Long-awaited findings from the IMMUNEBRIDGE study reveal gaps in SARS-CoV-2 immunity

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

In a recent study posted to the medRxiv* preprint server, researchers estimate the protection elicited against infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its severe outcomes.

Study: Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season – the IMMUNEBRIDGE project. Image Credit: Jake Pixo / Shutterstock.com

Germany’s response to COVID-19

During the coronavirus disease 2019 (COVID-19) pandemic, Germany lacked population-based panels that could provide rapid and adaptive assessments of population immunity, infection dynamics, vaccination coverage, and under-detection of reported SARS-CoV-2 infections.

After the summer of 2022, the lack of data suitable for providing evidence of population immunity across Germany was due to the absence of coordinated population panels. In addition, there was considerable uncertainty surrounding the selection of appropriate endpoints related to correlates of protection against severe SARS-CoV-2 infection that would facilitate their usage in real-time decision-making.

About the study

In the present study, researchers estimate protection levels against SARS-CoV-2 infection and severe COVID-19 between June 2022 and November 2022.

Using current population-based studies, along with newly established cross-sectional investigations, the IMMUNEBRIDGE project presented a complete assessment of the protection level reported by the German population against mild and severe COVID-19 between June 2022 and November 2022.

Antibodies elicited against the SARS-CoV-2 nucleocapsid (N) and spike (S) antigens were assessed in the participating studies. Proportions of seropositivity for designated subgroups were also calculated.

The vaccination and illness histories of participating individuals were collected. This information was harmonized across all studies utilizing a collectively developed minimal data set (MDS).

The present project was designed to provide early ad hoc feedback to a newly established modeling network for severe infectious diseases (MONID) beginning in early August 2022.

Additionally, the IMMUNEBRIDGE framework involved a targeted literature review, which derived a categorization of protection levels elicited against SARS-CoV-2 infection and severe infection into a "combined endpoint." The combined endpoint was derived from the number of prior self-reported SARS-CoV-2 infections and vaccinations, along with current antibody status noted against the S and N antigens.

Blood samples were obtained, and antibodies generated against SARS-CoV-2 were assessed in four population-based cohort studies. These included the Luebeck longitudinal investigation of SARS-CoV-2 infection (ELISA) study, the German National Cohort (NAKO), Stages A/B and Determinants of Progression (STAAB), and Multilocal and serial prevalence study for antibodies against SARS-CoV-2 in Germany (MuSPAD) between June 2022 and November 2022.

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Four additional cross-sectional studies were established, including the GUIDE study to assess regional depth and studies from the University Hospitals in Bochum, Dresden, and Wurzburg to provide pertinent data related to pediatric cases.

Study findings

The nine participating studies involved 33,647 participants that were queried between June and November 2022. The number of individuals with less than three confirmed SARS-CoV-2 exposures ranged from 5% to 16% in the adult age cohorts.

Conversely, 37% of people older than 79 years of age had fewer than four confirmed exposures. Furthermore, 80% of children and adolescents had fewer than three confirmed exposures, while 13% reported neither an immunocorrelate nor an exposure.

No significant variation in the outcomes was observed when borderline antibody values from the GUIDE study were interpreted as seronegative. Between 46% to 56% of individuals with self-reported comorbidities had fewer than four confirmed cases of SARS-CoV-2 exposures, while 5-10% had fewer than three cases.

Across all age categories, the proportion of individuals with fewer than three exposure cases was lower. However, the number of those with no documented exposure was higher, especially among those under the age of 18.

While seropositivity against the N antigen declined with age, the same was not observed for seropositivity against the S antigen, in which variations were only noted between children and adults.

Approximately 95% of study participants across all age categories reported antibodies elicited against the S antigen. In individuals between one and 17 years of age, S antigen antibodies were the lowest at 80%.

Additionally, 52% of study participants across all ages exhibited antibodies against the N antigen, whose proportion was the highest at 68% among those between one and 17 years of age and lowest at 28% among those aged over 79 years.

A general pattern of decreasing concentrations of antibodies against the N antigen was observed with increasing age. Antibodies elicited against the N antigen were less frequently detected in elderly patients over 64 years of age and those with comorbidities.

In participants who reported their initial infection after receiving at least two vaccine doses, seropositivity for antibodies elicited against the N antigen was 89% for up to five months after infection. However, this decreased to 68% in those who reported infections more than five months earlier. Similar but significantly less pronounced results were observed in unvaccinated individuals.

Conclusions

Moderate to high protection was observed against severe COVID-19 in most age groups, while low protection was observed against infection for all ages.

The communication of preliminary data into a new modeling network for severe infectious illnesses in Germany facilitated the incorporation of this information into ongoing modeling studies to assess the potential impact on infection dynamics. Thus, the findings of the IMMUNEBRIDGE project demonstrate the significance of networks comprising scientific institutions that are supported by adequate infrastructure and manpower.

*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

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.