Upper airway transcriptomics early after SARS-CoV-2 infection to identify individuals likely to develop symptomatic infection

Prediction of outcomes of SARS-CoV-2 infection remains challenging, particularly in the early days following exposure. To better understand the heterogeneity of disease progression, we investigated the early immune response in the upper respiratory tract using transcriptomic analysis, comparing individuals who remained asymptomatic to those who developed symptoms of COVID-19. We conducted a study of 74 individuals (43 children, 31 adults) with confirmed SARS-CoV-2 infection. Mid-turbinate nasal swabs were collected during the first few days of infection and again one week later. We performed a paired analysis comparing baseline and follow-up nasal human gene expression. Additionally, we conducted a predictive analysis to identify transcripts associated with the development of symptomatic infection. From the differentially expressed transcripts in both analyses, we developed a predictive model to assess the likelihood of symptomatic disease. We also compared gene expression patterns between children and adults. A robust interferon response in the upper respiratory tract was strongly associated with the development of symptomatic infection. A panel of five interferon-stimulated genes (TAP2, DDX60, IFIT5, APOL6, and IFI6) predicted symptomatic infection with reasonable accuracy (area under the curve = 0.84). Notably, adaptive immune responses, including T-cell activation and cytokine signaling, differed substantially between children and adults. Our findings suggest that early measurement of interferon-stimulated gene expression may help identify individuals at risk of developing symptomatic COVID-19.