Waning 2-dose and 3-dose Effectiveness of 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

Jill M. Ferdinands, PhD; Suchitra Rao, MBBS; Brian E. Dixon, PhD; Patrick K. Mitchell, ScD; Malini B. DeSilva, MD; Stephanie A. Irving, MHS; Ned Lewis, MPH; Karthik Natarajan, PhD; Edward Stenehjem, MD; Shaun J. Grannis, MD; Jungmi Han; Charlene McEvoy, MD; Toan C. Ong, PhD; Allison L. Naleway, PhD; Sarah E. Reese, PhD; Peter J. Embi, MD; Kristin Dascomb, MD; Nicola P. Klein, MD; Eric P. Griggs, MPH; Deepika Konatham; Anupam B. Kharbanda, MD; Duck-Hye Yang, PhD; William F. Fadel, PhD; Nancy Grisel, MPP; Kristin Goddard, MPH; Palak Patel, MBBS; I-Chia Liao MPH; Rebecca Birch, MPH; Nimish R. Valvi, DrPH; Sue Reynolds, PhD; Julie Arndorfer, MPH; Ousseny Zerbo, PhD; Monica Dickerson; Kempapura Murthy, MBBS; Jeremiah Williams, MPH; Catherine H. Bozio, PhD; Lenee Blanton, MPH; Jennifer R. Verani, MD; Stephanie J. Schrag, DPhil; Alexandra F. Dalton, PhD; Mehiret H. Wondimu, MPH; Ruth Link-Gelles, PhD; Eduardo Azziz-Baumgartner, MD; Michelle A. Barron, MD; Manjusha Gaglani, MBBS; Mark G. Thompson, PhD; Bruce Fireman


Morbidity and Mortality Weekly Report. 2022;71(7):255-263. 

In This Article


In a multistate analysis of 241,204 ED/UC encounters and 93,408 hospitalizations among adults with COVID-19–like illness during August 26, 2021–January 22, 2022, estimates of VE against laboratory-confirmed COVID-19 were lower during the Omicron-predominant than during the Delta-predominant period, after accounting for both number of vaccine doses received and time since vaccination. During both periods, VE after receipt of a third dose was always higher than VE following a second dose; however, VE waned with increasing time since vaccination. During the Omicron-predominant period, mRNA vaccination was highly effective against both COVID-19–associated ED/UC encounters (VE = 87%) and COVID-19 hospitalizations (VE = 91%) within 2 months after a third dose, but effectiveness waned, declining to 66% for prevention of COVID-19–associated ED/UC encounters by the fourth month after receipt of a third dose and to 78% for hospitalizations by the fourth month after receipt of a third dose. The finding of lower VE for 2 or 3 doses during the Omicron-predominant period is consistent with previous reports from the VISION network and others¶¶¶,****.[2,7] Waning of VE after receipt of a third dose of mRNA vaccine has also been observed in Israel[8] and in preliminary reports from the VISION Network.[2] This analysis enhances an earlier VISION Network report[2] by extending the Omicron study period to January 22, 2022, providing a more detailed breakdown of time since vaccination, and using an analytic technique that better controls for potential confounding by calendar week and geographic area. By comparing COVID-19 test-positive case-patients with COVID-19 test-negative control patients in the same geographic area and for whom encounter index dates occurred within the same week, bias in VE estimates resulting from temporal and spatial variations in virus circulation and vaccine coverage was reduced.

The findings in this report are subject to at least seven limitations. First, because this study was designed to estimate VE against COVID-19–associated ED/UC visits or hospitalizations, VE estimates from this study do not include COVID-19 infections that were not medically attended. Second, the median interval from receipt of a third dose to medical encounters was 49 days; thus, the observed performance of a third dose is limited to a relatively short period after vaccination. Third, the small number of COVID-19 test-positive patients in the most remote time-since-vaccination groups reduced the precision of the VE estimates for those groups (e.g., ≥5 months). Fourth, variations in waning of VE by age group, immunocompromised status, other indicators of underlying health status, or vaccine product have not yet been examined. This study could not distinguish whether a third dose was received as an additional dose as part of a primary series (as recommended for immunocompromised persons) or as a booster dose after completion of a primary series. Further research should evaluate waning VE of a third primary dose among immunocompromised adults compared with waning of VE after a booster dose among immunocompetent adults. Fifth, despite adjustments to account for differences between unvaccinated and vaccinated persons, VE estimates might have been biased by residual differences between these groups with respect to immunocompromised status and other health conditions, as well as from unmeasured behaviors (e.g., mask use and close contact with persons with COVID-19). For example, insufficient adjustment for immunocompromised status might have biased the estimates of VE downward among persons most remote from receipt of a third dose. Sixth, genetic characterization of patients' viruses was not available, and analyses relied on dates when the Omicron variant became locally predominant based on surveillance data; therefore, the Omicron period of predominance in this study likely includes some medical encounters associated with the Delta variant. Finally, although the facilities in this study serve heterogeneous populations in 10 states, the findings might not be generalizable to the U.S. population.

These findings underscore the importance of receiving a third dose of mRNA COVID-19 vaccine to prevent both COVID-19–associated ED/UC encounters and COVID-19 hospitalizations among adults. The finding that protection conferred by mRNA vaccines waned in the months after receipt of a third vaccine dose reinforces the importance of further consideration of additional doses to sustain or improve protection against COVID-19–associated ED/UC encounters and COVID-19 hospitalizations. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19–associated hospitalizations and ED/UC visits.