The general consensus among many studies on the relationship between physical activity and the immune system suggests that physical activity beneficially influences immunity [9,10,12,17]. Recent epidemiological studies have demonstrated that regular participants in physical activity showed lower rates of incidence, duration, and intensity of symptoms and risk of mortality from COVID-19 [18-22]. These reports suggest that moderate to high levels of regular activity above 150min/week show distinct beneficial effects compared to a low level of physical activity. Regular moderate physical activity leads to beneficial changes in the immune system through improved immune surveillance by providing an increase in the anti-pathogenic activity of macrophages as well as an increase in circulating immune cells (i.e., natural killer cells, neutrophils, lymphocytes, and immature B cells) and anti-inflammatory cytokines, consequently reducing the risk of lung damage due to influx of the novel coronavirus [20,23,24].

The degree of infection with SARS-CoV-2 is affected by various health-related factors, of which age is considered an important variable. This is because the severity and mortality rate of COVID-19 is the highest among the elderly [24]. Immunosenescence can be described as a deterioration of the immune system resulting from increasing age, and is considered a major cause of lowered immune surveillance, poor response to vaccination, and severity and high mortality associated with infectious diseases [17]. Immunosenescence is a complex aging-related change in the immune system duo to a series of biological events, including a reduction in humoral and cellular immunity, and an increase in inflammatory materials [25]. Aging stimulates the inflammatory process by increasing the secretion of pro-inflammatory cytokines (i.e., interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), IL-6, and C-reactive protein (CRP)) [9]. With aging, macrophages promote an inflammatory response that releases large amounts of TNF-α, IL-12, which can accelerate tissue damage [24].

Given the known positive effects of physical activity on immunity in the elderly, regular physical activity has been proposed as a reliable therapeutic strategy to mitigate the effects of aging on the immune system and offset the harmful effects of immunosenescence. More precisely, planned exercise considering the functional and physical level of the elderly is more effective than daily physical activity. This is well supported by a number of epidemiological and experimental studies in the elderly, indicating that participation in regular exercise reduces oxidative stress associated with aging and frequency of various immune biomarkers associated with decreased immunity [24,26-28]. This suggests that regular exercise in the elderly can delay the onset of immunosenescence and reduce the risk of infection by novel viruses such as SARS-CoV-2 [17].

Vaccines are one of the key public strategies for preventing COVID-19. Although vaccine-induced immunogenicity may be low in the elderly, regular exercise has also been shown to improve response to vaccination [29,30]. Gualano et al. (2022) reported that when COVID-19 vaccine is administered to individuals who have usually performed physical activity (> 150 min/week of moderate to vigorous intensity), they showed greater improved immunogenicity and higher antibody persistence compared to sedentary people [31,32]. They suggested that physical activity enhances immunogenicity for the SARS-CoV-2 vaccine and sustains its effects over time.

In general, regular or chronic physical activity that affects human systems is called “exercise training”, which can be defined as the repeated bouts of exercise during a short or longterm period. Many reports indicate that exercise training is an effective intervention that reduces immunosenescence and chronic inflammation, and it enhance the improvement of immunity and effectiveness of influenza vaccination in the elderly [33-35]. It is well known that adaptation of the immune system to exercise training depends on exercise modes, such as exercise type (i.e., endurance training, resistance training, etc., time, and intensity (low intensity (below 40% VO_2max), moderate (40-69% VO_2max), vigorous (70-90% VO_2max)) [25]. Exercise types can generally be divided into endurance training, such as brisk walking, jogging, swimming, cycling, resistance training using equipment or body weight without equipment, and flexibility training. Endurance training, which refers to regular aerobic exercise, generally appears to improve the function of the cardiovascular and respiratory systems. Resistance training is commonly used to increase muscular strength and reduce metabolic disease and risk of falling in the elderly [25].

Endurance exercise training, composed of moderate to relatively vigorous intensity workouts (40-70% VO_2max), is associated with a lower incidence of upper respiratory tract infection (URTI) [9,25]. These reports supporting the “J-curve” hypothesis showed that URTI incidence was decreased in moderate intensity physical training, but increased in participants in high-intensity training or long-term competitive sports. High intensity exercise (> 85% VO_2max) induces transient immunosuppression called “open windows”, which increases susceptibility to infection [23,27]. Shaw et al. (2018) suggested that exhaustive exercise bouts and heavy chronic training changed T-cell immunity to an anti-inflammatory state. This induces impairment of immunity by mounting an inflammatory response to immune challenges, consequently leading to weakened defenses against intracellular pathogens and increasing the risk of infection and viral reactivation [36]. In our previous study on the effect of acute aerobic exercise on immunity in healthy adults, we investigated the effect of different acute exercise intensities on serum leukocytes and lymphocyte subtypes in the exercise amount of 400 kcal, the daily exercise energy consumption recommended by the ACSM [37]. Our study showed that at a high intensity (85% VO_2max) of exercise, circulating lymphocytes, and NK cells were reduced to less than the rest level at recovery time after exercise, and T4/T8, the ratio showing immunosuppression, decreased to less than the rest level immediately after exercise. We suggested that low- to moderate-intensity exercise is recommended to prevent systemic immunosuppressive conditions [37]. Furthermore, in another study, long-term high intensity training led to a decline in the ability of innate immune cells to respond to acute challenges, thereby increasing the risk of infection [38].

Despite the vulnerability of the immune system to high intensity exercise training, the overall anti-inflammatory effect of regular physical activity can reduce the risk of aging-related chronic diseases characterized by chronic inflammation [39]. Less than 60 min of moderate endurance exercise training have already been proven to have anti-pathogenic activity through improved circulation of immunoglobulin, anti-inflammatory cytokines, neutrophils, NK cells, cytotoxic T cells, and immature B cells, which play important roles in body defense [40-45]. Non-pharmaceutical physical activity interventions may be an important source of immunological protection against novel coronaviruses. Well-managed endurance training may prevent the novel coronaviruses from spreading rapidly from one person to another [46]. According to a recent randomized controlled trial in COVID-19 patients with mild or moderate symptoms, two weeks of moderate aerobic exercise reduced the severity and progression of COVID-19 disorders and increased the levels of leukocytes, lymphocytes, and immunoglobulin A, positively affecting immune function [47]. <Table 1> shows studies about effects of endurance and resistance exercise training on immune functions in the elderly.

Resistance training involves all types of exercises that contract skeletal muscles in response to any kind of force with or without an equipment. Resistance training is one of the various modalities of exercise used to prevent diseases such as cardiovascular disease and type 2 diabetes. However, studies on the effect of resistance training on immunity in the elderly have yielded inconsistent results. Some studies [48-51] have shown that short-term resistance training interventions (8-12 weeks) in healthy elderly individuals (ages 65-84) have no beneficial or detrimental effects (impact count, apoptosis, proliferation, etc.), while other studies [52-54] have found beneficial effects on inflammatory status in patients with breast cancer, metabolic syndrome, or healthy elderly (69 years old). Some studies have reported that resistance training is effective in reducing the serum concentration of pro-inflammatory cytokines (TNF-α, IL-1, and IL-8) [55,56]. One study showed that eight weeks of resistance training reduces the serum concentration of cytokines (IL-6, TNF-α) and C-reactive protein and induces molecular changes in TNF-α gene expression in elderly women. They suggested that this may be related to immunomodulatory and anti-inflammatory effects because resistance training releases myokines (cytokines produced in contracting muscles), particularly IL-6, which acts as a TNF-α antagonist during exercise [57]. These inconsistent results could be due to distinct exercise prescriptions (Type, frequency, intensity, and time), sex and genetic discrepancies.

Structured and progressive resistance training programs can be developed according to the appropriate and specific training purposes for the elderly. Among the various protocols available, the bi-set method demonstrates an efficient proposal for a systematic and individualized resistance training program that follows the resistance training prescription recommendations for the elderly. ACSM and American Heart Association (AHA) recommend that resistance training should be performed for as little as 15-20 minutes a day, 8–12 repetitions, and 60–70% of one-repetition maximum (1RM) on two or three nonconsecutive days per week for the elderly [58,59]. There are various types of resistance exercises such as chest presses, squats, knee extensions, and lunges, but most of these exercises need to be appropriately modified for the elderly [58]. For example, it is recommended that the elderly hold chairs for squats or use elastic bands for chest presses.

The ACSM and WHO, which are authoritative organizations on global health issues, recommend that the elderly actively participate in physical activities to prevent COVID-19 during the pandemic. The WHO recommends that healthy individuals should exercise at least 150 min per week for adults and 300 min per week for children and adolescents. These times should be divided during the days of the week and according to individuals’ lifestyles [60]. The ACSM has also recommended guidelines for moderate intensity activities that can be practiced during the pandemic period, including aerobic exercises and strength training, indoors or outdoors, with permission of government authorities as long as infection prevention measures are maintained [61]. This organization recommends 150-300 min per week of moderate intensity aerobic physical activity and two sessions per week of muscle strength training. Additionally, the ACSM offered several useful tips for maintaining physical activity in older adults at a possible level during the COVID-19 pandemic [62].

Walking is a very useful outdoor activity for improving cardiorespiratory fitness, and exercising in local parks or natural environments, cycling, and gardening are good options for outdoor activities. If it is not possible to exercise outdoors, walking in a place at home, going up and down stairs, dancing to cheerful music, and using home cardio machines, such as stationary cycles, are can be alternatives. [61,62]. The WHO suggested some tips to reduce sedentary behavior and increase active daily life, including having short active breaks during the day, participating in an online exercise class, standing up whenever possible, and using indoor exercise equipment such as stationary bikes and rowing ergometers [63]. The WHO has also suggested examples of home-based exercises to strengthen musculoskeletal and cardiorespiratory fitness, including knee-to-elbow (increasing heart and breathing rates), plank (strengthening core muscles), back extensions (strengthening back muscles), squats (strengthening legs and gluts), side knee lifts (increasing heart and breathing rates), superman (strengthening back, glutes and core muscles), bridge (strengthening gluts), chair dips (strengthening triceps), chest opener (stretching chest shoulders), child’s pose (stretching back, shoulders and sides of the body), legs up the wall (being comfortable, relaxing and de-stressing), and seated meditation (relaxing and clearing one’s mind) [63].

In a previous study, I examined the effects of balance training to improve functional performance in the daily life of the elderly and suggested that balance training improves posture control and balance recovery ability of the elderly [64]. Balance training can be considered a useful homebased exercise program for the elderly in another pandemic era because it can improve various physical fitness, such as muscular strength, as well as balance ability to prevent falls that frequently occur in the elderly [65]. <Table 2> shows an example of some modifications to the proposed home- or community-based balance training programs in my previous study and another study [64,65].