In a way, multisystem inflammatory syndrome in children, or MIS-C, is a master of disguise. Appearing in Maryland in mid-to-late April, after making its presence known in Europe and New York City, the COVID-related syndrome is causing typical viral symptoms in children, including fever and stomach upset such as pain, diarrhea and vomiting, but generally not respiratory problems. However, some children are experiencing conjunctivitis, red eye, skin rash, swollen hands or feet, cracked lips and even a very red tongue — signs associated with classic Kawasaki disease, marked by inflammation of the coronary arteries supplying blood to the heart. Also confounding this clinical picture, some children experience neurologic symptoms such as headache, unusual sleepiness, disorientation and confusion. So, confronting such symptoms, how should parents react? Call their pediatrician? Drive to the nearest hospital? Watch and wait?

“It’s tough because we’re dealing with a newly identified illness,” says pediatric infectious disease specialist Anna Sick-Samuels. “We think this may be similar to Kawasaki disease, which we are familiar with, but we are still learning about this new condition.”

“The CDC [Centers for Disease Control and Prevention] is coming out with various treatment recommendations, but this is a new virus and without solid science or the time to do randomized control trials to figure out the exact science of this, it’s hard to predict which children need hospitalization and which will become critically ill,” adds pediatric intensivist Becky Riggs.

Riggs, Sick-Samuels and their colleagues at Johns Hopkins Children’s Center know that those afflicted with MIS-C likely had COVID-19 infection beforehand, evidenced by antibodies created by the immune system in response to healing from the virus. Many of these children may not have had symptoms of the original COVID-19 infection, but a few weeks later they developed symptoms of this newly recognized illness called MIS-C.

“Because we find antibodies to COVID-19 in these patients, we think this is an immune response, not an active viral infection anymore,” says Sick-Samuels. “The initial infection with COVID-19 triggered the child’s immune system to attack its own body, causing inflammation and injury.”

The initial symptoms of MIS-C may be vague and not necessarily something that a parent would typically bring their child to the doctor for, notes Riggs. Different from those found in other illnesses, symptoms of MIS-C may not go away and will get worse over time.

“The longer this inflammation continues without treatment or supportive care,” Riggs says, “the sicker these kids will continue to get.” Riggs and Sick-Samuels stress that the two symptoms of MIS-C most often seen are persisting fever and an upset stomach (pain, vomiting or diarrhea).

In addition to fever and stomach symptoms, other symptoms children with MIS-C have had include skin rashes, red eyes, swollen hands and feet, red “strawberry” tongue, symptoms of meningitis such as neck pain and headache, body aches, poor appetite, loss of taste or smell, and overall feeling unwell. The take-home message, say Sick-Samuels and Riggs, is parents should not hesitate to call their child’s pediatrician if they have any concerns.

Parents should bring their child to an emergency room if their child has any of the following symptoms:

• Persistent fever (greater than 38 degrees Celsius or 100.4 degrees Fahrenheit) for four or more days (even if there are no other symptoms).
• Difficulty feeding (infants) or too sick to drink fluids.
• Severe and persistent abdominal pain, diarrhea or vomiting.
• Dehydration with decreased frequency of urination.
• Change in skin color or appearance — becoming pale, patchy or blue, swelling, or turning bright red, especially in the hands or feet.
• Trouble breathing, painful breathing or breathing very quickly.
• Racing heart or chest pain that does not improve with a simple dose of acetaminophen or ibuprofen.
• Unusual sleepiness, dizziness or confusion.

Treatment includes IV fluids, medicines such as steroids or immunoglobulins to fight inflammation and, for some patients, blood thinning agents because these children are prone to developing blood clots. In the pediatric intensive care unit, patients may also receive medication to keep blood pressure at a normal level and to support the heart. In some very rare but severe cases, the child may require a breathing tube or support on extra corporeal membrane oxygenation (ECMO) heart/lung bypass to allow the heart and lungs, if injured, to heal. However, even with this extreme intensive support, some children do not survive, says Riggs, stressing the need for fast and early medical intervention.

The good news is that MIS-C seems to be a rare complication of COVID-19. Even though children with MIS-C can get very sick and a few children have not survived, most children with this illness have recovered fully. “We are still learning a lot about this condition,” says Sick-Samuels. “There is amazing collaboration between the hospitals and the CDC to learn from each other and quickly build our understanding and optimize management of MIS-C.”