Study: Three COVID-19 Vaccine Doses May Provide Better, Longer Protection Than Two


Receiving 3 doses of the COVID-19 vaccine can offer better and more long-lasting protection against the Omicron variant.

A third COVID-19 vaccine dose has been found to offer more durable and superior protection compared with 2 doses against contracting or being hospitalized from the Omicron variant of SARS-CoV-2 infection, according to research published in PLOS Medicine.1

“Despite being less effective against infection with Omicron than previous variants, a third mRNA COVID-19 vaccine dose offers better protection against Omicron infection than two doses and protects well against COVID-19 hospitalization,” said Mie Agermose Gram, of Statens Serum Institut, Copenhagen, Denmark, in a press release.1

Long-term vaccine durability can impact the rates of infections and hospitalizations against COVID-19. However, there is limited evidence about the efficacy of 2 vs 3 COVID-19 vaccine doses against these risks. Researchers conducted a nationwide cohort study to better understand the durability and efficacy of 3 vaccine doses over time.1

The study authors gathered individual-level data of uninfected Danish residents 12 years of age and older from national Danish Civil Registration System and Danish Vaccination Registry, estimating vaccine effectiveness with vaccination status as a time-varying exposure. The team adjusted for age, sex, geographic location, and comorbidities.1

Afterwards, investigators compared the infection and hospitalization rates of 3- and 2-time vaccinated individuals to unvaccinated individuals. Overall, the third dose provided greater and longer lasting protection against hospitalizations and infection from the Omicron variant than 2 doses.1

“Our findings indicate that a third dose is necessary to maintain protection against infection for a longer time and to ensure a high level of protection against COVID-19 hospitalization with the Omicron variant,” the authors said in the press release.1

In a previous study, researchers at Memorial Sloan Kettering Cancer Center compared the efficacy of 3 vs 2 doses of the COVID-19 vaccine.Nearly 100% of the participants got 2 vaccines during the study, while 60% received a third.2

One researcher wrote that the “study demonstrates improved vaccine-derived protection against COVID-19 infection in 3D [third-dose] vs. 2D [two-dose] mRNA vaccinees during the Omicron surge."2

Receiving 3 doses was found to increase protection against Omicron by more than 33%. 2

Further researcher suggests that 4 COVID-19 vaccine doses offer better protection against the Omicron variant than 2 or 3 doses.2 An Israel-based study compared infection rates among health care workers who had either 3 or 4 vaccine doses. The researchers found that individuals who received 3 doses had a 13% increased breakthrough infection rate.2

The current study was limited because the data were not randomized, which might exclude more data differentiating results from the vaccinated and unvaccinated groups.1

The authors concluded that the “continued emergence of new variants and waning vaccine durability require ongoing evaluation of vaccine effectiveness against infection and hospitalization to inform future vaccination strategies.”1


  1. PLOS. Three COVID-19 vaccines may provide greater protection from COVID-19 infections than two. EurekAlert! September 1, 2022. Accessed on September 2, 2022.
  2. Beusekom, Mary V. Studies: 3 or 4 COVID vaccine doses protective against Omicron. CIDRAP. August 3, 2022. Accessed September 2, 2022.

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