Cohort Profile: The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE)

PurposeThe ENFORCE cohort is a national Danish prospective cohort of adults who received a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination program. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark. ParticipantsA total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 Vaccination Program were enrolled in the study prior to their first vaccination. Participants will be followed for a total of two years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 polymerase chain reaction (PCR) results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53-75), 56.6% were females and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline. Findings to dateResults have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant, and on the antibody neutralizing capacity against different SARS-CoV-2 variants following primary and booster vaccinations. Future plansThe ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines. Registrationclinicaltrials.gov identifier: NCT04760132. Strengths and limitations- The ENFORCE study combines repeated detailed SARS-CoV-2 specific immunological measurements prior to, and throughout the course of SARS-CoV-2 vaccination, with register-based follow-up of safety data and microbiological test results. - The ENFORCE cohort includes a large proportion of elderly participants and participants with concomitant diseases. - The three vaccine groups display a high degree of variation in demographic factors and distribution across risk groups, due to the prioritization of specific vaccines to risk groups during the primary roll out of the SARS-CoV-2 vaccination program.