Growth Differentiation Factor 15 as a Prognostic Biomarker in COVID-19

Growth differentiation factor 15 (GDF-15) is a protein in the transforming growth factor beta superfamily present in low concentrations under normal physiologic conditions. GDF-15 concentrations increase in response to pathologic states of hypoxia, oxidative stress, and inflammation (e.g., diabetes mellitus, cancer, sepsis, cardiovascular disease). These researchers prospectively examined the prognostic implications of blood concentrations of GDF-15, compared with established biomarkers of disease severity, in 123 patients hospitalized with COVID-19 and severe acute respiratory distress syndrome. Patients' blood samples were collected at baseline, day 3, and day 9. The mean age was 59.6 years, 58% were male, and 55% were white. The primary endpoint was admission to intensive care or death during hospitalization. Serial GDF-15 concentrations were compared with those of other biomarkers.

Of the patients, 35 (28%) reached the primary endpoint (31 admitted to intensive care, 4 deaths), and these patients had significantly higher GDF-15 concentrations than those that did not reach the endpoint (median concentration, 4225 vs. 2187 pg/mL; C-statistic value, 0.78; 95% confidence interval, 0.70-0.86). This association was independent of age, sex, race, body-mass index, prior myocardial infarction, and renal function. The association between GDF-15 and outcome was stronger than with IL-6, CRP, procalcitonin, D-dimer, cardiac troponin, and pro–B-type natriuretic peptide. The increase of GDF-15 from baseline to day 3 was significantly higher in patients who reached the endpoint (median, +1208 vs −86 pg/mL). GDF-15 levels were higher in nonwhite than in white patients.