Upper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children

Eran Mick, Alexandra Tsitsiklis, Natasha Spottiswoode, Saharai Caldera, Paula Hayakawa Serpa, Angela M. Detweiler, Norma Neff, Angela Oliveira Pisco, Lucy M. Li, Hanna Retallack, Kalani Ratnasiri, Kayla M. Williamson, Victoria Soesanto, Eric A. F. Simões, Christiana Smith, Lisa Abuogi, Amy Kistler, Brandie D. Wagner, Joseph L. DeRisi, Lilliam Ambroggio, Peter M. Mourani and Charles R. Langelier ()
Additional contact information
Eran Mick: University of California
Alexandra Tsitsiklis: University of California
Natasha Spottiswoode: University of California
Saharai Caldera: University of California
Paula Hayakawa Serpa: University of California
Angela M. Detweiler: Chan Zuckerberg Biohub
Norma Neff: Chan Zuckerberg Biohub
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Lucy M. Li: Chan Zuckerberg Biohub
Hanna Retallack: University of California
Kalani Ratnasiri: Chan Zuckerberg Biohub
Kayla M. Williamson: University of Colorado
Victoria Soesanto: University of Colorado
Eric A. F. Simões: University of Colorado and Children’s Hospital Colorado
Christiana Smith: University of Colorado and Children’s Hospital Colorado
Lisa Abuogi: University of Colorado and Children’s Hospital Colorado
Amy Kistler: Chan Zuckerberg Biohub
Brandie D. Wagner: University of Colorado
Joseph L. DeRisi: Chan Zuckerberg Biohub
Lilliam Ambroggio: University of Colorado and Children’s Hospital Colorado
Peter M. Mourani: University of Colorado and Children’s Hospital Colorado
Charles R. Langelier: University of California

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children ( 40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Date: 2022
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DOI: 10.1038/s41467-022-31600-0

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