With COVID-19 vaccine boosters, one size does not fit all

CHICAGO --- COVID-19 vaccines continue to save lives. But a new paper published today (Feb. 7, 2023) in the journal Vaccines adds important nuance to our understanding of how vaccine protection varies with age, finding that people aged 50 and over benefit the most from a booster shot.

The study — which measured vaccine protection against death — also highlights important differences in background mortality rates between people who got vaccinated and those who did not.

In general, people who got vaccinated were healthier to begin with: They were less than half as likely to die from non-COVID causes relative to unvaccinated people, and thus also less than half as likely to die of COVID even if they had not been vaccinated.

Controlling for this strong selection effect, vaccines still reduced mortality significantly. Primary vaccination (two doses of the mRNA vaccines) still provides strong protection against death, but protection waned over time, especially during the Omicron-dominant period.

Boosters further reduced mortality risk, but the effect was most pronounced in older people (those over 50), and not detectable for younger people (age 18-49), who were well protected by primary vaccination.

“We need more refined messaging around boosters that explains who stands to benefit the most, and targets those people,” said senior author Bernard Black, a professor of law at Northwestern’s Pritzker School of Law who specializes in health policy research.

In addition to Black, the team included other researchers affiliated with Northwestern University, the Medical College of Wisconsin, and William and Mary. The authors used a dataset of linked mortality and vaccination records for all adults in Milwaukee County, Wisconsin (adult population 722,000) from Jan. 1, 2021 to June 30, 2022 to conduct their analysis.

Their study is the first to control for the tendency of people who get vaccinated to be healthier than unvaccinated people by comparing death rates from COVID-19 and other natural causes of death within groups defined by age, gender, race/ethnicity, socio-economic status, education and other characteristics.

The authors studied how vaccination affects the COVID Excess Mortality Percentage (CEMP), obtained by dividing COVID-19 mortality for a given group by mortality from non-COVID natural causes for the same group.

The researchers found that protection from the initial two vaccine doses for mRNA vaccines waned strongly over time, especially against the Omicron variant. After controlling for selection effects, the authors found much higher remaining mortality risk (lower vaccine effectiveness) after two vaccine doses than in prior research with weaker controls for selection effects.

During the Omicron period (first six months of 2022), risk for those who received two doses of an mRNA vaccine compared to unvaccinated individuals was 42% for ages 40-59, 27% for ages 60-79, and 46% for ages 80+, where 0% indicates complete protection and 100% indicates no protection.

The relatively high rate in the 40-59 group compared to the 60-79 group may be attributable to noise in the data, because of few all-cause deaths in the former group.

A booster dose substantially reduced mortality risk, with mortality risk after booster of 0% in those who received a booster (no deaths among over 100,000 persons in the studied population) under age 60, and 11% for ages 60+, relative to unvaccinated individuals.

Thus, booster protection is highly valuable for older people aged 60+, has substantial value for people in their 50s, but has limited additional value for younger people when evaluating death risk. The initial two doses retain strong protective value against death in this group.

Authors of the study "Understanding COVID-19 Vaccine Effectiveness Against Death Using a Novel Measure: COVID Excess Mortality Percentage" include Vladimir Atanasov, Natalia Barreto, Jeff Whittle, John Meurer, Benjamin W. Weston, Qian (Eric) Luo, Lorenzo Franchi, Andy Ye Yuan, Ruohao Zhang and Bernard Black in Vaccines 11(2), 379.

Contact Prof. Black at (847) 807-9599 or Prof. Atanasov at (781) 856-4735.