieved “by reducing the intensity or by changing the timing of the defense reaction."
The discovery still doesn’t explain exactly how pangolins can tolerate coronavirus, as Eckhart suggests that another gene called RIG-I, which is also a virus sensor, could potentially play a role. However, the findings provide the intriguing possibility of suppressing immune responses in the body as a means of securing better outcomes for Covid-19 patients.