How Well Does the Third Dose of COVID-19 Vaccine Work?

Researchers compared 2 large groups of veterans to find out how well a third dose protected against documented infection.


How effective are the COVID-19 vaccines, third time around? Researchers compared 2 large groups of veterans to find out how well a third dose protected against documented infection, symptomatic COVID-19, and COVID-19–related hospitalization, intensive care unit (ICU) admission, and death.

The research, published in Nature, used electronic health records of 65,196 veterans who received BNT162b2 (Pfizer-BioNTech) and 65,196 who received mRNA-1273 (Moderna). They chose to study the 16 weeks between October 20, 2021 and February 8, 2022, which included both Delta- and Omicron-variant waves.

During the follow-up (median, 77 days), 2994 COVID-19 infections were documented, of which 200 were detected as symptomatic, 194 required hospitalization, and 52 required ICU admission. Twenty-two patients died.

In a previous head-to-head trial comparing breakthrough COVID-19 outcomes after the first doses of the 2 vaccines (given when the Alpha and Delta variants were predominant), the researchers had found a low risk of documented infection and severe outcomes, but lower for the Moderna vaccine. They note that few head-to-head comparisons have been made of third-dose effectiveness.

As expected, in this trial, the researchers found a “nearly identical” pattern for the risk of the 2 vaccine groups. Although the risks for all of the measured outcomes over 16 weeks were low for both vaccines ≤ 4% for documented infection and < 0.03% for death in each group—those veterans who received the Pfizer-BioNTech vaccine had an excess of 45 documented infections and 11 hospitalizations per 10,000 persons, compared with the Moderna group. The Pfizer-BioNTech group also had a higher risk of documented infection over 9 weeks of follow-up, during which an Omicron-variant predominated.

Given the high effectiveness of a third dose of both vaccines, either vaccine is strongly recommended, the researchers conclude. They point to “evidence of clear and comparable benefits” for the most severe outcomes: The difference in estimated 16-week risk of death between the 2 groups was two-thousandths of 1 %.

They add that, while the differences in estimated risk for less severe outcomes between the 2 groups were small on the absolute scale, they may be meaningful when considering the population scale at which these vaccines are deployed.

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