Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 2026 4 2026 06 21 80 88 Hamidreza Shiri Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Ali Akbar Soleimani Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Behnam Omidi Sarajar Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Ghodratollah Panahi Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Sina Habibi Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Mohammad Hadi Nematollahi Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran 2026 05 05 2026 05 15 Objectives: COVID-19 is a disease associated with biochemical disruptions. This study aimed to evaluate changes in biochemical parameters in COVID-19 patients and to identify clinically applicable biomarkers for disease prognosis and severity assessment. Methods: This study enrolled 155 hospitalized COVID-19 patients classified as mild (n=35), moderate (n=40), severe (n=35), or critical (n=45), along with 40 healthy controls. Serum levels of blood glucose (BG), blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T‑Bil), direct bilirubin (D‑Bil), lactate dehydrogenase (LDH), high‑sensitivity C‑reactive protein (hs‑CRP), and electrolytes (Na⁺, K⁺) were measured. Logistic regression was performed to assess disease severity. Receiver operating characteristic (ROC) curve analyses were conducted to identify independent predictors and optimal cut‑off values for prognosis (patients vs. controls) and severity (mild vs. moderate, severe, and critical groups). Results: All hepatic, renal, and glycemic parameters, as well as LDH and hs‑CRP, were elevated across all patient groups compared to controls (P < 0.001). Adjusted logistic regression identified hs‑CRP (odds ratio (OR) = 25.76), D‑Bil (OR = 4.56), Cr (OR = 3.17), and LDH (OR = 1.26) as the strongest independent predictors of increased infection severity. ROC analysis determined LDH as the best biomarker for disease prognosis (AUC = 97.72%, cut‑off > 317 U/L) and D‑Bil for disease severity (AUC = 72.81%, cut‑off > 0.23 mg/dL). Conclusion: LDH and D‑Bil represent the most clinically useful biomarkers for COVID‑19 prognosis and severity detection, respectively. These results advocate for their routine integration into standard biochemical surveillance to facilitate early risk assessment; however, broader prospective investigations with larger cohorts are essential to confirm their generalizability. https://abi.tums.ac.ir/index.php/abi/article/view/189 https://abi.tums.ac.ir/index.php/abi/article/download/189/140