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Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

2021; Nature Portfolio; Volume: 40; Issue: 3 Linguagem: Inglês

10.1038/s41587-021-01037-9

1546-1696

Jennifer Loske, Jobst Röhmel, Soeren Lukassen, Sebastian Stricker, Vladimir Gonçalves Magalhães, Johannes Liebig, Robert Lorenz Chua, Loreen Thürmann, Marey Messingschlager, Anke Seegebarth, Bernd Timmermann, Sven Klages, Markus Ralser, Birgit Sawitzki, Leif Erik Sander, Victor M. Corman, Christian Conrad, Sven Laudi, Marco Binder, Saskia Trump, Roland Eils, Marcus Mall, Irina Lehmann,

COVID-19 Clinical Research Studies

Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults. Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children.