Multisystem Inflammatory Syndrome in Children (MIS-C): Longer Term Outcome Data

The rare condition can be devastating, but fortunately most kids recover.

Kids are back in school throughout the country now, and, in many locations, the Delta variant of coronavirus is highly prevalent – raising the possibility of an impending epidemic of covid cases among children too young to be vaccinated.

Overall, though, we know that kids do relatively well with COVID – including with the Delta variant, though recent reports – including this one from the CDC – remind us that most kids who become infected develop at least some symptoms.

MIS-C Symptoms

But early in the pandemic, a spike in cases of a strange inflammatory syndrome in children, usually (but not always) following a known COVID infection emerged. Multisystem Inflammatory Syndrome of Children or MIS-C is characterized universally by persistent fever, but has a slew of other organ system manifestations ranging from nausea, vomiting and diarrhea, to rash, and, concerningly, heart failure.

Of particular note is the finding of aneurysmal dilation in the coronary arteries and occasional “strawberry tongue” suggesting that MIS-C shares some pathophysiology with Kawasaki disease – a rare vasculitis in its own right that some have proposed is linked to an as-of-yet unidentified viral trigger.

MIS-C is, rare, fortunately, but can be devastating – carrying a 2% mortality rate. And though most kids survive, the long-term impacts are not yet clear.

But we got a bit more clarity this week with a letter from Patrick Davies and his team appearing in JAMA Pediatrics that provides us longer-term follow-up on a cohort of kids with MIS-C first identified in intensive care units in the UK.

Selected baseline lab values

We first learned about this cohort in an article from Lancet Child and Adolescent Health which characterized their hospital course. The 78 kids described were sick – with 90% presenting in shock. The massive levels of inflammation stand out here, with a median CRP on admission of 264, a d-dimer of 4032, and a ferritin of 1042.

Cardiac damage was evident on admission, with median troponin levels of 157. 28 of the 78 kids had coronary artery abnormalities on echo, mostly aneurysms. 

One thing to point out here is that only 22% of the kids in the cohort were PCR positive for SARS-CoV-2.

Cohort PCR Status

Of those PCR negative, 24 had serologic evidence of past infection, but many did not have serologies evaluated at all. There remains some concern that Kawasaki disease or other inflammatory childhood syndromes may be inadvertently included in the MIS-C pool. As we learn more, a more stringent case definition should emerge.

Treatment with steroids and IVIG was common, as was the use of more advanced biologic agents, and unfortunately 2 of the 78 kids died during the hospitalization.

Resolution of abonrmal echocardiography findings

The letter details what happens to the survivors, although data was only available on 68 kids. In broad strokes, the news is good. Of those 68, no additional deaths occurred, and only 2 required readmission to the ICU. And those inflammatory markers? Nearly entirely normalized. By the end of follow-up, 2 kids still had abnormal CRPs, 2 had abnormal d-dimers, and 1 had an abnormal troponin.

Encouragingly, 14 of the 19 kids with coronary artery aneurysms had resolved. In fact, of the 68 kids, only 6 had ongoing abnormalities on echocardiogram. Those 6 had pretty similar courses and labs as those who had complete resolution on echo, stymying attempts to identify risk factors for prolonged cardiac issues in MIS-C.

Good news so far, but I don’t think we have a full picture yet. In particular, the letter provides us no data on symptoms like shortness of breath or fatigue. No information on exercise tolerance, ability to attend school, or psychological sequela. If MIS-C does truly follow the pattern of Kawasaki disease, even longer term outcomes should be pretty good – but we just don’t know yet.

I’m certainly thankful we have this data – and encouraged that, once again, we can see that outcomes in kids with COVID are pretty good – even if they suffer a rare complication like MIS-C. I occasionally entertain the hypothetical scenario where COVID led to worse outcomes in kids than adults (like some flu strains do) and what a disaster that would be on a global scale. Fortunately, that thought experiment is just the stuff of late-night anxiety. The current pandemic doesn’t appear to work this way. But we might not be so lucky next time, highlighting the need to learn all we can this time around.

A version of this commentary first appeared on medscape.com.