BACKGROUND: While inflammatory and immune responses to 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 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 hospitalised with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days post-symptom onset) or late (6-20 days post-symptom onset).

RESULTS: Patients that survived severe COVID-19 showed IFN-dominated mucosal immune responses (IFN-γ, CXCL10 and CXCL13) early in infection. These early mucosal responses were absent in patients that would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by 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 anti-viral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.


This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Cite as

Sidhu, J., Siggins, M., Liew, F., Russell, C., Uruchurtu, A., Davis, C., Turtle, L., Moore, S., Hardwick, H., Oosthuyzen, W., Thomson, E., Semple, M., Baillie, J., Openshaw, P., ISARIC4C Investigators & Thwaites, R. 2023, 'Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19', Journal of Infectious Diseases, article no: jiad590. https://doi.org/10.1093/infdis/jiad590

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Last updated: 23 May 2024
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