A Dynamic Immune Response Shapes COVID-19 Progression

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies. [Display omitted] •Early immune response in COVID-19 patients is highly dynamic•Most pro-inflammatory genes, except IL1, were induced after respiratory function nadir•Reduced T cell activation in mild cases may contribute to prolonged RNAemia Through daily transcriptomic profiling of whole blood from SARS-CoV-2 patients, Ong et al. reveal that the early immune response is highly dynamic in COVID-19 patients. Aside from IL-1, peak cytokine expression occurs after the lowest point in respiratory function. These findings underscore the need for systematic sampling of COVID-19 patients.