Multisystem inflammatory syndrome in children: an evolving understanding of a syndrome amid the inflammatory continuum.

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory and immunosuppressed condition affecting children exposed to COVID-19. MIS-C has been associated with an over-exaggerated innate and adaptive immune response characterized by a 'selective' cytokine production and T cell suppression. As COVID-19 information has evolved, the knowledge and field surrounding MIS-C is ever evolving. Thus, a comprehensive clinical review that concisely presents current literature findings regarding common clinical presentations and comparisons with similar conditions, associations with the COVID-19 vaccine effects and relevant epigenetic markers and evaluates treatment and long-term outcomes to help guide future studies is needed and provided.

COVID-19 disease and immune dysregulation.

The SARS-CoV-2 virus has complex and divergent immune alterations in differing hosts and over disease evolution. Much of the nuanced COVID-19 disease immune dysregulation was originally dominated by innate cytokine changes, which has since been replaced with a more complex picture of innate and adaptive changes characterized by simultaneous hyperinflammatory and immunosuppressive phenomena in effector cells. These intricacies are summarized in this review as well as potential relevance from acute infection to a multisystem inflammatory syndrome commonly seen in children. Additional consideration is made for the influence of variant to variant host cellular changes and the impact of potential vaccination upon these phenotypes. Finally, therapeutic benefit for immune alterations are discussed.

MIS-C related to SARS-CoV-2 infection: a narrative review of presentation, differential diagnosis, and management.

Multisystem Inflammatory Syndrome in Children (MIS-C), a rare condition, has been reported approximately 2-4 weeks after the onset of COVID-19 in children and adolescents, causing inflammation in multiple systems, including cardiovascular and respiratory, digestive, and central nervous systems. This condition is also known as hyperinflammatory shock, Kawasaki-like disease, and Pediatric Inflammatory Multisystem Syndrome (PIMS). The signs and symptoms include but are not limited to fever, rash, peripheral edema, gastrointestinal symptoms, conjunctivitis, and shock. Thirty-eight studies met our criteria, with a total of 5822 patients. The most affected population was between 5-18 years of age. We noted that MIS-C presented with a wide range of signs and symptoms that overlap with Kawasaki Disease, including high fever, sore throat, malaise, tachypnea, tachycardia, conjunctival injection, mucosal edema, cardiac involvement, and gastrointestinal symptoms. It causes an increase in IL-17A, IL-6, and arterial damage, a distinct difference from Kawasaki disease. The laboratory findings in MIS-C showed an increase in inflammatory markers like CRP, ESR, ferritin, leukocytes, and TNF-α. WHO stated that 23% of affected children with MIS-C had underlying conditions like chronic lung diseases, cardiovascular disease, and immunosuppression. In most affected children, aspirin and IVIG were successful, which resulted in a decrease in the inflammatory markers. We find that MIS-C is a rare, but potentially fatal pediatric complication, after COVID-19 infection. The aim of this article is to study the emerging relationship between COVID-19 and MIS-C in children and adolescents affected by this condition, to discuss the immunological mechanisms, and explore potential therapies.