This study, conducted in England, aimed to estimate the effectiveness of Covid-19 vaccines against symptomatic disease caused by the Omicron (B.1.1.529) and Delta (B.1.617.2) variants. Using a test-negative case-control design, the researchers analyzed data from November 27, 2021, to January 12, 2022, involving 886,774 Omicron cases, 204,154 Delta cases, and 1,572,621 controls. The results showed that vaccine effectiveness against the Omicron variant was significantly lower than against the Delta variant. After two doses, vaccine effectiveness waned rapidly, with no significant protection observed 20 weeks after the second dose for any vaccine. Booster doses with BNT162b2 or mRNA-1273 significantly increased protection but also showed waning over time. The study concluded that primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 provided limited protection against the Omicron variant, and booster doses were necessary to maintain substantial protection. However, the duration and effectiveness of protection after booster doses remain uncertain.This study, conducted in England, aimed to estimate the effectiveness of Covid-19 vaccines against symptomatic disease caused by the Omicron (B.1.1.529) and Delta (B.1.617.2) variants. Using a test-negative case-control design, the researchers analyzed data from November 27, 2021, to January 12, 2022, involving 886,774 Omicron cases, 204,154 Delta cases, and 1,572,621 controls. The results showed that vaccine effectiveness against the Omicron variant was significantly lower than against the Delta variant. After two doses, vaccine effectiveness waned rapidly, with no significant protection observed 20 weeks after the second dose for any vaccine. Booster doses with BNT162b2 or mRNA-1273 significantly increased protection but also showed waning over time. The study concluded that primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 provided limited protection against the Omicron variant, and booster doses were necessary to maintain substantial protection. However, the duration and effectiveness of protection after booster doses remain uncertain.