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Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2.
Am J Respir Cell Mol Biol. 2022 02; 66(2):206-222.AJ

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it with the host response to respiratory syncytial virus (RSV) and influenza virus. We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with influenza virus, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an IFN response in the nasal mucosa. The magnitude of the IFN response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2-infected adults had increased expression of genes involved in neutrophil activation and T-cell receptor signaling pathways compared with SARS-CoV-2-infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness.

Authors+Show Affiliations

Department of Medicine.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Medicine.Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Medicine.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Medicine.Department of Medicine.Department of Medicine.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Pediatrics. Department of Preventive Medicine. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.Department of Medicine. Department of Biochemistry and Molecular Genetics, and.Department of Medicine.Department of Medicine. Department of Cell and Developmental Biology, Northwestern University, Evanston, Illinois; and.Department of Pediatrics. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34731594

Citation

Koch, Clarissa M., et al. "Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2." American Journal of Respiratory Cell and Molecular Biology, vol. 66, no. 2, 2022, pp. 206-222.
Koch CM, Prigge AD, Anekalla KR, et al. Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2. Am J Respir Cell Mol Biol. 2022;66(2):206-222.
Koch, C. M., Prigge, A. D., Anekalla, K. R., Shukla, A., Do Umehara, H. C., Setar, L., Chavez, J., Abdala-Valencia, H., Politanska, Y., Markov, N. S., Hahn, G. R., Heald-Sargent, T., Sanchez-Pinto, L. N., Muller, W. J., Singer, B. D., Misharin, A. V., Ridge, K. M., & Coates, B. M. (2022). Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2. American Journal of Respiratory Cell and Molecular Biology, 66(2), 206-222. https://doi.org/10.1165/rcmb.2021-0292OC
Koch CM, et al. Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2. Am J Respir Cell Mol Biol. 2022;66(2):206-222. PubMed PMID: 34731594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2. AU - Koch,Clarissa M, AU - Prigge,Andrew D, AU - Anekalla,Kishore R, AU - Shukla,Avani, AU - Do Umehara,Hanh Chi, AU - Setar,Leah, AU - Chavez,Jairo, AU - Abdala-Valencia,Hiam, AU - Politanska,Yuliya, AU - Markov,Nikolay S, AU - Hahn,Grant R, AU - Heald-Sargent,Taylor, AU - Sanchez-Pinto,L Nelson, AU - Muller,William J, AU - Singer,Benjamin D, AU - Misharin,Alexander V, AU - Ridge,Karen M, AU - Coates,Bria M, PY - 2021/11/4/pubmed PY - 2022/2/8/medline PY - 2021/11/3/entrez KW - COVID-19 KW - IFNs KW - T cells KW - pneumonia KW - viral infections SP - 206 EP - 222 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 66 IS - 2 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it with the host response to respiratory syncytial virus (RSV) and influenza virus. We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with influenza virus, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an IFN response in the nasal mucosa. The magnitude of the IFN response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2-infected adults had increased expression of genes involved in neutrophil activation and T-cell receptor signaling pathways compared with SARS-CoV-2-infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/34731594/Age_related_Differences_in_the_Nasal_Mucosal_Immune_Response_to_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -