Clinical application of serum zinc to copper ratio in COVID-19 severity and mortality

Objectives Despite the importance of COVID-19, very little is known about its exact pathophysiology. Recent studies suggest that COVID-19 triggers a cytokine storm that leads to acute respiratory distress syndrome. Zinc (Zn) and Copper (Cu) have various anti-inflammatory properties that affect innate and adaptive immune systems. The aim of this study was to assess the association of Zn and Cu levels and Zn/Cu ratio in COVID-19 severity and mortality. Methods This case-control study was conducted among 226 COVID-19 patients (117 males) and 226 healthy age and sex-matched controls. The disease diagnosis was based on positive COVID-19 qRT-PCR and/or clinical criteria (respiratory symptoms and chest CT findings) between February 2020 to August 2022 in Imam Reza Hospital of Mashhad, Iran. Serum Zn and Cu levels were assessed using a fully automated Indiko Plus analyzer (Thermo Scientific, USA) by colorimetric method. Results The mean age of COVID-19 patients and control subjects was 64.04 ± 18.36 and 64.09 ± 1.91 years old, respectively. Patients with COVID-19 were characterized by a significantly lower serum Zn level ( p < 0.001), lower Zn/Cu ratio ( p < 0.001) and higher Cu level compared to the control group ( p < 0.001). The mean serum Zn level was significantly higher in survivors than in non-survivors ( p = 0.01), but there was no significant difference in mean serum Cu level in patients. Multivariate logistic regression model showed that serum Zn/Cu ratio were independently associated with mortality and severity of COVID-19 (adjusted odds ratio: 0.01, and 0.003, p = 0.02, and p = 0.008, respectively). Conclusion The result of this study showed that patients with COVID-19 had lower serum Zn concentration and Zn/Cu ratio. Lower serum Zn/Cu ratio was associated with COVID-19 severity progression and mortality. Therefore, evaluating serum Zn and Cu levels may be helpful in monitoring COVID-19 patients.