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

Abstract

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.

Autoantibodies against Progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19

“…This contrasts with the recent finding that patients with COVID-19 had elevated PGRN plasma levels, as detected by 96-plex proximity extension assay (50). The reason for this discrepancy is unclear, but it might be explained by different assay kits measuring free or bound PGRN, and complete or converted fragments thereof.…”

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial

“…Severe COVID-19 was associated with increased concentrations of IL-6, according to previous studies, however, this was not specific for COVID-19, and IL-6 concentrations in COVID-19 are probably lower than in other forms of severe ARDS. 6,[32][33][34][35] The degree of systemic inflammation in our patient cohort was variable, as reflected by the large variability of IL-6, C-reactive protein, or procalcitonin. The extent of adsorption of a given factor by the CytoSorb device is concentration dependent.…”

ICODE: the international COVID-19 thrombosis biomarkers colloquium—novel soluble biomarkers: circulating cell-free nucleic acids and other molecules

“…PGRN is involved in inflammation, wound healing and cell proliferation [ 19 ]. It was recently identified in a serum protein expression screen of emergency room all-comers with COVID-19-typical symptoms and positive versus negative SARS-CoV-2 status [ 20 ]. PGRN was upregulated in COVID-19 patients and associated with adverse outcomes and increased IL-6 expression.…”