Abstract
Globally, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared to have a milder clinical course in children compared to adults. As severe forms of COVID-19 in adults included an aberrant systemic immune response, children with chronic systemic inflammatory diseases were cautiously followed. No evidence for a specific susceptibility was identified in this pediatric population. European and US Pediatricians started to notice cases of myocarditis, sharing some features with toxic shock syndrome, Kawasaki disease, and macrophage activation syndrome in otherwise healthy patients. Multisystem Inflammatory Syndrome in Children (MIS-C) and Pediatric Inflammatory Multisystem Syndrome (PIMS) have designated this new entity in the US and Europe, respectively. The spectrum of severity ranged from standard hospitalization to pediatric intensive care unit management. Most patients had a clinical history of exposure to COVID-19 patients and/or SARS-COV2 biological diagnosis. Clinical presentations include fever, cardiac involvement, gastro-intestinal symptoms, mucocutaneous manifestations, hematological features, or other organ dysfunctions. The temporal association between the pandemic peaks and outbreaks of PIMS seems to be in favor of a post-infectious, immune-mediated mechanism. Thus, SARS-CoV2 can rarely be associated with severe systemic inflammatory manifestations in previously healthy children differently from adults highlighting the specific need for COVID-19 research in the pediatric population.
Highlights
Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) responsible for the Coronavirus disease 19 (COVID-19) pandemic has affected almost 50 million people leading to more than 1 million deaths around the world [1].Originally, children were thought of having milder disease compared to adults [2,3,4,5]
Different markers of inflammation are frequently elevated like D-dimer levels above 500 ng/mL, ferritin, and procalcitonin levels with no bacterial infection associated, and lactate dehydrogenase (LDH)
staphylococcal enterotoxins B (SEB) causes a massive inflammatory cascade which results in high levels of proinflammatory cytokines like IFN-γ, IL-2, IL-1, and TNFα [95]. Because this cytokine storm is quite similar to the one we see in Pediatric Inflammatory Multisystem Syndrome (PIMS) patients, as we discussed with high levels of TNFα, the authors suggested that PIMS is a consequence of a superantigen-like activity of the SARS-CoV-2 S protein [96]
Summary
Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) responsible for the Coronavirus disease 19 (COVID-19) pandemic has affected almost 50 million people leading to more than 1 million deaths around the world [1].Originally, children were thought of having milder disease compared to adults [2,3,4,5]. They commonly include persistent fever, mucocutaneous involvement (hands and feet oedema, conjunctivitis, swollen and cracked red lips, rash), cardiac dysfunction Biological Treatments On the other side of wide non-specific downregulation, a more precise approach is to target inflammatory cytokines to reduce hyper inflammation in PIMS patients.
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