July 22, 2021 -- Clinical trials of mRNA vaccines have consistently demonstrated high effectiveness against COVID-19, but now a large, real-world study confirms that the Pfizer-BioNTech and Moderna vaccines are more than 95% effective in preventing confirmed infection.

Lead author Adeel A. Butt, MBBS, , professor of medicine at Weill Cornell Medical College in New York City, tells Medscape Medical News the numbers of people in the study population who received the Johnson and Johnson vaccine were too small to include in the study, as that vaccine was not widely available yet during the study period.

Similar rates of effectiveness of the COVID vaccines approved in the United States had been shown in clinical trials, but this is among the first large studies to show how the vaccines work outside a cohort of volunteers in a controlled setting.

"This is blinking neon lights, big news," William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville, Tennessee tells Medscape Medical News.

The study, which was published in Annals of Internal Medicine on Monday, included 54,360 people who tested positive for SARS-CoV-2 infection in the U.S. Department of Veterans Affairs healthcare system and 54,360 propensity score–matched control participants.

Overall vaccine effectiveness 7 or more days after the second dose was 97.1%. Effectiveness was 96.2% for the Pfizer-BioNTech vaccine and 98.2% for the Moderna vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or comorbidities.
Average age was 61 years, 83.6% were male, and 62% were White. Average body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative.

Gold Standard Methodology

Butt says the VA population was chosen because it is one of the largest integrated health systems in the nation and has a single electronic health records platform.

He explains that the methodology they used, test-negative case–control design, is the gold standard for vaccine effectiveness studies.

They used conditional logistic regression to calculate the odds of testing positive among the vaccinated group vs the unvaccinated group.

"Among those who tested positive, 18% had been vaccinated and among those who tested negative, 33% had been vaccinated," Butt says.

Schaffner says the news this study adds is particularly welcome as the population was older, with more vulnerabilities than the general population.

"This is a large, extremely solid study done in an older-male-dominated population at increased risk of severe disease. And the results are securely and completely confirmatory of what the clinical trials showed us: These are remarkably effective vaccines," he says.

The group had substantial comorbidities, Schaffner pointed out, including diabetes, heart disease, and lung disease.

"And these results stood up even when the subgroups were analyzed," he says. "This is a population enriched with people who COVID could make seriously ill."

Effectiveness in vaccine studies in highly structured environments of volunteers sometimes drops off in real-world studies, Schaffner notes, "but that didn’t happen here. These vaccines showed effectiveness levels that remained astounding."

Reassurance for Public, Policymakers

"I think it reassures the public and the policymakers that the current vaccines are highly effective in a real-world, high-risk population," Butt says about the significance of the findings.

It should also allay concerns about mRNA technology in its new use for vaccines, he says.

Next, the researchers will look at specific populations that may be highly vulnerable, such as people on hemodialysis, he says.

"We know from early studies that people on dialysis have less robust immune response to vaccines," Butt says. "Now, whether that translates to less effectiveness of vaccines remains to be seen, and that’s what we are studying. That paper is in peer review right now."

He says the two biggest challenges in translating their research into practice are "overcoming vaccine skepticism and hesitancy, and ensuring global equity in distribution, whereby the most vulnerable from the poorest nations also have equitable access to these highly effective vaccines."