✓ Multisystem inflammatory syndrome (MIS-C) and Covid-19: what we know so far

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One year after the outbreak of the Covid-19 pandemic, we understood that the disease generally manifests itself in a milder way in children. However, since last spring in Europe there have been a few cases of a new inflammatory syndrome affecting children following theSars-Cov-2 infection. This complication related to Covid-19, called Pediatric Multisystem Inflammatory Syndrome (MIS-C), is making pediatricians and parents worried, especially since the recorded cases seem to be increasing.

It was initially thought to be Kawasaki disease due to some very similar symptoms such as fever, conjunctivitis and skin rashes, but a few months ago a study by the Bambino Gesù Pediatric Hospital of the city and the Karolinska Institutet in Stockholm made it clear that it is of a new syndrome, renamed precisely MIS-C (Multisystem Inflammatory Syndrome in Children).

This complication, though rare, can be really dangerous for children, so much so that the hospitalization it is absolutely necessary. Thanks to the help of Professor Gabrielle Simonini, pediatrician and rheumatologist at the Meyer Hospital of the city, we try to understand what MIS-C is, how it manifests itself and what are the possible risks for children.

MIS-C, the strange post-Covid syndrome

The American Centers for Disease Control and Prevention (CDC) were among the first to define MIS-C, the pediatric multisystem inflammatory syndrome. It is a condition "in which different parts of the body can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Children with MIS-C may have fever and various symptoms, including abdominal (bowel) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes or a feeling of fatigue. "As Prof. Simonini points out later, "the main complication of MIS-C is the involvement of the heart, but every organ and system can be involved" and for this reason the speed of intervention is essential.

For the moment we know that many of the children with MIS-C they had previously contracted Sars-Cov-2 infection or had come into contact with positive people, however doctors and researchers are still trying to understand what the link between multisystem inflammatory syndrome and Covid-19 is.

MIS-C or PIMS-TS, different names for the same syndrome

There is currently no one-size-fits-all agreement on the name, so you may hear about this syndrome with different acronyms. For example, ECDC (European Center for Disease Prevention and Control) refers to the same syndrome with the acronym PIMS-TS (Pediatric multisystem inflammatory syndrome, temporally associated with SARS-CoV-2 infection) instead of MIS-C, but there is no difference.

Coronavirus and MIS-C: what is the link

A few months ago the Del Paesena Society of Pediatrics (SIP) had confirmed the correlation between Sars-Cov-2 and multisystem inflammatory syndrome following a study carried out by the SIP Rheumatology Study Group, arguing that MIS-C was probably "a very particular characteristic of the manifestation of Covid-19 in pediatric age". In fact, the study found that out of 53 children with MIS-C the 75% of them were positive for Covid.

According to the American CDC, however, although many children with MIS-C have been found to be affected by Covid-19, at the moment it is not yet possible to say with certainty what the cause of the disease is.

What we know so far is that in our country the number (fortunately very small) of children who manifest this immunological reaction is increasing as the spread of Covid-19 also increases.

"In this second epidemic wave and almost of systemic multi-inflammatory syndrome (MIS-C) in children have doubled. If from February to May we had registered 53, from September to today we already count 100 ", said in an interview the dr. , advisor to the SIP Rheumatology Study Group and author of the study published in the Del Paesen Journal of Pediatrics aimed at investigating the link between MIS-C and Covid-19. , again in the interview, he reassures families by claiming that although cases are on the rise, there is no reason to be alarmed.

In any case, it is worthwhile for mothers and fathers to be aware of how multisystem inflammatory syndrome manifests itself, especially because the speed of intervention is essential in these cases.

Also read: Covid-19 in children: it is less lethal and causes milder symptoms

How MIS-C manifests itself

Thanks to a document recently published by the Del Paesena Society of Pediatrics, we know that the multisystem inflammatory syndrome usually occurs after 3-6 weeks from Sars-Cov-2 infection and can be recognized by some symptoms that the child presents.

Prof. Simonini explains that "the typical signs of multisystem inflammatory syndrome are:

persistent fever;
tiredness;
less reactivity;
gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain);
conjunctivitis;
skin rashes;
difficulty in breathing.

These symptoms, in a child who has had Covid or has been in contact with someone positive, must alert the parent who will have to take the child directly to the hospital. "Only the doctors, through a series of analyzes and tests, they will be able to determine if it is actually MIS-C or if it is Kawasaki disease, another rare syndrome that presents with symptoms very similar to those listed above.

MIS-C or Kawasaki Syndrome: the differences

The symptoms with which multisystem inflammatory syndrome occurs can be very similar to Kawasaki disease, but not only. As reported by the Del Paesena Society of Pediatrics "MIS-C shares common features to other inflammatory syndromes present in pediatric age and must be placed in differential diagnosis with Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, macrophage activation syndrome and myocarditis ".

"MIS-C - Simonini argues - differs from Kawasaki disease because:

affects older children, above 6 years of age;
it is often preceded by gastrointestinal symptoms ;
there is heart involvement with a myocarditis-like picture;
there is multi-organ involvement (cardiac, dermatological, neurological, renal, etc.);
it is often accompanied by shock ".

These are the main differences between MIS-C and Kawasaki Syndrome also reviewed by a recent study published in the scientific Circulation in which the authors compared the two pathologies. Also in another study, published in September by researchers at the Bambino Gesù Children's Hospital of the city and the Karolinska Institutet in Stockholm in the journal Cell, they insisted that they were precisely two different syndromes, despite some similarities.

Additionally, children with MIS-C are more likely to need the pediatric intensive care , of the support of the Del Paesena Society or of having heart failure, as claimed by the nucleoside pediatric.

If the child has one or more of the symptoms listed above and has previously had Covid-19 or has been in contact with a positive person, then it is advisable to go to the emergency room to underestimate the situation and understand whether or not it is MIS. -C.

Read also: Kawasaki syndrome and Covid-19: what we really know

If in doubt, go to the ER

As we have seen, this is a pathology that is anything but trivial, for this reason if you think that your child may have Multisystem Inflammatory Syndrome it is necessary to discuss with your pediatrician and in case go immediately to the emergency room. "Better to have done a round trip in hospital than to postpone the possible diagnosis of MIS-C - Simonini argues - also because, in the presence of suggestive signs, it is still a question that no doctor could handle over the phone".

Read also: Children in the emergency room, when to take them

Diagnosis of pediatric multisystem inflammatory syndrome

To make the diagnosis of MIS-C it is strictly necessary the collaboration between several specialists, therefore using a multidisciplinary approach.

"For the diagnosis to be made it is necessary:

demonstrate theSars-Cov-2 infection by nasopharyngeal swab, rapid antigen test or serological test, or demonstrate contact with a Covid-19 positive subject in the 4 weeks prior to the onset of symptoms;
cardiology visit with echocardiogram;
haematological tests".

After having carried out all the necessary examinations, the doctors will arrange for admission to Pediatrics or intensive care. The use of intensive care is essential if the child is in shock or there is heart or other organ compromise, as indicated by the Del Paesena Society of Pediatrics and the Guidelines of the Swiss Society of Intensive Medicine. "Unfortunately, the use of intensive care is not a risk in the case of children with MIS-C, but evidence - explains Simonini - more than half of the young patients who suffer from this syndrome at least in the first 48 hours are managed in the wards of intensive care". In most cases, with the right treatment, pediatric multisystem inflammatory syndrome resolves completely.

As with diagnosis, a multidisciplinary approach involving multiple experts is also required to treat and cure pediatric multisystem inflammatory syndrome.

Treatment of MIS-C

For the treatment of MIS-C, the Del Paesena Society of Pediatrics recommends the use of:

new generation immunomodulatory therapies (if the severity of the situation allows it);
intravenous immunoglobulins;
high-dose cortisone therapies.

Fortunately the incidence of MIS-C is low since it is still a rare syndrome and at the moment no deaths have been recorded in our country following MIS-C, but the importance of follow-up should not be underestimated.

MIS-C and possible permanent damage

As reported in the document of the Paesena Society of Pediatrics, in Italy so far no deaths have been recorded, "but a small percentage of patients had remote cardiological outcomes". The multisystem inflammatory syndrome could in fact also cause permanent damage in children, especially at the level of myocardium.

As Prof. Simonini also recalls, however, at the moment there is insufficient scientific evidence in this sense as there is a lack of long-term data, it is therefore not yet certain to know whether subjects who have suffered from MIS-C may or may not present permanent results. organ at a distance. "Precisely for this reason it is necessary plan a follow-up with subsequent checks in order to assess the presence or absence of any remote outcomes, initially not known or evident.

Sources used:

Advice from Professor Gabriele Simonini, pediatrician and rheumatologist at the Meyer Hospital in the city
MIS-C and Covid, Centers for Disease Control and Prevention
Multidisciplinary approach to the Covid-19 related multisystem inflammatory syndrome, Del Paesena Society of Pediatrics
Syndrome inflammatoire multisystemique de l'enfant, Guidelines of the Swiss Society of Intensive Care Medicine
Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic, Circulation, 2022
Pediatric inflammatory multisystem syndrome temporally associated with COVID-19: a spectrum of diseases with many names, Canadian Medical Association Journal, 2022
The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19, Cell, 2022
Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Del Paesen Society of Pediatrics, Del Paesen Journal of pediatrics, 2022

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