CDC Quantifies Advantage of Boosted Vaccination Against Omicron and Delta

A third dose boost of mRNA vaccination was more effective in reducing risk for COVID-19 than the primary 2 doses, and both regimens were more effective against the Delta than Omicron variant, in a new study by the CDC.

Emma Accorsi, PhD, and COVID-19 Response colleagues at the CDC sought to examine the effectiveness of vaccinations against these variants that appear more transmissible, may have increased immune escape, and are implicated in exponential growth in cases, even in regions with high rates of previous vaccination or infection.

"There is an urgent need to understand the protection provided by current vaccination regimens against Omicron, including any additional protection derived from booster doses," the investigators wrote.

Accorsi and colleagues conducted a retrospective test-negative case-control analysis of samples collected between December 10, 2021 to January 1, 2022 from adults with symptomatic COVID-like illness. They explain that the test-negative design is a commonly used observational method for evaluating the performance of vaccines in participants enrolled by clinical case definition. The measure of effectiveness is in finding that fewer of those with COVID-19 confirmed symptoms had received the intervention than those with negative tests.

The study population was identified from data of the ICATT platform, a Department of Health and Human Services (HHS) partnership program of no-cost, drive-through SARS-CoV-2 testing at pharmacies throughout the US.The cohort comprised 13,098 with Omicron, 10,293 with Delta, along with 46,764 as controls. The mean age was 40.3 years and 60.1% were women.

The investigators found prior receipt of 3 mRNA vaccine doses by 18.6% (n=2441) of Omicron cases, 6.6% (n=679) of Delta cases, and 39.7% (n=18,587) of controls.Prior 2-dose vaccination was found in 55.3% (n=7245), 44.4% (n=4570) and 41.6% (n=19,456), respectively.There was no vaccination in 26% (n=3412), 49.0% (n=5044), and 18.6% (n=8721), respectively.

The adjusted odds ratio (OR) for 3 doses vs unvaccinated was 0.33 (95% CI 0.31-0.35) for Omicron and 0.065 (0.059-0.071) for Delta; for 3-doses vs 2-doses, 0.34 (0.32-0.36) for Omicron and 0.16 (0.14-0.17) for Delta.

A secondary outcome was a proxy measure of viral load, the cycle threshold (Ct), with a higher number of cycles required for detection in PCR indicating less detectable virus. The investigators reported that the median Ct values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta.

Accorsi and colleagues recounted, "vaccination with a third dose of an mRNA COVID-19 vaccine was significantly less common among individuals infected with either the Omicron or Delta variants compared with uninfected individuals."

"Although these findings provide evidence supporting that 3-dose schedules are protective and that booster doses are more protective than primary series alone, the significantly higher OR for Omicron suggests that booster doses are less protective against Omicron than against Delta," they conclude.

In an accompanying editorial, Saad Omer, MPH, PhD, Yale Institute for Global Health, New Haven Connecticut, and JAMA Associate Editor Preeti Malani, MD, MSJ, Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, concur that the findings support the 3-dose schedule for mRNA vaccines currently recommnended in the US for anyone older than 12 years.

They note, however, that the investigators did not estimate the absolute effectiveness of the 2-dose schedule."This is important, as many countries continue to have an insufficient supply of vaccine," they observed.

"If a 3-dose schedule is indeed more effective, it would be informative for these countries to know whether a 2-dose schedule may still provide considerable protection against severe disease when vaccine supplies are limited," Omer and Malani suggest.