Vaccination against COVID-19 prevents breakthrough infections, Stanford researchers find

A Stanford study finds that the mRNA vaccines, Pfizer and Moderna, offer strong protection against the California variant of the coronavirus.

- By Janelle Weaver

A study of workers at Stanford Health Care found that the mRNA vaccines offered a high level of protection, even against a widely circulating variant.

More than 99% of Stanford Health Care employees resisted breakthrough infections after receiving at least one dose of an mRNA-based vaccine for COVID-19, according to researchers at the Stanford School of Medicine.

Between Dec. 18, 2020, and April 2, 2021, at least 23,090 employees at Stanford Health Care received one or two doses of the Pfizer or Moderna vaccine. During that period, 189 of vaccinated individuals tested positive for SARS-CoV-​2, which causes COVID-19. By contrast, at least 660 of approximately 6,910 — nearly 10% — of unvaccinated workers became infected with the coronavirus.

Sixty percent, or 114, of the breakthrough infections occurred two weeks or less after the first shot. An additional 49 (26%) cases emerged more than two weeks after the first dose and less than two weeks after the second dose. Taken together, 86% of the individuals who tested positive after vaccination did so before immunity fully developed.

“These findings add to the mounting evidence demonstrating that vaccination is extremely effective at preventing COVID-19 infection,” said Marisa Holubar, MD, a clinical associate professor of infectious diseases. “The results also highlight the need to observe strict precautions until full immunity is achieved.”

Among all post-vaccine cases, only 26 (14%) emerged more than two weeks after the second dose. That is, approximately 0.1% of employees who completed the two-shot series tested positive for the coronavirus more than two weeks after full vaccination. Additional results suggest that mRNA-based vaccines work well against the California variant. The researchers were not able to determine how well the vaccines hold up against the delta variant, as their study ended before it had gained a foothold in the United States.

Marisa Holubar

A look at variants

“Our study is the first to look closely at the mutations in the post-vaccine viruses and compare them with the strains contemporaneously circulating in the population,” said Julie Parsonnet, MD, the George DeForest Barnett Professor in Medicine and a professor of epidemiology and population health. “This is also the largest study I’m aware of looking at mutations in post-vaccine cases.”

The study was published online June 17 in Clinical Infectious Diseases. Holubar and Parsonnet are co-senior authors. The lead author is Karen Jacobson, MD, a postdoctoral scholar in infectious diseases.

Evidence from clinical trials has suggested that the Pfizer and Moderna vaccines are approximately 95% effective at preventing COVID-19 illness. But according to Parsonnet, drugs and vaccines rarely work as well in real life as they do in the original clinical trials. In addition, little is known about how effectively COVID-19 vaccines protect against new genetic variants. “We just wanted to see how well the vaccine was working with heath care personnel and to confirm efficacy,” Parsonnet said. “As the new variants appeared, it became more important to figure out how they responded.”

During the new study, a variant called B.1.427/B.1.429, or epsilon, was rapidly spreading in California and becoming the dominant virus in circulation. Other research has shown that it is associated with an approximately 20% increase in transmission. But the researchers found no evidence that the mRNA-based vaccines are less effective against the epsilon variant. Approximately 40% of health care personnel who tested positive for the coronavirus had this variant, regardless of whether they had been vaccinated. The similar proportion of variants among vaccinated and unvaccinated individuals suggests that the epsilon variant is no more likely to break through vaccine protection.

Julie Parsonnet

Monitoring new variants

“It is a relief to see that in a real-world population, vaccinated individuals were not more at risk for this variant than those who remain unvaccinated,” Jacobson said. “We will continue to monitor COVID-19 infections in our vaccinated populations as more variants emerge.”

Even though 86% of breakthrough infections produced symptoms, post-vaccine cases led to only two hospitalizations during the early post-vaccination period and no deaths. “Right now, we are happy that the virus is so well controlled in our highly vaccinated population,” Parsonnet said. 

This work has helped strengthen hospital policies by promoting vaccination among colleagues and patients at a time when many are tempted to loosen precautions.

“This research highlights yet again the critical importance of vaccination,” said study co-author Bryan Bohman, MD, clinical professor of anesthesiology, perioperative and pain medicine. “It also illustrates the vital role of continuous monitoring to allow for quick detection of variant viruses and real-time assessment as to whether they are able to evade vaccine-induced immunity.”

Other Stanford co-authors are Benjamin Pinsky, MD, PhD, associate professor of pathology and of infectious diseases; Maria Montez Rath, PhD, senior research engineer; Hannah Wang, MD, resident in anatomic and clinical pathology; Jacob Miller, MD, resident in radiation oncology; Mehdi Skhiri, MD, clinical assistant professor of primary care and population health; John Shepard, lead of quality reporting analytics; Roshni Mathew, MD, clinical associate professor of pediatrics and infectious diseases; and Grace Lee, MD, professor of pediatric infectious diseases.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit

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