A US Centers for Disease Control and Prevention (CDC)-led study identifies three clusters of post-COVID multisystem inflammatory syndrome in children (MIS-C) based on the frequency of respiratory symptoms, frequency of shock and cardiac complications, and clinical severity.
The researchers used US surveillance data from 2020 to 2022 to conduct a latent class analysis on 8,944 MIS-C patients from 55 public-health jurisdictions to classify different presentations and severity by clinical sign and symptoms, percentage of patients admitted to an intensive care unit (ICU), length of hospital and ICU stay, death rate, and relative frequency over time. The median patient age was 8.7 years, and 60.5% were boys.
The findings were published today in JAMA Network Open.
MIS-C is a rare but serious hyperinflammatory disease that occurs in children 2 to 6 weeks after COVID-19 infection. Common symptoms are fever, vomiting, diarrhea, abdominal pain, cardiac dysfunction, rash, and conjunctivitis.
"MIS-C case finding potentially captures a range of conditions because presentation shares clinical features with other conditions, including acute COVID-19, Kawasaki disease, and toxic shock syndrome, which may complicate timely diagnosis and treatment," the authors wrote. "Clinical severity (including the occurrence of shock, intensive care unit [ICU] admission, and death) can also vary substantially, and understanding of risk factors for severe disease remains incomplete."
More organs involved in shock and cardiac cluster
The team distinguished three MIS-C clusters characterized by: (1) frequent respiratory findings primarily affecting older children (respiratory cluster, 713 cases [8.0%]; median age, 12.7 years); (2) frequent shock and/or cardiac complications (shock and cardiac cluster, 3,359 cases [37.6%]; median age, 10.8 years); and (3) remaining cases (undifferentiated cluster, 4,872 cases [54.5%]; median age, 6.8 years).
Patients in cluster 1 had the highest rate of cough, shortness of breath, pneumonia, chest pain or tightness, and acute respiratory distress syndrome and a lower rate of rash and conjunctivitis. The proportion of patients with at least one underlying illness was 41.1%, compared with 31.2% in cluster 2 and 17.8% in cluster 3. Common comorbidities in this cluster were obesity (31.8% of children older than 2 years), noncardiac congenital malformations (9.7%), and chronic lung disease (9.4%).
The shock and cardiac group (cluster 2) had the highest rate of shock (69.0%) and cardiac involvement (94.4%) and other cardiac complications, such as myocarditis or pericarditis and cardiac dysfunction on echocardiography. These patients also had the highest median number of involved organ systems (5 systems); the highest rate of hematologic, gastrointestinal, kidney, and neurologic involvement; and slightly younger median age (10.8 years) than respiratory cluster patients.
Cluster 3 patients were younger (median age, 6.8 years) and had fewer underlying illnesses (82.2% reported no comorbidities). Organ-system involvement in this cluster overlapped with those in the first 2 clusters. Cluster 3 patients had a slightly higher rate of rash and conjunctivitis (65.5%) than those in cluster 2, and 3.4% met the clinical criteria for Kawasaki disease, compared with 0 in cluster 1 and 2.0% in cluster 2.
Death rate highest in respiratory cluster
The proportion of MIS-C patients admitted to an ICU was highest for the shock and cardiac cluster (82.3%), followed by the respiratory cluster (49.5%) and undifferentiated cluster (33.0%). The crude case-fatality ratios were higher in the respiratory cluster (4.6%) and shock and cardiac cluster (1.0%) than in the undifferentiated cluster (0.1%), with nearly all deaths (67 of 70 [95.7%]) occurring in the first 2 clusters.
MIS-C remains a public health concern that is likely to accompany surges in SARS-CoV-2 activity, as highlighted by relative increases in case counts during late 2023 compared with prior months.
Among patients with data on length of stay, 129 of 632 hospitalizations (20.4%) and 54 of 281 ICU stays (19.2%) in the respiratory cluster were 10 or more days, compared with 708 of 3,085 (22.9%) and 157 of 2,052 (7.7%), respectively, in the shock and cardiac cluster and 293 of 4,467 (6.6%) and 19 of 1,220 (1.6%), respectively, in the undifferentiated cluster.
The percentage of cases in both the respiratory cluster and the shock and cardiac cluster declined after the 2022 emergence of the Omicron variant in the United States.
"MIS-C remains a public health concern that is likely to accompany surges in SARS-CoV-2 activity, as highlighted by relative increases in case counts during late 2023 compared with prior months," the authors wrote.
"With additional validation, use of MIS-C phenotypic clusters in public health and clinical settings may be helpful in refining surveillance case definitions, contributing to our understanding of MIS-C pathophysiology, and assisting with recognizing the varied clinical presentations of MIS-C," they concluded.