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As a physician taking care of hospitalized Covid-19 patients, I had very nearly become immune to the sickening sensation provoked by new, invariably frightening information about this disease. But as a parent, when I saw the first reports of multisystem inflammatory syndrome in children, the pit in my stomach churned with new ferocity: “15 Children Are Hospitalized With Mysterious Illness Possibly Tied to Covid-19” read the headline in the New York Times.

All of a sudden, the facts I relied on to steady myself — children are less affected by coronavirus; when they have symptoms they are generally mild; schools were closed not for the sake of the children but for the vulnerable people they came into contact with — became irrelevant, vanished in a fog of mystery. Fear for my toddler son’s life threatened to swallow me.

“The oldest and strongest emotion of mankind is fear, and the oldest and strongest fear is fear of the unknown,” wrote H.P. Lovecraft, a legendary horror fiction writer. It was this emotion that drove his audiences back again and again to his stories, searching for more enigma, more fright.


Seeking to quell my fear with data, I read the early reports from Europe and from New York City: small numbers of children were very sick in a way that seemed different from other children infected with the coronavirus. The Centers for Disease Control and Prevention issued preliminary guidance about this new entity with a list of elements that had to be present: a positive coronavirus test or known exposure, fever, lab tests showing inflammation, and severe illness with multiple organ systems involved.

The more I read, the less mystery I saw. As I cared for more patients with Covid-19, the number growing into the hundreds, it became clear to me that this wasn’t new: It was Covid-19, the same disease I was treating in my adult patients.


Why were they trying to scare me with all this mystery talk?

I can’t tell you why the pediatricians making the initial reports didn’t realize this was the same illness, but I can tell you why I did: I’m perfectly positioned to identify the similarities. Since graduating from a combined internal medicine and pediatrics residency training program, my career path has been as a med-peds hospitalist, meaning I take care of hospitalized patients ranging from newborn babies to centenarians. During the pandemic, I have cared for adults with Covid-19 on hospital floors and in ICUs, some in a hospital unit where I helped pediatric hospitalists and trainees in pediatrics residency programs take care of adults with Covid-19.

Here’s what Covid-19 looks like using the common story of an adult woman who eventually needed to be hospitalized: It starts with a few days of cough, tiredness, and muscle aches followed by a fever, some nausea, belly pain, and diarrhea. About a week after she started feeling unwell, she begins to have trouble breathing, which is what brings her to the hospital. By the time I see her, her blood oxygen level is low and she needs to breathe supplemental oxygen delivered through a tube in her nose. Her blood shows high levels of markers of inflammation.

This is the sickest the average hospitalized patient gets.

Depending on her oxygen and inflammation levels, according to our hospital treatment protocol she would be given anti-inflammatory medications and begin improving. Those who aren’t sick enough to need these medications might get worse and subsequently need to get them, or get better without them and gradually improve until it is safe for them to leave the hospital. Some patients start getting better and then quickly get worse before our eyes.

The pattern of this disease became clear to me: a viral phase during which some people develop symptoms several days after exposure to the virus, and an inflammatory phase days to weeks after infectious symptoms appear (or don’t), that is often much worse and more dangerous. The latter process is what was named multisystem inflammatory syndrome in children (MIS-C).

The illness my adult patients have is highly variable. Some have no symptoms before becoming short of breath, and many never experience that. In addition to the typical symptoms of fever and shortness of breath, some have liver problems; others have rashes or Covid toes or red eyes or blood clots. Some are confused or delirious; others have kidney injury or heart problems or dangerously low blood pressure. The diverse symptoms reflect all of the systems the virus directly injures as well as those harmed by the inflammatory proteins the body produces to fight the virus. This list matches up exactly with the criteria for multisystem inflammatory syndrome in children.

Kids tend to have prominent gastrointestinal symptoms. They tend to have fewer respiratory symptoms (likely due to fewer of the cellular particles that facilitate viral entry into cells of the respiratory tract) and higher likelihood of low blood pressure, although this finding is strongly correlated with severe disease in adults as well. They tend to have decreased heart pumping function during Covid-19, drawing similarities with other pediatric inflammatory conditions. And the older the child, the more the disease resembles the inflammatory syndrome witnessed in adults.

Just because some of the features are more or less prominent across the age spectrum does not make Covid-19 and multisystem inflammatory syndrome in children separate disease entities. It means that children are physiologically different from adults, which we already knew.

Sepsis is the body’s overblown response to infection. It occurs when pneumonia, for example, ceases to be restricted to the lungs and when the whole body becomes affected — perhaps the bacteria have moved into the bloodstream, or perhaps the inflammation has caused the blood vessels to become leaky and the blood pressure has dropped in response.

Overproduction of the infection-fighting proteins known as cytokines generates what’s known as cytokine storm syndrome. It is the “sepsis” of coronavirus infection — the way this virus results in deadly illness. Multisystem inflammatory syndrome in children is a form of cytokine storm syndrome. To the extent that we understand Covid-19, we understand MIS-C.

It’s possible that pediatricians did not know what to make of this illness because adult physicians had not come up with a set of criteria for describing or classifying Covid-19 patients with cytokine storm syndrome — perhaps they were too busy treating them. Pediatricians are meticulous and detailed, and immediately jumped to codification and communication. Perhaps it’s an effect of the siloization of medicine, trying to put each disease into a category for specialization. This silo problem is one that doctors who train in medicine and pediatrics face and address every day.

H.P. Lovecraft also wrote, “The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents.” To me, the mercy is to be able to correlate the Covid-19 syndrome I’ve seen across the age spectrum. To me, multisystem inflammatory syndrome in children is not a mystery. And with the mystery removed, the headline becomes, “Children Continue to Have Low Rate of Severe Disease Associated with Coronavirus.” Multisystem inflammatory disease becomes a name for the disease that has to date killed more than 130,000 people in the United States and more than 525,000 worldwide, but has taken the lives of relatively few children. As with adults, however, they are disproportionately children of color.

I am grateful to the pediatricians for coming up with a descriptive name for the disease I’ve been treating in my adult patients.

Sharon Ostfeld-Johns is a physician, assistant professor of clinical pediatrics, and voluntary clinical instructor in internal medicine at Yale University School of Medicine.

  • Excellent article. Like you, I have a toddler and very worried about him contracting COVID19.

    Have you figured out a way to convince a toddler to wear a mask and social distance? If not, do you think it’s safe for toddlers to go to preschool?

  • Dr. Ostfeld-Johns,
    As a member of the NIH COVID-19 guidelines task force, Chair of the American College of Chest Physicians (CHEST) COVID-19 Task Force, and Chief Medical Officer of Sepsis Alliance, I could not agree more. In fact, I believe that you can back up and say that severe COVID-19, even without “cytokine storm” or “MSIS” is viral sepsis. Perhaps hypoxemia and/or diarrhea represent direct affects of viral tissue invasion. Anything else, including fever, chills, tachycardia, tachypnea represents inflammatory response. “Cytokine storm” and MSIS (I think I can remove the ” “, since pediatricians did, as you say make criteria for the diagnosis) are the septic shock of SARS CoV-2 infection. What is for now our sole antiviral agent, remdesivir, is most efficacious in those patients with organ dysfunction, but not shock, “cytokine storm”, or multiple organ dysfunction. In this way, viral sepsis due to SARS-CoV-2 is analogous to sepsis from any other cause. I appreciate your cogent analysis.

    And FYI, these are my personal opinions and not those of any organization that I may represent or be employed by.

  • This was my question couple months back when MIS-C was reported. As a pediatrician, I suspected MIS-C was similar to adults cytokines inflammatory storms. Thanks for sharing your frontline experience and thought.

  • Hi Alll,

    I am a System and Data Engineer and I looked at it as well early on and it only made since as well. I also had covid myself and can confirm the odd symptoms. I had such things as canker sores all over my tongue then the next day gone. The change of taste and loss of smell and the delirium basically in me it was like a manic ocd type thing but I do have Cardiomyopathy and a ICD (Pacemaker/Defibulator). There is something called “Stress Cardiomyopathy” and it is already being looked at by the CDC.

  • I have been thinking the same thing for a while. Wondering if people who already have auto immune inflammatory responses are more likely to have those areas affected by Covid-19. Say you have sinus issues already- would your symptoms of Covid-19 be more likely to be present in your sinuses rather than lungs. What accounts for all the varied symptoms in covid-19 patients and how is this impacted by a person’s inflammatory immune responses.

  • The entire quote is “The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of the infinity, and it was not meant that we should voyage far.”

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