Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 25;17(4):e0267235.
doi: 10.1371/journal.pone.0267235. eCollection 2022.

Chromogranin A plasma levels predict mortality in COVID-19

Rebecca De Lorenzo  1   2 , Clara Sciorati  1 , Giuseppe A Ramirez  1   2 , Barbara Colombo  3 , Nicola I Lorè  1   4 , Annalisa Capobianco  1 , Cristina Tresoldi  5 ; Bio Angels for COVID-BioB Study Group; Daniela M Cirillo  1   4 , Fabio Ciceri  2   5 , Angelo Corti  2   3 , Patrizia Rovere-Querini  1   2 , Angelo A Manfredi  1   2
Affiliations

Chromogranin A plasma levels predict mortality in COVID-19

Rebecca De Lorenzo et al. PLoS One. .

Abstract

Background: Chromogranin A (CgA) and its fragment vasostatin I (VS-I) are secreted in the blood by endocrine/neuroendocrine cells and regulate stress responses. Their involvement in Coronavirus 2019 disease (COVID-19) has not been investigated.

Methods: CgA and VS-I plasma concentrations were measured at hospital admission from March to May 2020 in 190 patients. 40 age- and sex-matched healthy volunteers served as controls. CgA and VS-I levels relationship with demographics, comorbidities and disease severity was assessed through Mann Whitney U test or Spearman correlation test. Cox regression analysis and Kaplan Meier survival curves were performed to investigate the impact of the CgA and VS-I levels on in-hospital mortality.

Results: Median CgA and VS-I levels were higher in patients than in healthy controls (CgA: 0.558 nM [interquartile range, IQR 0.358-1.046] vs 0.368 nM [IQR 0.288-0.490] respectively, p = 0.0017; VS-I: 0.357 nM [IQR 0.196-0.465] vs 0.144 nM [0.144-0.156] respectively, p<0.0001). Concentration of CgA, but not of VS-I, significantly increased in patients who died (n = 47) than in survivors (n = 143) (median 0.948 nM [IQR 0.514-1.754] vs 0.507 nM [IQR 0.343-0.785], p = 0.00026). Levels of CgA were independent predictors of in-hospital mortality (hazard ratio 1.28 [95% confidence interval 1.077-1.522], p = 0.005) when adjusted for age, number of comorbidities, respiratory insufficiency degree, C-reactive protein levels and time from symptom onset to sampling. Kaplan Meier curves revealed a significantly increased mortality rate in patients with CgA levels above 0.558 nM (median value, log rank test, p = 0.001).

Conclusion: Plasma CgA levels increase in COVID-19 patients and represent an early independent predictor of mortality.

PubMed Disclaimer

Conflict of interest statement

NO authors have competing interests.

Figures

Fig 1
Fig 1
Panel A: CgA and VS-I plasma levels in age- and sex-matched healthy controls (HC) and COVID-19 patients at hospital admission. Panel B: CgA plasma levels in COVID-19 patients with favorable outcome (Alive) or who died (Dead). Panel C: VS-I in Alive or Dead patients. ** p<0.001.
Fig 2
Fig 2
Panel A: Correlation of CgA plasma levels with age. Panel B: CgA plasma levels in patients with or without comorbidities. *** <0.0001.
Fig 3
Fig 3. Kaplan-Meier survival curves in patients with CgA levels below (low) or above (high) the median value of 0.558 nM.
Log rank test, p = 0.001.
See this image and copyright information in PMC

References

    1. Blaschko H. Comline R. S. Schneider F. H. Silver M. Smith A. D.: Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature 1967, 215(5096):58–59. doi: 10.1038/215058a0 - DOI - PubMed
    1. Tasiemski A. Hammad H., Vandenbulcke F. Breton C. Bilfinger T., Pestel J. et al.. Presence of chromogranin-derived antimicrobial peptides in plasma during coronary artery bypass surgery and evidence of an immune origin of these peptides. Blood 2002, 100(2):553–559. doi: 10.1182/blood.v100.2.553 - DOI - PubMed
    1. Taupenot L., Harper KL, O’Connor DT: The chromogranin-secretogranin family. N Engl J Med 2003, 348(12):1134–1149. doi: 10.1056/NEJMra021405 - DOI - PubMed
    1. Pieroni M. Corti A. Tota B. Curnis F. Angelone T. Colombo B., et al.. Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function. Eur Heart J 2007, 28(9):1117–1127. doi: 10.1093/eurheartj/ehm022 - DOI - PubMed
    1. D’Amico M. A. Ghinassi B. Izzicupo P., Manzoli L. Di Baldassarre A. et al.. Biological function and clinical relevance of chromogranin A and derived peptides. Endocr Connect 2014, 3(2):R45–R54. doi: 10.1530/EC-14-0027 - DOI - PMC - PubMed

Publication types