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

<b>Background:</b> The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or se...

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Main Authors: Jesse M. van den Berg, Marieke T. Blom, Jetty A. Overbeek, Sharon Remmelzwaal, Ron M. C. Herings, Petra J. M. Elders
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/6/564
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author Jesse M. van den Berg
Marieke T. Blom
Jetty A. Overbeek
Sharon Remmelzwaal
Ron M. C. Herings
Petra J. M. Elders
author_facet Jesse M. van den Berg
Marieke T. Blom
Jetty A. Overbeek
Sharon Remmelzwaal
Ron M. C. Herings
Petra J. M. Elders
author_sort Jesse M. van den Berg
collection DOAJ
description <b>Background:</b> The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or severe COVID-19, both in individuals who had completed their primary COVID-19 vaccination, and in those who had received their first booster vaccination. Specifically, we aimed to evaluate whether persons with certain risk factors, such as age, gender, socioeconomic status (SES), and specified comorbidities have an increased risk of either breakthrough infection or severe COVID-19, compared to those without the respective risk factors. <b>Methods:</b> Data on COVID-19 vaccinations, infections, hospitalizations, and deaths were collected from the PHARMO Data Network, consisting of health records from Dutch residents. Two cohorts were established: (1) all persons who have completed their primary COVID-19 vaccination regimen, and (2) those who have received their first booster vaccination. The outcomes were 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. The adjusted incidence rate ratios of these outcomes in persons with certain risk factors were calculated, using generalized linear models with a Poisson distribution. <b>Results:</b> In 2021, a total of 1,090,567 individuals received either two doses of BNT162b2, AZD1222, 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. Overall incidence rates of SARS-CoV-2 breakthrough infection and severe COVID-19 after primary vaccination were 29.9 and 3.1 per 1000 person-years, respectively, and after booster vaccination were 256.4 and 2.3, respectively. Male gender, older age, lower SES, 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. The 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 or lung disease. <b>Conclusions:</b> Our study emphasizes the crucial role of boosters in reducing breakthrough infections, particularly in high-risk populations. The varied impact on severe outcomes in individuals with comorbidities underscores the need for ongoing surveillance and tailored vaccination strategies.
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spelling doaj-art-8219cb82fcbd433d9dd9d9dc049cb3d92025-08-20T03:29:52ZengMDPI AGVaccines2076-393X2025-05-0113656410.3390/vaccines13060564Rates of SARS-CoV-2 Breakthrough Infection or Severe COVID-19 and Associated Risk Factors After Primary and Booster Vaccination Against COVID-19 in the NetherlandsJesse M. van den Berg0Marieke T. Blom1Jetty A. Overbeek2Sharon Remmelzwaal3Ron M. C. Herings4Petra J. M. Elders5PHARMO Institute for Drug Outcomes Research, 3528 AE Utrecht, The NetherlandsDepartment of General Practice, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsPHARMO Institute for Drug Outcomes Research, 3528 AE Utrecht, The NetherlandsDepartment of General Practice, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsPHARMO Institute for Drug Outcomes Research, 3528 AE Utrecht, The NetherlandsDepartment of General Practice, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands<b>Background:</b> The effectiveness of COVID-19 vaccines appears to decline rapidly over time due to waning immunity and immune evasion by emerging variants of concern, and may be reduced in high-risk populations. We aimed to evaluate the rates of SARS-CoV-2 breakthrough infection or severe COVID-19, both in individuals who had completed their primary COVID-19 vaccination, and in those who had received their first booster vaccination. Specifically, we aimed to evaluate whether persons with certain risk factors, such as age, gender, socioeconomic status (SES), and specified comorbidities have an increased risk of either breakthrough infection or severe COVID-19, compared to those without the respective risk factors. <b>Methods:</b> Data on COVID-19 vaccinations, infections, hospitalizations, and deaths were collected from the PHARMO Data Network, consisting of health records from Dutch residents. Two cohorts were established: (1) all persons who have completed their primary COVID-19 vaccination regimen, and (2) those who have received their first booster vaccination. The outcomes were 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. The adjusted incidence rate ratios of these outcomes in persons with certain risk factors were calculated, using generalized linear models with a Poisson distribution. <b>Results:</b> In 2021, a total of 1,090,567 individuals received either two doses of BNT162b2, AZD1222, 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. Overall incidence rates of SARS-CoV-2 breakthrough infection and severe COVID-19 after primary vaccination were 29.9 and 3.1 per 1000 person-years, respectively, and after booster vaccination were 256.4 and 2.3, respectively. Male gender, older age, lower SES, 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. The 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 or lung disease. <b>Conclusions:</b> Our study emphasizes the crucial role of boosters in reducing breakthrough infections, particularly in high-risk populations. The varied impact on severe outcomes in individuals with comorbidities underscores the need for ongoing surveillance and tailored vaccination strategies.https://www.mdpi.com/2076-393X/13/6/564COVID-19SARS-CoV-2coronavirusvaccinationvaccine effectivenessrisk factors
spellingShingle Jesse M. van den Berg
Marieke T. Blom
Jetty A. Overbeek
Sharon Remmelzwaal
Ron M. C. Herings
Petra J. M. Elders
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
Vaccines
COVID-19
SARS-CoV-2
coronavirus
vaccination
vaccine effectiveness
risk factors
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic COVID-19
SARS-CoV-2
coronavirus
vaccination
vaccine effectiveness
risk factors
url https://www.mdpi.com/2076-393X/13/6/564
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