VASCO study: A population-based prospective cohort study on vaccine effectiveness of COVID-19 vaccines in the Netherlands

Several COVID-19 vaccines have been (and will be) registered for use in the
general population. COVID-19 vaccination started in the Netherlands in January
2021. Vaccination will sequentially target different groups, starting with
specific groups of health care professionals and vulnerable persons. The goal
is to vaccinate all adults in the course of 2021. COVID-19 vaccines have shown
to be efficacious against COVID-19 in registration trials. These trials were
not always powered to assess efficacy in subgroups, such as age and risk
groups. Also, follow-up to date has been limited to a few months, and the
duration of protection is not yet known for any of the licensed vaccines.
Furthermore, virus variants have and could emerge that might influence the
(duration of) protection. Therefore, post-marketing observational studies are
needed to assess vaccine effectiveness (VE) in the real world and assess
differences by vaccine and by age and risk group. This will inform on the
future vaccination strategy, i.e. the possible need for revaccinations/booster
vaccinations.

The primary objective is to estimate product-specific vaccine effectiveness
(VE) of the COVID-19 vaccines that are used in the Dutch national vaccination
program against symptomatic SARS-CoV-2 infection by age and medical risk group
at a time point where most participants received vaccination at least 6 months
before (i.e. approximately 9 months after start of the study).
Secondary objectives include estimating VE by time since vaccination, number of
doses and interval between doses, and over longer follow-up time; estimating VE
against SARS-CoV-2 infection by severity (asymptomatic, mild, severe); and
monitoring of unsolicited adverse events for which medical attention was
sought.

An observational population-based prospective cohort study. This study will use
the existing SARS-CoV-2 testing infrastructure and COVID-19 vaccination
strategy in the Netherlands. Preferably, participants will be included (as long
as possible) before they received a first COVID-19 vaccination. At baseline,
participants will be asked to take a self-collected fingerpick sample at home
and to complete a baseline questionnaire via app or website. Data collected in
the questionnaire includes sociodemographic variables, health status (including
underlying conditions and previous SARS-CoV-2 infection), vaccination, and
behaviour regarding COVID-19 measures. During follow-up participants will be
asked to fill out monthly questionnaires (quaterly after the first year) via an
app or website including questions about COVID-19 vaccination, testing for
SARS-CoV-2 infection, changes in health status and behaviour regarding COVID-19
measures. Participants are asked to notify in the app when they tested positive
for SARS-CoV-2 or when they received a COVID-19 vaccination. Also, participants
are asked to collect a self-collected fingerpick during follow-up every 6
months after inclusion in the study. Also 1 month after primary vaccination, a
fingerpick blood sample is taken. Fingerpick blood samples are collected to
measure antibodies to detect previous SARS-CoV-2 infections which were not
detected by PCR or antigen tests, due to asymptomatic infections or because
participants did not get tested. In samples collected after vaccination
vaccination response can be measured. In a subset of participants who report a
positive SARS-CoV-2 test, after being fully vaccinated, we will ask them to
donate an additional fingerpick blood sample to measure serum SARS-CoV-2
specific antibody concentrations and antibody avidity. Furthermore, information
on SARS-CoV-2 testing and COVID-19 vaccination will be obtained through linkage
with the national vaccination register and linkage with GGD-registrations where
possible. Additional information about health status and hospitalization will
be obtained through information from General Practitioners (GPs) and hospitals.
Participants will be followed up for 5 years. From April 2022 onwards,
participants will receive SARS-CoV-2 self-tests to be used when having symptoms
in order to keep track of SARS-CoV-2 infections. From June 2023, participants
are asked to send in positive self-tests for sequencing to determine the
variant causing the infection.

Further knowledge or changes in the COVID-19 pandemic might lead to new
research questions which cannot be foreseen. Sub-studies embedded into this
cohort study will be designed at a later stage, for example in-depth studies
investigating immunogenicity requiring more frequent blood sampling or other
data collection. The first sub-study includes the invitation of participants to
donate an extra fingerpick blood sample after testing SARS-CoV-2 positive after
being fully vaccinated (breakthrough infection).

At baseline and during follow-up participants are asked to complete
questionnaires via app or website. In addition, participants will be asked to
donate fingerpick blood (maximum of 0.5 ml/sampling timepoint) at baseline and
every 6 months during follow-up, and for some participants,1 month after
primary vaccination, and after a breakthrough infection, which may cause minor
discomfort. Overall, the burden for the participants will be small and is
justified given the importance of assessing the VE of the different vaccines to
inform (future) vaccination policy. There are no personal benefits for the
participants of the study, however the participants contribute to public health
insights relevant for future control of the COVID-19 pandemic, especially
related to the vaccination program.