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Local and systemic responses to SARS-CoV-2 infection in children and adults

Lookup NU author(s): Dr Gary Reynolds, Professor Muzlifah Haniffa

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Abstract

© 2021, The Author(s), under exclusive licence to Springer Nature Limited.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.


Publication metadata

Author(s): Yoshida M, Worlock KB, Huang N, Lindeboom RGH, Butler CR, Kumasaka N, Conde CD, Mamanova L, Bolt L, Richardson L, Polanski K, Madissoon E, Barnes JL, Allen-Hyttinen J, Kilich E, Jones BC, de Wilton A, Wilbrey-Clark A, Sungnak W, Pett JP, Weller J, Prigmore E, Yung H, Mehta P, Saleh A, Saigal A, Chu V, Cohen JM, Cane C, Iordanidou A, Shibuya S, Reuschl A-K, Herczeg IT, Argento AC, Wunderink RG, Smith SB, Gao CA, Dematte JE, Argento AC, Gao CA, Misharin AV, Budinger GRS, Dematte JE, Donnelly HK, Markov NS, Wunderink RG, Smith SB, Poor TA, Poor TA, Lu Z, Reynolds G, Haniffa M, Bowyer GS, Coates M, Clatworthy MR, Calero-Nieto FJ, Gottgens B, O'Callaghan C, Sebire NJ, Jolly C, de Coppi P, Smith CM, Misharin AV, Janes SM, Teichmann SA, Nikolic MZ, Meyer KB

Publication type: Article

Publication status: Published

Journal: Nature

Year: 2021

Pages: epub ahead of print

Online publication date: 22/12/2021

Acceptance date: 14/12/2021

ISSN (print): 0028-0836

ISSN (electronic): 1476-4687

Publisher: Nature Research

URL: https://doi.org/10.1038/s41586-021-04345-x

DOI: 10.1038/s41586-021-04345-x


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