Rieder M, Wirth L, Pollmeier L, et al. - In view of the growing body of evidence suggesting a broad and more complex disorder of pro-inflammatory and anti-viral responses with disturbed interferon signaling in COVID-19, researchers conducted this prospective single-center registry comparing serum protein expression profiles between SARS-CoV-2 positive patients and patients with similar symptoms and severity of disease but negative for SARS-CoV-2 admitted to the emergency department. SARS-CoV-2 positive patients (n = 24) were similar to SARS-CoV-2 negative control (n = 61) with respect to interleukin-6 abundance. In contrast, a specific upregulation of the immunomodulatory protein progranulin (GRN) was evident in SARS-CoV-2 positive patients. Adverse outcomes and increased expression of interleukin-6 were noted in COVID-19 in correlation with high GRN abundance. Overall findings suggest upregulation of specifically GRN in SARS-CoV-2 positive patients while interleukin-6 is suggested as valuable as marker for disease severity.