**9. AT, Coronavirus Disease 2019 (COVID-19), and Antioxidants**

AT is one of the essential tissues that modulate innate and adaptive immune responses in the body. This tissue modulates these responses by secreting adipokines such as leptin and adiponectin. However, during obesity, the function of this tissue is impaired. This means that the secretion of leptin and adiponectin increases and decreases, respectively, and eventually, the immune system's role is impaired [109]. In such cases, the chest wall is also affected by fat accumulation and impairs the lungs' proper functioning [110]. One of the consequences of an impaired immune system is the induction of inflammatory cytokines and the development of viral infections such as COVID-19 due to reduced natural killer (NK) cell activity. This infectious disease is caused by SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) (Figure 2) [111–113].

**Figure 2.** During obesity, adipose tissue (ATs) function is impaired, and secretion of leptin and adiponectin increases and decreases, respectively. Moreover, the immune system's function is impaired. One of the consequences of an impaired immune system is the induction of viral infections such as COVID-19 due to reduced natural killer (NK) cell activity. COVID-19 requires binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor and porphyrins on the cell surface to enter and then infect fat cells. Eventually, heme oxygenase-1 (HO-1) and ROS levels decrease and increase, respectively [109–113].

COVID-19 was first seen in December 2019 in Wuhan Province, China. Then, in January 2020, the disease's first cases were reported outside China (one in Japan and two in Thailand). Since then, the disease has spread rapidly to all countries of the world [114,115]. The condition was declared a pandemic on 11 March 2020, by WHO on 11 March 2020, and to date (22 February 2021), the total number of infected patients has reached 112,045,556, of which 2,479,625 people lost their lives (https://www.worldometers.info/coronavirus/, accessed on 20 February 2021). The virus requires binding to the Angiotensin-Converting Enzyme 2 (ACE2) receptor and porphyrins on the cell surface to enter and then infect fat cells. Eventually, heme oxygenase-1 enzymes (HO-1) and ROS levels decrease and increase, respectively [116–118].

Fatigue, headache, fever, and loss of taste and smell are symptoms associated with this disease, and most of these infected people recover without hospitalization. Various studies examining healthy people and people with underlying conditions have shown

that people with cardiovascular disease, kidney damage, diabetes, and severe obesity (BMI ≥ 30 kg/m2) are more susceptible to the virus [119]. The risk of developing COVID-19 does not depend on age, and the severity of the disease follows a different pattern at each age. According to Public Health England (PHE), the risk of COVID-19 death in people with a BMI between 35 and 40 kg/m<sup>2</sup> increases by 40%. However, this increase of risk in people with a BMI ≥ 40 kg reaches 90% [120]. As mentioned, obesity is directly related to COVID-19 disease and leads to increased inflammation, mitochondrial dysfunction, and increased ACE2 receptors. Numerous studies have shown that high BMI (≥30 kg/m2) and excess visceral fat (VF) are effective methods in diagnosing the severity of COVID-19, especially in obese patients [115,119,121].

For more than a year, the COVID-19 disease has affected human society in all aspects of life. The medical community has been able to develop effective vaccines against the disease. Furthermore, scientists in authoritative articles have suggested various drugs and nutrients reduce inflammation in the immune system, indirectly helping cure the disease. Among the various nutrients, antioxidants (vitamins C, D, and E, iron, and selenium) have always been at the forefront of strengthening the immune system and reducing inflammation in various body tissues, especially AT [122]. The recommended dose of vitamins C, D, and E in healthy individuals is 200 mg/day, 2000 IU/day (50 μg/day), and 15 mg/day, respectively. However, in patients who have inflammation in their immune system, it is better to increase the daily intake of vitamin C to 1-2 gr. It has also been suggested that the daily dose of vitamin D in these patients be increased to 10,000 IU in the first few weeks and then continued at a dose of 5000 IU. Also, the daily intake of vitamin E in these patients should be increased to 200 IU [123,124]. Consumption levels of another nutrient, iron, are usually about 8 mg daily in men, approximately 18 mg in women between the ages of 19 and 50, and around 8 mg in women over 51 years of age. However, if the person has inflammation in the immune system, 60 mg Fe should be consumed daily in both men and women and all age groups [114]. The daily intake of selenium in healthy men and women is 50 μg, respectively, but in inflammatory conditions, this amount increases to 200 μg per day [125].
