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

Steven P. Cass, Jr 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

Research output: Contribution to journalArticlepeer-review


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.

Objective 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, NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (FLU-PRO questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using predefined mathematical modelling of immune mediators, determined by Mesoscale 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 (CCL13, CCL17, IL-33, IL-5, IL-4, CCL26, IL-2, IL-12, and GM-CSF) 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 languageEnglish
JournalERJ Open Research
Issue number3
Publication statusPublished - Feb 2024
Externally publishedYes


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