Physically active people respond better to COVID-19 vaccine, study shows

More than 1,000 Brazilian volunteers immunized with the CoronaVac vaccine were assessed by researchers at the University of São Paulo. Those who were active for at least 150 minutes per week without long sedentary periods produced more antibodies against SARS-CoV-2.

By Karina Toledo  |  Agência FAPESP – Adopting a physically active lifestyle can be a strategy for boosting the immune response induced by COVID-19 vaccines. This is the conclusion of a study involving 1,095 volunteers conducted by researchers at the University of São Paulo (USP) in Brazil and collaborators. The results were published on August 9 in a pre-print posted to the platform Research Square. The article has not yet been peer-reviewed.

The beneficial effects of physical activity were observed mainly among participants who were active for at least 150 minutes per week and were considered not predominantly sedentary because they did not spend more than eight hours per day sitting or lying down. Active time was defined as the time spent on exercises, leisure activities (jogging, dancing, swimming, walking the dog, etc.), housework (cleaning, gardening, hand laundering), manual labor for a job (heavy lifting, doing repairs), and routine mobility (walking or cycling to work, the supermarket or school, for example). The level of physical activity was assessed by means of a telephone survey. 

“A person who goes jogging for an hour every day and spends the rest of the day sitting in front of a screen is considered both active and sedentary. We combined these two different concepts in our analysis,” said Bruno Gualano, a professor at the University of São Paulo’s Medical School (FM-USP) and first author of the article. “When we looked at the data, it was clear that there was a sort of ladder with active non-sedentary subjects displaying the best response to the vaccine at the top, followed by active sedentary subjects. Inactive sedentary subjects were at the bottom.”

All survey participants were immunized with the CoronaVac vaccine in February or March 2021. Blood samples were collected shortly after the second dose, and 28 and 69 days afterward. The response to the vaccine was appraised by means of several laboratory tests. The main tests measured total production of antibodies against SARS-CoV-2 (total IgG), and the amount of specific neutralizing antibodies (NAb), which prevent the virus from invading human cells.

The researchers determined that seroconversion (the development of specific antibodies in the blood serum as a result of infection or immunization) had occurred when the total IgG test showed at least 15 antibody arbitrary units (AU) per milliliter of blood. In the case of neutralizing antibodies, the in vitro plasma test was considered positive when the bond between viral spikes and ACE2 receptors was at least 30% inhibited.

Data analysis

According to Gualano, the main aim of the research project linked to the article was to assess the safety and effectiveness of CoronaVac in people with autoimmune rheumatic diseases, such as rheumatoid and psoriatic arthritis, lupus, vasculitis, and systemic sclerosis. Most are treated with drugs that reduce immune system activity so that a weaker response to the vaccine was expected.

Their first study, published in Nature Medicine and led by Eloísa Bonfá, a professor at FM-USP, confirmed that the vaccine was safe and induced an acceptable, albeit reduced, response in this group of patients (more at: agencia.fapesp.br/36544/).

“In the second study, we set out to test the hypothesis that an active lifestyle could strengthen the immune response to the vaccine among immunosuppressed patients and people without autoimmune diseases. That’s what our data did indeed show,” said Gualano, principal investigator for a Thematic Project on the subject funded by FAPESP.

The final analysis covered 898 immunosuppressed patients, of whom 494 were classified as active and 404 as inactive, as well as a control group comprising 197 volunteers without autoimmune diseases, 128 of whom were considered active and 69 inactive.

The researchers used a mathematical model to offset possible distortions caused by such variables as age, sex, body mass index (BMI), and use of immunosuppressants, given that the immune system is known to be weaker in older people and patients who take corticosteroids or other immune system modulators, and also possibly in obese people.

In the adjusted comparison, seroconversion was found to be 1.4 times more likely in physically active immunosuppressed patients. “In other words, for every 10 inactive patients who seroconverted after the second dose of the vaccine, 14 physically active patients reached the same result,” Gualano explained.

Being physically active was also associated with a 32% increase in the quantity of antibodies against the S1 and S2 regions of the spike protein (S), used by the virus to bind to the ACE2 receptor and invade cells.

“Neutralizing activity [NAb] was 4.5% higher on average in active patients, but this difference was not statistically significant,” Gualano said.

Among volunteers without autoimmune disease, the probability of seroconversion was 9.9 times greater than among physically active immunosuppressed subjects, and the quantity of antibodies against the spike protein was 26% higher. Because the number of participants in this subgroup was smaller, their neutralizing antibody data was also considered statistically insignificant.

“The results allow us to conclude that physical activity boosts the immune response to the vaccine regardless of age, sex and use of immunosuppressants. Getting a minimum of physical exercise produces a positive response, but the more movement the better. The most consistent response was observed in patients who were physically active for 50 minutes per day or more,” Gualano said.

Previous studies also showed that an active lifestyle protects people against severe COVID-19 and tends to reduce hospitalization (more at: https://agencia.fapesp.br/34841).

“Promotion of physical activity by public administrators and policymakers is really important. It’s an inexpensive intervention that can easily be scaled up for the entire population, and it can make all the difference to people with a less efficient immune system, such as patients with autoimmune diseases and older people,” Gualano said.

Although the study only evaluated people who had taken CoronaVac, it would be “plausible” to assume that the same applies to all vaccines against COVID-19 as well as vaccines for other diseases, he added.

Natural booster

Evidence in the scientific literature points to the benefits of a single session of physical exercise, which can mobilize billions of cells responsible for the organism’s immune surveillance and “wake up” the immune system. These cells patrol the sites used as gateways by pathogens and, when they detect a threat, recruit other defense cells to attack the invader. Regular exercise also lowers levels of systemic inflammation and cortisol (the stress hormone), contributing to an adequate immune response.

As the authors of the article note, there are studies that associate exercise with an enhanced response to vaccines against influenza (H1N1, H3N2 and type B), against varicella-zoster virus, and against pneumococcal disease.

“Our findings were expected, as physical activity is known to strengthen the immune system,” Gualano said. “However, it would be important to confirm them in a controlled randomized study in which a group of volunteers is submitted to an exercise protocol before vaccination and a control group consisting of subjects with similar characteristics remains inactive.”

The article “Physical activity associates with boosted immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases” by Bruno Gualano, Italo Lemes, Rafael Silva, Ana Pinto, Bruna Mazzolani, Fabiana Smaira, Sofia Sieczkowska, Nadia Aikawa, Sandra Pasoto, Ana Medeiros-Ribeiro, Carla Saad, Emily Yuk, Clovis Silva, Paul Swinton, Pedro Hallal, Hamilton Roschel and Eloisa Bonfa is at: www.researchsquare.com/article/rs-782398/v1.