According to an observational study published in The Lancet Infectious Diseases, a fourth dose of the bivalent (two-strain) COVID-19 vaccine is significantly more effective against medical treatment and hospitalization than a fourth monovalent (single-strain) dose among both previously infected and never-infected individuals who had received three monovalent doses. 

The study involved 2,749,829 participants and found that those who had never been exposed to COVID-19, a fourth dose of the monovalent vaccine did not provide any further protection over three doses against symptomatic infection while dose four of the bivalent vaccine did. 

The bivalent vaccine targets both the wild-type virus and the Omicron variant, as opposed to the monovalent which only targets the wild-type SARS-CoV-2.