Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against

On Feb 17, 2022

On February 11, 2022, this report was posted online as an MMWR Early Release.

Jill M. Ferdinands, PhD¹; Suchitra Rao, MBBS²; Brian E. Dixon, PhD³^,4; Patrick K. Mitchell, ScD⁵; Malini B. DeSilva, MD⁶; Stephanie A. Irving, MHS⁷; Ned Lewis, MPH⁸; Karthik Natarajan, PhD⁹^,10; Edward Stenehjem, MD¹¹; Shaun J. Grannis, MD³^,12; Jungmi Han⁹; Charlene McEvoy, MD⁶; Toan C. Ong, PhD²; Allison L. Naleway, PhD⁷; Sarah E. Reese, PhD⁵; Peter J. Embi, MD³^,12^,13; Kristin Dascomb, MD¹¹; Nicola P. Klein, MD⁸; Eric P. Griggs, MPH¹; Deepika Konatham¹⁴; Anupam B. Kharbanda, MD¹⁵; Duck-Hye Yang, PhD⁵; William F. Fadel, PhD³^,4; Nancy Grisel, MPP¹¹; Kristin Goddard, MPH⁸; Palak Patel, MBBS¹; I-Chia Liao, MPH¹⁴; Rebecca Birch, MPH⁵; Nimish R. Valvi, DrPH³; Sue Reynolds, PhD¹; Julie Arndorfer, MPH¹¹; Ousseny Zerbo, PhD⁸; Monica Dickerson¹; Kempapura Murthy, MBBS¹⁴; Jeremiah Williams, MPH¹; Catherine H. Bozio, PhD¹; Lenee Blanton, MPH¹; Jennifer R. Verani, MD¹; Stephanie J. Schrag, DPhil¹; Alexandra F. Dalton, PhD¹; Mehiret H. Wondimu, MPH¹; Ruth Link-Gelles, PhD¹; Eduardo Azziz-Baumgartner, MD¹; Michelle A. Barron, MD²; Manjusha Gaglani, MBBS¹⁴^,16; Mark G. Thompson, PhD¹; Bruce Fireman⁸ (View author affiliations)

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Summary

What is already known about this topic?

Protection against COVID-19 after 2 doses of mRNA vaccine wanes, but little is known about durability of protection after 3 doses.

What is added by this report?

Vaccine effectiveness (VE) against COVID-19–associated emergency department/urgent care (ED/UC) visits and hospitalizations was higher after the third dose than after the second dose but waned with time since vaccination. During the Omicron-predominant period, VE against COVID-19–associated ED/UC visits and hospitalizations was 87% and 91%, respectively, during the 2 months after a third dose and decreased to 66% and 78% by the fourth month after a third dose. Protection against hospitalizations exceeded that against ED/UC visits.

What are the implications for public health practice?

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.

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CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance^† (1–5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites^§ examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).^¶ Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021–January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4–5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. 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.

VISION Network methods have been previously published (6). Eligible medical encounters were defined as those among adults aged ≥18 years with a COVID-19–like illness diagnosis^†† who had received molecular testing (primarily reverse transcription–polymerase chain reaction assay) for SARS-CoV-2, the virus that causes COVID-19, during the 14…