Open Access
Open access
Springer Nature
Nature Communications
,  volume 16 ,  issue 1 ,  publication number 2383

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Jillian H. Hurst 1, 2
, 
Aditya A. Mohan 3
, 
Trisha Dalapati 4
, 
Ian A. George 5
, 
Jhoanna N. Aquino 1
, 
Debra J. Lugo 1
, 
Trevor S. Pfeiffer 1
, 
JAVIER RODRIGUEZ 6
, 
Alexandre Rotta 7
, 
Nicholas A. Turner 8
, 
Thomas W. Burke 8, 9
, 
Micah T. McClain 8, 9, 10
, 
Ricardo Henao 11, 12
, 
C Todd Demarco 13
, 
Raul Louzao 13
, 
Thomas N. Denny 13
, 
Kyle Walsh 2, 14
, 
Zhaohui Xu 15
, 
A Mejias 15
, 
OCTAVIO RAMILO 15
, 
Christopher W. Woods 8, 9, 10, 13
, 
Matthew S. Kelly 1
1
 
2
 
3
 
4
 
5
 
6
 
7
 
8
 
9
 
10
 
Durham Veterans Affairs Medical Center, Durham, USA | 
11
 
12
 
13
 
14
 
15
 
Publication type: Journal Article
Publication date: 2025-03-10
Springer Nature
scimago Q1
wos Q1
SJR: 4.761
CiteScore: 23.4
Impact factor: 15.7
ISSN: 20411723
Abstract

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy individuals. Among healthy children and adolescents, younger age is associated with higher URT expression of innate and adaptive immune pathways. SARS-CoV-2 infection induces broad upregulation of URT innate and adaptive immune responses among children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents are dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways is observed only in adults. Among SARS-CoV-2-infected individuals, fever is associated with blunted URT immune responses and more pronounced systemic immune activation. These findings demonstrate that immune responses to SARS-CoV-2 differ across the lifespan, from distinct signatures in childhood and adolescence to age-associated alterations in adults.

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Hurst J. H. et al. Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection // Nature Communications. 2025. Vol. 16. No. 1. 2383
GOST all authors (up to 50) Copy
Hurst J. H. et al. Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection // Nature Communications. 2025. Vol. 16. No. 1. 2383
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RIS Copy
TY - JOUR
DO - 10.1038/s41467-025-57655-3
UR - https://www.nature.com/articles/s41467-025-57655-3
TI - Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection
T2 - Nature Communications
AU - Hurst, Jillian H.
AU - Mohan, Aditya A.
AU - Dalapati, Trisha
AU - George, Ian A.
AU - Aquino, Jhoanna N.
AU - Lugo, Debra J.
AU - Pfeiffer, Trevor S.
AU - RODRIGUEZ, JAVIER
AU - Rotta, Alexandre
AU - Turner, Nicholas A.
AU - Burke, Thomas W.
AU - McClain, Micah T.
AU - Henao, Ricardo
AU - Demarco, C Todd
AU - Louzao, Raul
AU - Denny, Thomas N.
AU - Walsh, Kyle
AU - Xu, Zhaohui
AU - Mejias, A
AU - RAMILO, OCTAVIO
AU - Woods, Christopher W.
AU - Kelly, Matthew S.
PY - 2025
DA - 2025/03/10
PB - Springer Nature
IS - 1
VL - 16
SN - 2041-1723
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Hurst,
author = {Jillian H. Hurst and Aditya A. Mohan and Trisha Dalapati and Ian A. George and Jhoanna N. Aquino and Debra J. Lugo and Trevor S. Pfeiffer and JAVIER RODRIGUEZ and Alexandre Rotta and Nicholas A. Turner and Thomas W. Burke and Micah T. McClain and Ricardo Henao and C Todd Demarco and Raul Louzao and Thomas N. Denny and Kyle Walsh and Zhaohui Xu and A Mejias and OCTAVIO RAMILO and Christopher W. Woods and Matthew S. Kelly and others},
title = {Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection},
journal = {Nature Communications},
year = {2025},
volume = {16},
publisher = {Springer Nature},
month = {mar},
url = {https://www.nature.com/articles/s41467-025-57655-3},
number = {1},
pages = {2383},
doi = {10.1038/s41467-025-57655-3}
}