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Sera were collected before the first dose (\n                      <jats:italic>v<\/jats:italic>\n                      1), at 2\u00a0weeks (\n                      <jats:italic>v<\/jats:italic>\n                      7) and 6\u00a0months (\n                      <jats:italic>v<\/jats:italic>\n                      8) after the third dose. Taiwan\u2019s first major COVID-19 outbreak occurred between\n                      <jats:italic>v<\/jats:italic>\n                      7 and\n                      <jats:italic>v<\/jats:italic>\n                      8. 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By developing an iterative serial screening method, we identified asymptomatic breakthrough (post-vaccination) infections among unconfirmed cases. Our\n                      <jats:italic>v<\/jats:italic>\n                      7-\n                      <jats:italic>v<\/jats:italic>\n                      8 paired cohort resolved into three distinct groups: confirmed cases (21%), asymptomatic breakthrough infections (17%), and uninfected subjects (62%). In normalized\n                      <jats:italic>v<\/jats:italic>\n                      8 sera, confirmed cases exhibited an anti-S\n                      <jats:sup>+++<\/jats:sup>\n                      (high) \/anti-N\n                      <jats:sup>+++<\/jats:sup>\n                      (high) phenotype, while uninfected subjects showed an anti-S\n                      <jats:sup>+<\/jats:sup>\n                      (low)\/anti-N\n                      <jats:sup>+<\/jats:sup>\n                      (baseline) phenotype. Statistical analysis validated a distinct asymptomatic group characterized by an antibody profile anti-S\n                      <jats:sup>++<\/jats:sup>\n                      (intermediate) \/anti-N\n                      <jats:sup>+<\/jats:sup>\n                      (baseline).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-026-01276-5","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:22:02Z","timestamp":1784730122000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hidden asymptomatic breakthrough infection in a proof-of-concept longitudinal study on SARS-CoV-2 vaccine recipients"],"prefix":"10.1186","volume":"33","author":[{"given":"Chiaho","family":"Shih","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Zhen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Yu","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Ying Clair","family":"Chiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hui","family":"Kuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Ting","family":"Liou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chi","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jih-Jin","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Chang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Lung","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Long","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer-Ming","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Jyh","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chun","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Feng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inn-Wen","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Jyh","family":"Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-San","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"issue":"10223","key":"1276_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang C, Wang Y, Li X, et al. 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