Effectiveness of a Second Dose of an mRNA Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in Individuals Previously Infected by Other Variants
Authors: Monge Susana , Rojas-Benedicto Ayelén , Olmedo Carmen , Martín-Merino Elisa , Mazagatos Clara , Limia Aurora , Sierra María José , Larrauri Amparo , Hernán Miguel A ,   IBERCovid, Moreno David , Díaz Manuel Méndez , González Ismael Huerta , Truyols Antònia Galmés , Estévez Ana Barreno , Velasco Valvanuz García , Recio Mª Jesús Rodríguez , Sacristán José , Marcos Montserrat Martínez , Villalba Eliseo Pastor , Ortiz María José Macías , Vallejo Ana García , Carbajo María Dolores Lasheras , Gurea Aurelio Barricarte , Martínez Rosa Sancho , Ochoa Eva María , Cantero Mauricio Vázquez , Anés Atanasio Gómez , Megía María Jesús Pareja , Castán Yolanda , Álvarez Manuel Roberto Fonseca , Fiol Antonia Salvà , Janáriz Hilda Sánchez , Arce Luz López , Martín María Ángeles Cisneros , Gibernau Frederic Jose , Buey Cesar Fernandez , Bongiorno Katja Villatoro , Mera Luis Lozano , Guerra Fernando Santos , Mochales Jenaro Astray , Verdu Francisco Javier Francisco , Romero Isabel García , Bernal Rosa Oriza , Pérez Tomás Gómez , Villegas Salomé Hijano , Soto Sergio Román , Gómez-Barroso Diana , Lapeña María Fé , Galaup Virgilio Yagüe , Latorre Mercedes Alfaro , Guzmán Marta Aguilera , Sánchez-Eznarriaga Belén Crespo , León Montserrat Neira , Villa Noemí Cívicos 
Published: June 2022

Abstract

Background
Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown.

Methods
We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18–64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan–Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021.

Results
In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2–66.4%) 7–34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1–69.9%) for mRNA-1273 and 52.0% (41.8–63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4–89.9%), 66.1% (54.9–77.5%), and 60.2% (55.5–64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (−55.3% to 81.1%).

Conclusions
Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant.