Marina Rieder1,2, Luisa Wirth3, Luisa Pollmeier3, Maren Jeserich1,2, Isabella Goller1,2, Niklas Baldus1,2, Bonaventura Schmid4, Hans-Joerg Busch4, Maike Hofmann5, Robert Thimme5, Siegbert Rieg6, Winfried Kern6, Christoph Bode1,2, Daniel Duerschmied1,2, Achim Lother1,2,3. 1. Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3. Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 4. Department of Emergency Medicine, University Hospital of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 5. Medical Center-University of Freiburg, Department of Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 6. Medical Center-University of Freiburg, Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Abstract
BACKGROUND: Severe courses of coronavirus disease 2019 (COVID-19) are associated with elevated levels of interleukin 6 (IL-6). However, there is a growing body of evidence pointing to a broad and more complex disorder of proinflammatory and antiviral responses with disturbed interferon signaling in COVID-19. METHODS: In this prospective, single-center registry, we included severe acute respiratory syndrome coronavirus 2 (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: IL-6 abundance was similar in SARS-CoV-2-positive patients (n = 24) compared with SARS-CoV-2-negative controls (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 IL-6 in COVID-19. CONCLUSIONS: The data from this registry reveal that GRN is specifically upregulated in SARS-CoV-2-positive patients while IL-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.
BACKGROUND: Severe courses of coronavirus disease 2019 (COVID-19) are associated with elevated levels of interleukin 6 (IL-6). However, there is a growing body of evidence pointing to a broad and more complex disorder of proinflammatory and antiviral responses with disturbed interferon signaling in COVID-19. METHODS: In this prospective, single-center registry, we included severe acute respiratory syndrome coronavirus 2 (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: IL-6 abundance was similar in SARS-CoV-2-positive patients (n = 24) compared with SARS-CoV-2-negative controls (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 IL-6 in COVID-19. CONCLUSIONS: The data from this registry reveal that GRN is specifically upregulated in SARS-CoV-2-positive patients while IL-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.
Authors: Diana A Gorog; Robert F Storey; Paul A Gurbel; Udaya S Tantry; Jeffrey S Berger; Mark Y Chan; Daniel Duerschmied; Susan S Smyth; William A E Parker; Ramzi A Ajjan; Gemma Vilahur; Lina Badimon; Jurrien M Ten Berg; Hugo Ten Cate; Flora Peyvandi; Taia T Wang; Richard C Becker Journal: Nat Rev Cardiol Date: 2022-01-13 Impact factor: 49.421