Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2

Abstract

BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. METHODS. We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. RESULTS. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. CONCLUSION. Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.

Why COVID-19 is less frequent and severe in children: a narrative review

“…Viral cycle thresholds (Cts) and burr cells on blood smears also differentiated between patients with severe COVID-19 and MIS-C. The high Cts associated with MIS-C support a postinfectious etiology phenomenon that has previously been postulated but not demonstrated [18,82]. However, children with MIS-C have no higher IL-10 level, and this may be due to their higher lymphocyte counts hypothetically.…”

“…The recent reports from European countries and the US followed by growing universal reports support the emergence of this novel phenomenon [18]. The clinical presentations of this entity are variable and include persistent fever, severe illness, and involvement of two or more organ systems, in combination with laboratory evidence of both inflammation and SARS-CoV-2 infection.…”

“…The clinical presentations of this entity are variable and include persistent fever, severe illness, and involvement of two or more organ systems, in combination with laboratory evidence of both inflammation and SARS-CoV-2 infection. However, some presentations of MIS-C resemble Kawasaki disease (KD), toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome [18,19]. Of the 191 potential cases reported across 191 hospitals in New York State, 95 patients were classified as confirmed MIS-C.…”

“…ARDS is characterized by hypoxemic respiratory failure with bilateral lung infiltrates often necessitating invasive respiratory support. In contrast, this situation occurs less frequently in pediatric patients [18,19]. In a systematic review of 7480 pediatric patients with confirmed COVID-19, only 2% were severe (e.g., dyspnea, central cyanosis, and hypoxemia), and 0.7% were critical (e.g., ARDS, respiratory failure, and shock) [20].…”

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

“…Reports of children hospitalized with COVID-19 suggest similar clinical inflammatory profiles, including mild to moderate elevations of CRP, ferritin, PCT, and reduced ALC [30][31][32] . However, how these soluble inflammatory markers relate to cellular immune perturbations is not known, as clinical laboratory tests do not include cellular measures of immune activation and dysfunction.…”