Circulating trace elements status in COVID-19 disease: A meta-analysis

Abstract

Trace elements are a group of essential metals or metalloids, which are necessary for life, and present in minute amounts. Despite substantial researches highlighting the importance of trace elements in Coronavirus disease 2019 (COVID-19) diseases, a thorough evaluation of the levels of circulating trace elements is lacking. Therefore, we conducted a systematic review and meta-analysis to evaluate the trace element status (Zn, Fe, Cu, Mg, and Se) in COVID-19 disease. We also assessed the relationship between circulating trace elements and COVID-19 disease severity and survival status during follow-up. We searched comprehensively MEDLINE, Web of Science, CNKI, and WangFang databases without language restriction, between November 1, 2019 and April 1, 2022. The search identified 1,566 preliminary references. A total of 49 studies met the eligibility criteria and were included in the review, and 42 studies were included in the final meta-analysis. Meta-analysis showed that COVID-19 patients had significantly lower circulating Zn (SMD: −0.83, 95% CI: −1.19 to −0.46, P < 0.001), Fe (SMD: −1.56, 95% CI: −2.90 to −0.21, P = 0.023), and Se (SMD: −0.75, 95% CI: −0.94 to −0.56, P < 0.001) levels than healthy controls, and circulating Zn (SMD: −0.47, 95% CI: −0.75 to −0.18, P = 0.002), Fe (SMD: −0.45, 95% CI: −0.79 to −0.12, P = 0.008), and Se (SMD: −0.27, 95% CI: −0.49 to −0.04, P = 0.020) levels were associated with the presence of severity status in COVID-19 patients. Moreover, circulating Fe levels in non-survivors were significantly lower than survivors in COVID-19 (SMD: −0.28, 95% CI: −0.44 to −0.12, P = 0.001). However, there was no significant difference in Cu and Mg levels between COVID-19 patients and controls, severity and non-severity status, and survivors and non-survivors (all P > 0.05). Taken together, COVID-19 patients displayed lower circulating levels of Zn, Fe, and Se, and their levels were associated with severity status. Moreover, circulating Fe levels may provide part of the explanation for the unfavorable survival status. Therefore, we presumed optimistically that supplements of trace elements might provide an adjutant treatment in the early stages of COVID-19.Systematic review registration[https://www.crd.york.ac.uk/prospero], identifier [CRD42022348599].

Reduction in Serum Magnesium Levels and Renal Function Are Associated with Increased Mortality in Obese COVID-19 Patients

“…It is well established that deficiency of both Mg and other trace elements can result in abnormal cellular function or damage by increasing or decreasing susceptibility to infections, and negatively affecting the respiratory system [ 16 ]. Trace elements are a group of essential metals that include Mg, zinc (Zn), iron (Fe), copper (Cu), and selenium (Se) [ 17 ]. Mg is an essential divalent cation required for various metabolic and biochemical functions, with a potential role in the pathogenesis of COVID-19 by contributing to proper immune, vascular, and pulmonary function [ 18 , 19 ].…”

A comparative study of serum Zn, Cu, Mg, Mn, Cr, and Fe levels and their association with the vulnerability of Iraqi COVID-19 patients

“…Similarly, the Zn levels in each of the recovered samples were slightly lower than the control samples, which was a significant difference. Notably, many recent studies had reported that individuals with lower levels of Zn were more likely to get bacterial and viral infections, including COVID-19 [1] , [2] , [3] , [16] . Moreover, COVID patients with a Zn deficiency had a higher rate of complications and needed longer hospital stays [9] , [18] .…”

“…Interleukin-1 mediated increases in liver ceruloplasmin synthesis and release, an acute phase protein, cause these alterations in Cu metabolism. Therefore, reporting high level of Cu in infected patients is potentially attributed to the severe inflammatory responses that could lead to an increase in the concentration of toxic free radicals and consequently increase oxidative stress [1] , [24] , [25] , [26] . This potentially occurs due to the roles of Cu as a cofactor in several enzymes, such as superoxide dismutase, and also to the role of Cu in performing several tasks, such as cell defense against ROS- induced harm, anti-oxidative processes, and O 2 and electron transport in the respiratory chain [24] , [25] .…”

“…Coronavirus 2019 came from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which infects different species and has caused a worldwide pandemic since March 2020 [1] . It enters the cell, mainly Alveolar epithelial cells, by binding to the receptor “angiotensin-converting enzyme 2 (ACE2)” or to the transmembrane serine protease 2 (TMPRSS2) and affects the respiratory system, resulting in viral pneumonia and systemic immunopathologic effects [1] , [2] , [3] . Thus, COVID-19 infection has been reported to be very heterogeneous, ranging from being asymptomatic, mild, moderate, and severe, and resulting in death [4] , [5] .…”

Selenium: An Antioxidant with a Critical Role in Anti-Aging

“…A deficiency in Se was recorded in several health disorders caused by viruses, including COVID-19 [ 35 , 55 ]. Recent studies revealed that COVID-19 patients have lower circulating levels of iron (Fe), zinc (Zn), and Se [ 58 ]. Se supplementation in COVID-19 patients has been useful in preventing disease progression [ 59 ].…”