A recent study published in Nutrients reports that lower blood levels of certain trace elements are associated with critical coronavirus disease 2019 (COVID-19) outcomes.
Study: Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients. Image Credit: Fida Olga / Shutterstock.com
Background
COVID-19, which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a multifactorial disease associated with a wide range of symptoms from mild respiratory symptoms like cough and congestion to acute respiratory distress syndrome (ARDS) and death. Real-world evidence accumulated throughout the pandemic has shown that age, obesity, diabetes, and cardiovascular disease are the major risk factors associated with severe COVID-19.
Hyper-inflammation and the 'cytokine storm’ are major hallmarks of severe COVID-19, both of which increase the risk of intensive care unit (ICU) admission and mortality. In critically ill COVID-19 patients, only a select few immunomodulatory treatments have been associated with beneficial outcomes, including mortality reduction.
Trace elements, including zinc, copper, and selenium, are essential micronutrients required for protein synthesis and cell signaling. Trace elements with anti-inflammatory and antioxidant properties have essential roles in maintaining immune homeostasis, suppressing inflammatory response, and preventing viral replication.
In critically ill and hospitalized COVID-19 patients, low blood levels of zinc and selenium have been identified as prognostic biomarkers.
In the current study, scientists assess blood levels of zinc, copper, and selenium in COVID-19 patients with varying severity. The associations between blood levels of these trace elements and duration of mechanical ventilation, risk of septic shock, and mortality were also determined.
Study design
The study population included critically ill COVID-19 patients who were admitted to the ICU of the Geneva University Hospitals between March 2020 and May 2020. Patients requiring ICU admission for mechanical ventilation or high-flow nasal oxygenation were referred to as critically ill COVID-19 patients.
Blood levels of trace elements were assessed in three categories of patients, including critically ill COVID-19 patients admitted to the ICU, severely ill patients admitted to the hospital COVID-19 ward, and non-hospitalized COVID-19 patients. These cohorts comprised 118, 98, and 129 patients, respectively.
All ICU patients were monitored until hospital discharge or death, with survival status assessed at day 28. The levels of trace elements were measured on the first day of ICU admission, hospital admission, and ambulatory visit for the three categories of patients, respectively.
Important observations
A significant variation in the levels of zinc, selenium, and copper was observed between each patient cohort. More specifically, the median levels of zinc, selenium, and copper were 19.2, 1.5, and 15.6 µmol/L for non-hospitalized patients, 13, 1.1, and 17.5 µmol/L for COVID ward-admitted patients, and 8.2, 0.8, and 18.3 µmol/L for ICU-admitted patients, respectively.
Among ICU patients, lower levels of zinc and selenium were significantly associated with older age and higher levels of C-reactive protein at admission. Similarly, a significant association was observed between lower copper levels and male gender.
A higher risk of septic shock and mortality was observed among patients with low zinc levels; however, this association was not statistically significant. In contrast, a significantly longer duration of mechanical ventilation was observed in patients with low selenium and copper levels. A non-significant association was also observed between lower selenium levels and higher mortality risk.
Study takeaways
The study findings indicate that the blood levels of trace elements may vary in COVID-19 patients depending on disease severity. In fact, critically ill ICU COVID-19 patients were found to exhibit lower levels of selenium and zinc, as well as higher levels of copper, as compared to non-hospitalized and ward-admitted patients. In critically ill patients, significant associations were observed between lower selenium and copper levels and longer duration under mechanical ventilation.
Unlike selenium and zinc, higher blood levels of copper have been observed in critically ill patients. Notably, increased levels of the copper-binding protein ceruloplasmin during acute inflammation in critically ill COVID-19 patients could be responsible for a higher accumulation of copper in the blood.
Overall, the study establishes a link between low trace element levels and higher COVID-19 severity. Based on these findings, future interventional trials are needed to evaluate whether supplementation of these trace elements could reduce the severity of COVID-19.
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