Similarities and differences between the immunopathogenesis of COVID-19–related pediatric multisystem inflammatory syndrome and Kawasaki disease
Ana Esteve‐Solé, Jordi Antón, Rosa Maria Pino-Ramirez, Judith Sánchez-Manubens, Victòria Fumadó, Clàudia Fortuny, María Ríos-Barnés, Joan Sánchez-de-Toledo, Mònica Girona‐Alarcón, Juan Manuel Mosquera, Sílvia Ricart, Cristian Launes, Mariona Fernández de Sevilla, Cristina Jou, Carmen Muñoz‐Almagro, Eva González‐Roca, Andrea Vergara, Jorge Carrillo, Manel Juan, Daniel Cuadras, Antoni Noguera‐Julián, Iolanda Jordán, Laia Alsina
Abstract
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.