Model estimates who benefits most from frequent COVID-19 boosters

These findings support current CDC recommendations and the benefit of at least annual boosters to people 65 and older and immunocompromised populations, and suggest that public health strategies to increase booster uptake could get the most bang for their buck by focusing on the high-risk populations.

A thorny question

“In this study we focused on a goal of reducing severe COVID-19 leading to hospitalization, but there are numerous other considerations that influence vaccine decisions,” Lo said.

The team considered how novel variants and overall transmission play into decisions on how frequently to receive booster vaccines. They looked at the effect of new viral variants with regard to evasion of the immune system and found that the benefit of more frequent boosters for all groups was larger if new vaccine formulations were better matched to the latest variants.

In addition, the team looked at the impact of transmission: Compared with more restricted booster programs targeting only higher risk populations, more inclusive frequent booster programs (for all age and risk groups) led to lower transmission, with additional benefit for the highest risk groups.

The researchers note that frequent vaccination also helped reduce non-severe cases in all risk groups. “There are a multitude of considerations here, and the optimal vaccine recommendations will depend on what is factored into the decision,” Lo said.

The scientists also included prior COVID-19 infection in their model, finding less benefit from frequent vaccination to prevent severe disease for those who had previously had a case of COVID-19 compared with those who hadn’t. Prior infection gives a short window of protection against infection, so the booster’s protection on top of that is smaller.

Due to a lack of data and to simplify the model, some variables weren’t accounted for in the study: The likelihood of infection for each group was assumed to be the same over time, even though infection risk differs in real life. The model was also based on data from earlier circulating variants and vaccine formulations. Immunocompromised people were clustered into two groups in the model, although these populations are actually much more variable, and the model did not address vaccine hesitancy or the risks of long COVID.

Lo and his colleagues plan to share their findings with policy makers and will update the model with new data as it becomes available, hoping to shed even more light on the tricky question of vaccine frequency.

“In science, there are some questions that get easier over time and some that get more challenging over time,” Lo said. “This is one of the latter.”

Researchers from the Yale School of Public Health; the University of California, San Francisco; and the California Department of Public Health also contributed to the study.

The study was funded by the National Institutes of Health (grant DP2 AI170485) and the California Department of Public Health.