Department of Research & Evaluation News

People who were vaccinated for shingles had a lower risk of COVID-19 diagnosis or hospitalization, according to a Kaiser Permanente study of people ages 50 and older. The research was published December 28 in The Journal of Infectious Diseases.

“Our findings add to a compelling body of evidence that some vaccines may provide some protection against unrelated infections,” said one of the study’s co-first authors Bradley Ackerson, MD, a physician at the Kaiser Permanente South Bay Medical Center in Harbor City, Calif. “Bottom line, our work highlights the importance of keeping up to date and receiving all recommended vaccines—including COVID-19 vaccines.”

Recombinant adjuvanted zoster vaccine (RZV, brand name Shingrix) is recommended for people ages 50 and older to protect against the disease shingles.

Previous research had suggested that certain other vaccines—including a tuberculosis vaccine and flu vaccines—may not only work against the specific diseases for which they were designed, but also against unrelated diseases.

“Our thought was that the shingles vaccine could potentially ramp up the immune system in a way that would also protect against COVID-19,” Dr. Ackerson said.

A multifaceted analysis

To investigate the possibility that the RZV shingles vaccine protects against COVID-19, the researchers conducted 2 different kinds of analyses: a cohort analysis and a test-negative analysis. Both used data from the electronic health records of Kaiser Permanente Southern California members ages 50 and older for the period of March 1 to December 31, 2020—before COVID-19 vaccines became widely available.

“Each analysis has its own unique set of advantages and disadvantages, so we applied both approaches to strengthen our study,” said the study’s other co-first author, Katia Bruxvoort, PhD, MPH, adjunct investigator with the Kaiser Permanente Southern California Department of Research & Evaluation.

The cohort analysis compared COVID-19 diagnosis and hospitalization between 149,244 people who had received at least one dose of the shingles vaccine and 298,488 people who had not. The test-negative analysis examined shingles vaccination status among 75,726 people who tested positive for COVID-19 during the study period and 340,898 with only negative results.

The researchers used an array of statistical tools to account for other factors that could influence COVID-19 infection and severity, such as members’ sociodemographic characteristics and underlying health conditions.

The 2 separate analyses gave highly consistent results, showing that people who had received at least 1 dose of the shingles vaccine were 16% less likely to be diagnosed with COVID-19—no matter how long ago they had received the vaccine. The cohort analysis also showed that shingles vaccine recipients were 32% less likely to be hospitalized for COVID-19.

It is remarkable that a vaccine designed for a completely different disease was associated with one-third lower risk of COVID-19 hospitalization,” Dr. Ackerson said.

The researchers also compared whether shingles vaccine was associated with COVID-19 diagnosis and hospitalization among a smaller group of patients who had all received a flu vaccine. The results were nearly identical to those for the larger group.

“This lends further statistical strength to the idea that the shingles vaccine may underlie the COVID-19 benefits we saw, rather than the flu vaccine or factors associated with people’s different tendencies to seek vaccination,” Dr. Bruxvoort said.

An emerging field with big potential

The new findings support the possibility that some vaccines might affect the spread and severity of unrelated diseases, perhaps via trained immunity. That emerging mechanism  is expanding our understanding of how the immune system can be induced to respond quickly and more effectively to invading pathogens, providing long-lasting non-specific defenses against a wide array of infections.

“Our study also supports the concept of a trained immunity-based vaccine, which could be designed in the future to protect against a broad spectrum of diseases,” Dr. Ackerson said. “You could imagine the huge benefit such a vaccine might have early on in a pandemic, before a more specific vaccine is available.”

Additional research will be needed to illuminate the mechanisms behind the new findings. For instance, the shingles vaccine RZV contains a AS01, an adjuvant designed to improve the immune system’s response to vaccines. AS01 and other adjuvants could potentially underlie the protective effects of vaccines against unrelated diseases.

“This field is just beginning to be explored and could ultimately help optimize the impact of vaccines and vaccine programs,” Dr. Bruxvoort said.

In addition to Dr. Ackerson and Dr. Bruxvoort, other authors on the study were Lina Sy, MPH, Hung Fu Tseng, PhD, Ana Florea, PhD, Yi Luo, PhD, Yun Tian, MS, Zendi Solano, BS, and Lei Qian, PhD, of Kaiser Permanente Southern California Department of Research & Evaluation; Amit Bhavsar, MBBS, MHA, Robyn Widenmaier, MBiotech, Meng Shi, MS, Robbert Van Der Most, PhD, Johannes Eberhard Schmidt, MD, MPH, Jasur Danier, MD, and Thomas Breuer, MD, MSc, of GSK.

GSK, the manufacturer of Shingrix, provided funding for this study.