Staying physically active can be a strategy to boost the immune response induced by vaccines against covid-19. This is the conclusion of a study carried out with 1,095 volunteers by USP researchers and collaborators. The data was released on Monday, August 9, on the Research Square platform , yet without peer review.
The benefit provided by physical activity was observed mainly among participants who remained active for at least 150 minutes a week and did not present sedentary behavior, that is, who did not spend more than eight hours a day sitting or lying down. “Active time” was considered both that dedicated to exercise and other leisure activities (walking, running, dancing, swimming, walking the dog, etc.), as well as domestic activities (cleaning the house, taking care of the garden, washing clothes in hand), to work (carrying weights, carrying out repairs) and routine commuting (walking or cycling to work, the supermarket or school, for example). The level of physical activity was measured through telephone interviews.
“A person who runs for an hour every day and spends the rest of the time sitting in front of a screen is considered active and sedentary at the same time. We combined these two different concepts in our analysis”, explains Bruno Gualano, professor at USP’s Faculty of Medicine (FM) and first author of the article. “When we look at the data, we clearly see that they form a ‘ladder’: at the top, with the best vaccine response, are the non-sedentary assets. Next come active and sedentary individuals. Finally, the inactive and also sedentary”, he says.
All research participants were immunized with CoronaVac between February and March 2021. Blood samples for analysis were collected soon after the application of the second dose, as well as 28 and 69 days later. The quality of the vaccine response was evaluated through several laboratory tests, the main ones being those that measure the total production of antibodies against sars-cov-2 (total IgG) and the specific amount of neutralizing antibodies (NAb) – those capable of prevent the virus from entering the human cell.
According to the criteria adopted by the researchers, the so-called “seroconversion” reached the volunteers who, in the total IgG test, presented at least 15 arbitrary units (AU) of antibodies per milliliter (mL) of blood. In the case of neutralizing antibodies, a positive response was considered when, in the in vitro assay carried out with blood plasma, there was at least 30% inhibition of the binding between sars-cov-2 and the angiotensin-converting enzyme receptor 2 (ACE2, its acronym in English) – protein found on the surface of some human cells to which the virus connects to enable infection.
As Gualano informs, the primary objective of the research project of which his article is a fruit was to evaluate the safety and effectiveness of CoronaVac in patients with autoimmune rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, primary vasculitis and systemic sclerosis . Most of these patients use medications that reduce the activity of the immune system and, therefore, a weaker vaccine response was expected.
“In this second study, we sought to evaluate the hypothesis that an active lifestyle could strengthen the vaccine response both in the immunosuppressed population and in individuals without autoimmune disease. And in fact, this is what our data indicate”, says Gualano, who coordinates a thematic project financed by the Foundation for Research Support of the State of São Paulo (Fapesp) related to the subject.
A total of 898 immunosuppressed patients were included in the final analysis. Of these, 494 were classified as active and 404 as inactive. Furthermore, as a kind of control group, 197 volunteers without autoimmune disease participated – 128 active and 69 inactive.
A mathematical model was used by the researchers to compensate for possible distortions that variables such as age, sex, body mass index (BMI) and use of immunosuppressants could cause. This is because it is known that the functioning of the immune system is impaired in elderly individuals and in users of steroids and other immune modulators, as well as possibly in obese individuals.
In the adjusted comparison, physically active immunosuppressed patients had a 1.4 times greater chance of achieving seroconversion.
“To put it another way: for every ten inactive patients who seroconverted after the second dose of the vaccine, there are 14 physically active patients who achieved the same result”, compares Gualano.
“The promotion of physical activity by managers and public policy makers is fundamental. It is a cheap intervention, easy to scale for the entire population and can make even more difference in the case of people with less efficient immune systems, such as patients with autoimmune diseases and the elderly” , says Gualano.
Being physically active was also associated with a 32% increase in the amount of antibodies against the “S1” and “S2” regions of the spike protein (S) – used by the virus to connect to the ACE2 receptor and enter the human cell .
“The neutralizing activity [NAb] was, on average, 4.5% higher in active patients, but this difference was not statistically significant”, explains the researcher.
Among volunteers without autoimmune disease, the chance of seroconversion was 9.9 times greater among physically active individuals and there was a 26% increase in the amount of antibodies against the spike protein. As the number of volunteers was smaller in this subgroup, the data referring to neutralizing antibodies were also not statistically significant.
“The results allow us to conclude that physical activity potentiates the vaccine response against covid-19 regardless of factors such as age, sex and use of immunosuppressants. Performing a minimum of physical activity already produces a positive response, however, we observed that the more movement the better. The most consistent responses were seen among patients who performed 50 minutes or more of physical activity daily,” says Gualano.
“The promotion of physical activity by managers and public policy makers is fundamental. It is a cheap intervention, easy to scale for the entire population and can make even more difference in the case of people with less efficient immune systems, such as patients with autoimmune diseases and the elderly”, says Gualano.
Although only individuals immunized with CoronaVac have been evaluated, the researcher considers it “plausible” that the same effect is observed with all vaccines against covid-19 and also against other diseases.
Evidence from the scientific literature shows that a single session of physical exercise can mobilize billions of cells responsible for carrying out the body’s immunosurveillance, “waking up” the immune system. They are cells that travel through places used as a gateway by pathogens and, upon detecting a threat, recruit other defense cells to attack the invader. Those who exercise regularly also have lower levels of systemic inflammation and cortisol (the stress hormone), which contribute to an adequate immune response.
As the authors report in the article, there are studies associating exercise practice with a better response to the flu vaccine (H1N1, H3N2 and influenza type B), against varicella-zoster virus and against pneumococcal disease.
“Our findings were already expected, as physical activity is known to strengthen the immune system. Anyway, it would be important to confirm them in a controlled and randomized study, in which a group of volunteers would be submitted to an exercise protocol before the vaccination period, while another control group, composed of individuals with similar characteristics, would remain inactive ”, says the researcher.