Local and systemic responses to SARS-CoV-2 infection in children and adults Masahiro Yoshida orcid.org/0000-0002-3521-53221,7 na1, Kaylee B. Worlock orcid.org/0000-0002-5656-76341 na1, Ni Huang2 na1, Rik G. H. Lindeboom orcid.org/0000-0002-3660-504X2 na1, Colin R. Butler5, Natsuhiko Kumasaka orcid.org/0000-0002-3557-03752, Cecilia Dominguez Conde orcid.org/0000-0002-8684-46552, Lira Mamanova orcid.org/0000-0003-1463-86222, Liam Bolt orcid.org/0000-0001-7293-07742, Laura Richardson orcid.org/0000-0002-8075-38162, Krzysztof Polanski orcid.org/0000-0002-2586-95762, Elo Madissoon2,10, Josephine L. Barnes orcid.org/0000-0001-9938-31761, Jessica Allen-Hyttinen orcid.org/0000-0003-4644-03621, Eliz Kilich3, Brendan C. Jones orcid.org/0000-0002-2637-88595, Angus de Wilton3, Anna Wilbrey-Clark2, Waradon Sungnak orcid.org/0000-0002-0136-49602, J. Patrick Pett orcid.org/0000-0002-5249-444X2, Juliane Weller orcid.org/0000-0002-1310-61682, Elena Prigmore orcid.org/0000-0001-8870-03162, Henry Yung1,3, Puja Mehta1,3, Aarash Saleh4, Anita Saigal4, Vivian Chu orcid.org/0000-0003-1376-11864, Jonathan M. Cohen orcid.org/0000-0003-1004-55983, Clare Cane orcid.org/0000-0002-3545-768X4, Aikaterini Iordanidou4, Soichi Shibuya orcid.org/0000-0002-4274-13125, Ann-Kathrin Reuschl6, Iván T. Herczeg orcid.org/0000-0003-1281-36341, A. Christine Argento8, Richard G. Wunderink orcid.org/0000-0002-8527-41958, Sean B. Smith8, Taylor A. Poor8, Catherine A. Gao orcid.org/0000-0001-5576-39438, Jane E. Dematte8, NU SCRIPT Study Investigators, Gary Reynolds orcid.org/0000-0002-8142-870813, Muzlifah Haniffa orcid.org/0000-0002-3927-20842,13, Georgina S. Bowyer orcid.org/0000-0002-2058-404511, Matthew Coates11,12, Menna R. Clatworthy2,11, Fernando J. Calero-Nieto orcid.org/0000-0003-3358-82539, Berthold Göttgens orcid.org/0000-0001-6302-57059, Christopher O’Callaghan5, Neil J. Sebire5, Clare Jolly orcid.org/0000-0002-4603-22816, Paolo de Coppi orcid.org/0000-0002-1659-02075, Claire M. Smith orcid.org/0000-0002-8913-00095, Alexander V. Misharin orcid.org/0000-0003-2879-37898, Sam M. Janes orcid.org/0000-0002-6634-59391,3, Sarah A. Teichmann orcid.org/0000-0002-6294-63662,14, Marko Z. Nikolić orcid.org/0000-0001-6304-68481,3 na2 & Kerstin B. Meyer orcid.org/0000-0001-5906-14982 na2 Nature (2021)Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. InfectionRNA sequencingSARS-CoV-2Transcriptomics It is not fully understood why COVID-19 is typically milder in children1–3. To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy paediatric airways, we observed cells already in an interferon-activated state, that upon SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression. The systemic response in children was characterised by increases in naive lymphocytes and a depletion of natural killer cells, while in adults cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signaling in early infection, and identify novel epithelial cell states that associate with COVID-19 and age. Our matching nasal and blood data showed a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were massively reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children. This Supplementary information file contains the following sections: Detailed Cell Type Annotation; Cell type abbreviations for airway and blood immune cells; IFN production in dendritic cells; and additional references. By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
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