Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19

Steven P. Cass; Dan V. Nicolau; Jonathan R. Baker; Christine Mwasuku; Sanjay Ramakrishnan; Mahdi Mahdi; Peter J. Barnes; Louise E. Donnelly; Rocio T. Martinez-Nunez; Richard E.K. Russell; Mona Bafadhel

doi:10.1183/23120541.00919-2023

Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19

Steven P. Cass^*, Dan V. Nicolau, Jonathan R. Baker, Christine Mwasuku, Sanjay Ramakrishnan, Mahdi Mahdi, Peter J. Barnes, Louise E. Donnelly, Rocio T. Martinez-Nunez, Richard E.K. Russell, Mona Bafadhel

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results Interferon-and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte–macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

Original language	English
Article number	00919-2023
Journal	ERJ Open Research
Volume	10
Issue number	3
DOIs	https://doi.org/10.1183/23120541.00919-2023
Publication status	Published - 1 May 2024

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10.1183/23120541.00919-2023

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@article{570397867fbb47cab801db284d457ade,

title = "Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19",

abstract = "Introduction Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results Interferon-and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte–macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.",

author = "Cass, {Steven P.} and Nicolau, {Dan V.} and Baker, {Jonathan R.} and Christine Mwasuku and Sanjay Ramakrishnan and Mahdi Mahdi and Barnes, {Peter J.} and Donnelly, {Louise E.} and Martinez-Nunez, {Rocio T.} and Russell, {Richard E.K.} and Mona Bafadhel",

note = "Publisher Copyright: {\textcopyright} The authors 2024.",

year = "2024",

month = may,

day = "1",

doi = "10.1183/23120541.00919-2023",

language = "English",

volume = "10",

journal = "ERJ Open Research",

issn = "2312-0541",

publisher = "European Respiratory Society",

number = "3",

}

TY - JOUR

T1 - Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19

AU - Cass, Steven P.

AU - Nicolau, Dan V.

AU - Baker, Jonathan R.

AU - Mwasuku, Christine

AU - Ramakrishnan, Sanjay

AU - Mahdi, Mahdi

AU - Barnes, Peter J.

AU - Donnelly, Louise E.

AU - Martinez-Nunez, Rocio T.

AU - Russell, Richard E.K.

AU - Bafadhel, Mona

PY - 2024/5/1

Y1 - 2024/5/1

N2 - Introduction Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results Interferon-and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte–macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

AB - Introduction Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results Interferon-and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte–macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

UR - http://www.scopus.com/inward/record.url?scp=85194142992&partnerID=8YFLogxK

U2 - 10.1183/23120541.00919-2023

DO - 10.1183/23120541.00919-2023

M3 - Article

AN - SCOPUS:85194142992

SN - 2312-0541

VL - 10

JO - ERJ Open Research

JF - ERJ Open Research

IS - 3

M1 - 00919-2023

ER -

Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19

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