Top 5 Takeaways

  1. Vaccine Effectiveness (VE) varies with dose number and Omicron sublineage. VE was generally lower during the Omicron BA.2/BA.2.12.1 period compared to the BA.1 period. A third dose improved protection across all age groups, and a fourth dose offered additional benefits for those ≥50 years.
  2. Recommendation for booster doses. Immunocompetent individuals are encouraged to get recommended COVID-19 booster doses, including a first booster for all eligible persons and a second booster for those aged ≥50 years at least 4 months after the initial booster.
  3. Detailed VE analysis by the VISION network. The study included over 214,487 emergency department/urgent care visits and 58,782 hospitalizations, comparing VE across two, three, and four doses of mRNA vaccines against no vaccination among adults without immunocompromising conditions.
  4. Decline in VE over time and by additional dose. VE against hospitalization 7–119 days after the third dose was 92% during the BA.1 period and dropped to 69% during the BA.2/BA.2.12.1 period. A fourth dose increased VE to 80% in adults aged ≥50 years during the BA.2/BA.2.12.1 period.
  5. Significance of staying up to date with vaccinations. The study underscores the importance of adhering to vaccination recommendations to maintain higher levels of protection against COVID-19, especially with emerging variants and sublineages.

Original Article Author and Citation

Corresponding Author

Ruth Link-Gelles,

Suggested Citation

Link-Gelles R, Levy ME, Gaglani M, et al. Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022. MMWR Morb Mortal Wkly Rep 2022;71:931–939. DOI:


This MMWR report evaluates the effectiveness of two, three, and four doses of mRNA COVID-19 vaccines during the period when Omicron sublineages BA.1 and BA.2/BA.2.12.1 were predominant. The study highlights lower VE during the BA.2/BA.2.12.1 period compared to the BA.1 period and demonstrates the added protection offered by third and fourth vaccine doses.


The VISION network analyzed over 273,269 medical encounters across 10 states to assess VE against COVID-19–associated hospitalization and emergency department/urgent care visits. The study used a test-negative case-control design, adjusting for several variables including age, vaccination status, and local virus circulation.


The findings emphasize the reduced VE during the Omicron BA.2/BA.2.12.1 period and the significance of booster doses in enhancing protection against COVID-19. The study also addresses the need for continued monitoring of VE with emerging variants.


Staying up to date with COVID-19 vaccination, including obtaining recommended booster doses, is crucial for preventing moderate to severe COVID-19, especially with the evolution of SARS-CoV-2 variants.

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