The Most Unusual COVID-19 Symptom of All

Can COVID-19 kill pain? That is the possibility raised by University of Arizona researchers who found SARS-CoV-2, the virus that causes COVID-19, might function as a pain killer.

If that theory proves to be true, it might be one of the reasons so many infected people walk around unaware they have the disease. While the Centers for Disease Control and Prevention has an exhaustive list of COVID-19 symptoms, ranging from fever to loss of taste and smell, so far, "feeling no pain" has not made that list.

"It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you're walking around all fine as if nothing is wrong because your pain has been suppressed," said Dr. Rajesh Khanna, Ph.D., a professor in the University of Arizona's College of Medicine.

He said in a news release, if his tests prove that pain relief is a symptom and possible cause of what is triggering the spread of the virus, that would be "of tremendous value."

The Arizona researchers believe the spike protein on the SARS-CoV-2 virus silences the body's pain signaling pathways, explained Dr. Michael D. Drake, senior vice president of UA Health Sciences. He added scientists at the University of Arizona's Comprehensive Pain and Addiction Center are using this unique finding to help develop a new, non-opioid class of therapeutics for pain.

According to Ladders, it has been known for some time the SARS-CoV-2 virus infects people by attaching its spike protein to the ACE2 receptors on human cells. New research reveals the virus also uses a second receptor, called the neuropolin-1, to adhere to cells. Dr. Khanna and his team have been studying the effect on pain pathways involving neuropolin-1 for over 15 years, and realized there might be a correlation between how the virus attacks the body and subsequent pain reduction.

It turns out, by attaching to human cells, SARS-CoV-2 stops a pain-producing protein called VEGF-A from also binding to the cells and "completely reversed pain signaling" in rodents tested, Khanna said, according to Ladders.

As the opioid and coronavirus epidemics collide, Khanna said at least one good thing about COVID-19 might be forthcoming. Researchers are exploring ways to block VEG-F by using small molecule inhibitors instead of the coronavirus and hopefully will be able to develop new non-opioid methods to reduce pain using this approach.

The full study was published in the Journal of the International Association for the Study of Pain.