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Multisystem Inflammatory Syndrome in Children – How “Immune” are Children to COVID-19?

Multisystem inflammatory syndrome in children has recently been described as a rare severe inflammatory condition affecting children and teenagers. Despite its potential link to SARS-CoV-2, its causality and clinicopathology are a matter of ongoing intensive investigation.

It has become widely accepted that the elderly are more likely to be severely hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19). In contrast, infected children often develop fewer and less severe symptoms, except for those with underlying conditions that compromise their health. However, if and to what extent children are less susceptible to the short-term or long-term effects of SARS-CoV-2 infection remains unclear.

Multisystem inflammatory syndrome in children (MIS-C), formerly known as pediatric multisystem inflammatory syndrome (PMIS), is a very rare and severe inflammatory condition affecting children and teenagers, which is potentially associated with SARS-CoV-2. MIS-C cases were first reported in April 2020 in the United Kingdom and in New York, the epicenter of the COVID-19 outbreak in North America [1,2].

The manifestation of MIS-C is similar to that of Kawasaki disease and toxic shock syndrome. Although its symptoms and their severity may vary among individuals, MIS-C commonly manifests as persistent high fever, fatigue, systemic inflammation, multiorgan dysfunction, rash, bloodshot eyes, cardiac dysfunction, and gastrointestinal symptoms such as abdominal pain, diarrhea, and vomiting [3]. However, unlike Kawasaki disease, MIS-C develops in children of any age and does not have a higher prevalence among Asians [1,2].

According to the clinical criteria of the Royal College of Paediatrics and Child Health (RCPCH) case definition, blood biomarkers of MIS-C include neutrophilia, lymphopenia, abnormal fibrinogen levels, low albumin, and high levels of D-dimers, C-reactive protein, troponin, and ferritin. Furthermore, imaging and echocardiography (ECG) findings indicating MIS-C include coronary artery abnormalities, myocarditis, and pericardial effusion [4].

Although the cause of MIS-C is yet to be identified, many – but not all – children who develop this condition have antibodies against SARS-CoV-2, indicating that their immune system has come into contact with the virus [5]. Numerous ongoing studies are investigating the relationship between MIS-C and SARS-CoV-2.

There is currently no specific treatment for the disease, and the treatment protocol for MIS-C is similar to that used to treat Kawasaki disease. Plasma transfusion and the administration of steroids and other anti-inflammatory agents improve the symptoms of those suffering from MIS-C, while severe cases may need to be treated in pediatric intensive care units (ICU) [4].

Interestingly, although COVID-19 is highly transmissible, MIS-C does not seem to be contagious. Despite the link between MIS-C and SARS-CoV-2, children develop MIS-C after they have cleared SARS-CoV-2 infection.

Due to the urgent need for the collection of standardized data regarding the clinical presentation, severity, outcomes, and epidemiology of this MIS-C, the World Health Organization (WHO) has established a database for the collection of standardized, anonymized clinical data, through the web-based WHO COVID-19 Clinical Data Platform.

Unfortunately, the current understanding of MIS-C pathophysiology and etiology remains extremely limited, largely due to the rarity of this life-threatening condition. The elucidation of MIS-C causality and clinicopathology, as well as the impact of SARS-CoV-2 on children and teenagers, are among the many questions currently being investigated.

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