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

<title>Abstract</title> Viral infection due to severe acute respiratory syndrome coronavirus 2 (<bold>SARS-CoV-2</bold>) induce a dynamic immune environment. Using nasal mucosal samples in 139 participants from the STOIC study (community-based randomised clinical trial for the use of budesonide in early onset SARS-CoV-2, NCT04416399), we applied predefined immune mediator nodes in relation to clinical outcomes and viral burden. Interferon- and chemokine-dominant nodes increased expression as compared to health, validating our modular approach. Next, we demonstrated that an increase in mucosal immunity-like node consisting of CCL13, CCL17, IL-33, among others was associated with a mean 3.7-day quicker recovery with no primary outcome events, irrespective of treatment arm. By day 14 the mucosal node divided into two daughter nodes linked to interferon molecules and was transcriptionally detectable in nasal cavity basal, hillock and ciliated cells (as per public single cell dataset EGAD00001007718). Our data suggest mucosal-associated mediators are key for early symptom resolution of SARS-CoV-2.