COVID-19, Autoantibodies, and Multisystem Inflammatory Syndrome in Children

February 23, 2021

Throughout the pandemic, cases have been reported of children experiencing a hyper-inflammatory response after a COVID-19 infection (1, 2). What was first described as a cluster of intense symptoms, has since come to be known as Multisystem Inflammatory Syndrome in Children (MIS-C). 

The pool of data around SARS-CoV-2 infection and MIS-C is still small, and a lack of consistency in clinical presentations of MIS-C makes it easy for clinicians to misdiagnose symptoms for other conditions where hyper inflammation is prevalent, like Kawasaki disease, toxic shock syndrome, and macrophage-activation syndrome (MAS). Due to the general ambiguity around MIS-C’s cause and development, as well as its mechanisms for tissue damage, the CDC and WHO have constructed different clinical criteria for the diagnosis of MIS-C (3).

The American Academy of Pediatrics (AAP) recently published the results of an international survey detailing MIS-C cases from April-June 2020. Data was provided from 33 hospitals and included 183 pediatric patients ages 1.2 months to 18 years. In the clinical presentations of MIS-C, all patients presented with a fever (>100.4 F), and over 60% had gastrointestinal symptoms. The second most common symptom was cardiovascular. These findings coincide with previously published reports and classification criteria for MIS-C; other common clinical manifestations include dermatologic/ mucocutaneous symptoms, cardiovascular symptoms, respiratory symptoms, and neurologic symptoms (4). Examples can include rash, swelling of hands and/or feet, change to the oral mucosa, pink eye, and swollen lymph nodes. It is unknown why a hyperimmune response occurs, and why autoantibodies against endothelial, gastrointestinal, and immune cells are produced. One study conducted by the Icahn School of Medicine found that MIS-C may share some pathophysiology with autoimmune disease. 
114 of the 183 patients included in the AAP survey tested positive for current or recent SARS-CoV-2 infection (3). Patients who did not test positive for COVID but presented symptoms concurrent to MIS-C may have experienced a COVID-19 exposure 2-6 weeks prior to the onset of symptoms (4). 

Continued research studying this occurrence will help to shed light on the long-standing damage this hyperimmune response may have on the body. Additionally, as criteria for clinical diagnosis is standardized, children experiencing MIS-C can have more immediate access to tailored therapies and treatment, to mitigate the often severe symptoms that accompany MIS-C.