Serum Protein Profiling Reveals a Specific Upregulation of the Immunomodulatory Protein Progranulin in Coronavirus Disease 2019

J Infect Dis. 2021 Mar 3;223(5):775-784. doi: 10.1093/infdis/jiaa741.

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.

Keywords: COVID-19; SARS-CoV-2; biomarker; interferon; proteome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19 / blood
  • COVID-19 / immunology
  • COVID-19 / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Progranulins / blood
  • Progranulins / metabolism*
  • Prospective Studies
  • Registries
  • SARS-CoV-2*
  • Severity of Illness Index
  • Up-Regulation*

Substances

  • Interleukin-6
  • Progranulins