TY - JOUR T1 - Local and systemic responses to SARS-CoV-2 infection in children and adults JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.LSC-2022.88 VL - 8 IS - suppl 8 SP - 88 AU - Masahiro Yoshida AU - Kaylee Worlock AU - Ni Huang AU - Rik Lindeboom AU - Colin Butler AU - Natsuhiko Kumasaka AU - Cecilia Dominguez Conde AU - Lira Mamanova AU - Liam Bolt AU - Laura Richardson AU - Krzysztof Polanski AU - Elo Madissoon AU - Josephine Barnes AU - Jessica Allen-Hyttinen AU - Eliz Kilich AU - Brendan Jones AU - Angus De Wilton AU - Anna Wilbrey-Clark AU - Waradon Sungnak AU - Jan Patrick Pett AU - Juliane Weller AU - Elena Prigmore AU - Henry Yung AU - Puja Mehta AU - Aarash Saleh AU - Anita Saigal AU - Vivian Chu AU - Jonathan Cohen AU - Clare Cane AU - Aikaterini Iordanidou AU - Soichi Shibuya AU - Ann-Kathrin Reuschl AU - Iván Herczeg AU - Christine Argento AU - Richard Wunderink AU - Sean Smith AU - Taylor Poor AU - Catherine Gao AU - Jane Dematte AU - Gary Reynolds AU - Muzlifah Haniffa AU - Georgina Bowyer AU - Matthew Coates AU - Menna Clatworthy AU - Fernando Calero-Nieto AU - Berthold Göttgens AU - Christopher O'Callaghan AU - Neil Sebire AU - Clare Jolly AU - Paolo De Coppi AU - Claire Smith AU - Alexander Misharin AU - Sam Janes AU - Sarah Teichmann AU - Kerstin Meyer AU - Marko Nikolić Y1 - 2022/03/10 UR - http://openres.ersjournals.com/content/8/suppl_8/88.abstract N2 - Background: Children typically present with milder coronavirus disease 2019 (COVID-19) severity compared to adults. The molecular basis of the differences in COVID-19 progression between children and adults remains to be elucidated. Here we investigated the age-specific differences of airway mucosal immunology as well as systemic immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: We analysed matched nasal, tracheal and blood samples from healthy and COVID-19 patients from infancy to adulthood (n=93) by means of single cell multi-omic profiling.Results: In healthy children, airway mucosal immunity is in a pre-activated interferon state which is further induced in response to SARS-CoV2 infection. This higher local innate immune response in children could restrict disease progression. We identified novel epithelial cell states that associate with COVID-19 and age. The systemic immune response in children was characterised by increases in naive lymphocytes and greater clonotype diversity, while in adults was dominated by cytotoxic populations. Integration of matched nasal and blood data showed that interferon response in the airways correlate with the induction of novel systemic interferon-stimulated subpopulations within multiple immune cells, which were greatly reduced in children.Conclusions: Our study demonstrates multiple age-specific differences in airway and systemic response to SARS-CoV-2, reflecting the changes of the immune landscape over development. These insights could contribute to pinpointing the triggers of severe disease in adults with a view towards risk stratification and therapeutic intervention.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 88.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -