Role of interleukin-6, serum ferritin, and d-dimer in hospitalized COVID-19 patients

Cytokine. 2024 Oct 8:184:156776. doi: 10.1016/j.cyto.2024.156776. Online ahead of print.

Abstract

Background: Various studies have observed an association between interleukin-6 (IL-6), serum ferritin, d-dimer, and in-hospital mortality in COVID-19 patients. However, multivariate regression analysis was not done in the majority of the studies, Also, the role of interleukin-6 (IL-6), serum ferritin, and d-dimer in hospitalized COVID-19 patients was not adequately studied and reported from our region.

Method: It was a retrospective cohort study in which the serum IL-6, serum ferritin, and d-dimer of 305 hospitalized COVID-19 patients were analyzed, and their association with mortality was determined.

Results: In COVID-19 patients, the levels of IL-6 (P = 0.007), serum ferritin (P = 0.011), and d-dimer (P = 0.004) were significantly elevated in patients with severe SARS-CoV-2 illness (SpO2 < 90 % at admission). IL-6 levels were significantly elevated (186 pg/ml vs. 215 pg/ml, P = 0.003) in non-survivors compared to survivors. However, d-dimer (mg/ml) (P = 0.129) and serum ferritin (mg/ml) (P = 0.051) levels were similar between the two groups. The ROC curve (receiver operating characteristic curve) analysis showed a significant but poor area under the curve (AUC) between elevated IL-6 (>208 pg/ml) and in-hospital mortality (P < 0.008, AUC = 0.61). Kaplan-Meir survival analysis showed poor survival in patients with elevated IL-6 (>208 pg/ml) (Pby log-rank: 0.010) and elevated d-dimer (>1780 mg/ml) (P by log-rank: 0.036). The multivariate cox-regression analysis did not show any association between IL-6, serum ferritin, d-dimer, and in-hospital mortality (P > 0.05). Also, no association was found between serum levels of IL-6, serum ferritin, d-dimer, and the use of a ventilator (P > 0.05) and the severity of SARS-CoV-2 illness (P > 0.05) on multivariate binary logistic regression analysis.

Conclusion: In this study, the serum levels of IL-6, serum ferritin, and d-dimer were not associated with in-hospital mortality in hospitalized COVID-19 patients on multivariate cox-regression analysis, and were the markers of severe SARS-CoV-2 illness.

Keywords: COVID-19; Interleukin-6 (IL-6); SARS-CoV-2; Serum ferritin; d-Dimer.