Serum Hypoxia-Inducible Factor 1 Alpha Levels Decrease in Patients with COVID-19: A Case-Control Study

Abstract

This study investigated the association between serum hypoxia-inducible factor 1-alpha (HIF-1 alpha) levels and clinical severity in patients with coronavirus disease 2019 (COVID-19). This prospective case-control study included 91 patients with confirmed COVID-19, of whom 51 had severe-critical disease with pneumonia and 40 had mild disease without pneumonia, as well as 39 healthy controls. Vital signs, including body temperature, pulse rate, respiratory rate, oxygen saturation, and blood pressure, were recorded. Biochemical parameters such as complete blood count, D-dimer, ferritin, creatinine, urea, and high-sensitivity cardiac troponin T were analyzed. Serum HIF-1 alpha levels were measured using ELISA. Median HIF-1 alpha levels were 132.9 pg/mL (IQR: 131.7-138.0) in the severe-critical disease group, 137.35 pg/mL (IQR: 131.65-152.75) in the mild disease group, and 136.6 pg/mL (IQR: 132.2-162.2) in controls. Significant differences were observed between groups (p = 0.012). ROC analysis showed a discriminatory performance for HIF-1 alpha, with a sensitivity of 89.01% and specificity of 35.90% at a cut-off value of <= 154 pg/mL for distinguishing mild disease from controls, and a sensitivity of 86.3% and specificity of 42.5% at a cut-off value of <= 141.1 pg/mL for distinguishing severe-critical disease from mild disease. HIF-1 alpha levels decreased with increasing disease severity. HIF-1 alpha levels were found to be associated with disease severity; however, the low AUC values indicate that this parameter has limited discriminative ability for clinical use when used alone.