ABC7 News reporter Luz Pena went to the lab where this discovery took place.
It was 2020 when Dr. Aaron Bodansky was seeing a high number of children coming into the ICU with a mysterious inflammatory disease.
"They had very high fevers, they had severe inflammation of all their bodies, but in particular, their lungs and really their hearts. It made it so their hearts were not able to pump enough blood to keep them alive," said Dr. Bodansky, assistant professor of UCSF pediatric critical care.
The illness came to be known as Multi-System Inflammatory Syndrome in Children, or MIS-C.
"The scariest part of it was that we couldn't explain at all what was causing the disease. The only thing we knew was that they previously had a SARS-CoV-2 infection. Then about a month later, they would get this mysterious severe illness that put them on death's door," said Dr. Bodansky.
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As cases intensified, doctors suspected the severe inflammation was connected to the immune system.
"We used medicines to suppress and calm their immune system which thankfully worked extremely well to save their lives," said Dr. Bodansky.
Dr. Bodansky remembers reaching a breaking point after seeing one of his patients.
"We had to put a breathing tube in and put on medicine to essentially induce a coma and put on so many strong medicines to keep his heart bumping. It was really hard to look the parents in the eyes and tell them we had no idea what was happening, and I didn't want to keep doing that," said Dr. Bodansky.
As he searched for answers, said Dr. Bodansky contacted some of the top infectious disease experts and scientists in San Francisco.
"I reach out to world famous scientists in the area and in particular, an immunologist - Mark Anderson and the real pivotal figure was Joe DeRisi, who had pioneered this new technology that would allow us to look at the entire immune system's response all at once," said Dr. Bodansky.
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Their meeting sparked a collaboration that led to their discovery years later.
"We collaborated with a group the CDC was helping to coordinate along with Adrienne Randolph who was sort of the central figure in collecting samples from all over the country. We got all of those samples sent to us as the central hub and then used the Biohub and Joe DeRisi's technology that allows us to profile the entire immune system all at once on all of the samples," said Dr. Bodansky.
The group collected 199 blood samples from children across the country.
"With that we were able to really see what was different about the immune response in these children that got the disease compared to in children that had COVID a month ago but didn't get this disease. That really allowed us to crack the case," said Dr. Bodansky.
Dr. Joe DeRisi is the president of the Chan Zuckerberg Biohub San Francisco and professor in the Department of Biochemistry and Biophysics at the University of California. He described the illness as an enduring mystery of the COVID-19 pandemic.
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"This has been a puzzle that researchers and clinicians across the country, and in fact across the world have tried to figure out and yet it has alluded almost everyone until now," said Dr. DeRisi.
Dr. DeRisi recalls the moment they made the key connection.
"The 'aha' moment was realizing that unusual reaction to COVID matched something in our own immune system. It acquired a target against COVID that matched us. So, it was attacking both at the same time," said DeRisi.
They are hoping to use their findings to advance science and help treat other diseases.
"Knowing that a virus can provoke an auto-immune reaction later on and having this proof allows us to potentially develop therapeutics and diagnostics for anything like this that might occur in the future," said Dr. DeRisi.