By January 2024, the BiCoVac cohort comprised four questionnaire surveys. The distribution of the questionnaires according to the national vaccination program is illustrated in Fig. 1. The baseline questionnaire was distributed in May 2021 before COVID-19 vaccines were given to the general population below 65 years of age to obtain background information before COVID-19 vaccination. The 1st and 2nd follow-up questionnaires were distributed according to the vaccination schedule: the 1st follow-up questionnaire was sent approximately two to four weeks after the age group was scheduled to complete the first dose of a COVID-19 vaccine (June-July 2021), whereas the 2nd follow-up questionnaire was sent approximately three months after the age group was scheduled for the 2nd dose (October 2021). A 3rd follow-up questionnaire was distributed approximately one year after the baseline questionnaire (May 2022).

All surveys collected self-reported information on COVID-19 vaccination, COVID-19, and symptoms including immediate symptoms following vaccination, common general non-specific symptoms (such as headache, fatigue, and nausea), and COVID-19 severity. The baseline survey additionally collected self-reported information on general health, lifestyle, mental health, health anxiety, and COVID-19 vaccine hesitancy. Those vaccinated with COVID-19 vaccines were asked about the number of vaccine dose(s), type of vaccine(s), date(s) of vaccination(s), and 21 local and systemic symptoms in the immediate period following each COVID-19 vaccination (e.g., redness and/or pain at the injection site, fever, headache, pain in muscles and joints, bruises, and allergic reaction). These symptoms were reported as; ‘None’, ‘Mild’, ‘Moderate’, or ‘Severe’. Individuals reporting prior COVID-19 were asked to report whether they were tested, the date of infection, and the degree of experienced symptoms (asymptomatic, mild, moderate, severe, or severe with hospitalization). We used validated questionnaires including the 25-item Bodily Distress Syndrome (BDS) checklist [15], the Symptom Checklist 13 (SCL-13) [16], Cohen’s Perceived Stress Scale (PSS) [17, 18], and the Whiteley-6-R scale [19]. Due to the emergence of new potential adverse events, the follow-up questionnaires were extended during the follow-up period to gather information on additional symptoms, such as tinnitus, shingles, and details regarding menstrual cycle characteristics. An overview of the collected information in each questionnaire can be found in Table 1. The questionnaires were available in Danish, English, and Arabic. For questions where official validated translations existed, the respective language versions were used. For the remaining questions, translation was conducted by a professional translator. The baseline and three follow-up questionnaires can be found in Supplementary File S1, S2, S3, and S4, respectively (Online Resource 1–4).

The Danish Civil Personal Registration (CPR) identification (a unique 10-digit civil registration number assigned to all Danish citizens) allowed linkage to individual-level data from the national Danish registers. This included, among others, the National Patient Register and the Surveillance data on COVID-19 (COVID-19 test results and COVID-19 vaccines) monitored by Statens Serum Institut (a research institution under the Danish Ministry of Health) with the potential for further linkage to additional Danish registers e.g., The Laboratory Information Systems, The Danish Medical Birth Register, The Cancer Registry, and more. A list of the most relevant linked registers can be found in Table 2. All linked registers were made available by Statistics Denmark.

The cohort consists of a sample of Danish citizens aged 16–65 years and living in Denmark in April 2021. In total, 911,613 were randomly sampled from the unique CPR System, stratified by year of birth (25% from each birth year of eligible individuals). Invitations were linked to the CPR identification and distributed through the national digital mailbox system ‘e-Boks’, used for communication between authorities and Danish citizens. A reminder was sent out 2–3 weeks after the initial invitation. More than 40% of invited participants above 50 years of age responded to the baseline questionnaire, whereas the participation rate among those younger than 30 years of age was less than 15%. A total of 252,401 (28%) citizens initiated the baseline questionnaire. Of these, 60% were women and 68% were unvaccinated at the time of initiating the baseline questionnaire. Participants who answered follow-up questionnaires were more often older, of Danish origin, from higher socioeconomic classes, and with longer education. At the end of the study period, 98% of the participants were vaccinated against COVID-19. Characteristics of the random sample and the participants who initiated each questionnaire can be seen in Table 3.

All participants who completed a questionnaire were invited to answer the following questionnaire (renewed consent was required to participate in the 3rd follow-up questionnaire). For those who participated in the baseline questionnaire, the participation rates for the follow-up questionnaires were: 1st follow-up: 59% (n = 149,070); 2nd follow-up: 43% (n = 107,655); 3rd follow-up: 25% (n = 63,737). Due to an error in the distribution of questionnaires in the 3rd follow-up, individuals aged 30–34 years were not invited to participate. Figure 2 contains a flow diagram of the participation in each questionnaire. Participation stratified by vaccine dose can be found in Supplementary Fig. S1 (Online Resource 5).