Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2

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.

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

“…In adults, ACE2 expression is induced by IFN 30 and in response to infection 28 , but we observe no significant increase of ACE2 expression in children with COVID-19 (Extended Data Fig. 4c), consistent with recent bulk RNAseq comparisons 10 . As reported 31,32 , no SARS-CoV-2 viral reads were detected in peripheral blood.…”

Differences between Children and Adults with COVID-19: It’s Right under Our Nose

“…In this issue of the Journal , Koch and colleagues (pp. 206–222 ) present findings that suggest the type I and II IFN response in the nasal mucosa of children and adults infected with SARS-CoV-2 are similar but that TCR signaling, T-cell activation, and neutrophil chemotaxis may be exaggerated in infected adults versus children ( 9 ). The authors performed a cross-sectional analysis of bulk–RNA-sequencing (RNA-seq) signatures from nasal mucosal curettage from children ( n = 36) and adults ( n = 16) infected with SARS-CoV-2.…”

Comparison of SARS-CoV-2 Evolution in Paediatric Primary Airway Epithelial Cell Cultures Compared with Vero-Derived Cell Lines

“…However, much of our understanding using in vitro models of SARS-CoV-2 evolution is from cell cultures derived from adults. Therefore, questions remain concerning the consequences of passage in paediatric cultures, especially as children have distinct outcomes following SARS-CoV-2 infection [27][28][29][30][31].…”