Effectiveness of heterologous 3rd and 4th dose COVID-19 vaccine schedules for SARS-CoV-2 infection during delta and omicron predominance in Thailand.

Abstract The Coronavirus disease 2019 (COVID-19) pandemic has evolved quickly, with numerous waves of different variants of concern resulting in substantial morbidity and mortality globally. With the rapid availability of vaccines, Thailand has responded with a robust campaign to protect those at highest risk first, followed by population level protection. To ensure adequate vaccination coverage, agility was required, and Thailand has proactively adopted heterologous vaccination schedules to manage vaccine availability. While randomised controlled trials have assessed homologous schedules in detail, limited data has been reported for heterologous vaccine effectiveness (VE). Utilising a unique active surveillance network established in Chiang Mai, Northern Thailand, we conducted a test-negative case control study to assess the vaccine effectiveness of heterologous third and fourth dose schedules against SARS-CoV-2 infection during delta-predominant and omicron predominant periods. We noted very high effectiveness against delta infection after the third dose (adjusted VE 97%, 95% CI 94–99%) in comparison to moderate protection against omicron infection after a third dose (adjusted VE 31%, 95% CI 26–36%) and good protection after a fourth dose (adjusted VE 75%, 95% CI 71–80%). VE was consistent across age groups for both delta and omicron infection. The VE of third or fourth vaccine doses against omicron infection were equivalent for the three main vaccines used for boosting in Thailand suggesting coverage, rather than vaccine type is a much stronger predictor of protection. Additionally, a separate evaluation of a hospital patient management system noted extremely high effectiveness against severe COVID-19 and mortality outcomes after the third and fourth doses. Our data suggests that a fourth vaccination dose has a high probability of preventing infection and a very high probability of preventing death and severe COVID-19. This is critically important in preventing severity and unnecessary deaths but will also help to support the ongoing efforts to increase population coverage of booster doses.