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COVID-19 vaccine effectiveness against hospitalizations and ICU admissions in the Netherlands, April- August 2021

Our take —

This study, available as a preprint and thus not yet peer reviewed, used data from nationwide registries in the Netherlands to estimate vaccine effectiveness against COVID-19 hospitalization during periods when the Alpha and Delta variants were dominant. The study found that full vaccination (from the Pfizer, Moderna, AstraZeneca, and Janssen vaccines) was highly effective in both periods (94% and 95%, respectively), and found no evidence that effectiveness waned over a 5-month span after full vaccination or across different age groups. Although there are some possible sources of bias in this study, the use of nationwide registries provides strong evidence for persistently robust protection of vaccination against COVID-19-associated hospitalization, even with the dominance of the Delta strain.

Study design

Retrospective Cohort

Study population and setting

This study in the Netherlands linked a nationwide vaccination registry with a nationwide hospitalization database to estimate vaccine effectiveness (VE) against COVID-19 hospitalization and ICU admission from April 4 to August 19, 2021. VE was estimated by vaccine (Pfizer, Moderna, AstraZeneca, and Janssen), age group (15-49 years, 50-69 years, 70 years and older), time since vaccination, and prevailing SARS-CoV-2 variant (April 4 to May 29, when 95% of sequenced SARS-CoV-2 isolates were Alpha, vs. July 4 – August 29, when 99% of sequenced isolates were Delta). COVID-19 hospitalizations and ICU admissions were taken from NICE, a nationwide registry of all hospitalized individuals with a positive SARS-CoV-2 test or COVID-19 diagnosis. Vaccination status was ascertained via the nationwide vaccine registry CIMS. Upon vaccination, informed consent was sought for CIMS registration; among the 84% of vaccinations provided through the Netherlands municipal health services, 7.3% declined to be registered in CIMS. The size of the unvaccinated group was calculated by subtracting the vaccinated group from the full population. Vaccination status was considered to be “partial” 14 days after the first dose and “full” 14 days after the second dose (or 28 days after the single dose of the Janssen vaccine). The median duration from symptom onset to hospitalization, by age group (3-7 days), was applied to each admission date to classify vaccination status. Incidence rates per 10,000 person-days were calculated and incidence rate ratios (IRRs) were calculated with negative binomial regression adjusted for calendar date.

Summary of Main Findings

Of the 15,571 patients hospitalized with COVID-19 during the study period, 6% were fully vaccinated, 7% were partially vaccinated, and 87% were unvaccinated. For full vaccination, the estimated VE against hospitalization during the Alpha period was 94% overall (95% CI: 93% to 95%) and was consistently high across all three age groups. The estimated VE against hospitalization during the Delta period was 95% (94% to 95%) and also above 90% across age groups. Estimated VE against hospitalization by vaccine during the Delta period was as follows: Pfizer 96% (95% to 96%), Moderna 84% (80% to 87%), AstraZeneca 94% (92% to 95%), and Janssen 91% (88% to 94%). Estimated VE against ICU admission was generally slightly higher than that for hospitalization across categories of age, vaccine, time since vaccination, and viral variant period. There was no evidence of waning VE in any age group up to 20 weeks after full vaccination.

Study Strengths

Linkage of national hospitalization and vaccination registries allowed for a full nationwide cohort analysis of vaccine effectiveness and a comparison of vaccine effectiveness across age and vaccine cohorts.


Vaccine allocation was nonrandom; for example, the authors noted that the Moderna vaccine was provided to medically high-risk patients, which may explain the lower apparent VE for that vaccine relative to the other vaccines. Furthermore, individuals who received the Pfizer and Moderna vaccine received the doses with a median interval of five weeks, which is longer than the intervals tested in their clinical trials (three and four weeks respectively), but may have implications for long-term effectiveness. Additionally, other than age, no information on patient characteristics or comorbidities were available, so unmeasured confounding is likely. There were few hospitalizations in several strata, limiting precision of estimates. An unknown proportion (likely around 7%) of vaccinated individuals did not consent to CIMS registration, and the resulting misclassification would result in overestimation of VE. However, a sensitivity analysis showed minimal impact on VE estimates. The population at risk included people with prior SARS-CoV-2 infection, which may have also led to bias if prior infection was associated with both vaccination status and hospitalization. Finally, COVID-19 hospitalization may have included some people who were hospitalized for other reasons but who incidentally tested positive for SARS-CoV-2, which may have led to a slight bias in an unknown direction.

Value added

This study is one of the first nationwide cohort studies to estimate vaccine effectiveness in the era of dominance of the Delta strain of SARS-CoV-2.

This review was posted on: 18 October 2021