Study: Fourth Dose of COVID-19 Vaccine Provides Protection Against Omicron Variant

A majority of long-term care patients who received a fourth vaccination against COVID-19 were found to have increased protection against the omicron variant.

A fourth dose of the mRNA vaccine was found to be effective against the fast-spreading omicron variant in long term care residents in Ontario, Canada, according to the authors of a study published in The BMJ.

In Ontario, two-thirds of deaths from COVID-19 occurred in long-term care facilities during the first 2 waves. The first vaccines reduced infections by 89% and decreased mortality by 96%, but deaths have slightly increased as vaccine effectiveness waned with time.

Omicron emerged in November 2021, after the first booster, or third dose, was rolled out in the United States. Omicron was the most transmissible variant, increasing the risk of reinfection and foreshadowing a new surge in the pandemic.

Beginning at the end of 2021, researchers used a test-negative design to estimate the marginal and vaccine efficacy for residents aged 60 years or older. In total, there were 13,654 participants who tested positive for the omicron variant in the study population, and were subsequently compared to the participants in the negative control group of 205,862 individuals who had not tested positive for omicron.

Between December 30, 2021 and April 27, 2022, 87.2% of the long-term care residents included in the study population were tested for SARS-CoV-2. At the time of testing, 58.1% of positive cases and 53.3% of negative test controls had 3 vaccine doses already--this was a preliminary requirement to the study.

Participants were actively or passively screened for the virus depending on their presentation ofsymptoms. Groups were then stratified depending on the date of their third dose, with evaluations conducted over time.

Based on the study results, researchers concluded that a fourth dose of mRNA COVID-19 vaccine improved protection against infection, symptomatic infection, and severe outcomes from omicron infection in long-term care residents. Specifically, a fourth dose was shown to increase the efficacy of protection against infection by 49%, against symptomatic infectionby 69%, and against severe infection by 86%.

Furthermore, although the vaccines were found to lose their efficacy after approximately 4 months, their efficacy increased with each dose. However, researchers noted that the fourth vaccine was also less effective if it was administered within 3 months of receiving the first vaccine.

The study further evaluated duration between the third and fourth dose and efficacy. They found that administering the fourth dose 3 months after their first booster (or third dose) was an effective wait period between the 2 doses.

Additionally, the efficacy of the fourth vaccine rose 7 days after patients received it, contributing to the overall increased efficacy of the vaccine for patients after 7 days following a fourth vaccination with a 3 month break between doses, providing 95% efficacy for patients who received a fourth vaccination.

The study was limited to participants with symptoms recorded in the Ontario Laboratories Information System, which excludes patients not in the system. Some of the cases were also not classified with the correct variant, causing researchers to potentially overestimate the severity of the outbreak. Finally, they were limited because they did not have records of staff vaccination statuses.

The authors of the study noted that further studies were needed to explore the efficacy of the fourth doses of the COVID-19 vaccine for other age groups and for different emerging variants.


Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study. BMJ website. July 6, 2022. Accessed July 28, 2022.