The ongoing evolution of SARS-CoV-2 and COVID-19 morbidity has raised interest in protective immunity indicators. At the population level, assessing the risk of severe disease is vital for healthcare resource allocation and vaccination policy decisions. At the individual level, prioritizing vulnerable patients is essential.
Immunocompetent individuals develop antibodies after exposure to SARS-CoV-2, indicating past infection or vaccination. Evidence suggests a link between neutralizing antibodies and protection against infection and severe disease, with the risk of symptomatic infection increasing as antibody levels diminish. Antibody titers may serve as a surrogate measure of individual protection against COVID-19.
Identifying meaningful titer thresholds that correlate with protection against symptomatic or severe disease is crucial for investigating epidemiological trends. Breakthrough infections are likely as immunity wanes, evident from decreasing antibody titers, and patients with pre-existing conditions are at higher risk for poorer outcomes. New variants may further compromise clinical outcomes by evading immunity. The use of antibody titers against SARS-CoV-2, as a method to estimate the risk of subsequent infection following infection or vaccination, remains largely unclear.
Research linking the seroimmunological status to subsequent SARS-CoV-2 infection and outcomes is limited due to data collection challenges. An alternative is to use real-world data (RWD) from clinical practices, covering large sample sizes that facilitate the study of rare events with sufficient statistical evidence. Another advantage of RWD is that it usually encompasses the relevant population because of the ongoing medical interest in testing. While a previous study1 using RWD found that individuals with SARS-CoV-2 antibodies reported fewer COVID-19 outcomes, there is still a lack of robust RWD linking specific antibody titers to clinical outcomes, especially in the context of new variants and vaccine rollouts.
Roche sponsors extensive real-world evidence study on the predictive value of SARS-CoV-2 antibody levels for COVID-19 outcomes
To address the need to understand whether and how SARS-CoV-2 antibody levels can predict the risk of symptomatic re-infection or severe COVID-19 outcomes, and to assess this relationship across different patient subgroups (age, immunocompromised status) and against different variants (Delta and Omicron), Roche sponsored one of the largest real-world evidence studies of its kind.2 This study was conducted as a retrospective cohort analysis, utilizing RWD from U.S. laboratory testing and medical insurance claims. Data were sourced from Elecsys® Anti-SARS-CoV-2 S test results generated at and provided by a U.S. clinical reference laboratory. The Roche Elecsys® Anti-SARS-CoV-2 S assay quantifies antibodies against the receptor-binding domain (RBD) of the spike protein, with results reported in U/mL, which are equivalent to binding antibody units (BAU)/mL. This test data was linked to a U.S. insurance claims database through a patient de-identification and tokenization process. A total of 268,844 individuals who underwent SARS-CoV-2 antibody tests between April 2021 and June 2022 were successfully linked with their insurance data and were included in the final study cohort after applying the exclusion criteria. The primary study outcomes were symptomatic and severe COVID-19 during a follow-up period of up to 365 days after the antibody test data. Statistical analysis employed Cox regression with inverse probability weighting to estimate hazard ratios of subsequent infections based on different antibody levels, using non-reactive results as the reference group, and included various subgroup analyses.
