A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

COVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unraveling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls. Blood, nasal epithelium, and saliva samples were sampled from patients and controls at the same timepoints. Blood samples (2.5ml) were collected in PAXgene tubes (BD). RNA was isolated using PAXgene blood miRNA extraction kit (Qiagen) following manufacturer recommendations. Saliva and nasal epithelium samples were collected in Oragene CP-190 kit (DNA Genotek). Patients and healthy controls were self-reported as of South-European ancestry; and cases were classified at the time of sample collection by severity illness: severe (ICU admission), moderate (non-ICU but admitted to hospital) and mild (domiciliary lockdown patients with mild symptoms or asymptomatic). Sample numbers are distributed as follows: (i) whole blood from 41 patients and 13 controls, (ii) nasal epithelium from 38 patients and 11 controls, and (iii) saliva from 41 patients and 12 controls. The complete tissue sample set could be collected for 27 out of the 52 patients. Immunological gene expression patterns of different tissues were evaluated using a SPRINT nCounter system (NanoString Technologies) and the Human Immunology v2 Panel.