Adverse Events of Special Interest (AESI) and Related Risks: Multisystem Inflammatory Syndrome in Children

About AESI: Children and adolescents are just as susceptible to SARS-CoV-2 infection as adults, but they develop primary symptomatic COVID-19 infection at significantly lower rates and rarely develop severe illness. However, it has become clear that a small proportion of children develop a life-threatening hyperinflammatory condition four to six weeks after infection with primary COVID-19, known as Multisystem Inflammatory Syndrome in Children (MIS-C). Patients with MIS-C experience persistent fever, fatigue, and a variety of signs and symptoms (e.g., cardiac, gastrointestinal, renal, hematological, dermatological, neurological) involving multiple organs, in addition to elevated inflammatory markers.

A similar condition has also been reported since June 2020 as a rare complication of COVID-19 in adults (MIS-A), which can, however, be more complicated than in children. Adults with MIS-A may experience fever, low blood pressure, abdominal (intestinal) pain, vomiting, diarrhea, neck pain, rash, tightness/pain in the chest, and fatigue. MISA can be very serious, so it is important to seek medical attention as soon as possible. It requires hospitalization if, in the absence of severe respiratory disease, there is laboratory evidence of current or previous SARS-CoV-2 infection (within 12 weeks), severe extrapulmonary organ dysfunction (including thrombosis), or laboratory evidence of severe inflammation. There have been reports of patients with MIS-A up to the age of 50 and, compared with MIS-C, they are more likely to have underlying health problems and an identifiable background of respiratory disease.

Patients with MIS-A have clinical features that overlap markedly with MIS-C, although the severity of cardiac dysfunction, incidence of thrombosis, and mortality can be higher in the case of MIS-A.

Differential diagnoses for MIS-C/A include Kawasaki Disease (KD), Kawasaki Shock Syndrome (KSS), Hemophagocytic Lymphohistiocytosis (HLH), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), and a variety of other conditions, particularly those that cause myocarditis or hyperinflammation.

Diseases and other factors: According to the CDC, research on MIS-C and MIS-A, and on how they affect children and adults, is continuing. It is not known why some children and adults develop MIS-C or MIS-A and others do not, and whether children with certain health conditions are more likely to develop MIS-C.

Medications: There are no medications associated with MIS C/A. 

Vaccines in general: There have been reports, following vaccination with DTaP and DTaP-IPV/PRP-T, of cases of Kawasaki disease (KD), however it is unknown whether MIS-C/A could occur after routine immunization. 

COVID-19 vaccines: At present it is not known whether MIS-C/A could occur following SARS-CoV-2 vaccination, however this condition, as a potential adverse event following immunization (AEFI), needs to be explored. MIS-C is a novel syndrome in children, one that is temporally associated with SARS-CoV-2 infection, and has not previously been described in association with any vaccine. To date, MIS-A has not been reported in adult participants in SARSCoV-2 vaccine trials, and so far few children have been included in these trials.  

Sources:  

Black SB, Law B, Chen RT, et al. The critical role of background rates of possible adverse events in the assessment of COVID-19 vaccine safety. Vaccine, 39(19), 2021, 2712–2718. https://doi.org/10.1016/j.vaccine.2021.03.016

Multisystem Inflammatory Syndrome in Adults (MIS-A) | CDC. https://www.cdc.gov/mis-c/hcp/index.html