VIDEO: Cardiologists share the latest details on COVID-related MIS-C

 

Nemours Children's Hospital pediatric cardiologists spoke with Cardiovascular Business about some lessons they have learned about cardiac involvement and long-term related to multisystem inflammatory syndrome in children (MIS-C), a rare but serious disease caused by exposure to the COVID-19 virus. Deepika Thacker, MD, director of inpatient cardiology at Nemours Children's Hospital and associate professor of medicine at Thomas Jefferson University, and Shubhika Srivastava, MD, chief of cardiology at Nemours Children's Hospital and a professor of pediatrics at Thomas Jefferson University, were both involved in the care of some of the first U.S. patients diagnosed with MIS-C. They have since been involved in research on the disease and their center has treated close to 100 MIS-C patients since the start of the COVID pandemic.

MIS-C is a rare condition associated with SARS-CoV-2 virus that usually occurs two to six weeks after a child is infected with COVID-19. Most children have very mild or asymptomatic cases of COVID-19, but children with MIS-C are further stricken by a massive inflammatory response as their body's immune system overreacts to the virus. This can cause damage to the patient's organs. MIS-C causes internal and external parts of the body to become inflamed, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal tract. The U.S. Centers for Disease Control and Prevention (CDC) said MIS-C can be a serious and even deadly condition. However, most children who are diagnosed with the condition fully recover with medical care. 

MIS-C is very similar to Kawasaki disease, which some patients were initially diagnosed. However, the numbers of pediatric patients presenting at pediatrics hospitals skyrocketed from the normal number and it was quickly identified as a new type of inflammatory response disease related to COVID. This greatly alarmed public health authorities worldwide, who quickly mobilized to educate clinicians to identify MIS-C cases and pool data to better understand how to treat it.

Thacker said the initial CDC definition for the disease and its symptoms created in 2020 has withstood the test of the pandemic and has not really changed. This stability helped with being able to identify these patients and treat them.

Since the start of the COVID pandemic, the CDC reported 9,333 cases of MIS-C as of January 2, 2023. The CDC also reported a total of 76 children died from MIS-C since 2020.

Fortunately, Thacker said the number of cases really decreased in starting in mid-2022. She said they went from having one or two patients a week showing up with MIS-C, to having no cases for two months leading up to November 2022, when she spoke to Cardiovascular Business. 

"We believe the current variant of COVID Omicron variant does not produce the same types of COVID effects on the heart as it used to in the past, and vaccination has definitely played a role as well," Thacker explained. "The severity of the MIS-C cases we saw in 2022 also have gone down significantly. So these kids are less likely to be intubated, less likely to have renal failure and less likely to need ICU management."  

How to diagnosis and treat for MIS-C

For patients suspected of having MIS-C, she said they usually order blood tests including troponin, an echocardiogram, ECG and an X-ray to assess the heart. Treatment includes efforts to suppress the hyper-immune response using steroids and intravenous immunoglobulin, which is commonly used to treat patients with antibody deficiencies. Biological agents such as infliximab and anakinra are also used. She said supportive care is given for other issues the condition causes. 

"When and how echocardiograms are performed is crucial because there is a subset of children who get severe myocardial involvement, and a subset who can get coronary artery involvement," Srivastava explained. "So it is really important that an echocardiogram is performed when the child is admitted or is seen in the emergency room. It needs to follow a certain protocol so that one does not miss involvement in the coronary arteries."

The echo exam includes ejection fraction, evaluation for valve and coronary involvement, and a myocardial strain assessment. If there seems to be a high level of cardiac involvement, then a cardiac MRI is performed for a more detailed assessment looking for scarring or involvement with the myocardium. MRI's are also performed if there are elevated troponin levels, indicating there might be cardiac muscle damage or severe inflammation. 

"In just under half the kids that we have seen, we find the troponin is elevated," Thacker explained. "Early on, we realized these kids showed up with a lot of myocardial muscle disfunction. Fortunately, the coronary involvement is usually mild and it does not persist."

Thrombosis is a common problem found in COVID patients due to the way the virus damages vascular beds.

"We do see clotting, but the numbers of children showing clotting is way lower than what we originally thought we would see," Thacker said. Overall, she said adults have a much higher incidence of clotting than children. "Generally in children, we do not see that, but we will usually put them on aspirin and low-molecular weight heparin to prevent clotting."

Since most pediatric patients have asymptomatic COVID cases, parents are often not even aware their child may be at risk for MIS-C until the onset of symptoms like high fever and rashes, often combined with other issues. 

COVID antibody testing was used early on to test children with MIS-C to confirm their previous exposure to COVID. Thacker said this is a little harder to do today, because most people have now been exposed to COVID, and vaccinations will show up as exposure to COVID in spike protein antibody testing. Today, they have moved to nucleocapsid (N) protein of SARS-CoV-2 antibody testing. She said a negative N-antibody test can help rule-out MIS-C when trying to diagnose patients.

In a small number of adults infected that were infected with COVID, there are cases of MIS-A (A for adult), Thacker said. This is the same Kawasaki disease-like condition that causes the an adult's immune system to switch into an overdrive immune response. She said MIS-A is very rare, and MIS-C is much more commonly seen in children.

Find updated information on the diagnosis and treatment of MIS-C.

What are the long-term health issues from MIS-C?

While there were serious concerns about long-term consequences of MIS-C, the data collected on these patients to date have shown most will recover fully. Nemours is involved in several long-term MIS-C studies to assess long-term damage and other issues. This includes involvement in the National Institutes of Health (NIH) COVID MUSIC, RECOVER and National COVID Cohort Collaborative (N3C) studies.  

"So far, the data have been very reassuring, very few of them have long-term symptoms," Thacker said.

Of the patients who do have long-term issues, most of these are "brain-fog" and confusion issues, similar to a common complaint in long-COVID patients. 

While major cardiac issues are not seen, Srivastava said data from N3C shows there might be issues later on in some of these patients, similar to what is being seen in some adult long-COVID patients. In adults who had cardiac involvement during the acute phase of their illness, COVID appears to damage the substrate of the cardiac muscle, which can cause the onset of cardiac arrythmias. This includes the onset of atrial fibrillation, including in young patients.  

"There is some indication of continued involvement of the heart in terms of electrical disturbances or arrhythmias, so we have added Holter monitor and screening questions for patients. We also give patients a checklist of things they should watch out for and to come back to us is any issues arise, because we continue to learn from this patient population," Srivastava explained. 

When can children with MIS-C return to school and sports?

Initially guidelines for myocarditis were followed for MIS-C patients. Those guidelines recommended keeping the child out of sports and other intense activities for three to six months. This has changed at some centers that have become more familiar with the condition.

"I think now that we have more experience with MIS-C, we realize that even though there is cardiac involvement, a lot of these children recover quickly. So if there is no cardiac involvement, we tell them they can return to being involved in sports and other activities. With patients who do have cardiac involvement, we have reduced the time we are asking them to not participate in sports actives from three to six months, down to about one to three months, depending on how severe they were," Thacker explained. 

She said they perform a stress test in these children and sometimes an MRI to assess the inflammation. But overall, she said they have become much more lenient on allowing kids to get back into sports. 
 

Dave Fornell is a digital editor with Cardiovascular Business and Radiology Business magazines. He has been covering healthcare for more than 16 years.

Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com

Around the web

Ron Blankstein, MD, professor of radiology, Harvard Medical School, explains the use of artificial intelligence to detect heart disease in non-cardiac CT exams.

Eleven medical societies have signed on to a consensus statement aimed at standardizing imaging for suspected cardiovascular infections.

Kate Hanneman, MD, explains why many vendors and hospitals want to lower radiology's impact on the environment. "Taking steps to reduce the carbon footprint in healthcare isn’t just an opportunity," she said. "It’s also a responsibility."