OBJECTIVES: The relevance and sustainability of the humoral immune response following SARS-CoV-2 infection or vaccination are not yet fully understood. In this retrospective cohort study, we assessed the association between SARS-CoV-2 spike antibody levels and risk of COVID-19-related outcomes.

METHODS: Two real-world data sources were linked via data tokenization: 1) Antibody data from the Elecsys^® Anti-SARS-CoV-2 S assay obtained from routine clinical testing by Labcorp laboratories in the US between 2021-04-01 and 2022-06-30; 2) infection and vaccination records of the same subjects captured from PurpleLab Open and Closed claims repository. Individuals with a prior COVID-19 diagnosis and/or vaccination ≥14 days before an antibody assessment were included. Associations between antibody levels and subsequent symptomatic and severe infections were estimated using Cox regression with inverse probability weighting.

RESULTS: Of 1.3m subjects with available tests, 489,933 were linked to the claims database and 117,513 met the inclusion criteria. Of these, 10,310 had symptomatic SARS-CoV-2 infections within 12 months of the test and 1,718 were severe cases requiring additional medical care. Individuals with antibody levels of 0.8–2499 U/mL and ≥2500 U/mL, respectively, had 34% and 51% reduced risk of symptomatic infection within 12 months (HR=0.66, 95% CI [0.60, 0.73] and 0.49 [0.44, 0.55]) vs those who tested negative (<0.8 U/mL). The risk of severe infection was also reduced by 60% and 76%, respectively (0.40 [0.33, 0.48] and 0.24 [0.20, 0.30]) vs those with a negative test.

CONCLUSIONS: This is one of the largest real-world data studies, to date, demonstrating a significant association between higher antibody levels and reduced risk of SARS-CoV-2 infection outcomes. The results suggest the potential utility of antibody titers in offering risk assessment and supporting disease prevention strategies.