Immunity benefits of yoga and physical exercises in the era of COVID-19 Pandemic

Assessment of the functional status and level of physical fitness of people living Immunity benefits of yoga and physical exercises in the era of COVID-19 Pandemic. Abstract Purpose. The novel coronavirus is the recently emerged disease of the respiratory system for which various national and international research agencies are putting joint efforts towards finding a permanent cure. Recently, the vaccine against coronavirus has been designed by various pharmaceutical agencies that are currently undergoing clinical trials. Since vaccines prevent infection by strengthening the defense system of the body, we proposed that yoga and physical exercises could act as an integrative approach to synergize the immunogenic response of the coronavirus vaccine. Yoga and physical exercises are already known to boost immunity against several other infections. Materials and Methods. In the present review article, we aimed towards exploring the role of yoga and physical exercise as an immunity booster against coronavirus infection. Being India is a low-income country, yoga and physical exercises could be an excellent cost-effective strategy that could be administrated along with vaccine trials to enhance immunity against virus infection. Results. In the present review, we analyze the studies conducted to date focusing on finding the role of yoga and physical exercises to prevent coronavirus infection. We also described the potential exercises, which are already known to enhance the immunity of the body by particularly targeting respiratory disease. Conclusion. The present review article will help in providing the health agencies potential targets, which could further be explored to established a standard exercise module to enhance the vaccine-mediated immunity against coronavirus infection.


Introduction
The organized, coordinated, and repeated movement of body parts created by skeletal muscles that result in energy expenditure is known as physical exercises. Physical exercise can include sports activity, yoga, aerobics, running and other outdoor games [1]. Yoga is the traditional an ancient art of mind body balance which is practiced in India from centuries. Yoga and physical exercises are popular worldwide for achieving physical and mental fitness and are recommended as core elements of balanced living. Yoga and physical exercise, besides managing excess body weight, helps in fighting communicable diseases which may include viral infections, systemic inflammation and chronic non-communicable diseases. A large volume of studies has highlighted the applications of physical activities in maintaining homeostasis in non-communicable diseases also by lowering stress levels and boosting of immune power of the body [2]. Due to the lack of allopathic treatment of recently emerged novel coronavirus disease, various strategies such as social distancing and personal sanitization has been recommended by various health agencies to prevent COVID-19 infection. Health agencies have recommended that individuals should take necessary protective steps to increase their immunity, strengthen the respiratory system, and alleviate fear, fatigue, and depression. Currently, vaccines have been designed by various pharmaceutical companies to activate the body defense system to prevent coronavirus infection [3].
Since vaccines prevent viral infection by strengthening the immune system of the body, we proposed that if vaccine trials are integrated with yoga and physical exercises, it can help in boosting the immunogenic response of the coronavirus vaccine. In the present article, we performed an integrative analysis of literature on the role of physical activity in enhancing immunity against coronavirus infection. For this, the bibliographic analysis performed for the knowledge of respiratory diseases, effects of physical activity on the immune system and indicated an understanding of the latest research on coronavirus infection immunopathogenesis, including its interaction with the physical and health conditions of the host.

Search Strategy and Selection Criteria
References for this review were identified through searches of PubMed for articles published by the use of the terms "Coronavirus," "COVID-19," "SARS-CoV-2," and "Yoga and physical exercise and immunity." Relevant articles published were identified through searches in the authors' files, in Google Scholar, Research Gate, and Springer Online Archives Collection. Materials resulting from these searches and relevant references cited in those articles were reviewed, and information from relevant articles was incorporated in the present review. Articles published in a language other than English were not included in the present review. We administered a search strategy designed with the help of a multidisciplinary team including a librarian MeSH terms "Coronavirus," "COVID-19," "SARS-CoV-2," and "Yoga and physical exercise and immunity" on January 12th, 2021. To be included, the studies should have administered physical activity or Yoga for improving immunity in any population. We have not excluded the studies based on the diseased population as we wished the present study findings should be generalized for the global population. Articles published in a language other than English were not included in the present review. Our sample search strategy administered in the Embase is "('physical activity'/exp OR 'physical activity OR 'exercise'/exp OR exercise OR 'yoga'/exp OR yoga) AND ('immune system' OR immunity) AND 'coronavirus disease 2019'".We found 16 articles relevant and included for the final analysis and narrative synthesis ( fig.1).

Novel Coronavirus COVID-19 Pandemic
The novel coronavirus is a disease of the respiratory system, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In February 2020, the world health organization declared the name COVID-19 to coronavirus infection [4]. The outbreak of novel coronavirus occurred from the Wuhan city of China in December 2019 by the zoonotic transmission of viruses from animals to humans. COVID-19 is the fourth emerged novel coronavirus after HCoV-229E, SARS, and MERS-CoV [5]. Being contagious, the disease is spreading fiercely around the world within weeks taking the form of a pandemic. The infected person shows the symptoms of fever, fatigue, cough, chest congestion, difficulty in breathing, and inflammation in the lungs [6]. The appearance of symptoms may take a week after the infection, which makes it very difficult to diagnose the infection based on symptoms. Molecular testing methods that confirm the three viral genes-E, RdRp and N, in nasopharyngeal and oropharyngeal swabs using the 102 Health, sport, rehabilitation Здоров'я, спорт, реабілітація Здоровье, спорт, реабилитация

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RT-PCR can diagnose disease before the appearance of symptoms [5], but due to the high cost and requirement of sophisticated laboratory facilities, mass testing is not feasible at the time of an outbreak. Due to unavailability of cheap detection method and specific pharmaceutical treatment or vaccine of the viral infection, alternative strategies which could limit the infection, is implemented all around the world. The worldwide outbreak of the pandemic of COVID-19 has contributed to a massive global health crisis. In contrast to seasonal influenza, SARS-CoV-2 mainly spreads through droplets, and is suggested to have greater transmissibility. Due to spread of COVID-19 vis asymptomatic or minimally symptomatic individuals who do not pursue any clinical examination, pandemic emerges as a major health concern [7].  Cytokines Inhibition of pro-infammatory cytokines production including IL-1, IL-2, IL-12, IL-18, IFN-γ and TNF-α Muscle contraction during exercise leads to upregulation of antinfammatory and proinfammatory cytokines by [17] Neutrophils Recruit inflammatory mediators like TNF-α and IL-1β Aerobic exercise led to significant reduction in neutrophil [18] Leukocytes Fight infection and defend the body against other foreign material Physical activity enhances concentration of circulating leukocyte [19] Natural killer cells (NKs) Control several types of tumors and microbial infections NK cells enhance due to cellular stress promoted by physical exercise [20] Immune Compromisation in COVID-19 Immune response of the body act at two levels, innate immunity and adaptive immunity. The innate immune response involves the physical and chemical barriers which restrict the entry of pathogen in the body. Certain immune cells such as macrophages, dendritic cells, natural killer cells, Health, sport, rehabilitation Здоров'я, спорт, реабілітація Здоровье, спорт, реабилитация 8(3) neutrophils are part of innate immunity. Apart from the cellular barriers, there are molecular barriers such as cytokines, interleukins), nitric oxide and anion superoxide which eliminate the invading pathogen. The more specific immune response is adaptive immunity which has cellular barriers made up of T lymphocytes and B lymphocytes and their products, such as antibodies and cytokines [2]. The host's immunity is an essential factor to promote infection eradication. Severely affected COVID-19 patients exhibit the compromised immune systems indicated by lymphopenia and elevated levels of C-reactive protein. Fever, exhaustion, and dry cough are predominant symptoms present in patients with COVID-19. Most patients have a better prognosis, but elderly patients and those with chronic underlying disorders may have worse outcomes [8].
In the early infection stages, patients are usually afebrile with only chills and respiratory symptoms [9]. The clinical symptoms may range from asymptomatic or moderate symptomatic to extreme forms of respiratory failure that may require ventilation support in the intensive care unit (ICU). Additional symptoms may involve sepsis, septic shock, and multiple organ dysfunction syndromes or multi-organ and systemic manifestations [10].

Yoga and physical exercises Can Boost Immunity against coronavirus
The host's immunity is an essential condition to promote infection eradication and, therefore, to combat the COVID-19 infection, the host must possess and robust immune system. Patients infected with the coronavirus known to have a disturbed immune system [12]. An important clinical feature of COVID-19 is impaired immunity characterized by lymphopenia and elevated CRP levels [9]. The frequent representation of elderly people in cases infected with COVID-19 indicates the possible role of immunosenescence that underlies their vulnerability to the infection. The magnitude and outcome of the viral infection may be either the result of a successful cellular/innate immune response that fights SARS-CoV-2, as seen in patients with mild clinical signs of infection, or a state of immunosuppression weakens the host's defense and often overwhelms it. Several studies have highlighted the positive effect of yoga and physical exercises in the management of communicable diseases like influenza, tuberculosis (TB), and acquire immune deficiency syndrome in which the state of the immune system is an essential factor in the development of the disease [10]. Yoga and physical exercises have been found to prevent acute respiratory illness [12]. Breathing exercises have been reported in previous studies to enhance immunity, which helps combat viral infections subsequentially [13].
Despite the lack of reliable evidence on how physical activity strengthens the immune response to the coronavirus, multiple studies show that daily yoga and physical exercise is explicitly connected to reduced mortality from respiratory diseases, better vaccination response, and general metabolic homeostasis [14]. Daily yoga and physical exercise helps to strengthen the immune system while helping to reduce respiratory disorders and thereby defend against infections such as COVID-1 [15]. Yoga and physical exercise is much more critical for the elderly population, as these people typically have larger comorbidities and are more prone to developing the disease in comparison to the current coronavirus [16]. Proposed that people who have been healthy during their lives have less prominent features of immunosenescence, which could be a likely preventive factor against the occurrence of COVID-19 complications.
Innate and adaptive immunity function in a synchronized manner to fight against viral infections which otherwise can cause immunopathology. Physical activity of moderate strength is responsible for enhancing the anti-pathogenic activity of macrophages thus increasing the circulation of immune cells, immunoglobulins and antiinflammatory cytokines, thereby reducing the pathogenic load on organs such as the lung and decreasing the risk of lung damage due to inflammatory cell infiltration [21]. Inflammatory responses and stress factors are reduced during daily yoga and physical exercise while lymphocytes, NK cells, immature B cells and monocytes are elevated. Therefore, there is an increase in immune vigilance and a decline in the systemic inflammatory response. Molecular mechanisms based on yoga and physical exercise are known to increase or decrease the levels of INF-γ, thus exhibiting a buffering action to restore the imbalance marked by either suboptimal or excessive expression of immune responses. Yoga and physical exercises could improve innate immune responses during incubation periods of viral infection by regulating the IFN-γ levels [22]. The level of various immune cells including CD4, CD8, Blymphocytes and Natural Killer cells, knows to shift towards homeostasis level via yoga and physical exercises [23]. NK cells are innate lymphocytes that act as the first line of protection against the spread and eventual tissue damage of invading viruses. The available evidence confirms that pro-inflammatory markers, including interleukin-1 (IL-1) beta, IL-6 106 Health, sport, rehabilitation Здоров'я, спорт, реабілітація Здоровье, спорт, реабилитация 8(3) and tumor necrosis factor (TNF)-alpha, maybe downregulated by yoga and physical exercises [2].
Severe COVID-19 infection is correlated with cytokine storms represented by increased cytokine levels (IL-6, IL-10, and TNF-a), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells [24]. The contraction of the muscle during the yoga and physical exercise enhances the production of antiinflammatory (IL-10 and TGF-β) and proinflammatory cytokines (IL-1, IL-2, IL-12, IL-18, IFN-γ and TNF-α) in a duration and strength dependent manner [25]. The stimulation of the muscle fiber during yoga and physical exercise is responsible for increasing the release of calcium (Ca2 +) and thereby facilitating the synthesis of proinflammatory cytokines, namely TNF-alpha and IL-1β, which function in the production of selectins, which in turn draw neutrophils to the site [26]. Physical activity is also responsible for increasing circulating leukocyte concentrations due to the shearing of immune cells, especially secondary lymphoid tissues such as the liver, spleen and lungs, in the blood vessels. After continuous yoga and physical exercise, the leukocyte concentration stays high with a peak of 30-120 minutes, which can last for up to 24 hours [19]. For populations at risk or already suffering from COVID-19, yoga and physical exercises could be a complementary intervention.

Conclusion
Coronavirus vaccines are a promising measure to end to COVID-19 pandemic. The yoga and physical exercise, which is already known to enhance the immune response in many vaccine trials, could be integrated with the COVID-19 vaccine trials to enhance the immunogenic potential of the vaccine.
Other advantages offered by yoga and physical exercise may include improved immune vigilance, enhanced immune competence, avoidance or elimination of overweight, improved physical and cardiopulmonary conditioning, attenuation of systemic pro-inflammatory and pro-thrombotic disorders, reduction of oxidative stress, improvement of glycemic, insulinic and lipid metabolisms, as well as improvement of the reaction to vaccination. Therefore, the studies which could highlight the role of yoga and physical exercises in enhancing immunogenic response to coronavirus vaccine should be conducted to establish a direct correlation.

Conflicts of interest
None of the authors have any competing interests concerning the review.

Ethics approval and consent to participate
Not Applicable