key: cord-1002305-hsehdaci
authors: Majeed, Muhammed; Nagabhushanam, Kalyanam; Gowda, Sujay; Mundkur, Lakshmi
title: An Exploratory Study of Selenium Status in Normal Subjects and COVID-19 Patients in South Indian population: Case for Adequate Selenium Status: Selenium Status in COVID-19 Patients
date: 2020-11-11
journal: Nutrition
DOI: 10.1016/j.nut.2020.111053
sha: 9e0ff76c737a7d443c59673c6cafa7cc99a70e83
doc_id: 1002305
cord_uid: hsehdaci

The pandemic of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of individuals, causing major health and economic disruption worldwide. Although the numbers of infections are declining in some parts of the World, new infections are steadily rising in India. Nutrition and immune status are two critical aspects of fighting the virus successfully. Recently, the selenium status was reported to positively correlate with the survival of COVID patients as compared with non-survivors. We analysed the blood serum levels in apparently healthy (N=30) individuals and those with confirmed COVID -19 infection(N=30) in the southern part of India. Patients showed a significantly lower selenium level of 69.2 ±8.7 ng/ml than controls 79.1 ± 10.9 ng/ml, the difference was statistically significant (P=0.0003). Interestingly the controls showed a borderline level of selenium, suggesting that the level of this micronutrient is not optimum in the population studied. The results of this exploratory study pave the way for further research in a larger population and suggest that selenium supplementation may be helpful to reduce the impact of the virus.

The pandemic of Severe acute respiratory syndrome coronavirus-2 (SARS- infection has led to a devastating effect on the health and economy of the World.

Age and presence of comorbidities such as obesity, diabetes, cardiovascular diseases, hypertension, and pulmonary diseases are associated with disease severity [1] . Over 80% of the cases are reported to be mild, while the rest is associated with severe pulmonary distress, shock, myocardial injury, heart failure, dysfunctional coagulation, and renal failure. The severity of the disease is associated with an overreaction of the immune system leading to a release of several cytokines and chemokines, also known as cytokine storm [2] .

There is no specific therapeutic drug recommended for the treatment of COVID-19. Antiflu drugs and corticosteroids are being used in clinical settings. Other therapeutic strategies include convalescent sera from recovered individuals, interferon, anti-inflammatory therapies, and ventilator support. The search for vaccines and other pharmacological agents to prevent viral infection is underway to fight the pandemic.

Selenium is an essential trace element incorporated into 25 selenoproteins having selenocysteine in their active center. Some of these selenoproteins are essential for defense against viral infections, control of thyroid hormone signaling, protection against oxidative stress, protein folding and mitochondrial health [3] . Glutathione peroxidases and thioredoxin reductase are selenoproteins critical for antiviral defense through their redox signaling and homeostatic activities [3] . Viral infection causes oxidative stress enhancing the replication and accumulation of mutations in the viral RNA genome, leading to increased virulence and damage to host [4] .

Selenium deficiency contributes to mutations in the viral genome to highly virulent forms, and is associated with increased susceptibility and pathogenicity of viral infections, which can be alleviated by adequate levels [4] . Selenoproteins are also essential for an effective immune response to infections. Selenium supplementation has been reported to reduce allergic asthma, augment vaccine responses, and reduce the progression of tuberculosis or HIV-1 [5] . India is now reporting increased incidences of COVID-19 infection. There are very few reports on the average serum selenium levels in Indians. Interestingly, an association was reported between the cure rate from COVID-19 and the basal selenium status in different regions of China [6] .

Strengthening this observation, a deficiency of elemental selenium, and its transporter protein (SELENOP) levels were reported in COVID-9 patients in Germany [7] . Based on these reports, in the present exploratory study, we assessed the serum selenium levels in COVID-19 patients and control individuals to understand the correlation between selenium levels and viral infection and recovery.

The study was conducted in 60 subjects with 30 COVID-19 positives and 30 apparently healthy individuals as controls in the age group of 18-45 years. Control subjects were without any signs and symptoms of viral/bacterial infection with body temperature between 96 0 to 99 0 F and greater than 90% oxygen saturation. SARS-CoV-2 infection in patients was confirmed by the nasopharyngeal swab RT-PCR test. The patients were in stable condition with fever, dyspnea without hypoxemia. Asymptomatic patients, those requiring on tube feeding or parenteral nutrition, patients on ventilator support or in unstable condition and those admitted to isolation ward for greater than 24 hours of confirmed COVID-19 positive test were excluded from the study. Subjects participating in any other study, including any form of dietary supplements/multivitamins or disease-specific oral nutrition supplements, were excluded from the study. Informed consent was taken from all the subjects. The study was conducted in accordance with the regulatory requirements as per ICMR [9] .Further, in the National Nutrition Examination Survey, serum selenium levels (1.51 μmol/l or 118.8 ng/ml) was independently associated with anemia in older adults [10] . In the Nutritional Prevention of Cancer (NPI) serum selenium concentrations at 1.34-1.54 µmol/l (106-121 ng/ml) showed a protective effect against cancer in clinical studies [11] [12] [13] We observed that 43.3% of subjects in COVID-19 infection had a lower selenium levels in comparison to 20% of the control subjects ( Figure 1 ). Selenium concentrations below 70ng/ml in serum are correlated with limiting supplies of the micronutrient as per the Food and Nutrition Board of the Institute of Medicine. [14] Intriguingly, we observed that the mean levels in control individuals were only 79.1 ± 10.9 ng/ml, which is much lower than the optimum required levels, suggesting a general deficiency of this micronutrient in the population studied.

The urine samples did not show a detectable value of selenium.

Nutrition and diet influence the competence of the immune system and influence the risk and severity of an infection [15] . The micronutrients such as vitamins iron, selenium, and zinc provide the antioxidant and anti-inflammatory support and are essential for optimal functioning of the immune system [16] . The nutritional status of an individual is associated with the risk, severity, and outcome of SARS-CoV-2 infection, thus stressing the importance of maintaining macro-and micronutrient status as a preventive measure for COVID-19 [17] .

Selenium deficiency is reported to affect 500 million to 1 billion people worldwide, mainly due to inadequate intake from diet. Dietary selenium availability, in turn, is controlled by soil-plant interactions. Loss of selenium rich soil has reduced the dietary availability of selenium, thus increasing the deficiency of this micronutrient worldwide [18] .India is a vast country with wide geographical soil status. In one study, the northern part of India was reported to have normal levels of soil selenium [19] . Similar data is not available for southern part where the present study was conducted. In one study in 201 adults in Mumbai reported an average concentration of 100ng/ml, was reported [20] . In contrast, our results show a borderline low level in the control subjects, suggesting that selenium deficiency may be more widespread than reported.

In conclusion, this exploratory study demonstrates that selenium status is lower in COVID-19 patients than in healthy control subjects, in corroboration with two studies published recently. In the present study relatively young patients with mild symptoms with slight hypoxia were analyzed, unlike the German study, wherein patients were older and had severe symptoms.

The observational nature of the study precludes any conclusion on the casual relationship between selenium status and COVID-19. Future studies in a larger population would be valuable. 

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We thank the clinicians from Apollo hospital Chennai, and Vagus hospital Bangalore for providing the COVID-19 patients samples and control samples. We thank the Neuberg Anand Reference Laboratory, Bangalore for analyzing the serum selenium levels. We thank all the members of ClinWorld team who were involved with the study. 

Improving the Se status by nutritional measures or supplementation may be helpful in reducing the devastation caused by this virus in India