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February 11, 2022

First study to show waning effectiveness of 3rd dose of mRNA vaccines

Dr. Brian DIxon and Dr. Shaun Grannis were authors on paper about waning effectiveness of third dose of mRNA vaccines
Dr. Brian Dixon (left) and Dr. Shaun Grannis (right)

Data also show people who are Hispanic or Black half as likely to receive booster than people who are white

A nationwide study from the U.S. Centers for Disease Control and Prevention (CDC) is the first to show that immunity against severe COVID-19 disease begins to wane 4 months after receipt of the third dose of an mRNA vaccine (Pfizer or Moderna). Waning immunity was observed during both the Delta and Omicron variant waves in similar fashion to how mRNA vaccine effectiveness wanes after a second dose. Although protection decreased with time, a third dose was still highly effective at preventing severe illness with COVID-19.

Until this study, little was known about durability of protection following three doses, especially during periods of Delta or Omicron predominance in the U.S.

“The mRNA vaccines, including the booster shot, are very effective, but effectiveness declines over time. Our findings suggest that additional doses may be necessary to maintain protection against COVID-19, especially for high-risk populations,” said study co-author Brian Dixon, PhD, MPA, Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health director of public health informatics. “We also found that people who are Hispanic or Black are half as likely to have a third vaccine dose than people who are white, making people who are Hispanic or Black more vulnerable to severe COVID and highlighting the need for public health officials to double down on efforts to protect these vulnerable populations.”

According to a CDC dashboard, as of February 8, 2022, among Americans 65 years or older who received a booster dose: 72.3 percent were people who were white, 8.9 percent were people who are Hispanic, and 7.6 percent were people who are Black. The rates among people who are Black or Hispanic are lower than the proportion of those groups with two doses, and these proportions are lower than the percentage of the U.S. population composed of people from those groups, indicating disparities in who has received third doses in the U.S. In the last two weeks, however, higher rates of vaccination have been observed among these minority groups (16.9 percent of recent boosters are among people who are Hispanic; 12.7 percent of recent boosters are among people who are Black). In the study, among patients who are white in the ED/UC, 12 percent had received a third dose compared to 7 percent of patients who are Hispanic and 6 percent of patients who are Black. Similar disparities in third dose administration were observed among those patients hospitalized for severe COVID-19.

Overall, the study reported that individuals with second and third doses of an mRNA vaccine had greater protection against hospitalizations (severe disease) than against emergency department/urgent care (ED/UC) visits (symptoms which may not require hospitalization). Vaccine effectiveness was also lower overall during the Omicron period than during the Delta period.

Vaccine effectiveness against ED/UC visits declined from 97 percent within the first two months of receipt of a booster to 89 percent effectiveness at four months or more during the Delta-predominant period (summer/early fall 2021). During the Omicron-predominant period (late fall 2021/winter 2021-22), vaccine effectiveness against ED/UC visits was 87 percent during the first two months after a third dose, decreasing to 66 percent at four months after a third dose.

After the third dose, protection against Delta variant-associated hospitalization declined from 96 percent within two months to 76 percent after four months or longer. Vaccine effectiveness against Omicron variant-associated hospitalizations was 91 percent during the first two months declining to 78 percent at four months.

“Our findings confirm the importance of receiving a third dose of mRNA COVID-19 vaccine to prevent moderate-to-severe COVID-19 illness, especially among those with comorbidities,” said study co-author Shaun Grannis, M.D., M.S., vice president for data and analytics at Regenstrief Institute and professor of family medicine at Indiana University School of Medicine. “That protection conferred by mRNA vaccines waned in the months following a third vaccine dose supports further consideration of booster doses to sustain protection against moderate-to-severe COVID-19 illness.”

“Waning Effectiveness 2-dose and 3-dose mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022” is published in the CDC’s Morbidity and Mortality Weekly Report.

The CDC collaborated with six 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 and University of Colorado. Regenstrief contributes data and expertise to the VISION Network.

Authors of the study are from 10 states and 14 institutions, including the public sector, research, clinical and academia. Regenstrief Institute authors, in addition to Drs. Dixon and Grannis, are William F. Fadel, PhD, a Regenstrief fellow; Nimish Ramesh Valvi, DrPH, MBBS, a Regenstrief fellow and Peter J. Embi, M.D., M.S., former Regenstrief president and a current affiliate scientist.

Authors on this paper are Jill M. Ferdinands, PhD, CDC COVID-19 Response Team; Suchitra Rao, MBBS, MSCS, School of Medicine, University of Colorado Anschutz Medical Campus; Brian E. Dixon MPA, PhD, Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health; Patrick K. Mitchell, ScD, Westat; Malini B. DeSilva, M.D., MPH, HealthPartners Institute; Stephanie A. Irving, MHS, Center for Health Research, Kaiser Permanente Northwest; Ned Lewis, MPH, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research; Karthik Natarajan, PhD, Department of Biomedical Informatics, Columbia University Irving Medical Center, New York Presbyterian Hospital; Edward Stenehjem, M.D., MSc, Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare; Shaun J. Grannis M.D., MSc, Regenstrief Institute and Indiana University School of Medicine; Jungmi Han, B.S., Department of Biomedical Informatics, Columbia University Irving Medical Center; Charlene McEvoy, M.D., MPH, HealthPartners Institute; Toan C. Ong, PhD, School of Medicine, University of Colorado Anschutz Medical Campus; Allison L. Naleway, PhD, Center for Health Research, Kaiser Permanente Northwest; Sarah E. Reese, PhD, Westat; Peter J. Embi, M.D., MS, formerly with Center for Biomedical Informatics, Regenstrief Institute and Indiana University School of Medicine; Kristin Dascomb, M.D., PhD, Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare; Nicola P. Klein, M.D., PhD, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research; Eric P. Griggs, MPH, CDC COVID-19 Response Team; I-Chia Liao, MPH, Baylor Scott & White Health; Anupam B. Kharbanda, M.D., MSc, Children’s Minnesota; Duck-Hye Yang, PhD, Westat; William F. Fadel, PhD, Center for Biomedical Informatics, Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health; Nancy Grisel, MPP, Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare; Kristin Goddard, MPH, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research; Palak Patel, MBBS, CDC COVID-19 Response Team; Kempapura Murthy, MBBS, MPH, Baylor Scott & White Health; Rebecca Birch, MPH, Westat; Nimish R. Valvi, DrPH, Center for Biomedical Informatics, Regenstrief Institute; Sue Reynolds, PhD, CDC COVID-19 Response Team; Julie Arndorfer, MPH, Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare; Ousseny Zerbo, PhD, Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research; Monica Dickerson, B.S., CDC COVID-19 Response Team; Chandni Raiyani, MPH, Baylor Scott & White Health; Jeremiah Williams, MPH, CDC COVID-19 Response Team; Catherine H. Bozio, PhD, CDC COVID-19 Response Team; Lenee Blanton, MPH, CDC COVID-19 Response Team; Jennifer R. Verani, M.D., CDC COVID-19 Response Team; Stephanie Schrag, DPhil, CDC COVID-19 Response Team; Alexandra F. Dalton, PhD, CDC COVID-19 Response Team; Mehiret H. Wondimu, MPH, CDC COVID-19 Response Team; Ruth Link-Gelles, PhD, CDC COVID-19 Response Team; Eduardo Azziz-Baumgartner, CDC COVID-19 Response Team; Michelle A. Barron, M.D., School of Medicine, University of Colorado Anschutz Medical Campus; Alicia Fry, M.D., CDC COVID-19 Response Team; Manjusha Gaglani, MBBS FIDSA, FPIDS, FAAP, Baylor Scott & White Health; Mark G. Thompson, PhD, CDC COVID-19 Response Team; Bruce Fireman, M.A., Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research.

About Brian E. Dixon, PhD, MPA

In addition to his role as Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health director of public health informatics, Brian E. Dixon, MPA, PhD, is a research scientist at Regenstrief and an associate professor of epidemiology at the Fairbanks School of Public Health, located on the IU campuses at Indianapolis and Fort Wayne. 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 of data and analytics at Regenstrief Institute, Shaun Grannis, M.D., M.S., is the Regenstrief Chair in Medical Informatics and a 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 IU campuses at Indianapolis and Fort Wayne, 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.

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