CHOC's Executive Medical Director and Vice President of the Children's Primary Care Network, Dr. Charles Golden, spoke to Eyewitness News Tuesday about the increase.
"The percentage of positive cases that we've seen over the last two months has been doubling virtually every two weeks," Golden said, adding, "Sixty-five cases have been hospitalized in the last three months cumulatively. Right now we have 13 patients in the hospital."
The 638 positive cases since mid-March from CHOC's hospitals and clinics ranged from infants to 24-year-olds.
WATCH: Here's what goes into creating a vaccine for COVID-19
As of Tuesday, 75 infants had tested positive there. Golden said 18 had to be hospitalized, but, "thankfully, have gone home and are doing well."
The majority of patients testing positive were children between the ages of 4 and 15, with 38 hospitalizations in this group.
Golden said it's important for these students to get back in the classroom.
"Not only is it academically important for them, but it's also socially important for them to be there and from the physical health perspective, it's also important, but for kids to go back to school it has to be done safely," Golden said.
Safety to the pediatrician and father means physical distancing, disinfecting of the areas students learn in and cloth face coverings.
For parents with kids not wanting to keep their masks on, Golden's advice is to make it fun.
"If you do things like make it an activity, give children the opportunity to create their own face mask. Give them the power. Give them the control. What kind of face mask would you like to wear today? What color would you like to wear?" Golden said.
Golden said it's important for kids to continue getting their wellness checks, vaccinations and specialty care as needed during the pandemic.
He said of the 13 hospitalized Tuesday, seven were in the intensive care unit.
CHOC has a 24-hour hotline open to anyone in the community for pediatric medical questions, including those related to COVID-19. That number is 1-844-GET-CHOC.