Fig. 8: Graphical abstract.

Upper left: schematic of the combined patient cohorts used. Upper right: Schematic of experimental setup. The study was divided into an exploratory cohort using scRNA-Seq, multidimensional flow cytometry of PBMCs, and shotgun plasma proteomics. The confirmation cohort was used to validate findings from the exploratory cohort, using in-depth RNA-Seq of FACS-sorted PBMCs and multiplex plasma cytokine profiling. Nasal swabs were included from both hospitalized and ambulatory patients that were either already included in the two independent cohorts mentioned above or were additionally recruited. Exact numbers for every cohort and method are depicted in Fig. 1a, b and in methods. Bottom: explanation of findings. After infection with SARS-CoV-2, the virus is either contained in the upper airway tract (“non-pneumonic SARS-CoV-2 infection”) or it disseminates into the lung (“pneumonic COVID-19”). Our study shows that non-pneumonic SARS-CoV-2 infection is characterized by an early strong interferon-stimulated-gene (ISG) signature, as well as an immune regulatory lymphocyte signature and pro-resolving monocytes in the peripheral blood. In contrast, in case of viral dissemination, pneumonic COVID-19 is characterized by lymphocyte cytotoxicity and a proinflammatory marker profile in the peripheral blood.