Evaluation of zinc, copper, and Cu:Zn ratio in serum, and their implications in the course of COVID-19.

BACKGROUND: The dynamics of essential metals such as Copper (Cu) and Zinc (Zn) may be associated with the novel coronavirus disease 2019 (COVID-19) that has spread across the globe. OBJECTIVES: The aim of this study is to investigate the relationship between serum levels of Cu and Zn, as well as the Cu:Zn ratio in the acute phase of COVID-19 along with the assessment of their connection to other laboratory parameters (hematological, biochemical, hemostatic). METHODS: Serum levels of Cu and Zn were measured by atomic absorption spectrometry in 75 patients in the acute COVID-19 phase and were compared with those of 22 COVID-19 patients evaluated three months after the acute phase of the disease ('non-acute' group) and with those of 68 healthy individuals. RESULTS: In comparison with both the non-acute patients and the healthy controls, the acute patients had lower levels of hemoglobulin and albumin, and higher levels of glucose, creatinine, liver transaminases, C-reactive protein (CRP), and higher values of the neutrophils to lymphocytes ratio (NLR) at the hospital admission. They also exhibited increased levels of Cu and decreased of Zn, well represented by the Cu:Zn ratio which was higher in the acute patients than in both non-acute patients (p = 0.001) and healthy controls (p < 0.001), with no statistical difference between the last two groups. The Cu:Zn ratio (log scale) positively correlated with CRP (log scale; r = 0.581, p < 0.001) and NLR (r = 0.436, p = 0.003). CONCLUSION: Current results demonstrate that abnormal dynamics of Cu and Zn levels in serum occur early during the course of COVID-19 disease, and are mainly associated with the inflammation response.

Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators.

Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu, also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show that copper decreases in brain but increases in serum, due to the nCp Cu component increase. Despite the similarities, a direct comparison of copper biological status in the two diseases has never been carried out. To fill this gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336 healthy controls previously investigated that were compared with 9 newly diagnosed WD patients. We then assessed 24h copper urinary excretion in 24 WD patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and compared results with those of AD patients participating to a D-pen phase II clinical trial previously published. After adjusting for sex and age, serum nCp-Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both p<0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD (p<0.016). 24h urinary copper excretion in AD patients (12.05µg/day) was higher than in healthy controls (4.82µg/day; p<0.001). 77.8% of the AD patients under D-pen treatment had a 24h urinary excretion higher than 200µg/day, suggestive of a failure of copper control. This study provides new insight into the pathophysiology of copper homeostasis in AD, showing a failure of copper control and the Cu:Cp ratio as an eligible marker.