New study finds kids with COVID-19 or MIS-C have surprisingly high rates of neurological symptoms

Children and adolescents are at risk of developing serious neurological complications from COVID-19 that require hospitalization.

Elizabeth Mack, M.D., chief of pediatric critical care medicine at MUSC, contributed to a study that found that 22% of children and adolescents hospitalized with acute COVID-19 developed neurological symptoms such as altered awareness, seizures and difficulty walking or crawling. The findings were published earlier this year in the Journal of the American Medical Association (JAMA) Neurology.

Although symptoms were for the most part temporary, they were more long-lasting and severe in some children. Out of 1,695 patients nationwide, 43 developed life-threatening neurological disorders such as brain damage or stroke, 11 children died and 17 survived with continuing neurological problems.

The study was part of Overcoming COVID-19, a national registry of hospitalized patients with COVID-19 who are less than 25 years old. The study is funded by the Centers for Disease Control and Prevention (CDC) and involves 61 hospitals across the U.S., including MUSC Shawn Jenkins Children’s Hospital.

“Of the patients, 22% had neurologic involvement, which I think surprised us all quite a bit. Of those cases, 88% experienced only temporary symptoms, which is certainly reassuring, but the other 12% did not bounce back and some did not survive, which are big numbers when you’re looking at over 1,000 patients.”

-- Dr. Elizabeth Mack

Mack is an Overcoming COVID-19 researcher and part of a team specializing in multisystem inflammatory syndrome in children (MIS-C), a rare inflammatory disorder that can affect multiple organ systems, including the central nervous system, in children and adolescents with a recent COVID-19 infection.

Inflammation in the central nervous system, which includes the brain and spinal cord, can cause a spectrum of neurological issues, such as stroke and neurodegeneration.

Mack and her team screened pediatric patients with COVID-19 or MIS-C for neurological involvement, such as stroke, encephalitis or seizures. With approval of the institutional review board, they reported their findings to the Overcoming COVID-19 Registry.

“Of the patients, 22% had neurologic involvement, which I think surprised us all quite a bit,” said Mack. “Of those cases, 88% experienced only temporary symptoms, which is certainly reassuring, but the other 12% did not bounce back and some did not survive, which are big numbers when you’re looking at over 1,000 patients.”

 

It’s unclear why some children developed serious neurological involvement from COVID-19 and MIS-C and others didn’t. Most of the patients with life-threatening neurological complications did not have any major underlying conditions.

“For whatever reason, in some kids the immune system goes wild in response to prior COVID infection,” said Mack.

MIS-C is an emerging disease and is still poorly understood. Consequently, its diagnosis is often missed.

“We’re learning a new disease,” said Mack. “There’s not any sort of singular finding that defines MIS-C. It’s just something you have to think about and dig into a little bit more.”

Mack’s team diagnoses MIS-C according to the definition provided by the CDC.

“For whatever reason, in some kids the immune system goes wild in response to prior COVID infection.”

-- Dr. Elizabeth Mack.

“The case definition of MIS-C is a patient younger than 21 years of age with fever and lab evidence of inflammation in at least two organ systems,” said Mack. “The patient also needs to have evidence of COVID exposure in the last four weeks or known infection and no other plausible diagnosis.”

To date, no therapies have been approved by the U.S. Food and Drug Administration to treat neurological diseases from acute COVID-19 in children or MIS-C.

To guide treatment, pediatric specialists have turned to measures that have been successful in managing Kawasaki Disease, a well-known inflammatory condition that affects blood vessels in infants and young children and shares some similarities with MIS-C.

“When we first started looking into MIS-C, we thought it was going to be similar to Kawasaki and the therapies would be similar,” said Mack. “But we’ve learned quite a bit, and there are certainly some nuances.”

Mack was an author on another Overcoming COVID-19 study published in April in the New England Journal of Medicine that assessed the effectiveness of immunomodulatory medications for MIS-C therapy. The study found that a combination of steroids and intravenous immunoglobulin is effective against MIS-C.

Long-term follow-up studies may be needed to find out what’s causing neurological complications in pediatric COVID-19 and MIS-C patients and their effects on cognition and development.

“We’re collecting samples, looking into family medical histories and performing whole genome sequencing to figure out why some kids develop severe disease and other kids don’t,” said Mack.

Going forward, neurological involvement in children and adolescents with acute COVID-19 infection may need to be monitored more closely. A better awareness and understanding of MIS-C is also critical to providing appropriate medical care.

“I think that neurological complications are more common than we may have initially thought,” said Mack. “Pediatricians will need to consider the possibility of MIS-C in children presenting with fever and evidence of inflammation, once other diagnoses have been excluded.”