A recent case-controlled study in South Africa finds that regular physical activity enhances vaccine effectiveness against Covid-19. While the positive impact of regular physical activity against severe Covid-19 outcomes is well understood, the association between regular physical activity and vaccine effectiveness is underexplored.

The study predominantly used physical activity data from 196,444 participants and concluded that increased levels of regular physical activity improved the protective effects of vaccination against Covid-19 hospitalization and exhibited a dose-response.

Researchers conducted a negative case-control study and a retrospective analysis from data collected by Discovery Health and Vitality. A negative case-control is commonly used to assess the effectiveness of the annual influenza vaccine; studies would calculate the odds ratio of testing positive when vaccinated against specific pathogens and testing negative when vaccinated against a specific pathogen. In this case, researchers were interested in estimating the hospitalization admission for Covid-19 among those who are vaccinated and unvaccinated based on their “regular” physical activity levels.

Collie et al. used anonymized data from Discovery Health and Vitality and derived information from members who had a partnership from mid-February to late October 2021. Participants were at least eighteen years old and categorized into one of the three physical activity levels based on their average monthly physical point allocation two years prior to the study: low activity (less than 60 minutes of at least moderate intensity activity per week), moderate activity (those engaging in 60 and 149 minutes of at least moderate intensity activity per week), and high activity (engaged in at minimum of 150 minutes of at least moderate activity per week).  To qualify for the study, participants had to submit their proof of Covid-19 infection at the beginning of the study, given that they did test positive up to 3 months prior.

Vaccinated participants were healthcare professionals who were vaccinated as the result of a separate study. Unvaccinated participants were a mix of healthcare and nonhealthcare professionals that are members of Discovery Health and Vitality. Through stratified random sampling, roughly proportional ratios of unvaccinated to fully vaccinated participants within each physical activity group. There was a slight difference in the biological sex between the three groups: 64.1% of the low-activity group were female, compared to the 56.4% and 50.9% of the moderate and high-intensity physical activity groups. Participants in the moderate and high activity groups also had slightly higher Covid-19 risk factors on average compared to the low-acting group.

Collie et al conducted three sensitivity analyses to investigate the vaccine effectiveness among and within the three groups in relation to their physical activity levels. In the first sensitivity analysis done, the vaccine effectiveness among the fully vaccinated participants in each group compared to the full population. No statistical differences were found, suggesting that the sample was representative of the population.

Collie et al conducted a single multinomial Poisson regression model, which estimates the relative risk of hospitalization given the physical activity level. Compared to unvaccinated individuals with low physical activity, there was a 91.5% vaccine effectiveness for vaccinated individuals with high physical activity. Additionally, using unvaccinated individuals with low physical activity as baseline, there was a difference of vaccine effectiveness between vaccinated individuals in the high intensity physical activity and vaccinated individuals in the moderate intensity exercise of about 28.1%. This sensitivity measure also found the difference between hospitalization vaccine effectiveness between those who were vaccinated at least 28 days prior to the study with low physical activity and those who vaccinated at least 28 days prior to the study with high physical activity to be 25.8%, which aligns with the main study’s findings.

In a third sensitivity analysis, Collie et al used Bayesian modeling, allowing to test the hypothesized causal relationships between vaccine effectiveness and physical activity levels. This analysis determined a 25% difference in vaccine effectiveness between vaccinated participants performing high-intense physical activity and vaccinated participants performing moderate-intensity physical activity, relative to those unvaccinated with low activity. It also demonstrated the main difference to be 25.8%, which supports findings from the multinomial position regression analysis and main study’s findings.

Collie et al found that vaccine effectiveness and physical activity seem to have a dose-response relationship, where increased regular physical activity enhances vaccine effectiveness against Covid-19 hospitalization. Among the fully vaccinated, vaccine was most effective among those with high activity levels (85.8%), which was notable higher than those with low physical activity (60%). The difference of 25.8% was supported by the two sensitivity analyses, and these findings further validate the World Health Organization recommendation of regular physical activity (150-300 minutes of moderate to intense activity per week), as it may have meaningful health benefits like preventing severe disease.

Collie et al’s findings align with existing literature focusing on increased vaccine effectiveness with regular physical activity. One study measured antibody levels among 898 patients with autoimmune rheumatic disease roughly two months after becoming fully vaccinated with the CoronaVac vaccine. After adjusting for covariates, active patients exhibited greater antibodies and geometric mean titers(GMT) compared to their counterparts with sedimentary or very low physical activity. Researchers also noticed a dose-response relationship between physical activity and the presence of Covid-19 antibodies and GMT: patients performing at least 350 minutes of physical activity a week had more Covid-19 antibodies and higher GMT compared to the least active group exercising at most 30 minutes a week. This study suggested that a lifestyle incorporating greater physical activity may help protect immunocompromised communities by enhancing Covid vaccine immunogenicity. In a separate study, physical activity was associated with enhanced antibody presence up to 6 months post-vaccination among immunocompromised patients. Through logistic regression analysis, higher rates of seroconversion and neutralizing antibodies were found among patients with higher levels of regular physical activity.

Although Collie et al encourages increased regular activity to maximize the protection of the Covid-19 vaccine, it is important to recognize that the study is not without limitations. This study was done prior to the emergence of Omicron. Additionally, it is likely that participants in the sample were of higher socioeconomic status, which is an inadequate representation of the entire population of South Africa. A healthier diet and better sleeping patterns may also contribute to higher vaccine effectiveness among the highly active participants compared to their low physical activity counterparts. Lastly, the biological mechanism behind vaccine effectiveness and physical activity remains unclear, in large part because of the lack of immunogenicity and cell-mediated response analyses within the study. Additional studies are needed to validate the study’s main findings.

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