Large, real-world study finds COVID-19 vaccination more effective than natural immunity in protecting against all causes of death, hospitalization and emergency department visits

INDIANAPOLIS – In one of the first large, real-world studies comparing the effectiveness of COVID-19 vaccines versus natural immunity in protecting against death, hospitalizations and emergency department (ED) visits for any cause, including COVID, research-scientists from Regenstrief Institute, Indiana University School of Medicine and Vanderbilt University Medical Center report that people of all age groups benefited significantly more from vaccination than natural immunity acquired from a previous COVID infection. The lower death rate of vaccinated individuals was especially impressive for adults ages 60 years or older.   

Significantly, the all-cause death and hospital admission rates for vaccinated individuals were 37 percent lower than the rates for those with natural immunity acquired from previous COVID infection. The rate of ED visits for all causes was 24 percent lower for vaccinated individuals than for the previously infected.

“This large population study of the entire state of Indiana should encourage individuals everywhere to get themselves and their children vaccinated and not rely on natural immunity. While the incidence of COVID infection was higher in vaccine recipients (6.7 percent) than in individuals previously infected (2.9 percent), the vaccine protected against severe disease while natural immunity did not confer the same benefit,” said study corresponding author and Regenstrief Institute Vice President for Data and Analytics Shaun Grannis, M.D. “As vaccinated individuals were more likely to actually get COVID than those with natural immunity, the lower death rate of vaccine recipients who develop COVID appears to be due to vaccination and not to a tendency for risk-averse behaviors, such as mask-wearing, hand sanitizing and social distancing.”

Data on pairs of vaccine recipients and individuals with prior infections, aged between 12 and 110 years, matched on age, sex, CDC-defined COVID risk scores and dates of initial exposure (to the vaccines or the virus itself) were compared. This information was extracted from the Indiana Network for Patient Care, one of the nation’s largest health information exchanges. Death reports from the State of Indiana were also analyzed.  

“This study has important public health implications as previous studies investigated COVID-specific ED visits, hospitalizations and mortality but didn’t capture the non-COVID related ones,” said study first author Regenstrief Institute Research Scientist Wanzhu Tu, Ph.D. “Our work confirms that mRNA vaccines have kept people out of the ED and the hospital as well as lowered the likelihood of death from any cause. And we saw this pattern in every age group.”

The study concludes, “The significantly lower rates of all-cause ED visits, hospitalization and mortality in the vaccinated highlight the real-world benefits of vaccination. The data raises questions about the wisdom of reliance on natural immunity when safe and effective vaccines are available.”

“SARS-CoV-2 infection, hospitalization and death in vaccinated and infected individuals in Indiana USA, November 2020 - February 2022,” is published in the American Journal of Public Health. In addition to Drs. Grannis and Tu, authors are Pengyue Zhang, PhD, IU School of Medicine; Anna Roberts, M.S. and Katie S. Allen, B.S., Regenstrief Institute; Jennifer Williams, MPH, formerly with Regenstrief Institute; and Peter Embi, former Regenstrief Institute president and CEO, currently at Vanderbilt University Medical Center. 

About Shaun Grannis, M.D., M.S. 

In addition to his role as vice president for data and analytics at Regenstrief Institute, Shaun Grannis, M.D., M.S., is the Regenstrief Professor in Medical Informatics and is a professor of family medicine at Indiana University School of Medicine

About Wanzhu Tu, PhD 

In addition to his role as a research scientist at Regenstrief Institute, Wanzhu Tu, PhD, is a professor of biostatistics and health data science at Indiana University School of Medicine and the Richard M. Fairbanks School of Public Health at IUPUI.

About Regenstrief Institute 

Founded in 1969 in Indianapolis, the Regenstrief Institute is a local, national and global leader dedicated to a world where better information empowers people to end disease and realize true health. A key research partner to Indiana University, Regenstrief and its research scientists are responsible for a growing number of major healthcare innovations and studies. Examples range from the development of global health information technology standards that enable the use and interoperability of electronic health records to improving patient-physician communications, to creating models of care that inform practice and improve the lives of patients around the globe.

Sam Regenstrief, a nationally successful entrepreneur from Connersville, Indiana, founded the institute with the goal of making healthcare more efficient and accessible for everyone. His vision continues to guide the institute’s research mission.

About IU School of Medicine 

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability. 

About Richard M. Fairbanks School of Public Health   

Located on the IUPUI and Fort Wayne campuses, the Richard M. Fairbanks School of Public Health is committed to advancing the public’s health and well-being through education, innovation and leadership. The Fairbanks School of Public Health is known for its expertise in biostatistics, epidemiology, cancer research, community health, environmental public health, global health, health policy and health services administration.