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Upper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children.
Mick, Eran; Tsitsiklis, Alexandra; Spottiswoode, Natasha; Caldera, Saharai; Serpa, Paula Hayakawa; Detweiler, Angela M; Neff, Norma; Pisco, Angela Oliveira; Li, Lucy M; Retallack, Hanna; Ratnasiri, Kalani; Williamson, Kayla M; Soesanto, Victoria; Simões, Eric A F; Smith, Christiana; Abuogi, Lisa; Kistler, Amy; Wagner, Brandie D; DeRisi, Joseph L; Ambroggio, Lilliam; Mourani, Peter M; Langelier, Charles R.
  • Mick E; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Tsitsiklis A; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
  • Spottiswoode N; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Caldera S; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Serpa PH; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Detweiler AM; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Neff N; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Pisco AO; Division of Infectious Diseases, University of California, San Francisco, CA, USA.
  • Li LM; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Retallack H; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Ratnasiri K; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Williamson KM; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Soesanto V; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Simões EAF; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
  • Smith C; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Abuogi L; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA.
  • Kistler A; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA.
  • Wagner BD; Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, CO, USA.
  • DeRisi JL; Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, CO, USA.
  • Ambroggio L; Department of Pediatrics, University of Colorado and Children's Hospital Colorado, Aurora, CO, USA.
  • Mourani PM; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Langelier CR; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO, USA.
Nat Commun ; 13(1): 3937, 2022 07 08.
Article in English | MEDLINE | ID: covidwho-1927085
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 (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 older adults (>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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Randomized controlled trials Limits: Adult / Aged / Child / Humans / Young adult Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-31600-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Randomized controlled trials Limits: Adult / Aged / Child / Humans / Young adult Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-31600-0