The early results

A preliminary analysis of samples from 150 children found that levels of certain cytokines were higher in children with a severe COVID infection compared to those without a severe infection.

“We measured six cytokines in our study,” Hicks said. “We found two that had higher levels in the saliva of children who went on from the emergency department to require intensive care.”

Researchers’ goal with the study is to be able to identify children at risk of a severe COVID infection by integrating the biomarkers and social determinants of health using artificial intelligence.

The researchers are working on collecting saliva samples from 400 children, ages 18 and younger, with a COVID infection who seek emergency medical care at one of two hospitals: Children’s Hospital of Michigan and UPMC Children’s Hospital in Pittsburgh.

The samples are being analyzed at Penn State College of Medicine. The model development using artificial intelligence is being performed at Wayne State University.

“We set out to enroll roughly one-quarter of our population in the study having severe COVID,” Hicks said. “We chose that proportion because we think it reflects roughly the higher end of estimates about what portion of children who get COVID end up with symptoms that require hospitalizations.”

He added that the rates are likely a little bit lower, but up to 25 percent of the children who get COVID might have severe symptoms.

In addition to preliminary analysis showing higher levels of certain cytokines in children with a severe infection, dozens of microRNA levels were also found to be altered.

The majority of microRNA levels were found to be significantly lower in the saliva of children

with a severe infection. Further analysis will seek to validate these results and confirm the importance of saliva cytokines and microRNAs, in additional to social factors.

While the study is focusing on children, due to it being supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Hicks said there is good evidence the cytokines are also impacted in adults.

It is possible the findings in this study on children could be applied to adult populations, but such findings would have to be validated in an additional study using that population.

A less invasive test

The study is also using a less-invasive testing strategy.

“A major focus of our study was to try to improve upon some of the shortcomings that I think we’ve all experienced with current COVID testing strategies,”

Hicks said. “We use a saliva swab that goes in the mouth, under the tongue. It does not gag the child. It’s in there for 10 seconds or less. Then when it comes out, we can analyze that sample in a machine that provides us an answer in under an hour.”

Hicks said the accuracy of the test so far in regards to the cytokines is only in the 70 percent accurate range.

But, the accuracies are above 90 percent at predicting severe COVID when the cytokines and microRNAs are used together.

Hicks believes the test at the completion of the study would measure both molecule types as it would lead to better accuracy and be more useful to health care providers and parents.

The results of the study so far have not resulted in a test approved by the U.S. Food and Drug Administration, nor has such a test been submitted to the FDA for approval. That is the end goal of the study, Hicks said.

“Once we’ve enrolled 400 children, that is what we’re hoping to do,” he said.

At that point, Hicks said the researchers would approach the FDA and ask what additional results would be needed to approve such a test for use.

“I think if we continue to be able to display the accuracies we’re seeing in the first half of participants, then that will lend itself towards an approved test,” Hicks said.

Though the study is a four-year study, Hicks said the researchers are on track to enroll everyone within a year with the 400th participant expected to be enrolled around the end of the year.

He then expects the researchers to be finish analyzing the data in early 2022 which would then mean a saliva test used to predict COVID severity risk in children could potentially be implemented or approved by the end of 2022.