Elevated Serum Levels of Progranulin and Soluble Vascular Cell Adhesion Molecule-1 in Patients with COVID-19

Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the angiocentric inflammation and angiogenesis, yet the molecules involved in this process remain to be determined. Methods We did a cross-sectional study of a cohort of patients with COVID-19 in Zunyi, China between February 1 and March 30, 2020. Serum concentrations of PGRN were determined by enzyme-linked immunosorbent assay in patients with COVID-19 at hospital admission and at discharge. In parallel, the serum levels of soluble adhesion molecules, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin), and E-selectin (sE-selectin) were assayed by a human adhesion molecule multiplex kit. The association between serum PGRN levels and other laboratory test results was analyzed by Spearman correlation analysis. Results At baseline, the median serum PGRN levels in patients with COVID-19 were 94.8 ng/mL [interquartile range (IQR): 66.6–119.6 ng/mL], which was significantly elevated compared with those in healthy controls (46.3 ng/mL, IQR: 41.8–55.6 ng/mL). Moreover, the median serum sVCAM-1 levels were significantly higher in COVID-19 patients (1396.0 ng/mL, IQR: 1019.1–1774.8 ng/mL) than those in healthy controls (612.4 ng/mL, IQR: 466.4–689.3 ng/mL). However, the levels of sICAM-1, sP-selectin, and sE-selectin were not significantly elevated in patients with COVID-19 when compared to healthy controls. Further analysis showed that serum PGRN levels were significantly positively associated with sVCAM-1 (r= 0.675, P = 0.008) and inversely with sICAM-1 (r= −0.609, P = 0.021) and aspartate aminotransferase levels (r= −0.560, P = 0.037) in patients with COVID-19 at hospital admission. In COVID-19 patients, serum PGRN and sVCAM-1 levels fell significantly after successful treatment. Conclusion The present study demonstrates elevated serum PGRN and sVCAM-1 levels in patients with COVID-19, which may provide clues as to the mechanisms underlying the pathogenesis of COVID-19. Further studies are warranted to evaluate the potential of PGRN and sVCAM-1 as biomarkers and investigate their role in the pathogenesis of COVID-19.

Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study

“…showed elevated VCAM-1 concentrations, while ICAM-1 and E-selectin did not differ in cases vs. disease controls. In line with these findings, Cugno and Yao ( 19 , 37 ) showed no difference in E-selectin concentrations between mild to moderate COVID-19 cases and healthy controls. Our results regarding the cellular adhesion molecules are in line with these studies, but we demonstrate markedly lower E-selectin concentrations in cases vs. controls, mostly driven by control patients with bacterial pneumonia.…”

High Serum Progranulin Levels in COVID-19 Patients: A Pilot Study

“…Serum protein expression in the COVID-19 patients was examined in the literature, and there was no difference in IL-6 levels in the SARS-CoV-2 positive patients compared to the patients with similar symptoms and disease severity but negative for SARS-CoV-2, whereas a specific increase of the PGRN level has been shown [ 26 ]. Yao et al [ 27 ] found that serum VCAM-1 and PGRN levels were higher in the patients with COVID-19 than in the healthy controls in their study of PRGN and VCAM-1 levels in the patients with COVID-19.…”

Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients

“…Yao et al . [ 34 ] reported that patients with COVID-19 had higher PGRN levels than healthy controls, and that these levels decreased after successful treatment. In the present study, we demonstrated that PGRN levels were higher among ICU-treated patients; however, these values were not predictive of mortality in patients with COVID-19.…”