ArticlemedRxiv : the preprint server for health sciences2026
Longitudinal antibody correlates of SARS-CoV-2 infection in a US household cohort during Omicron waves.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
Funding
Abstract
Background: SARS-CoV-2 vaccines have been updated based on circulating variants and the antibody protection from prior vaccination and infection against emerging variants. We evaluated longitudinal antibody correlates of SARS-CoV-2 infection risk during Omicron waves. Methods: We used data from a longitudinal cohort study from 2021 through 2025 with prospective surveillance for acute respiratory illness, and repeated blood collection. A subset of participants also provided weekly respiratory specimens to identify asymptomatic infections. Serum samples were tested using multiplex assays measuring anti-Spike (S) binding IgG and angiotensin-converting enzyme 2 (ACE2) inhibition (a measure of inhibition of the ACE2 receptor interaction) across multiple SARS-CoV-2 variants. Cox models were used to evaluate associations between antibody, prior vaccination and infection, and SARS-CoV-2 infections. Findings: Among 119 participants who contributed 438.8 person-years of follow-up, 81 symptomatic SARS-CoV-2 infections and 4 asymptomatic infections (from 33 participants with weekly swabs) were detected. Each two-fold increase in anti-S IgG concentration was associated with a 15% lower hazard of symptomatic infection (hazard ratio [HR]=0.85, 95%CI:0.82-0.88). Similarly, each 10% increase in ACE2 inhibition was associated with a 7% lower infection hazard (HR=0.93, 95% CI:0.90-0.95). After adjusting for antibody levels, prior SARS-CoV-2 infection remained protective, while recent vaccination was not associated with infection hazard. The peak predicted antibody after repeat COVID-19 vaccinations was estimated to confer 62-65% protection against symptomatic infection. Interpretation: Higher levels of binding and functional antibodies were associated with reduced the risk of SARS-CoV-2 infections across multiple waves between 2021-2025. These findings support the use of longitudinal serologic surveillance to inform vaccine evaluation and future booster strategies against evolving SARS-CoV-2 variants.
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