A population-level cohort study evaluating the efficacy and safety of all COVID-19 vaccines in use in Denmark

In a recent study posted on medrex sib* Preprint server, researched long-term by researchers Effectivenesssafety and durability of all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines used in Denmark.

Background

Denmark plans to administer the fourth dose of coronavirus disease 2019 (COVID-19) vaccine to selected population segments. Additionally, the Danish government plans to introduce an Omicron-specific bivalent vaccine into its vaccination programme. Therefore, there is an ongoing need to monitor long-term vaccine efficacy (VE) and safety, especially in high-risk groups. In particular, for new SARS-CoV-2 variants of concern (VOCs), particularly his Omicron and its substrains, his VE, magnitude and persistence of response to various vaccines change.

About research

In the current study, researchers enrolled 6943 adult participants who planned to receive the SARS-CoV-2 vaccine through the Danish COVID-19 vaccination program and called them the ENFORCE cohort. They arranged for her 5 pre-specified follow-up visits for these participants after receiving the first vaccination during the 2-year follow-up period. In addition, the team collected blood samples for serological analysis after each study visit.

Enrollment in the ENFORCE study began 14 to 30 minutes before the first SARS-CoV-2 vaccine dose, administered at vaccination centers near the seven study sites or five regional hospital clinics in Denmark . The team invited potential research participants to participate in the study through several channels. For example, we invited healthcare workers (HCWs) through hospital information channels. Study registration took place from February 13, 2021 to August 5, 2021.

In addition, researchers identified risk factors for humoral hyporesponsiveness and assessed the persistence of vaccine responses. Additionally, the team compared the risk of breakthrough infection after the emergence of Omicron. They stratified by SARS-CoV-2 variant and by level of SARS-CoV-2 spike (S) immunoglobulin G (IgG).

Survey results

The ENFORCE analysis included 6943 participants with a median age of 64 years. Nearly 57% of the study population was female, and 23% of the study cohort had a severe increased risk of her COVID-19 due to concomitant illness. The adenoviral vector/mRNA vaccine group consisted of her 499 relatively young participants with a median age of her 45 years. Of these 499 participants, 90.8% were healthcare workers, with a higher percentage undergoing SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) before baseline. There were 3824 participants in the Pfizer-BioNTech vaccine arm, of whom 37.6% had an increased risk of severe disease. These participants were generally older, with a median age of 71 years.

Nearly 5% of a total of 6889 participants were SARS-CoV-2 spike (S) immunoglobulin G (IgG) positive at baseline, indicating previous infection with SARS-CoV-2. Among them, 10.8% are 18-25 years old and 2.9% are 80 years old and over. The authors observed that hyporesponsiveness and non-durable vaccine response to vaccine correlated with male gender, comorbidities, and type of vaccine.

Furthermore, researchers found an inverse correlation between elevated S IgG levels and the risk of breakthrough infection with Delta variants. On the contrary, S IgG levels did not increase the risk of Omicron breakthrough infection. Most importantly, the neutralizing capacity of S IgG was significantly decreased for each emergent variant compared to the wild-type SARS-CoV-2 strain after vaccination. This reduction was most pronounced for Omicron. But after receiving a booster dose it increased again.

Conclusion

The ENFORCE study measured significant humoral and cellular immune responses specific to SARS-CoV-2. We repeatedly evaluated the safety data and microbiological test results of all recipients for almost 2 years. The study cohort included many elderly and people with significant comorbidities. These individuals are at increased risk of developing severe COVID-19 and are therefore particularly important when evaluating vaccine efficacy and durability. Preliminary research results are published on his website at ENFORCE. Participants can even subscribe to receive regular updates on research progress, including serology results.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .