(351) Rates of SARS-CoV-2 Breakthrough Infection or Severe COVID-19 and Associated Risk Factors After Primary and Booster Vaccination Against COVID-19 in the Netherlands

Background: COVID-19 vaccines have shown high efficacy in preventing severe COVID-19 and SARS-CoV-2 infection. Effectiveness of these vaccines appears to decline over time and may be reduced in high-risk populations. The effectiveness of COVID-19 vaccination in high-risk populations, such as those with certain comorbidities or older age, remains relatively unknown.

Objectives: We aimed to evaluate possible risk factors associated with either SARS-CoV-2 breakthrough infection or severe COVID-19 in individuals who have completed their primary COVID-19 vaccination regimen and those who have received their first booster vaccination, particularly in high-risk populations.

Methods: Data on COVID-19 vaccinations, infections, hospitalizations, and deaths were collected from the PHARMO Data Network, consisting of records of approximately 2.5 million Dutch residents. Two cohorts were established: (1) all persons who have completed their primary COVID-19 vaccination regimen, and (2) a subcohort of those who have received their first booster vaccination. The study period was from January to December 2021. The outcomes are SARS-CoV-2 breakthrough infection and severe COVID-19, defined as either hospitalization or death following SARS-CoV-2 infection. Incidence rates of these outcomes were calculated in both cohorts. Adjusted incidence rate ratios of these outcomes in different risk-groups were calculated, using generalized linear models with a Poisson distribution.

Results: In 2021, a total of 1,090,567 individuals received either two doses of BNT162b2, ChAdOx1, or mRNA-1273, or one dose of AD26.COV2.S and were included in the primary vaccination cohort, of which 344,153 (31.6%) received a booster vaccination. During follow-up in 2021, a total of 50,661 events of breakthrough infection were recorded, and 1574 events of severe COVID-19. Male gender, older age, lower socioeconomic status, history of COVID-19, and recent hospitalization were factors associated with a lower risk of breakthrough infection after primary vaccination, and a higher risk of severe COVID-19. Risk of severe COVID-19 after primary vaccination was increased in persons with several comorbidities, compared to those without, and remained elevated after booster vaccination in persons with diabetes (IRR 1.58; 1.05-2.38) or lung disease (IRR 1.56; 1.07-2.29).

Conclusions: Our study adds to the evidence of risk factors associated with breakthrough infection and severe COVID-19 in vaccinated persons, emphasizing the possible role of boosters in reducing breakthrough infections and severe COVID-19, particularly in high-risk populations. The varied impact on these outcomes in individuals with comorbidities underscores the need for ongoing surveillance and tailored vaccination strategies.