SARS-CoV-2 is responsible for the COVID-19 pandemic that started in Wuhan, China, and has already claimed more than 4000 lives in Latvia (inhabitants in Latvia on 01.01.2019: 1.908.000, number of COVID-19 cases: 291.000 on 10.01.2022).
SARS-CoV-2 is a single-stranded RNA virus, such as Ebola virus, HIV, coxsackievirus, influenza, SARS, MERS (Zhang et al. 2020). Recent investigations, mostly conducted in the country of SARS-CoV-2 origin, China, showed an interaction between selenium (Se) level in the body and the SARS-CoV-2 virus. It has been shown that Se deficiency promotes mutations, replications and virulence of different RNA viruses (Moghaddam et al. 2020).
Despite the existing evidence, discussions are still taking place on what role, if any, Se may play in reducing the severity and mortality of COVID-19 infection. Studies of recent months show a close relationship between Se, Selenoprotein P (Sepp1) deficiency, oxidative stress level and COVID-19 disease incidence, severity and prognosis (Cheng and Prabhu 2019; Moghaddam et al. 2020; Saito 2020; Zhang et al. 2020). Se deficiency is thought to suppress the non-specific cell-mediated immune response and adaptive antibody response, which leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality (Jayawardena et al. 2020). Se deficiency can therefore weaken the immune response to viruses and increase the virulence of particular viruses, also including coronaviruses. Meantime, viral infections correlate with increased reactive oxygen species (ROS) production. Oxidative stress can in fact be considered the hallmark of viral infections. ROS, on the other hand, can enhance viral replication (Saito 2020).
Se is fundamentally important to human health because it acts as an essential part of several major metabolic pathways, such as antioxidant defense functions, immune functions and is incorporated in more than 20 seleno-proteins (SelP). Sepp1 is one of the most important seleno-proteins. It is well known that Se has a protective effect against some forms of cancer, it decreases cardiovascular disease mortality, regulates the inflammatory mediators in pulmonary diseases, etc.
Besides, Se plays complex roles in the immune system, especially in the oxidative stress processes. The main pathways of ROS-producing systems include mitochondrial oxidative phosphorylation, phagocytic cell NADPH oxidase, xanthine oxidase. Se is an essential ultra-trace element, which is incorporated into more than 20 SelP, as seleno-cysteine in their active center (Guillin et al. 2019).
Sepp1 is an extracellular, monomeric glycoprotein that contains up to 10 seleno-cysteine residues in the polypeptide chain. In human plasma, it accounts for at least 40% of the total Se concentration. Sepp1 can bind to heparin, cell membranes and is associated with endothelial cells. Sepp1 is considered to function as an extracellular oxidant defense; in human plasma, it protects against peroxy-nitrite-mediated oxidation and reduces phospholipid hydro-peroxide in vitro. Its concentration in plasma varies much with Se intake as immunochemical assays have demonstrated, but other factors may also have an influence (Åkesson et al. 1994).
Some of these SelP are important for defense from viral infections, oxidative stress and participate in thyroid hormone metabolism. A recent investigation showed that Se deficiency is associated with greater susceptibility to viral RNA infections and more severe outcomes (Hiffler and Rakotoambinina 2020). Similar to Se, SelP such as Sepp1, are essential for an effective immune response to different infections.
Among the 25 SelP genes identified to date, several have important cellular functions in antioxidant defense, cell signaling and redox homeostasis. There are many ways in which the host metabolism could be affected during viral infections, leading to a dysregulation of redox homeostasis and therefore oxidative stress. Viral pathogens usually induce oxidative stress by increasing the generation of ROS and alternating the cellular ROS scavenging or dis-mutation systems. It is known that Se and SelP, however, play important roles in controlling redox homeostasis (Guillin et al. 2019).
Oxidative stress (OS) is a biological circumstance driven by the imbalance between pro-oxidant and antioxidant equilibrium (Taso et al. 2019). OS is caused by free radicals (FR), reactive oxygen species (ROS) and RNS which damage lipids, proteins, bio-membranes, DNA and many other macromolecules. The degree of lipid peroxidation is often used as an indicator of OS-mediated damage. Whereas, the concentration of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and their metabolite adducts in the whole blood, blood plasma, serum, other body liquors, and tissues are generally used as biomarkers of lipid peroxidation.
In recent decades, Latvian agriculture has mainly used mineral fertilizers produced in Finland and Sweden, which are enriched with microelements, including Se. This has increased the amount of trace elements, including Se, in local foods. Consequently, Se deficiency in the population of Latvia has decreased in the last 10−15 years (Kumerova et al. 1998, 2000).
Consequently, in the field of public health, one of the priority areas is the reduction of Se deficiency.
The aim of this study was to detect levels of Se, Sepp1, MDA and 4-HNE adducts in the acute period. First, in patients hospitalized in Pauls Stradiņš Clinical University Hospital in the COVID-19 department or intensive care unit, and patients 2 months following their discharge from the hospital. Thus, several hypotheses would be tested, including Se deficiency may reduce immunity and thus contribute to the high incidence of COVID-19; the degree of Se and/or Sepp1 deficiency may be directly related to the severity and prognosis of the disease; oxidative stress directly affects the incidence and severity of the disease.