Serum protein profiling reveals a specific upregulation of the immunomodulatory protein progranulin in COVID-19

Rieder, Marina; Wirth, Luisa; Pollmeier, Luisa; Jeserich, Maren; Goller, Isabella; Baldus, Niklas; Schmid, Bonaventura; Busch, Hans-Joerg; Hofmann, Maike; Thimme, Robert; Rieg, Siegbert; Kern, Winfried; Bode, Christoph; Duerschmied, Daniel; Lother, Achim

BACKGROUND: Severe courses of COVID-19 are associated with elevated levels of interleukin 6. However, there is a growing body of evidence pointing to a broad and more complex disorder of pro-inflammatory and anti-viral responses with disturbed interferon signaling in COVID-19. METHODS: In this prospective single-center registry, we included 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 and compared their serum protein expression profiles. RESULTS: Interleukin-6 abundance was similar in SARS-CoV-2 positive patients (n = 24) compared to SARS-CoV-2 negative control (n = 61). In contrast, we observed a specific upregulation of the immunomodulatory protein progranulin (GRN). High GRN abundance was associated with adverse outcomes and increased expression of interleukin-6 in COVID-19. CONCLUSION: The data from this registry reveals that GRN is specifically upregulated in SARS-CoV-2 positive patients while interleukin-6 may serve as marker for disease severity. The potential of GRN as a biomarker and a possible impact of increased GRN expression on interferon signaling, virus elimination, and virus-induced lung tissue damage in COVID-19 should be further explored.