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News — LOS ANGELES (February 12, 2024)—Up to 5.8 million children and youth in the U.S. have experienced symptoms of COVID-19 that persisted long after initial infection. But diagnosing postacute sequelae of SARS-CoV-2 (PASC)—known as long COVID—in children remains challenging, as long COVID can affect any organ system in the body, symptoms vary widely by individual, and little is known about its trajectory in patients over time. Children’s Hospital Los Angeles is one of 10 pediatric sites involved in the nationwide Researching COVID to Enhance Recovery (RECOVER) Initiative, sponsored by the National Institutes of Health to improve the diagnosis, treatment and prevention of long COVID in children. CHLA researchers and their collaborators in the RECOVER Initiative have published a comprehensive report on pediatric long COVID symptoms in the journal . 

“At our clinic, some patients have symptoms for two months and there are others whose symptoms have still not gone away two years later,” says , co-Director, Immunocompromised Infectious Diseases Program at Children’s Hospital Los Angeles and study co-author. “But we still don’t know which patients are at risk for long-term symptoms. Until this report, doctors looking for information could only refer to small, case-based studies. Pediatric clinicians and researchers can now use this paper to quickly access the latest research on long COVID in children and reference the source studies.

Summarizing the research

The RECOVER collaborators across the country reviewed existing research on long COVID in kids in their respective areas of expertise, including its epidemiology, risk factors, clinical characteristics and outcomes. “Our goal was to summarize all available knowledge from those smaller articles, case reports and clinic-based studies on the full range of long COVID symptoms that we are seeing across the U.S.,” says Dr. Mohandas.

Their findings have so far uncovered a few clues to long COVID risk. For instance, about 45% of the children who developed long COVID experienced COVID-19 symptoms rather than symptomless infections (15%). Other factors include older age, more severe initial COVID-19 infection, the number of different organ systems initially affected, underlying medical conditions and higher weight.

The most common long COVID symptoms in children involve fatigue, persistent headaches, weakness, musculoskeletal pain, shortness of breath, loss of taste and smell, and dizziness. Between 2% to 44% of kids with long COVID can experience difficulties in concentration—known as brain fog—after physical or mental effort. Brain fog/fatigue can also mimic the symptoms of myalgic encephalomyelitis—known as chronic fatigue syndrome. This can last for at least six months and impair daily function.

Long COVID is linked with the new onset of Type 1 or Type 2 diabetes about a month after initial infection. Long COVID is also associated with the development of multisystem inflammatory syndrome in children (MIS-C)—thought to be caused by abnormally high activation of the immune response—involving heart damage, irregular heart rhythms and conduction abnormalities.

“Most MIS-C symptoms disappear after six months, but a minority of children still experience unexplained exercise intolerance and fatigue,” says , cardiologist and investigator at CHLA, and study co-author.

Pediatricians are under-diagnosing long COVID, Dr. Wood adds. “Some believe children don’t get long COVID and others just don’t know the signs and symptoms. I think the big ’added value’ to this published study is that it provides some of the characteristic ’fingerprints’ that pediatricians can use to recognize long COVID.” 

Worsening pre-existing conditions

Long COVID can aggravate chronic respiratory conditions such as asthma. Several studies showed that while asthma didn’t worsen during initial COVID-19 infection, it did so during the six months after infection.

Long COVID can also worsen rare fibromyalgia and connective tissue disorders such as Ehlers Danlos syndrome or Marfan syndrome. These conditions are also linked with chronic fatigue syndrome and the dysregulation of involuntary body functions such as blood pressure and heart rate, causing dizziness when shifting position or standing, a condition like postural orthostatic tachycardia syndrome (POTS).

“We needed to follow a large group of kids over a long span of time to see the prevalence and clinical course of some of these rare symptoms,” says , stem cell researcher and neonatologist at CHLA. “Our hope is that this effort to better understand long COVID can lead to a deeper understanding of these other conditions as well—and to effective treatments. We are now collecting information on symptoms that re-emerge over time during periods of physical and/or psychological stress and re-infection, to learn how to prevent chronic conditions from emerging in adulthood.”

The CHLA study is still enrolling volunteers. Physicians and families can find out more about the study or join by emailing the study team at [email protected].

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The first author of the study was Suchitra Rao, MBBS, MSCS, University of Colorado School of Medicine and Colorado Children’s Hospital. Additional contributors include: Rachel S. Gross MD, MS, Cheryl R. Stein, PhD, New York University Grossman School of Medicine; Abigail Case, MD, Children’s Hospital of Philadelphia; Benard Dreyer, MD, CHLA; Nathan M. Pajor, MD, Cincinnati Children's Hospital Medical Center; H. Timothy Bunnell, PhD, Nemours Children’s Hospital; Elizabeth Berg, MD, Jonathan Overdevest, MD, Mark Gorelik, MD, Joshua Milner, MD, Sejal Saxena, BA, Columbia University Vagelos College of Physicians and Surgeons; Ravi Jhaveri, MD, Ann & Robert H. Lurie Children's Hospital of Chicago; Kyung E. Rhee, MD, MSc, MA, UC San Diego School of Medicine; Rebecca Letts, BA, Christine Maughan, BS, Nick Guthe, BA, Leah Castro-Baucom, MA, New York University Grossman School of Medicine; and Melissa S. Stockwell, MD, MPH, Columbia University Vagelos College of Physicians and Surgeons.

About Children’s Hospital Los Angeles

Founded in 1901, Children’s Hospital Los Angeles is at the forefront of pediatric medicine and is the largest provider of hospital care for children in California. Children’s Hospital is home to renowned experts who work together across disciplines to deliver inclusive and compassionate care and drive advances that set pediatric standards across the nation and around the globe.

Children’s Hospital Los Angeles provides a level of care to its diverse population of children that is among the best in the world. The hospital is consistently ranked in the top 10 in the nation on U.S. 麻豆传媒 & World Report’s Honor Roll of Best Children’s Hospitals, including No. 1 in California and No. 1 in the Pacific U.S. region. Children’s Hospital Los Angeles embraces its mission to create hope and build healthier futures. Children’s Hospital Los Angeles is among the top 10 children’s hospitals for National Institutes of Health funding. The Saban Research Institute of Children's Hospital Los Angeles supports the full continuum of research, allowing physicians and scientists to translate discoveries into treatments and bring answers to families faster. The pediatric academic medical center also is home to one of the largest training programs for pediatricians in the United States, and the hospital’s commitment to building strong communities is evident in CHLA’s efforts to fight food insecurity, enhance health education and literacy, and introduce more people to careers in health care. To learn more, follow CHLA on , , LinkedIn, and (formerly Twitter), and visit .