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In early April, I discussed some reassuring data from the CDC on pediatric COVID-19 cases. The bottom line was that kids tend to have mild symptoms, a very low number have required hospitalization, and deaths have been extremely rare. That is still the case. In that post, however, I did raise the concern that there are likely many asymptomatic cases, or at least cases where mild symptoms fly below the radar, potentially allowing the spread of the virus to unsuspecting higher risk people.

On Wednesday, new research was published revealing that asymptomatic cases and the potential for silent spread to high risk individuals may be more of a concern than previously thought. Published in JAMA Network and Thorax, two papers reported that patients were asymptomatic in 40% and 80% of cases respectively. My hunch is that children are even more likely than adults to fall into this category, and although it isn’t the point of my post, I’ll put a plug in right here for masks and following guidelines for social distancing as much as possible.

While children are still extremely unlikely to develop serious disease when infected with the novel coronavirus, there has been a major development since my last post. On April 27th, the NHS sent out a letter warning British physicians to be on the lookout for children with a severe systemic inflammatory disease after 12 cases had been reported that shared a similar presentation of diffuse inflammation, abdominal symptoms, and cardiac involvement. Although not every case was proven to be associated with recent Sars-CoV-2 infection by positive confirmatory labs, several were, raising concern that it played a role.

My initial response to this was skepticism that the novel coronavirus was truly to blame. These early cases were being compared to conditions that, while not common, are well known pediatric diseases. I have taken care of a child or three with Toxic Shock Syndrome over the years, and many with Kawasaki Disease, which seemed to be the primary condition being used to illustrate how these children presented. Furthermore, since the pandemic began we have been on very high alert for new or unusual COVID-19 clinical presentations, and anecdotal reports have been prevalent. So I worried that we might be forcing a pattern into the clumpy randomness of medicine.

I’m a lot less skeptical now.

Two weeks after that initial warning went out in England, more data from Italy had emerged which helped to better-define this mysterious condition. France, Switzerland, and Spain were also reporting children affected by systemic inflammation that required hospitalization and intensive care. And by May 21, around 100 cases of what is now called Multisystem Inflammatory Syndrome in Children (MIS-C) had been reported in New York, with smaller numbers of cases popping up in several other states where there have been significant outbreaks of COVID-19.

More and more it appeared that the novel coronavirus was to blame, and that these weren’t just typical pediatric inflammatory conditions. While a decent percentage of these pediatric patients had negative PCR studies, which attempt to detect the presence of viral DNA and acute infection, most of them had positive antibody tests. Although we still weren’t looking at huge numbers of cases, a pattern was emerging.

To start, these patients skewed older than what is typical for Kawasaki Disease by a few years. And while Kawasaki is infamous for the degree of irritability it can cause, and for its ability to damage the heart when not appropriately treated, MIS-C was resulting in much more severe inflammation and injury. Most of the patients were 3-4 weeks out from coronavirus infection, when timing was known, and no other causes, such as an infection with a toxin-producing bacteria or an autoimmune condition such as JIA or Lupus, were being identified. Rather than direct damage from the virus, the severe multisystem inflammation appears to be related to an acquired immunity to it.

On May 14th, the CDC issued recommendations to report any cases meeting MIS-C criteria to local health departments:

Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)

  • An individual aged <21 years presenting with feveri, laboratory evidence of inflammationii, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
  • No alternative plausible diagnoses; AND
  • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms

iFever ≥38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
iiIncluding, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

Additional comments

  • Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
  • Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection

We still have a lot to learn about MIS-C. For example, is there something unique about these particular kids or is it just bad luck? Could there be a genetic predisposition? So far, it doesn’t appear that there are any specific health conditions that increase the risk, but cases have occurred a bit more frequently in boys, which fits the overall trend with COVID-19. What is the best treatment is also unclear. Many of these cases have been managed the same way that we treat Kawasaki Disease, but outcomes have been pretty good in those who weren’t. Simply put, we need more data, and now that this is a reportable disease we will likely get it.

Since the CDC advisory went out on the 14th, New York has reported another 70 cases. In the United States, there have been less than 300 cases spread across 26 states, with at least one death. Thankfully, this is still a very rare outcome and the vast majority of cases have ended with a full recovery. But if novel coronavirus infections among children were to increase, perhaps if schools or businesses are opened in an unsafe way, we will almost certainly see more MIS-C.

Parents and caregivers shouldn’t panic at every fever or complaint of tummy pain, but they should touch base with their child’s pediatrician or family doctor if they are ill appearing. If a child is experiencing difficulty breathing, chest pain, altered mental status, blue discoloration of the lips, or severe abdominal pain, they should be evaluated more urgently. Throw on a mask and don’t let fear of exposure to coronavirus delay appropriate medical care.

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Posted by Clay Jones

Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.