Landmark study of COVID-19 infection among K-12 students debunks early fears about transmission at schools

Debunking a fear that was widespread at the beginning of the COVID-19 pandemic, a novel CHOC- and UC Irvine-led study of SARS-CoV-2 infection rates among the K-12 population concludes that within-school transmission of the virus is limited.

The “Healthy School Restart Study,” one of the first to provide essential research on COVID-19 transmission in children and adolescents as schools started reopening last fall, also concludes that although the compliance rate to such mitigation guidelines as wearing face coverings and practicing social distancing at the four Orange County schools directly observed by investigators varied, it averaged about 90 percent.

The seminal research paper is under review and is expected to be published soon, says Dr. Dan Cooper, who treats kids with lung conditions at CHOC and who serves as director of UC Irvine’s Institute for Clinical & Translational Science. Dr. Cooper is a multiple principal investigator of the study along with Dr. Erlinda Ulloa, a CHOC infectious disease specialist and an assistant professor in the Department of Pediatrics at the UCI School of Medicine.

Dr. Dan Cooper, pediatric pulmonologist at CHOC

“The number one fear was that, just like influenza, children would be a reservoir for COVID-19 and would spread it to each other at schools and then spread it to adults,” Dr. Cooper says. “The data is showing us, fortunately, that that’s not the case. While such spread can occur, it is limited and when schools follow standard mitigation procedures, spread is minimal.”

The study, a joint effort of CHOC, UCI Health and the Orange County Health Care Agency, found that infection rates at schools reflected those of the community, and that neither remote learning nor highly mitigated onsite school attendance could eliminate SARS-CoV-2 infection.

“It would be disingenuous to say it’s 100-percent safe to return to schools – we’re still in a pandemic,” Dr. Cooper says. “It would be wrong to say there’s absolutely no risk in sending your child back to school, but it would also be wrong to say there’s no risk in not sending your child back to school.”

A total of320 students ages 7 to 17, as well as 99 school staff members, participated in the research project by agreeing to nasal swab and blood testing. Two of the schools in the study serve low-income Hispanic learners. One school serves a high proportion of kids with special needs, and the fourth school serves predominately white kids from upper- and middle-class families. The first three schools mainly provided remote instruction, while the fourth school predominantly provided onsite instruction.

“The four participating schools reflected the enormous diversity of income, community COVID-19 case rates, school type (private, charter, public), and learning status (remote vs. onsite) that face learners, school staff, and policy makers across the United States,” the paper states.

The study was done in two phases – in early fall, when there were lower levels of COVID-19 cases, and a second time during the late fall-winter surge, when there was a tenfold increase in COVID-19 cases. Trained observers studied kids four times a day – during classroom learning, at active recess, during PE, and during communal lunch.

During the first testing phase, no kids tested positive for COVID-19. During the second phase, 17 kids tested positive for the virus, along with six staff members.

School A, which primarily serves lower-income Hispanic students and had 97 percent of its students engaged in remote learning, had the highest infection rate, at 12.9 percent. School D, which serves upper- and middle-class students who primarily attended class in person, had the lowest infection rate, at 1.2 percent.

In the aggregate, there was no statistically significant difference in SARS-CoV-2 positive rates among remote or onsite learners, the study found.

In addition, the study found there was a significant relationship between SARS-CoV-2 positivity and presence of symptoms – data that supports the use of limited symptom screening as a mechanism to enhance healthy school reopening.

Investigators also tested for 21 other circulating respiratory pathogens and turned up no signs of the influenza virus – just the common-cold rhinovirus, which stays functional on surfaces such as desktops for much longer intervals than the coronavirus or influenza virus.

“The mitigation procedures and cleanliness procedures that had been put in place got rid of the flu,” Dr. Cooper notes.

He adds: “This study should make parents feel better and prompt them to ask the right questions to their school. Parents should ask, ‘What are your mitigation plans? How are you making sure people are paying attention to your plan? What happens to a child who reports symptoms during the day? Do you have a plan?’ That’s what I would want to know as a parent.”

Mitigation procedures should remain

With widespread implementation of pediatric COVID-19 vaccination still many months away, it’s likely that adherence to COVID-19 mitigation procedures, including physical distancing and face covering, will need to continue for the near future, the study concluded.

Dr. Cooper notes that some students, mostly from lower-income families, are going on a year without in-classroom learning – an unfortunate situation that comes with many disadvantages, such as more sedentary time at home on the computer and increased obesity and depression.

“We have to weigh the damage to kids of keeping schools closed,” he says. “Who is being impacted most? It’s the low-income kids.”

In addition to Dr. Cooper and Dr. Ulloa, other CHOC and UCI personnel who participated in the “Healthy School Restart Study” included Jessica Ardo, Kirsten Casper, Andria Meyer, and Diana Stephens, clinical research coordinators; Dr. Charles Golden, vice president and executive medical director of the CHOC Primary Care Network; and Dr. Michael Weiss, vice president of population health at CHOC.

The authors of the research paper also acknowledged the “outstanding management” of the complex study by Phuong Dao, director of research operations; Brent Dethlefs, executive director of research; and other staff members of the CHOC Research Institute.

In another research paper, published in late February 2021 in the journal Pediatric Research, Dr. Cooper and Dr. Ulloa addressed the biologic, ethical, research and implementation challenges of SARS-CoV-2 vaccine testing and trials in the pediatric population.

Among others, the paper was co-authored by Dr. Coleen Cunningham, CHOC’s new senior vice president and pediatrician-in-chief, as well as chair of the UCI Department of Pediatrics, and Dr. Jasjit Singh, a CHOC infectious disease specialist.

Children under the age of 12, this paper notes, have yet to be enrolled in COVID-19 vaccine trials.

The paper states that enrolling children in medical research involves a balance between access to experimental but potentially life-saving therapeutics and protection from unsafe or ineffective therapeutics.

The paper notes that in the early stages of the pandemic, a national working group convened and published a commentary outlining the challenges ahead that would inevitably need to be addressed as schools reopened. That commentary, the paper says, included a message that resonates with the immediate challenge of pediatric SARS-CoV-2 vaccine testing and clinical trials:

“This could be accomplished by building public health-focused collaboratives capable of continuous learning and rapid cycles of implementation, as COVID-19 information evolves at breakneck speed. Otherwise, we risk further compounding the incalculable damage already incurred by COVID-19 among children across our country and the world.”

Read more about the Healthy School Restart Study.

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CHOC awarded $2.3-million grant to study how toxic stress and unpredictability in the early environment affects neurodevelopment

The state of California has awarded CHOC, in partnership with UC Irvine and Chapman University, a $2.3-million grant to screen patients for adverse childhood experiences (ACEs) and childhood unpredictability to assess how such high-stress events affect the brain and put kids at increased risk of later developing physical and mental illnesses.

In a novel aspect of the study, researchers also will determine if there are epigenetic markers on the DNA that predict whether any given child will be more adversely affected than another.

The team is among four awardees statewide that have been given a total of $9 million to assess which children are most vulnerable to the effects of ACEs and unpredictability in the home environment, and to design medical care to improve the outcomes for this particular group of patients – a model known as “precision medicine,” which eschews a one-therapy-fits-all approach to healthcare.

“The whole concept here is that kids who grow up in environments with frequent exposures to toxic levels of stress can have all kinds of internal things happen in their bodies related to prolonged or extensive stress hormone response – their brains can develop differently, and when they become adults, research has shown that they have a higher risk of developing medical conditions such as heart disease, asthma and cancer,  among other physical diseases, as well as mental disorders,” says Dr. Charles Golden, a co-investigator on the study and executive medical director of the CHOC Primary Care Network (PCN).

Dr. Charles Golden, executive medical director of the CHOC Primary Care Network (PCN)

The California Governor’s Office of Planning & Research, in partnership with the Office of the California Surgeon General, awarded the three-year research project as part of the California Initiative to Advance Precision Medicine (CIAPM). The other three recipients were Children’s Hospital Los Angeles, University of California, San Francisco, and Loma Linda University.

The CHOC-UCI-Chapman research project begins in July 2021, with screening expected to start in CHOC PCN clinics by November 2021. Lead principal investigator on the project is Dr. Tallie Baram, Bren Distinguished Professor and director of the Conte Center at UCI. The National Institute of Mental Health-funded Conte Center also addresses how early-life experiences influence the brain and contribute to mental illnesses.

Results of the study are expected by the end of 2024, says Laura Glynn, PhD, a Professor of Psychology and Associate Dean for Research at Chapman University and one of the principal investigators on the study.

CHOC’s PCN has been screening its Medi-Cal patient population for ACEs since February 2020, and expanded such screening – using a tool called PEARLS, for Pediatric ACEs and Related Life Events Screener – to all patients in November 2020, Dr. Golden says.

The 17-question PEARLS tool screens for such experiences as a parent being jailed, the prevalence of alcohol or drug abuse in the household, and whether the child has been a victim of violence in his or her neighborhood, in the community at large, or at school.

“This existing infrastructure at CHOC was a very important part of the application for this grant,” Glynn says.

The CHOC-UCI-Chapman study, “Using Precision Medicine to Tackle Impacts of Adverse and Unpredictable Experiences on Children’s Neurodevelopment,” will dig deeper than standard PEARLS screening.

The children will be asked an additional five questions to assess exposure to unpredictability in the social, emotional, and physical domains. Such questions are an attempt by researchers to develop an instrument that will predict this population of kids’ resilience to, or risk of developing, physical or mental illnesses. Children from low socioeconomic and racial/ethnic minority communities are at greater risk of exposure to ACEs.

“This study will involve looking at whether routine, or lack of routine, in a child’s life contribute as an ACE,” Dr. Golden explains. “In other words, do they eat dinner every night at 6 p.m., do they have a routine bedtime, do they have a stable household versus a family with no routine or little structure.”

Such factors of unpredictability potentially are amenable to intervention, Glynn notes.

Emerging evidence from experiments with rodents show that fragmented or unpredictable maternal signals influence the maturation of systems governing emotional and cognitive function in the developing brain. In preclinical work led by Dr. Baram, the group has shown that rats exhibited diminished memory function when exposed to unpredictable maternal signals early in life, as well as anhedonia (reduced ability to experience pleasure) beginning in adolescence.

Also, as part of the study, DNA swabs will be performed on a cohort of 120 children who experience high levels of ACEs to determine if genetic expression patterns indicate a vulnerability to chaos and unpredictability in their lives. The team also will be examining whether epigenetics – the process of how genes may be altered based on environmental events – may play a role in the development of ACE-related medical conditions.

“We think potentially we can look at these epigenetic profiles to predict neurodevelopmental outcomes,” Glynn says.

Dr. Michael Weiss, vice president of population health at CHOC and a primary investigator on the study, says such information may make it easier for doctors to identify a child who has a genetic predisposition to experiencing a bad outcome from being exposed to ACEs – thus leading to targeted interventions to kids who need them the most.

“This project is a great demonstration of a collaboration between CHOC and UCI and Chapman University involving primary care research,” Dr. Weiss says.

Other CHOC researchers who will participate in the research project are Dr. Dan Cooper, who treats kids with lung conditions at CHOC and who serves as director of UC Irvine’s Institute for Clinical & Translational Science; Dr. Candice Taylor Lucas, co-director of LEAD-ABC (Leadership Education to Advance Diversity–African, Black and Caribbean) at UCI/CHOC; Louis Ehwerhemuepa, PhD, a senior data scientist; and Dr. Mary Zupanc, co-medical director of the Neuroscience Institute.

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Meet Dr. Charles Golden

CHOC wants community providers to get to know its physicians. Today, meet Dr. Charles Golden, a board-certified pediatrician and executive medical director, Primary Care Network, CHOC.

Q: What is your education and training?

A: I earned a Bachelor of Science in Biology at University of California, Riverside. After completing my undergraduate studies, I attended Western University of Health Sciences College of Allied Health and earned a certificate as a physician assistant. I worked at Southern Orange County Pediatric Associates (SOCPA) as a physician assistant until I started medical school at Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, in Pomona. I completed my internship and residency, including a year as chief resident, at Children’s Hospital Los Angeles.

Q: How long have you been at CHOC?

A: Just over a year.

Q: What are your special clinical interests?

A: I love all aspects of clinical medicine, but get energized when I have the opportunity to teach. I believe that every encounter with a patient is an opportunity to teach them something about the body and explain why we make the decisions that we do in medicine. I’m also passionate about teaching medical students and residents, as they continually challenge me to stay up to date with new research. I love the feeling I get from contributing to the development of their careers as physicians.

Q: Are there any new programs or developments within CHOC’s Primary Care Network?

A: In the near future, we plan to open an after-hours clinic for the entire community. By the end of summer, we’re planning on implementing a single electronic health record (EHR) through Cerner for all our primary care offices so that all of our providers chart on patients in the same record, and a patient’s medical information can securely be available to whoever they see in our group. This will continue to improve communications within the practices.

We’re also growing our comprehensive adolescent medicine services. We will be hiring another adolescent medicine specialist to address this unique, complex patient population. Additionally, we’re working on the use of digital vision screening devices to look for problems with vision in children younger than 4 years old, who are often too young to read a visual acuity chart.

In addition, we’re working closely with CHOC’s chief psychologist, Dr. Heather Huszti and her team to provide a mental health professional in each of our primary care offices to help the medical team screen for and address mental health issues. This is a component of CHOC’s mental health initiative, including the mental health inpatient center opening this spring.

Q: What would you like specialists to know about primary care at CHOC?

A: I would want the specialists to know about the high-quality care that our physicians provide on a daily basis, as well as the breadth of our network – from central and north Orange County to the most southern part of the county in San Clemente – and the broad diversity of the patients that we care for.

I’d also like them to know that they can feel comfortable collaborating with our pediatricians, and that they can count on us to provide evidence based care to our patients, consistent with what we know their divisions to do. Lastly, I’d want them to see CHOC primary care as a trusted partner in our health system, where we are keeping children healthy through regular examinations, screening, education and integration, and strive to treat our patients and their families holistically rather than simply by disease process.

Q: What would you like patients and families to know about your division at CHOC?

A: For many people, bringing your child to seek medical care can be a stressful event. There are many sources of information out there regarding children’s health, and in some cases those sources may contribute to more confusion and anxiety. I would like patients and families to know that when they choose a CHOC pediatric provider, they can trust that the care being delivered is state of the art, up to date and based on clinical and scientific evidence, combined with years of expertise. They will be greeted by empathic staff who are skilled in making children feel comfortable, and providers who are not only skilled at diagnostics, but bring a warm and compassionate touch to the visit.

Further, our pediatricians are partners with our specialists, and through this partnership they share knowledge, collaborate in patient care, and help to create a sense of calm for patients and their families.

Q: What inspires you about the care being delivered at CHOC?

A: Every day pediatricians, pediatric specialists, nursing staff, technicians and so many other professionals come to CHOC to make a difference in the lives of children in need. It’s a calling, and they’re passionate about it. You can feel it when you walk through the door, whether it’s from the smiles and greetings from the folks at the information desk, or when you see a security guard assist a family. Perhaps it’s when you see an associate go out of their way to offer hospitality to a random person in an elevator, or the cutting edge surgical and medical treatments that are happening every day. To try to answer what inspires me most about the care being delivered by CHOC would do a disservice to every little thing that occurs on our campus that makes CHOC a special place. I’m incredibly proud to be a part of it!

Q: Why did you decide to become a doctor?

A: I fell in love with science as a teenager. Around the same time, my father had a heart attack. I remember going to the hospital and learning about his heart and how the medicine was working to provide care for him. I was fascinated by it all and never looked back.

Q: If you weren’t a physician, what would you be and why?

A: I would probably be a general contractor. I’ve always enjoyed working with my hands.

Q: What do you like to do in your spare time?

A: I love spending time with my wife and children. I also enjoy cycling and mountain biking, and being involved in my kids’ sports.

To refer a patient, please call 1-855-212-6740.

Learn more about CHOC Primary Care Network.