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We know that COVID-19, the new coronavirus infection, affects the elderly and chronically ill more severely than anyone else. Yet, a new hyper-inflammatory syndrome—known as multi-system inflammatory syndrome in children (MIS-C) or paediatric multisystem inflammatory syndrome (PMIS)—is quickly becoming a cause for concern in children during the COVID-19 pandemic.

Calling on the global scientific community to collect information on this Kawasaki disease-like inflammatory syndrome, the World Health Organization (WHO) on 15 May 2020 said that while most children are likely to have a mild case of COVID-19 if they contract the infection, more and more cases of children being admitted to hospital with “acute illness accompanied by a hyperinflammatory syndrome, leading to multiorgan failure and shock” are also coming to light. 

Indeed, 18 out of 100 children admitted with COVID-19 in a Mumbai hospital in July 2020 had the following symptoms of PMIS:

MIS-C has been linked to poorer outcomes in children who have (or have had) COVID-19 infection. The syndrome can affect the blood vessels and multiple body systems like the cardiovascular system, digestive system, respiratory system, mucocutaneous membranes (skin and mucous membranes) and haematological (blood) system.

For now, doctors are treating children admitted with this syndrome with intravenous immune globulin, glucocorticoids, interleukin-6 (IL-6) inhibitors like tocilizumab and siltuximab or 1RA inhibitors like anakinra. Many children with this syndrome need critical care in the intensive care unit, and a fraction may also need oxygen support through a ventilator or ECMO (extracorporeal membrane oxygenation).

MIS-C is a serious complication of COVID-19 infection in children—it can be fatal if left untreated. Here’s what you need to know about MIS-C:

  1. Symptoms of paediatric multisystem inflammatory syndrome
  2. What causes multi-system inflammatory syndrome in children?
  3. Diagnosis of paediatric multisystem inflammatory syndrome
  4. Treatment of multi-system inflammatory syndrome in children
  5. Prevention of paediatric multisystem inflammatory syndrome
  6. Takeaways
  7. Doctors for Multi-system Inflammatory Syndrome in Children

Researchers are still trying to understand this syndrome that causes inflammation in the blood vessels (vasculitis), heart, brain and kidneys in children.

Indeed, the WHO and US Centers for Disease Control and Prevention among other health agencies are actively collecting information on this syndrome. They have managed to glean some of its symptoms from the cases reported so far.

In children who have tested positive for COVID-19 (either active or past infection) and have increased markers of inflammation as confirmed by laboratory tests, these symptoms include:

  • Body temperature over 38 degrees Celsius for more than one day
  • Tiredness
  • Vomiting
  • Diarrhoea
  • Stomach pain
  • Neck pain (could be due to cervical lymphadenopathy)
  • Skin rash
  • Extremely red or bloodshot eyes
  • Lips and tongue may become red or swollen
  • Hands and/or feet become swollen and red

The more serious signs of multi-system inflammatory syndrome in children or paediatric multi-system inflammatory syndrome include:

  • Difficulty breathing
  • The child is unable to wake up and stay awake
  • Persistent feeling of pressure or pain in the chest
  • Confusion: it is important to note if there has been a change in behaviour or ability to understand things suddenly.
  • Lips or face turning blue is a sign that the child needs urgent medical attention
  • Unbearable stomach pain

If you notice any of these signs in a child sick with COVID-19, call a COVID-19 ambulance or take him or her to the hospital immediately.

The WHO in May called on the global medical community to share their findings to enable a faster and deeper understanding of the syndrome. According to the WHO’s scientific briefing, a combination of these signs could point to this condition in children aged 0-19:

  • Confirmed COVID-19 (it may be a past infection) but no other infection such as bacterial sepsis
  • Fever up to three days
  • Rash
  • Conjunctivitis in both eyes, but without pus
  • Inflammation in the skin and mucous membranes of the mouth, hands or feet
  • Hypotension or low blood pressure
  • Shock
  • Signs of heart problems like myocardial dysfunction, pericarditis, valvulitis or coronary abnormalities
  • Coagulopathy: a disorder in which blood clots take longer to form
  • Acute or sudden-onset gastrointestinal problems such as diarrhoea, vomiting or abdominal pain

The exact cause of multi-system inflammatory syndrome in children or paediatric multi-system inflammatory syndrome (PMIS) isn’t known. However, researchers in the US have reported that the surge in cases of PMIS coincided with a drop in COVID-19 cases—more research is needed to understand if this is in any way relevant to the prevention or treatment of this syndrome.

PMIS is mostly seen in children over five years of age who have COVID-19, have recovered from COVID-19 or were in close contact with someone who was later diagnosed with COVID-19.

Researchers are also looking into the role of pre-existing or underlying conditions in the development of PMIS in children after COVID-19. However, the evidence available so far suggests that PMIS can also affect previously healthy children.

More often than not, doctors are finding signs of inflammation in multiple systems as a result of PMIS with the involvement of the cardiovascular system, with aneurysm (inflammation/bulge) in the cardiac artery, being the most common—which is why doctors may recommend an echocardiogram for a child suspected to have PMIS.

Tests are important to find out all we can about paediatric multisystem inflammatory syndrome (PMIS) right now. Doctors may recommend the following tests to make a diagnosis of PMIS:

  • COVID-19 test: The first thing doctors will need to know to diagnose this condition is if the child has COVID-19, has had COVID-19 in the past or was in touch with someone who was later diagnosed with this new coronavirus infection. For this, doctors will depend on laboratory tests like RT-PCR (for active infection) and COVID-19 ELISA antibody tests (for past infection).
  • Tests for inflammation: Next, they will do blood tests to look for elevated markers of inflammation such as ESR (ESR test), C-reactive protein, or procalcitonin (procalcitonin test).
    Erythrocytes sedimentation rate (ESR) is the speed with which a patient’s red blood cells settle down at the bottom of a test-tube; a faster rate indicates inflammation in the body.
    The liver makes C-reactive protein in response to inflammation in the body—this, too, can be measured in the blood through the C-reactive protein test.
    Procalcitonin is a type of protein—elevated levels of this protein can indicate organ dysfunction.
  • Abdominal ultrasound: Doctors may recommend an ultrasound to get a good look at the organs in the abdominal cavity, including the kidneys and intestines.
  • Heart exam: An echocardiogram is a kind of heart ultrasound that can help doctors see if there is any inflammation in the heart—involvement of the heart and blood vessels is seen in most children with this syndrome. Doctors would also recommend a chest X-ray.
  • Other tests: Doctors may also recommend other tests for the heart such as the troponin-T test (typically used to check if someone has had a heart attack) and NT-proBNP test.
  • Blood-related problems: Doctors may look for anaemia, lymphocytopenia (low levels of white blood cells in the body), neutrophilia (the presence of excess neutrophils, a type of white blood cells) and elevated d-Dimers—a product of broken-down blood clots in the body. (Read more: D-Dimer test)

Read more: Intensive care for severely ill COVID-19 patients

Data published in The New England Journal of Medicine (NEJM) on 29 June 2020 showed that 80% of patients with this syndrome had to be admitted to ICU. Additionally, 20% of patients had to be given oxygen therapy through invasive mechanical ventilation while another 17% got non-invasive mechanical ventilation and 4% got ECMO—an elaborate procedure in which deoxygenated blood is taken out of the body, oxygenated in a machine and then pumped back into the body.

The article in NEJM was documenting the cases of 186 patients admitted to US hospitals that are part of the Overcoming COVID-19 study and members of the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Intensive Care Influenza and Emerging Pathogens Subgroup, between 15 March 2020 and 20 May 2020.

This syndrome is treated in the hospital with medicines like immune globulin (given through IV), tocilizumab, siltuximab or anakinra to fight inflammation.

Some children with this syndrome may also need supplemental oxygen using mechanical ventilation or ECMO.

Children with active COVID-19 infection may also be given antiviral drugs or steroids.

Doctors may also give medicines and fluid therapy to treat and prevent any damage to the organs.

Read more: What is a cytokine storm?

As the cause of this syndrome in children is unknown, it is difficult to say how to prevent it. However, parents can take precautionary measures to prevent COVID-19 in children. These measures include, but are not limited to:

  • Teaching children the right way to wash their hands with soap and water. They should wash hands regularly and for at least 20 seconds each time.
  • Show them how to use a hand sanitizer with 60% or more alcohol when soap and water aren’t available.
  • Instruct children to avoid people who are coughing, sneezing or seem sick.
  • Show them how to practise social distancing, and what it means to stay at least six feet (two meters) away from other people.
  • Show them how to wear a cloth face cover when they are outside the house—school-going children should learn how to do this by themselves so they can put on their mask if it comes off. Teaching them how to handle the face cover only by the strings is also important.

As with a lot of other things about COVID-19, there are some things about the paediatric multisystem inflammatory syndrome that we just don’t know yet. For example, the cause—why PMIS affects some children and not others—is not known yet.

According to the World Health Organization, this syndrome shares characteristics with Kawasaki disease and toxic shock syndrome. (First reported in 1961, Kawasaki disease causes vasculitis or inflammation in blood vessels—especially the blood vessels of the heart—in children under five years of age. The prevalence varies hugely, from about two per 100,000 children in Israel to 308 per 100,000 children under five in Japan.) Unlike Kawasaki disease, though, this hyperinflammatory syndrome seems to be affecting children older than five years.

It is important to keep a lookout for the symptoms of the paediatric multisystem inflammatory syndrome if your child has COVID-19 or is recovering from it. The signs of an emergency include:

  • The child not waking up or having difficulty staying awake
  • The child’s lips or face turning blue
  • Extreme stomach pain
  • Breathing difficulties
  • Feeling of pressure or pain in the chest

It is also important to remember not to panic—most children who contract COVID-19 will have mild illness. In a fraction of cases where it does trigger a hyperinflammatory response, early diagnosis and treatment with anti-inflammatory drugs, oxygen, and medicines to prevent organ damage can help improve the situation.

Dr. Arun R

Dr. Arun R

Infectious Disease
5 Years of Experience

Dr. Neha Gupta

Dr. Neha Gupta

Infectious Disease
16 Years of Experience

Dr. Lalit Shishara

Dr. Lalit Shishara

Infectious Disease
8 Years of Experience

Dr. Alok Mishra

Dr. Alok Mishra

Infectious Disease
5 Years of Experience

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References

  1. Feldstein LR, Rose EB, Patel MM, Randolph AG, the Overcoming COVID-19 Investigators and the CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. The New England Journal of Medicine, 29 June 2020; 383(4): 334-346.
  2. Centres for Disease Control and Prevention [Internet]. Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). CDC, U.S. Department of Health & Human Services.
  3. Centres for Disease Control and Prevention [Internet]. For parents: Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. CDC, U.S. Department of Health & Human Services.
  4. World Health Organization, Geneva [Internet]. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 Scientific Brief, 15 May 2020.
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