Third Vaccine Shown as Key to Preventing Hospitalization from COVID-19 Variant

Third Vaccine Shown as Key to Preventing Hospitalization from COVID-19 Variant
Vanderbilt and CDC research shows importance of boosters to maintain protection.

New research shows that two doses of an mRNA COVID-19 vaccine have lower effectiveness for preventing hospitalization for the omicron variant (65 percent) than previous variants, including alpha (85 percent) and delta (85 percent).

However, a third vaccine dose, described as a “booster,” significantly improves vaccine protection against omicron hospitalization – up to 86 percent. 

The study, led by researchers at Vanderbilt University Medical Center, the CDC, and the University of Michigan, looked at the alpha, delta and omicron variants of SARS-CoV-2 in a continuation of the research conducted by the Influenza and Other Viruses in the Acutely Ill (IVY) Network and enrolled nearly 12,000 patients at 21 hospitals across the U.S. 

“There is effectiveness from the Pfizer and Moderna mRNA vaccines, but they’re not as effective as they were against the earlier variants,” said principal investigator Wesley Self, M.D., associate professor of Emergency Medicine and vice president for Clinical Research Networks and Strategy at Vanderbilt.

About 90 percent of people vaccinated against COVID-19 in the U.S. received the mRNA vaccines. As of early March 2022, the CDC is reporting 65 percent of the U.S. population to be fully vaccinated and over 43 percent to also have received a booster. 

“Our research shows that booster or third vaccine doses, which are now recommended for all adults, are critically important for protection against omicron,” Self said. “It’s good news that the current vaccine formulations do have effectiveness against omicron, but it means you need to get that third dose.” 

Severe Disease and Hospitalization

The vaccine effectiveness study applied a test-negative design to evaluate the large, hospitalized adult population with symptomatic, laboratory-confirmed COVID-19 and concurrent controls. This enabled evaluation of outcomes beyond hospital admission, including level of respiratory support and mortality.

“The severity of illness for people who have been vaccinated is less than those who have not been vaccinated – for all three variants.”

Trained personnel conducted patient interviews and searched multiple sources of vaccination records on a patient-by-patient basis. Because there was a mix of SARS-CoV-2 strains in hospitalized patients, respiratory samples collected in the study underwent centralized RT-PCR testing and viral whole genome sequencing, which enabled precise characterization of time periods dominated by different variants.

While previous studies suggested the omicron variant was less likely than the delta variant to send patients to the hospital, those quite sick with omicron are still being seen.

“The early discussion on omicron was, ‘This is good news; the variant’s not causing severe disease – it’s equivalent to outpatient common cold symptoms,’” Self said. “However, we found that omicron is still causing people to go to the hospital. And, if you are hospitalized with omicron, it’s still a very severe disease.”

In the study, 15 percent of people hospitalized with the omicron variant required ventilators and 7 percent died.

Waning Immunity and Breakthrough Cases

Two things may be contributing to the vaccine’s diminished protection against omicron, including waning immunity and evasion of the omicron variant from the effects of vaccines.

“Our research shows that booster or third vaccine doses, which are now recommended for all adults, are critically important for protection against omicron.”

“Because more people are getting vaccinated over time and omicron seems to be somewhat less susceptible to vaccines, we are seeing people in the hospital who have been fully vaccinated who are sick with omicron,” Self said.

“However, the severity of illness for people who have been vaccinated is less than those who have not been vaccinated – for all three variants,” he added. “This type of disease attenuation is important to understand because it shows that the vaccines are helpful even to people who do get COVID-19 after vaccination.” 

As the COVID-19 pandemic continues to evolve, the authors wrote, routine vaccine effectiveness monitoring, especially against severe disease, and surveillance programs to identify viral variants will be essential to inform decisions about booster vaccine policies and vaccine strain updates.