Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients

Abstract

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47-9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79-0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

Figure 1

Galectin-3 serum levels in COVID-19 patients. (a) Galectin-3 circulating levels upon hospital admission of COVID-19 patients (n = 156) and age-matched healthy pre-pandemic controls (n = 10). (b) Severe outcomes in COVID-19 patients were associated with elevated levels of galectin-3. Data in (a, b) are shown as median with IQR. ****p < 0.0001; two-tailed Mann–Whitney U test or two-tailed t-test. Samples were assessed in duplicate in ELISA assays.

Figure 2

Galectin-3 correlates with inflammatory markers in COVID-19 patients. Spearman correlations show significant associations between galectin-3 and commonly measured inflammatory markers in SARS-CoV-2 infected patients. (a) CRP, (b) Neutrophil count, (c) Lymphocyte count, (d) NLR, (e) Ferritin, (f) D-dimer, (g) INR, (h) Fibrinogen, (i) Platelets, (j) Albumin, (k) AST and (l) Triglycerides.

Figure 3

Galectin-3, CRP, albumin and CT pulmonary affection > 50% as independent predictors of severe outcome in COVID-19 patients. Receiver-operating characteristic curves (ROCs) of the independent predictors for the classification of binary outcomes (severe/non-severe) using (a) galectin-3, (b) CRP, (c) albumin and (d) the combined predicted probabilities of galectin-3, CRP albumin and CT pulmonary affection > 50%.