Two new studies detail unique signs and symptoms in US children and teens with the rare but severe coronavirus-related multisystem inflammatory syndrome in children (MIS-C), helping distinguish it from severe COVID-19.
Age, race, organ system involvement
The first study, a case series led by researchers from the US Centers for Disease Control and Prevention published yesterday in JAMA, was a comparison of 539 patients younger than 21 years with MIS-C and 577 with severe COVID-19 at 66 hospitals in 31 states from Mar 15 to Oct 31, 2020. Patients with MIS-C had fever, inflammation, and multisystem involvement, while those with severe COVID-19 had severe organ system involvement.
The scientists found that MIS-C patients were more likely than those severely ill with coronavirus to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4%) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8%) and have serious cardiovascular involvement (56.0% vs 8.8%; RD, 47.2%), cardiovascular but no respiratory involvement (10.6% vs 2.9%; RD, 7.7%), and mucocutaneous (involving both the mucous membrane and skin) with no cardiovascular involvement (7.1% vs 2.3%; RD, 4.8%).
Patients with severe COVID-19 more often had respiratory but no cardiovascular involvement or had hematologic, neurologic, or gastrointestinal involvement but no cardiovascular, respiratory, or mucocutaneous involvement.
Compared with their counterparts, MIS-C patients were more likely to have no underlying medical conditions (69.% vs 37.9%). Signs and symptoms were comparable between the two groups of patients, except for mucocutaneous involvement (66.8% vs 10.2%).
Compared with patients with severe COVID-19, MIS-C patients had higher neutrophil-to-lymphocyte ratios, indicating infection or distress; higher C-reactive protein concentrations, indicating inflammation; and lower platelet counts, indicating abnormal immune response.
Of the 539 patients with MIS-C, 398 (73.8%) were admitted to an intensive care unit (ICU), compared with 253 of 577 (43.8%) of those with severe COVID-19. Ten MIS-C patients (1.9%) and 8 with severe COVID-19 (1.4%) died in the hospital.
Among the MIS-C patients with reduced left-ventricular systolic function (172 of 503 [34.2%]) and coronary artery aneurysm (57/424 [13.4%]), about 91.0% and 79.1%, respectively, recovered by 30 days.
While most MIS-C patients had severe respiratory involvement, some may also have had COVID-19 with cardiovascular involvement, as has been reported in adult patients, rather than MIS-C, according to the researchers. "Misclassification of these patients might impede optimal treatment if the pathogenesis differs between MIS-C and COVID-19; however, it is possible that anti-inflammatory agents like steroids could be beneficial for both," they wrote.
The authors said that the study findings can help clinicians distinguish MIS-C from severe COVID-19 to inform efforts and improve outcomes in affected children and teens by refining the case definition and boosting specificity for use of diagnostic testing, immune treatments, and follow-up.
Lingering ears, nose, throat manifestations
A research letter published today in JAMA Otolaryngology Head & Neck Surgery, meanwhile, describes a single-center observational cohort study of otolaryngologic (ears, nose, and throat) signs and symptoms in 50 children younger than 18 years hospitalized in the United Kingdom for pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or PIMS-TS, which is defined similarly to MIS-C in the United States.
From Apr 1 to Jun 22, 2020, a team led by physicians from the Great Ormond Street Hospital for Children in London studied 50 children with PIMS-TS, of whom 19 (38%) had a follow-up visit for lingering ear, nose, and throat problems with an otolaryngologist.
The most common otolaryngologic signs and symptoms were dysphonia (difficulty speaking), dysphagia (trouble swallowing), anosmia (loss of smell), or hyposmia (reduced ability to smell). Fifteen of 50 patients (30%) had significant and persistent otolaryngologic involvement at follow-up, and 4 (8%) had it during their illness.
Thirty-eight of the 50 patients (76%) required ICU care, and 18 (36%) needed mechanical ventilation.
The authors said that several explanations for adult otolaryngologic manifestations may also apply to children. "Dysphonia, for instance, may be caused by laryngeal involvement of the airway inflammatory process leading to vocal fold edema or inflammation," they wrote.
Further research is needed to identify factors such as race or a need for intubation that may increase the risk of prolonged otolaryngologic signs and symptoms, according to the researchers. "Because the long-term sequelae of this disease are unknown, it is prudent for children with a history of PIMS-TS to be reevaluated by the infectious diseases team within 12 months and referred to otolaryngology for any persistent symptoms," they wrote.