AUTHOR=Kaufman Harvey W. , Letovsky Stanley , Meyer William A. , Gillim Laura , Assimon Magdalene M. , Kabelac Carly A. , Kroner John W. , Reynolds Shannon L. , Eisenberg Marcia TITLE=SARS-CoV-2 spike-protein targeted serology test results and their association with subsequent COVID-19-related outcomes JOURNAL=Frontiers in Public Health VOLUME=Volume 11 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1193246 DOI=10.3389/fpubh.2023.1193246 ISSN=2296-2565 ABSTRACT=Importance In the absence of evidence of clinical utility, the United States Centers for Disease Control and Prevention does not currently recommend assessment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-protein antibody levels. Clinicians and their patients, especially immunocompromised patients, may benefit from an adjunctive objective clinical laboratory measure of risk, using SARS-CoV-2 serology. Objective To estimate the association between levels of SARS-CoV-2 spike-protein targeted antibodies and clinically relevant outcomes, overall and among clinically relevant subgroups, eg, by vaccine and immunocompetency statuses. Design A retrospective cohort study was conducted using laboratory-based data containing SARS-CoV-2 antibody testing results, along with medical and pharmacy claims data. SARS-CoV-2 testing was performed by two large United States-based reference clinical laboratories, Labcorp® and Quest Diagnostics, and were linked to medical insurance claims, including vaccination receipt, via the HealthVerity Marketplace. Follow-up for outcomes began after each eligible participant’s first SARS-CoV-2 semiquantitative spike-protein targeted antibody test, measured November 16, 2020 through December 30, 2021. Exposures Having detectable versus nondetectable SARS-CoV-2 spike-protein targeted antibodies. Main Outcomes and Measures Study outcomes were SARS-CoV-2 infection and a serious composite outcomes (hospitalization with an associated SARS-CoV-2 infection or all-cause death). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Propensity score matching was used for confounding covariate control. Results In total, 143,091 (73.2%) and 52,355 (26.8%) eligible individuals had detectable and nondetectable levels of SARS-CoV-2 spike-protein targeted antibodies, respectively. In the overall population, having detectable versus nondetectable antibodies was associated with an estimated 44% relative reduction in SARS-CoV-2 subsequent infection risk (HR, 0.56; 95% CI 0.53-0.59) and an 80% relative reduction in risk of serious composite outcomes (HR 0.20; 95% CI 0.15-0.26). Relative risk reductions were observed across subgroups, including among immunocompromised persons. Conclusions and Relevance Individuals with detectable SARS-CoV-2 spike-protein targeted antibody levels had fewer associated subsequent SARS-CoV-2 infections and serious adverse clinical outcomes. Policymakers and clinicians may find SARS-CoV-2 spike-protein targeted serology testing to be a useful adjunct in counseling patients with nondetectable antibody levels about adverse risks and reinforce appropriate actions to mitigate such risks.