ABSTRACT
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.
Subject(s)
Bronchi/immunology , Bronchi/virology , COVID-19/immunology , COVID-19/virology , Immunity, Innate , SARS-CoV-2/immunology , Adolescent , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , Child , Child, Preschool , DEAD Box Protein 58/metabolism , Dendritic Cells/immunology , Epithelial Cells/immunology , Epithelial Cells/virology , Female , Humans , Infant , Infant, Newborn , Interferon-Induced Helicase, IFIH1/metabolism , Macrophages/immunology , Male , Middle Aged , Receptors, Immunologic/metabolism , Single-Cell Analysis , T-Lymphocytes, Cytotoxic/immunology , Young AdultABSTRACT
BACKGROUND: The vigilance-(attentional) avoidance hypothesis (VAH) developed for explaining phobic reactions describes an early attentional bias towards a feared stimulus followed by attentional avoidance of this stimulus. Such a pattern of attentional shifts might also be found when processing of pain-related stimuli is required. The purpose of the present study was to test the VAH for pain-associated stimuli, i.e., faces displaying pain, using the method of eye-tracking in a pain-free sample. METHODS: Forty-eight healthy participants observed pictures of faces displaying pain and other emotions (anger, joy), presented concurrently with neutral faces, while their gaze behaviours were recorded continuously. RESULTS: Analysis of the time course of fixation durations revealed a distinct pattern for pain faces. Participants gazed at pain faces longer than at neutral faces at the beginning (up to 1000 ms) but reduced preference for pain faces increasingly thereafter (up to 2000 ms); this decline in vigilance did not occur for anger and joy faces. Strong fear of pain (Fear of Pain Questionnaire) tended to increase attentional preference for negative faces (pain, anger), a finding, which however did not reach significance. CONCLUSIONS: We assume that initial vigilance for pain-associated stimuli might reflect an adaptive reaction to detect a potentially harmful stimulus. Subsequently, the pain-associated stimulus might be less attended for the purpose of mood regulation when all clear is given in this situation.
