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 ABSTRACT

The new severe acute respiratory syndrome corona virus 2 (COVID-19) is a highly infectious viral disease that mainly causes respiratory symptoms. Given the limited knowledge of this pathology, to try to make it less serious, specific medicines are being used and strategies has been tried to prevent the infection. There are numerous hypotheses for which lifestyle and previous conditions positively or negatively affect the pathogenesis, and particular attention is placed on nutrition and exercise. The article highlighted the importance of healthy lifestyle for strongly counteracting the disease.

Keywords: COVID-19; SARS-CoV-2; adiponectin; lifestyle; cytokine

Corona viruses (CoVs) belong to the sub family Orthocoronavirinae in the family of Coronaviridae and order Nidovirales, and this subfamily includes ⍺-coronavirus, β-coronavirus, ɣ-coronavirus and delta-coronavirus (Banerjee et al., 2019). In early January 2020, a new virus from bronchoalveolar lavage fluid samples was developed and it was discovered to be a beta coronavirus (SARS-CoV-2). The virus has spread to every corner of the world, and in 1 month many cases and many deaths have been diagnosed. A recent meta-analysis of the symptoms of COVID-19 patients from several studies has shown that the most common symptoms are fever and cough. In general, COVID-19 is an acute disease resolved but it can also be fatal, with a mortality rate of 4.3%. Death is caused by severe alveolar damage with progressive respiratory failure.

Most cases concern adults with an average age of 59. The risk factors for the more severe form of the disease are not yet fully understood, although older patients and those with complex medical conditions may be at higher risk. A high risk condition is represented by an immunodeficiency condition such as in patients with HIV (Esposito et al., 2012; 2015; Sun et al., 2020). COVID-19 causes destruction of the lung parenchyma and interstitial inflammation; the lungs gain weight with the formation of an edema, and interstitial thickening with moderate fibrosis is observed in some areas (Tse et al., 2004).

Considering that a high plasma level of IL-6 was found in deceased patients, mortality from COVID-19 was assumed to be due to virus-activated "cytokine storm syndrome” (Ruan et al., 2020).  At the moment it is difficult to talk about the immunological response to COVID-19, since there is not yet an ample knowledge, it is only possible to refer to what is known about SARS-CoV and MERS-CoV; it is therefore assumed that the first response is obtained through pattern recognition receptors (PRR), including type C lectin-like receptors, Toll-like receptors (TLR), NOD-like receptors (NLR) and receptors RIG-I-like (RLR). In addition, several inflammatory factors such as IL-6 and TNF-alpha are high (Addi et al., 2008). In the light of this, knowing that chronic inflammation, characterized by high levels of cytokines, is a condition present in people who are heavily overweight and obese, or simply with an unhealthy lifestyle, it can be assumed that the lifestyle is a factor that can make the disease more severe. So the purpose of this article is to evaluate whether lifestyle can have an impact on the incidence of the disease.

 The role of IL-6 in the viral response

In acute infections, IL-6, an endocrine cytokine produced by adipose tissue, represents pro-inflammatory signaling, important in regulating the host response. Several studies have shown that over-expression of IL-6 promotes viral survival and exacerbation of clinical disease; this is because it is produced in response to tissue damage and infections. IL-6 is able to activate the JAK / STAT3 pathway by promoting the transcription of downstream genes that transcribe for cytokines, receptors, adapter proteins and protein kinases (Tanaka et al., 2014). The action of IL-6 is essential in the antiviral response, as it regulates the response of T cells, remodels tissues, induces phagocytosis by macrophages and inflammatory resolution,  and prevents virus-induced apoptosis; however, if the IL-6 levels rise too high, adverse responses can occur, where mechanisms can be created that favor a persistent viral state (Agriesti et al., 2020).

An important role in the regulation of systemic inflammations is represented by the tumor necrosis factor, a cytokine released mainly by macrophages and a variety of other immune cells. Various studies have shown that, during infection with the influenza virus, epithelial cells lungs increased TNF- alpha expression, exerting strong activity against the virus (Seo and Webster, 2002).

In anti-COVID-19 therapy, IL-6 and TNF-alpha seem to be two important objectives, as high serum levels of these have been shown to be negatively correlated to T cells, while a reduction in concentrations leads to a recovery of the number of T cells and therefore an adequate immune response (Diao et al., 2020). Taking this into account, could lifestyle help to create conditions that are susceptible to disease, knowing that many factors can influence the response capacity of our immune system?

 Healthy habits

To strengthen our immune system, a great role is given to nutrition and exercise. A sedentary lifestyle and a high intake of foods rich in sugars and fats has led to an increase in conditions such as obesity, diabetes, cardiovascular diseases and autoimmune diseases, with a basic chronic inflammation that predisposes to a high susceptibility to bacterial and viral infections.

Important factors are not regulated, such as adiponectin. The adipose tissue secretes adipokines, adipocytokines that regulate the pathophysiological processes in organs and tissues. Adiponectin is the most abundant and important as it regulates the response of cytokines and is involved in energy metabolism, inflammation and vascular physiology; protects the tissues of the cardiovascular system and blood vessels by inhibiting pro-inflammatory and hypertrophic responses (Li et al., 2008). In the case of lung infection, during the early acute stages the systemic concentration of adiponectin decreases as there are high concentrations of TNF-alpha and IL-6 which inhibit it; however, when TNF-alpha and IL-6 factors decrease, adiponectin concentrations increase (Perrotta et al., 2019; Venkatesh et al., 2009).

To try to improve the health conditions and the immune response, the consumption of a Mediterranean diet accompanied by regular exercise is recommended. The reduction of the consumption of total energy, of simple fats and sugars, with the increase of the consumption of fruit, vegetables, lean fish, spices and aromatic herbs, is reflected in a reduction of chronic inflammation, with a recovery of the immune activity. The success of the Mediterranean diet is given by its composition, by the presence of functional foods containing polyphenols, terpenoids, flavonoids, alkaloids, sterols, pigments, unsaturated fatty acids and others (Alkhatib et al., 2017; Åsgård et al., 2007). Lifestyle could also include healthy hygiene habits, which play a vital role in COVID-19 disease; attention to the disinfection of food, especially fresh products, which often host a large number of microorganisms  (Guevara et al., 2015) and their conservation.

 Role of antioxidants

In the presence of viral infections there is an increase in the oxidative load, in particular, in the case of lung infections, affecting the lung cells. In the case of illness, the balance between oxidants and antioxidants is altered (redox balance), with various consequences such as oxidative stress and inflammation (Christofidou-Solomidou and Muzykantov, 2006).

Immune and inflammatory modulators are vitamin C, flavonoids, polyphenols and curcuminoids (Esposito et al., 2019; Esposito & Varriale, 2015; Hay et al., 2019; Perna et al., 2018), which can play a protective role in lung infections. Useful is a supplement of vitamin C, which is often used up, which can inhibit the infection, also used as an adjuvant in COVID-19 therapy (Carr, 2020).

In green tea polyphenols exhibit antibacterial, antiviral, anticancer, antioxidant activities, and represent a support against asthma and other lung diseases, managing to inhibit inflammation and epithelial mesenchymal transition (Yang et al., 2018). Flavonoids and curcuminoids manage to block the nuclear translocation of NF-kB, and therefore the signaling of Toll-like receptors, attenuating the lung lesions induced by the virus; they could play a role in both prevention and improvement of the prognosis of infected patients (Ling et al., 2020).

 Role of vitamin D

Vitamin D known for its role in the regulation of bone calcium homeostasis, both in children and adults; in recent years, however, it has been studied for its "accessory" functions, such as for the regulation of the development and function of the immune system. There is a correlation between vitamin D deficiency and autoimmune conditions, such as type I diabetes, multiple sclerosis, various allergies, and inflammatory diseases (Mailhot and White, 2020).

Vitamin D is a key regulator of the innate and adaptive arms of the immune system; the production of CYP27B1 in immune cells is induced by the detection of pathogens, regulated by a complex network of cytokines. In the presence of pathogens, macrophages can produce the hormone 1,25-dihydroxyvitamin D (1,25 (OH)₂D₃₎ which can act locally in the immune system (Iannuzzi, Rybicki, & Teirstein, 2007). The hormone 1, 25 (OH)₂D₃ induces the expression of several cytokines, such as interleukin 1β (IL-1β), important in innate immune response, and the neutrophilic chemokine IL-8 / CXCL8; it also regulates the innate adaptive immune interface, making dendritic cells less inflammatory (Adorini, 2005; Verway et al., 2013).

Concerning COVID-19 disease, a recent British Medical Journal editorial reported that vitamin D deficiency may be a potential risk factor. The disease is severe in the elderly population, but all age groups, including children, are sensitive. Supplementation with vitamin D is thought to be a prevention / treatment therapy: this has already been demonstrated for other viral respiratory tract infections, (Telcian et al., 2017; Yan et al., 2020).

 Role of exercise

Physical activity, regardless of being moderate or intense, stimulates the function of the white blood cells and a positive effect on the immune system. However, the answer is transitory, even if the effects accumulated over time seem to induce an immunological adaptation; regular training can reduce the risk of disease. Thanks to enhanced anti-inflammatory and immune activity, especially in diseases of upper respiratory tract infections.

Physical background can directly influence the response to cancer, asthma, chronic diseases and cardiovascular diseases, by regulating both cytokines production and the innate immune system, also known as nonspecific immune system or internal immune system, which includes cells such as neutrophils, macrophages, dendritic cells (DC) and natural killer cells (NK) (Wang et al., 2020).

 Conclusions

Infection with the SARS-Cov-2 virus causes COVID-19 disease, a condition in which you can have a mild respiratory or acute syndrome with the release of pro-inflammatory cytokines, IL-6 and TNF-alpha. To counter COVID-19 disease, it may be very helpful to try to reduce susceptibility with a regime of healthy behaviors, such as exercise, healthy eating and adequate hygiene rules. Carrying out daily exercise and trying to follow the Mediterranean diet, which involves a rich consumption of antioxidants, omega 3 fats and vitamin D, could help stimulate our immune system, making us stronger in counteracting the disease.

Acknowledgements

The Authors would like to thank Dr. Pia Furno and Dr. Rosalina Perna for editorial assistance. Eleonora Hay is supported by Ph.D program of University of Campania “Luigi Vanvitelli”, Naples, Italy and University of Medicine Greifswald, Greifswald, Germany.

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Can lifestyle have an impact on the incidence of COVID-19 disease.pdf