Nodal analysis determined nasal mucosal-associated mediators were associated with accelerated clinical recovery from SARS-CoV-2 infection

The inflammatory environment which protects against viral infections such as SARS-CoV-2 is dynamic. Elucidating the interaction of immune mediators will provide insight into disease pathogenesis and assist the development of therapeutics to treat disease caused by viral insults. Using previously published upper respiratory tract network analysis, we dissected clinical symptom severity (FLU-PRO questionnaire) and self-reported clinical recovery based on immune node clusters from 139 participants in a community-based randomised clinical trial in early onset SARS-CoV-2 (The STOIC study, NCT04416399). Primary outcome events reported included urgent care, emergency department visit or hospitalisation for COVID-19. Nodes at study enrolment were defined as interferon, innate immunity-like, chemokine-dominant, and mucosal immunity-like. Participants were stratified based on viral burden (30-cycle thresholds) and treatment (budesonide or usual care) with node expression also compared to 22 healthy controls. Interferon and chemokine node expression increased dependent on viral burden as compared to health, as expected. Elevated IL-33, CCL26, CCL13, CCL17 and IL-5 expression in the mucosal node (p=0.0163) was associated with a mean 3.7-day quicker clinical recovery with no primary outcome events irrespective of treatment. Symptom severity differences were specific to nasal (p=0.0264) and throat (p=0.0020) symptoms at day 0 only in high mucosal node expressing participants. Overall, these data offer insight into mucosal mediators key to the control and swift symptom resolution of SARS-CoV-2 which can be utilised for future therapeutics.