In a recent study posted to the medRxiv pre-print* server, a team of researchers evaluated the effectiveness of the XBB.1.5 coronavirus disease 2019 (COVID-19) vaccine in reducing hospitalizations and Intensive Care Unit (ICU) admissions among previously vaccinated adults aged 60 and over in the Netherlands from October to December 2023.

Study: Early COVID-19 vaccine effectiveness of XBB.1.5 vaccine against hospitalization and ICU admission, the Netherlands, 9 October – 5 December 2023. Image Credit: NIAID

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

In 2023, the Netherlands initiated its seasonal COVID-19 vaccination campaign on October 2, focusing on individuals 60 years and older, healthcare workers, pregnant women, and those with medical risks using the XBB1.5 Comirnaty vaccine. Personal vaccination invitations were mailed to residents 60+ from early October to late November. As of early December,  42.9% of this demographic had been vaccinated, and the campaign is set to continue until the end of December. Further research is necessary to fully understand the long-term effectiveness and impact of the XBB.1.5 COVID-19 vaccine on hospitalization and ICU admission rates, especially as the ongoing seasonal vaccination campaign progresses and more data becomes available post-December 2023.

About the study 

The research team employed the screening method to assess the vaccine effectiveness (VE) of the 2023 seasonal COVID-19 vaccination among individuals aged 60 and older in the Netherlands who had received at least one prior COVID-19 vaccination. The analysis focused on those recorded in the national population register as of September 25, 2023. Hospitalization data, covering the period from October 9 to December 5, 2023, were sourced from the National Institute for Health and Care Excellence (NICE) COVID-19 database on December 11, 2023, to allow for reporting delays. This dataset accounted for approximately 55% of all COVID-19 hospitalizations in the Netherlands during the study period, according to comparisons with anonymous data from the National Coordination Center for Patient Distribution.

Hospitalization records were deterministically linked to the national COVID-19 vaccination database (CIMS) via the Citizen Service Number. The CIMS registry, which relies on vaccine consent for recording vaccinations, showed a consent rate of over 95% in previous booster campaigns and 98% for the 2023 seasonal campaign. On the other hand, individuals included in this study who had at least one vaccination recorded in CIMS since January 2021 expected that these people would also consent to record their current year's (seasonal) vaccine doses and, therefore, reduce classification errors.

Although the official start of the 2023 seasonal vaccination campaign in the Netherlands was October 2, some centers began vaccinations as early as September 25, which were included in the campaign analysis. Individuals vaccinated within 90 days before September 25 were excluded. To account for the vaccine's immunological response time, a person's status was updated to "seasonal dose received" seven days post-vaccination, excluding this period from the analysis. The vaccination status was similarly determined at hospital admission. Using the CIMS registry, the vaccinated population's proportion was calculated, stratified by region, date, sex, and age up until the 15th of the month of death, emigration, or study end.

A logistic regression model estimated VE and its 95% confidence intervals. In this model, vaccination status was the dependent variable, and the covariate-specific logit of the seasonal dose received in the population served as an offset. The model's exponentiated intercept was interpreted as the relative risk (RR), and VE was calculated as (1-RR) x 100%.

VE estimates 

The 2023 seasonal COVID-19 vaccination campaign in the Netherlands concentrated on high-risk groups, such as those aged 60 and above. Of these, the study excludes 86 hospitalizations (including three ICU admissions) within seven days post-vaccination, and included in their analysis are a total of 2,050 cases admitted to hospitals. Among them, 295 (14.4 %) had received the seasonal COVID-19 vaccine for 2023. It was found that there were more hospitalizations among those aged 75 and older than in the age group of 60-74. During the course of the campaign, hospitalizations among vaccinated persons have increased progressively; this clearly reflects that a large-scale rollout is underway.

The VE against hospitalization was 70.7 % (CI, 66.6 to 74.3). Among the 92 cases of ICU admissions analyzed, VE was estimated at approximately 73.3 % (CI 42.2 to 87.6). The VE for the 60-74 age group (VE = 68.3%, CI :58.3 to 75.9) was slightly lower than that of those aged seventy-five and over (VE=V:Y%). Compared with last year's fall campaign, this study's VE estimates were slightly higher for those aged 60-79.

The researchers utilized the screening method, considering the incomplete data from the NICE hospitalization database due to the registration burden on hospitals. They included geographic regions in the model to adjust for possible differences in data completeness. However, there were limitations that might have led to an underestimation of VE, such as the inability to adjust for comorbidities, which typically results in higher VE estimates. Additionally, the study's initial period likely represented early vaccine recipients, who might have been frailer. The vaccination status of cases was determined at the time of hospitalization, which might not have allowed sufficient time for the vaccine to prevent severe disease.

In contrast, there might have been an overestimation of VE due to the generally better health of vaccine recipients (healthy vaccine bias). The study also noted that most individuals received their fourth booster dose during the campaign, with only 0.2% receiving a fifth booster. The median time since the last booster dose was significantly different between those who had and had not received the 2023 vaccine, potentially affecting VE estimates. However, a study across six European countries indicated that the number of booster doses did not significantly impact VE against hospitalization, and effectiveness generally waned six months after any booster dose.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.