ArticleJournal of biomedical science2026
Hidden asymptomatic breakthrough infection in a proof-of-concept longitudinal study on SARS-CoV-2 vaccine recipients.
Article in Journal of biomedical science, 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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Abstract
backgroundIndividuals with asymptomatic SARS-CoV-2 infection can unknowingly transmit the virus, yet identifying such subclinical infections in post-vaccinated populations remains challenging.
methodsWe conducted a longitudinal study of 129 infection-naïve vaccine recipients immunized with various combinations of SARS-CoV-2 spike (S) protein vaccine platforms. Sera were collected before the first dose (v1), at 2 weeks (v7) and 6 months (v8) after the third dose. Taiwan's first major COVID-19 outbreak occurred between v7 and v8. We measured anti-nucleocapsid (anti-N) and anti-S IgG antibody titers by ELISA and assessed virus-neutralizing activity using live virus and pseudovirus assays.
resultsBy developing an iterative serial screening method, we identified asymptomatic breakthrough (post-vaccination) infections among unconfirmed cases. Our v7-v8 paired cohort resolved into three distinct groups: confirmed cases (21%), asymptomatic breakthrough infections (17%), and uninfected subjects (62%). In normalized v8 sera, confirmed cases exhibited an anti-S
conclusionsThis approach may enable more accurate estimates of vaccine efficacy and infection prevalence. In a spike-vaccinated population, anti-N antibody is more a potential specific marker for COVID-19 symptomatic disease than an ideal marker for SARS-CoV-2 infection. To our knowledge, this is the first preliminary report of identification of asymptomatic breakthrough infection from a well-vaccinated population using self-matched longitudinal pairs of serum samples.
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