This Dangerous Covid-19 Syndrome Hits Children and Adults
Mysterious Covid-19 conditions
For some people, Covid-19 triggers symptoms that are dangerous and life-threatening—and there’s still a lot about the disease experts don’t fully understand. One example: There’s a bizarre response in some cases of Covid-19 where the entire body comes under attack. Called multi-system inflammatory syndrome (MIS), this rare condition sets off severe inflammation in different parts of the body and can lead to critical health problems, long-term complications, and even death. Doctors have mainly documented MIS in children and teens (where it’s designated as MIS-C); there have been more than 1,000 cases and 20 deaths so far. However, a recent study published by the Centers for Disease Control and Prevention (CDC) in Morbidity and Mortality Weekly Report (MMWR), revealed there’s also MIS-A: Adults are susceptible, too.
To understand MIS, first you have to understand how it’s linked to the Covid-19 pandemic, says Seuli Brill, MD, an associate professor of clinical medicine and section chief of combined internal medicine and pediatrics at The Ohio State University Wexner Medical Center. While scientists still don’t know exactly what causes MIS, it’s been linked to the virus that causes Covid-19, officially known as SARS-CoV-2.
“MIS and Covid-19 are not the same illness, they are two distinct manifestations of SARS–CoV-2 infection,” Dr. Brill says. “Patients with severe Covid-19 disease causing acute respiratory distress syndrome have different antibody and inflammatory responses than patients with MIS.” Different illnesses mean that there are different treatments for each disease.
However, MIS typically develops two to four weeks after a Covid-19 infection, which means having Covid-19 is a major risk factor for MIS. Ninety-eight percent of pediatric patients with MIS tested positive for SARS CoV-2 and the remaining two percent were around someone with Covid-19, according to the CDC. Evidence of a Covid-19 infection (or exposure to an infected person) is required for a diagnosis of MIS.
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The link between Covid-19 and MIS-C and MIS-A
There may be a biological explanation for the link, says Rajeev Fernando, MD, an infectious disease expert based in Southampton, New York, and the only American doctor to go to Wuhan, China, to investigate Covid-19. “Many people think of Covid-19 as a respiratory virus which causes a cough, shortness of breath, and pneumonia, but it is actually a virus that can involve many systems, including cardiac dysfunction, neurological, and kidney syndromes,” he says.
How MIS starts
The key may be a membrane called the epithelium, which is found in the lungs, brain, heart kidney, and other organs. The epithelium contains protein receptors called ACE2 (angiotensin-converting enzyme 2); these receptors dice up large proteins into smaller ones that cells can use. The problem is that ACE2 receptors are also targeted by the novel coronavirus: “This is where SARS-CoV-2 binds to and causes clinical disease, inflaming these tissues which can cause problems throughout the body,” he says.
For instance, if the virus binds to the ACE2 receptors in the lungs, then you’ll experience respiratory symptoms. However, if the virus binds to the ACE2 receptors in the vascular blood vessels, you’ll experience heart-related symptoms, he says. “This is due to the inflammation of the blood vessels which also predisposes people to developing clots.”
The inflammation may explain why 78 percent of adults with Covid-19 have heart damage, according to a July study published in JAMA Cardiology. The virus can attack more than one system at a time, which may also explain the strange constellation of Covid-19 symptoms doctors have been seeing in patients. These include nausea, diarrhea, loss of smell or taste, kidney failure, and neurological problems, including stroke and Covid-19 brain fog. This is a newer syndrome where patients experience mental clouding for months.
Even after the virus subsides, inflammation may remain and some people continue to experience symptoms for weeks or months afterward. A small percentage of these people will go on to get MIS.
Symptoms of MIS-C and MIS-A
MIS usually comes on two to four weeks after someone has been infected with Covid-19. Symptoms in both children and adults include persistent fever, abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, muscle weakness, chest pain, shortness of breath, and feeling extra tired. Blood and other diagnostic tests will show high levels of inflammatory markers and dysfunction of multiple organ systems, Dr. Brill adds.
It can be challenging to diagnose MIS because it’s new, very rare, and is similar to better-known diseases such as Kawasaki’s disease and toxic shock syndrome, she says.
The symptoms are often quite severe and should be treated immediately. “This is not something that can be treated at home,” she says. “MIS is, by nature, characterized by severe illness, requiring hospitalization and often intensive care.”
MIS in children
Covid-19 is not nearly as severe in children as it is in adults which has led some people to believe it isn’t a concern for kids, says Joshua Rocker, MD, chief of the division at pediatric emergency medicine at Cohen Children’s Medical Center and assistant professor in the School of Medicine at Hofstra/Northwell. “It is true that they are more likely to have mild or no symptoms, but there is one major concern for children and that is MIS-C, as it causes a severe inflammatory response,” he says.
MIS-C is rare, affecting a small percentage of children who have had Covid-19. It can be serious, even deadly, but most children who were diagnosed with this condition have gotten better with medical care, he says.
MIS in adults
Many questions remain about MIS-C, but even less is known about the syndrome in adults, Dr. Brill says. At this time there are only a few dozen documented cases. To better understand how MIS affects adults, the CDC published the recent MMWR study. To be a part of the study, the patients had to have cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness while also testing positive for antibodies for SARS-CoV-2. This means they had a previous Covid-19 infection.
All but one of the patients were either Hispanic, African American, African, or Asian, according to the CDC. This may mean that race is a risk factor, although the researchers note it’s unclear whether that’s due to inequities in health care or some other reason. (Your blood type may be a risk factor for Covid-19.)
There were other commonalities. In a study of 16 patients, all showed evidence of cardiac effects and despite reporting minimal respiratory symptoms, 10 patients had a type of lung damage called “ground-glass opacities”; six had the buildup of fluid around the lungs known as pleural effusions. All patients had elevated markers of inflammation in their blood. (Note that ground-glass opacities are a very common finding in general, in Covid-19 and not just MIS.)
Of the 27 cases studied, 24 people survived. However, the researchers cautioned that it’s difficult to draw firm conclusions from this as all the cases were voluntarily reported and may not represent an accurate sample.
The best protection against MIS-C and MIS-A
This rare syndrome highlights a critical blindspot with the pandemic: We’re still learning how Covid-19 infections progress, whether or not people can be reinfected, and who is at risk for getting complications like MIS, Dr. Fernando says.
Doctors and researchers are working to find answers, but in the meantime, the key is to do your best to prevent transmission of the SARS-CoV-2 virus, he says. If you can avoid getting Covid-19, then you won’t have to worry about MIS.
“This virus continues to spread and it’s possible that the worst of the pandemic is still ahead, so it’s more important than ever to do those three critical things: Practice good hygiene, social distance, and wear your mask,” he says.
- Seuli Brill, MD, an associate professor of clinical medicine at The Ohio State University Wexner Medical Center and section chief of combined internal medicine and pediatrics
- Rajeev Fernando, MD, an infectious disease physician, director of the division of infectious diseases at Stony Brook Southampton Hospital in New York, and founder of CHIRAJ
- Joshua Rocker, MD, chief of the division at pediatric emergency medicine at Cohen Children's Medical Center and assistant professor in the School of Medicine at Hofstra/Northwell
- JAMA Cardiology: "Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)"
- Centers for Disease Control and Prevention: "Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States "
- Centers for Disease Control and Prevention: "Multisystem Inflammatory Syndrome"
- Centers for Disease Control and Prevention: "Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020"