@article{Thwaites:2024:infdis/jiad590,
author = {Thwaites, R and Sidhu, J and Siggins, M and Liew, F and Russel, C and Uruchurtu, A and Davis, C and Turtle, L and Moore, S and Hardwick, H and Oosthuyzen, W and Thomson, E and Semple, M and Baillie, JK and Openshaw, P},
doi = {infdis/jiad590},
journal = {Journal of Infectious Diseases},
pages = {e17--e29},
title = {Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19},
url = {http://dx.doi.org/10.1093/infdis/jiad590},
volume = {230},
year = {2024}
}

Download

TY  - JOUR
AB  - Background:While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.Methods:We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0–5 days after symptom onset) or late (6–20 days after symptom onset) phase.Results:Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease.Conclusions:Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.
AU  - Thwaites,R
AU  - Sidhu,J
AU  - Siggins,M
AU  - Liew,F
AU  - Russel,C
AU  - Uruchurtu,A
AU  - Davis,C
AU  - Turtle,L
AU  - Moore,S
AU  - Hardwick,H
AU  - Oosthuyzen,W
AU  - Thomson,E
AU  - Semple,M
AU  - Baillie,JK
AU  - Openshaw,P
DO  - infdis/jiad590
EP  - 29
PY  - 2024///
SN  - 0022-1899
SP  - 17
TI  - Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19
T2  - Journal of Infectious Diseases
UR  - http://dx.doi.org/10.1093/infdis/jiad590
UR  - http://hdl.handle.net/10044/1/108915
VL  - 230
ER  - 

Download