The Multifaceted Benefits of Exercise in Prevention of COVID-19

EXERCISE AND COVID-19

As the global death toll from the novel coronavirus disease 2019 (COVID-19) rises above 1.5 million, with more than 300,000 deaths in the US compared to 1,000 in Australia (1), health professionals must consider all interventions that have potential to reduce infection rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and morbidity and mortality associated with COVID-19. Exercise is a potent immune system stimulus (2) that mitigates many health risk factors associated with COVID-19 hospitalization. In this article we review how exercise enhances immune system function, discuss conditions and diseases associated with COVID-19 mitigated by exercise, and provide exercise prescription information for primary and secondary prevention of SARS-CoV-2 infection.

EXERCISE ENHANCES THE IMMUNE SYSTEM

The immune system includes many types of cells that work together to locate and destroy viruses, as illustrated in Figure 1. These include lymphocytes, neutrophils, and macrophages. Lymphocytes and neutrophils increase in number and function during exercise, enhancing the immune system response. It is commonly well-accepted that moderate intensity cardiorespiratory exercise benefits immune system function by increasing white cell counts and activity (4), but there is debate about the risks and benefits associated with vigorous intensity exercise.

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A long-standing tenet of exercise immunology, called the open window theory, suggests that after very intense and prolonged exercise the body enters a period of immunosuppression (5). Recently, some researchers have begun questioning this principle, arguing that the science which supports the open window theory lacks necessary rigor to reveal the true relationship between exercise intensity and immune system function (6). They suggest many variables, such as increased exposure to pathogens at large events and circadian rhythm disturbances caused by travel, contribute to increased upper respiratory tract infection rates in athletes. This increased upper respiratory tract infection incidence is a commonly cited justification for the open window theory. Some scientists advocate that common-sense examination of the relationship between exercise and disease risk, which demonstrates that exercise benefits health, is reason enough to suspect that intense and prolonged exercise does not, in fact, suppress the immune system. Indeed, this theory is at best limited to endurance athletes performing these types of exercise bouts; no evidence has been found during moderate intensity or shorter (<2 hours) exercise bouts. Readers interested in further discussion are encouraged to read a recently published debate on the topic (7).

Another way exercise, particularly resistance training, may help support a robust immune system is by promoting gains in muscle mass. Muscle, relative to other body compartments, is a low-inflammatory environment during periods of infection. A recent study in mice demonstrated that lymphocyte CD8+ T cells, which kill virus-infected cells, were protected from cellular exhaustion during viral infection when they resided in muscle tissue versus the circulation. These intramuscular CD8+ cells produce more progeny, allowing for greater CD8+ cell proliferation, and more virus-infected cell death (8). Thus, in theory people with greater muscle mass should be able to produce a more robust immune response during times of infection.

Interesting work in astronauts suggests individuals with higher cardiorespiratory fitness who already have a viral infection are less likely to experience virus reactivation. If reactivation does occur it produces lower viral loads (9). This may have implications for SARS-CoV-2 as there is some indication that people can become reinfected. Because research in this area is new, it is unclear whether reinfection is occurring from latent virus in the body or by new viral exposure.

EXERCISE REDUCES RISK OF SERIOUS INFECTION AND ASSOCIATED CHRONIC DISEASE

A recent analysis of comorbidities associated with hospitalization due to SARS-CoV-2 infection in the US suggests the 3 comorbid conditions most strongly linked to hospitalization are obesity, hypertension, and diabetes (Figure 2) (10). Decades of research have proven the strong link between exercise and reduction in all 3 of these conditions (11).

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EXERCISE PROMOTES A ROBUST RESPONSE TO VACCINATION IN OLDER ADULTS AND PERHAPS YOUNGER PEOPLE

It is now apparent that vaccines against SARS-CoV-2 will become widely available in 2021. How effective these vaccines will be (i.e., how much of, and importantly, how enduring the immune response elicited will be) remains to be understood. There is robust research evidence that cardio-respiratory exercise promotes a stronger vaccine response in older adults (17), resulting in more efficacious vaccination, with at least 8 studies in adults aged over 60 years (18). In younger persons the effect of exercise is less pronounced, possibly because their immune systems are more robust. However, it is possible that this exercise benefit to vaccination extends to all age groups who are immunocompromised. In general it appears that exercise improves vaccine effectiveness in older adults, and may improve effectiveness in other adults and children.

In addition to the effects of frequent exercise (or cardiovascular fitness), there is evidence that a single acute bout of exercise may boost vaccine response. One interesting study with younger people assessed how a 15-minute bout of upper body resistance training performed immediately before vaccination affected subjects who received a half pneumococcal intramuscular vaccine dose vs full dose (19). The results suggest that arm exercise prior to injection may provide benefit to younger people if a vaccine is not sufficiently effective, with significantly stronger antibody responses in the exercise group compared to control when a half dose vaccine was used. There was no difference between groups using a full dose. It is also worth considering the additional benefits of exercise immediately prior to vaccination; exercise is a known analgesic, and recent evidence suggests that pain at the site of a vaccination and subsequent vaccine reactions (tenderness, swelling, reduced appetite, and feeling unwell) are decreased by exercise (20).

It is possible that some COVID-19 vaccines will induce a response that is not completely protective in all populations. If this is the case, exercise may have an important role to play for not only older adults, but for all age groups, particularly people with comorbidities. There is emerging evidence that vaccine response is blunted in those who are obese (21) and have hypertension (22); diabetes does not appear to reduce effectiveness (23).

Initial research findings on the effects of acute and chronic exercise on vaccination responses suggest that as we learn more about this topic we may discover that exercise benefits younger as well as older individuals.

EXERCISE PRESCRIPTION FOR COVID-19 PREVENTION AND TREATMENT OF COMORBIDITIES

CONCLUSION

Both acute and chronic exercise have a robust effect on the immune system. Exercise and high fitness can protect people against initial and worsening infection, may protect against reinfection, and may reduce community spread by lowering viral loads in people who are infected and increasing the effectiveness of vaccines. Exercise should be recommended as a primary prevention strategy and a secondary COVID-19 recovery treatment modality.