ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.
Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Systemic Inflammatory Response Syndrome/pathology , Autoantibodies/blood , Betacoronavirus/isolation & purification , COVID-19 , Child , Child, Preschool , Coronavirus Infections/complications , Coronavirus Infections/virology , Cytokines/metabolism , Female , Humans , Immunity, Humoral , Infant , Male , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/pathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Principal Component Analysis , Proteome/analysis , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismSubject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Host-Pathogen Interactions/immunology , Pneumonia, Viral/immunology , Systemic Inflammatory Response Syndrome/immunology , Age Factors , Aged , COVID-19 , Child , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/virologyABSTRACT
Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.