National study confirms breakthrough COVID cases are less severe than COVID in unvaccinated adults

INDIANAPOLIS -- Individuals who, despite having been vaccinated against COVID-19, develop the disease and are hospitalized are less likely to go to an intensive care unit (ICU), more likely to have a shorter hospital stay, and less likely to die in the hospital than individuals hospitalized for COVID who were never vaccinated, according to a national study from the Centers for Disease Control and Prevention’s VISION Network.

These findings confirm that vaccination, while not 100 percent effective in preventing COVID, has reduced disease severity during the periods of Delta and Omicron dominance.

Time from hospital admission to discharge was 15 to 20 percent shorter for vaccinated patients than unvaccinated patients.

During the period of Delta predominance, vaccinated patients were half as likely as unvaccinated patients to be admitted to the ICU during their hospital stay. During Omicron predominance, vaccinated patients were 30 percent less likely than unvaccinated patients to be admitted to the ICU.

Slightly more than 10 percent of those hospitalized for COVID-19 died while in the hospital. Nearly 81 percent of those who died were unvaccinated.

“This is one of the first studies to compare vaccine status of adults who were so sick with COVID that they were hospitalized,” said study co-author Brian Dixon, PhD, MPA, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health. “The bottom line is that even with breakthrough cases – disease occurring in spite of vaccination -- you were better off having been vaccinated and boosted as vaccine effectiveness waned, than not. The hospital course of stay was less severe, and you are less likely to go to the ICU and less likely to die.”

Vaccine effectiveness against severe COVID requiring hospitalization declined less than vaccine effectiveness against infection only (mild disease). Other VISION Network studies have shown that booster shots restore effectiveness.

Breakthrough COVID cases admitted to a hospital tended to be in older individuals and those with additional medical conditions.

Compared with vaccinated individuals, unvaccinated individuals in the study were generally younger and healthier, with a lower percentage having any underlying medical conditions such as cardiovascular disease or diabetes, but a higher percentage having underlying respiratory conditions.

“We know that certain racial and ethnic groups, younger adults, those living in rural areas, those with low socioeconomic status, and uninsured persons in the U.S. tend to be less likely to be vaccinated,” said study co-author Shaun Grannis, M.D., M.S., of the Regenstrief Institute and Indiana University School of Medicine. “Hopefully this study will encourage those who have been hesitant to get vaccinated and boosted to reduce their risk of severe disease and death. Vaccination benefits individuals, families, communities and the healthcare system.”

The CDC collaborated with seven U.S. healthcare systems plus the Regenstrief Institute, to create the VISION network to assess COVID-19 vaccine effectiveness. In addition to Regenstrief Institute, other members are Columbia University Irving Medical Center, HealthPartners, Intermountain Healthcare, Kaiser Permanente Northern California, Kaiser Permanente Northwest, University of Colorado and Paso Del Norte Health Information Exchange (PHIX). Regenstrief contributes data and expertise to the VISION Network.

Regenstrief Institute authors of this VISION Network study, “Protection of 2 and 3 mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized with COVID-19 – VISION Network, August 2021 – March 2022,” in addition to Drs. Dixon and Grannis, are William F. Fadel, PhD, Nimish Ramesh Valvi, DrPH, MBBS and former institute president and current affiliated scientist Peter Embi, M.D.

Complete author list: Malini B. DeSilva, M.D., MPH, HealthPartners Institute; Patrick K. Mitchell, ScD, Westat; Nicola P. Klein, M.D., PhD, Kaiser Permanente Northern California Division of Research; Brian E. Dixon, PhD, MPA, Regenstrief Institute, IU Richard M. Fairbanks School of Public Health; Mark W. Tenforde, M.D., PhD, Centers for Disease Control and Prevention COVID-19 Response Team; Mark G. Thompson, PhD, Centers for Disease Control and Prevention COVID-19 Response Team; Allison L. Naleway, PhD, Kaiser Permanente Northwest; Shaun J. Grannis, M.D., M.S., Regenstrief Institute, Indiana University School of Medicine; Toan C. Ong, PhD, University of Colorado Anschutz Medical Campus; Karthik Natarajan, PhD, Columbia University Irving Medical Center, New York Presbyterian Hospital; Sarah E. Reese, PhD, Westat; Ousseny Zerbo, PhD, Kaiser Permanente Northern California Division of Research; Anupam B. Kharbanda, M.D., Children's Minnesota; Palak Patel, MBBS, MPH, Centers for Disease Control and Prevention COVID-19 Response Team; Edward Stenehjem, M.D., MSc, Intermountain Healthcare; Chandni Raiyani, BDS, MPH, Baylor Scott & White Health; Stephanie A. Irving, MHS, Kaiser Permanente Northwest; William F. Fadel, PhD, Regenstrief Institute, IU Richard M. Fairbanks School of Public Health; Suchitra Rao, MBBS, MSCS, Indiana University School of Medicine; Jungmi Han, B.S., Columbia University Irving Medical Center; Jonathan M. Davis, PhD, Westat; Ned Lewis, MPH, Kaiser Permanente Northern California Division of Research; Charlene McEvoy, M.D., MPH, HealthPartners Institute; Monica Dickerson, Centers for Disease Control and Prevention COVID-19 Response Team; Kristin Dascomb, M.D., MPH, Intermountain Healthcare; Nimish R. Valvi, DrPH, Regenstrief Institute; Michelle A. Barron, M.D., University of Colorado Anschutz Medical Campus; Kristin Goddard, MPH, Kaiser Permanente Northern California Division of Research; Gabriela Vazquez-Benitez, PhD, HealthPartners Institute; Nancy Grisel, MPP, Intermountain Healthcare; Mufaddal Mamawala, MBBS, MPH, Baylor Scott & White Health; Peter J. Embí, M.D., M.S., Regenstrief Institute, Indiana University School of Medicine, Vanderbilt University Medical Center; Bruce Fireman, M.A., Kaiser Permanente Northern California Division of Research; Inih J. Essien, O.D., MPH, HealthPartners Institute; Eric P. Griggs, MPH, Centers for Disease Control and Prevention COVID-19 Response Team; Julie Arndorfer, MPH, Intermountain Healthcare; and Manjusha Gaglani, MBBS, Texas A&M University College of Medicine.

The study, published in Journal of Infectious Diseases, was funded by the CDC.

About Brian E. Dixon, PhD, MPA

In addition to his roles as interim director of the Regenstrief Institute’s Clem McDonald Center for Biomedical Informatics and director of public health informatics for Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Brian E. Dixon, PhD, MPA is a professor of epidemiology at the Fairbanks School of Public Health. He is also an affiliate scientist at the U.S. Department of Veterans Affairs Health Services Research and Development Center for Health Information and Communication, Richard L. Roudebush VA Medical Center. 

About Shaun Grannis, M.D., M.S.

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

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 the 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.

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.