Longitudinal immune and inflammatory responses in the respiratory mucosa and blood of patients after hospitalisation with COVID-19.

This study will test the hypothesis that natural infection with SARS-CoV-2 results in virus-specific IgA and T cell responses in the nasal mucosa, which are sustained for up to one year.In order to study the longevity of immune responses, 400 participants who have been hospitalized with COVID-19 will have blood and nasal samples collected at 3, 6 and 12 months post-discharge.Nasosorption allows collection of concentrated nasal fluid which is amenable to studies of antibody specificity. ELISA will be used to determine mIgA/IgG titres at each time-point to longitudinally assess the mucosal antibody response. Responses to viral epitopes including spike and nucleocapsid will be measured. Participant vaccination status and timing will be recorded during the study. This will allow comparison of spike and non-spike antibody titres following vaccination in order to compare the course of natural immunity and vaccine boosted immunity. This will also identify if vaccination can boost mucosal immune responses to SARS-CoV-2. MHC Tetramer staining on nasal curette samples will be used to analyse virus-specific tissue resident CD8+ and CD4+ T cell responses. This will be assessed at each time point to determine the strength and durability of responses. Cytokine levels in plasma and nasal mucosa will be measured through multiplex ELISA. This will be related to data from flow cytometry in selected patients, characterising neutrophil and NK cell populations in the blood and nasal mucosa. This will enable study of the chronic inflammatory response in those with symptoms of Long COVID.This is the first study to provide insights into long-term mucosal antibody and T cell responses to SARS-CoV-2 in convalescent patients. This study will identify if mucosal responses are a potential correlate of protection which can be evaluated further in mechanistic studies. This has important implications for vaccine development and understanding the future course of the pandemic.