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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.

Background The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need to offer continued protection through booster vaccinations. The duration of enhanced protection with booster doses against severe COVID-19 is still unclear. Understanding this is critical to recommendations on the frequency of future booster doses. Methods Utilising a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data of laboratory-confirmed COVID-19 cases to the national immunization records, during the omicron predominant period (1 February– 31 July 2022). Results Out of 261,103 adults with COVID-19 included in the study, there were 333 (0.13%) severe COVID-19 cases and 190 (0.07%) deaths. Protection against severe COVID-19 was highest with boosters received >14–60 days prior to positive test (93%) and persisted at >60–120 days (91%) but started to wane at >120–180 days (77%) and further at >180 days (68%). The rate of waning differed with age. Those ≥70 years showed faster waning of booster vaccine responses as compared to those aged 18–49 years, who retained good responses up to 180 days. Equivalent risk reduction against severe COVID-19 was seen with all the vaccine types used as boosters in Thailand. Conclusions Booster doses provided high levels of protection against severe COVID-19 with omicron, up to 4 months. Repeat boosters will be required to continue protection beyond 4 months, particularly in the elderly. mRNA and viral vector vaccines can be used flexibly to improve booster coverage.

Background: The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need to offer continued protection through booster vaccinations. The duration of enhanced protection with booster doses against severe COVID-19 is still unclear and understanding this is critical to recommendations on frequency of future booster doses. Methods: Utilising a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data of laboratory-confirmed COVID-19 cases to the national immunization records, during omicron predominant period (1 February – 31 July 2022). Results: Out of 261,103 adults with COVID-19 included in the study, there were 333 (0.13%) severe COVID-19 cases and 190 (0.07%) deaths. Protection against severe COVID-19 was highest with boosters received >14-60 days prior to positive test (93%) and persisted at >60-120 days (91%) but started to wane at >120-180 days (77%) and further at >180 days (68%). The rate of waning differed with age. Those ≥70 years showed waning of booster vaccine response as early as >60 days as compared to those aged 18-49 years, who retained good response up to 180 days. Equivalent risk reduction against severe COVID-19 was seen with all the vaccine types used as boosters in Thailand. Conclusions:Booster doses provided high level of protection against severe COVID-19 with omicron, up to 4 months. Repeat boosters will be required to continue protection beyond 4 months, particularly in elderly. mRNA and viral vector vaccines can be used flexibly to improve booster coverage.