Atypical Inflammatory Syndrome Triggered by SARS-CoV-2 in Infants with Down Syndrome

Malle, LouiseBastard, PaulMartin-Nalda, AndreaCarpenter, TayaBush, DouglasPatel, RoosheelColobran, RogerSoler-Palacin, PereCasanova, Jean-LaurentGans, MelissaRivière, Jacques GBogunovic, Dusan


Adults with Down syndrome who contract COVID-19 are at a much higher risk of developing COVID-19 pneumonia, but little is known about children with DS and the risks to their respiratory system. This case study looks at atypical multisystem inflammatory syndrome (MCI-C) that was triggered in two infants with DS who contracted COVID-19. These cases highlight that a severe atypical form of MIS-C may occur in children with DS.


While adults with Down syndrome (DS) are at increased risk of severe COVID-19 pneumonia, little is known about COVID-19 in children with DS. In children without DS, SARS-CoV-2 can rarely cause severe COVID-19 pneumonia, or an even rarer and more typically pediatric condition, multisystem inflammatory syndrome in children (MIS-C). Although the underlying mechanisms are still unknown, MIS-C is thought to be primarily immune-mediated. Here, we describe an atypical, severe form of MIS-C in two infant girls with DS who were hospitalized for over 4 months. Immunological evaluation revealed pronounced neutrophilia, B cell depletion, increased circulating IL-6 and IL-8, and elevated markers of immune activation ICAM1 and FcɣRI. Importantly, uninfected children with DS presented with similar but less stark immune features at steady state, possibly explaining risk of further uncontrolled inflammation following SARS-CoV-2 infection. Overall, a severe, atypical form of MIS-C may occur in children with DS.


COVID-19, Infections, Inflammation, MIS-C, Pneumonia, Syndrome, Systemic Inflammatory Response Syndrome