Study: 3 Vaccine Doses Are Critical for Protection Against the COVID-19 Omicron Variant


Investigators call for routine monitoring of vaccination effectiveness as the pandemic continues to evolve.

Three doses of an mRNA vaccine are needed to achieve a similar level of protection against the COVID-19 Omicron variant that 2 doses provide against the Alpha and Delta variants, results of a study published in The BMJ showed.

Additionally, the findings show that though the severity of disease among individuals admitted to the hospital is lower with Omicron than with Delta, the former are still at risk of critical illness and death.

The results of earlier studies suggested reduced vaccine effectiveness against infection and hospital admissions for Omicron compared with earlier variants. However, little is known about that effectiveness of vaccines to prevent the most severe infections of COVID-19 for individuals with Omicron.

Investigators aimed to address this question and assessed the clinical severity of COVID-19 associated with the Alpha, Delta, and Omicron variants among adults admitted to the hospital and compared the effectiveness of 2 and 3 doses of mRNA vaccines to prevent hospital admissions related to the variants.

The study included 11,690 adults admitted to 21 hospitals across the United States between March 2021 and January 2022. There were 5728 individuals with COVID-19 and 5962 individuals without COVID-19, who were used as controls.

The individuals were classified into 3 groups based on viral gene sequencing for the variant or by the predominant circulating variant at the time.

Between March 11, 2021, to July 3, 2021, the Alpha variant was the primary strain; between July 4, 2021, and December 25, 2021, it was the Delta variant; and between December 26, 2021, and January 14, 2022, it was the Omicron variant.

Vaccine effectiveness was calculated for each variant, and disease severity was compared among the variants. Investigators used the World Health Organization’s clinical progression scale, which evaluates how severely ill an individual becomes in the hospital.

The effectiveness of 2 doses of an mRNA vaccine to prevent hospital admission with COVID-19 was lower for the Omicron variant than for the Alpha and Delta variants at 65%, 85%, and 85%, respectively, whereas 3 doses achieved 86% effectiveness against Omicron, similar to 2 doses Alpha and Delta.

Among those who were not vaccinated and admitted to the hospital with COVID-19, the Delta variant was associated with the most severe disease, followed by the Alpha, and then Omicron.

By contrast, the Omicron variant was associated with substantial critical illness and death, with 15% of individuals admitted to the hospital with this variant, both unvaccinated and vaccinated, progressing to invasive mechanical ventilation and 7% dying in the hospital.

Additionally, vaccinated individuals admitted to the hospital with COVID-19 had a significantly lower disease severity than unvaccinated individuals for all the variants.

“As the COVID-19 pandemic continues to evolve, routine monitoring of vaccine effectiveness, especially against severe disease, and surveillance programs to identify viral variants will be essential to inform decisions about booster vaccine policies and vaccine strain updates,” investigators of the study said in a statement.

The study was observational, so investigators acknowledged that variant misclassifications could have occurred, adding that they did not account for differences in clinical management during different variant periods.


Third vaccine dose critical for protecting populations against omicron variant. EurekAlert. News release. March 9, 2022. Accessed March 10, 2022.

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