{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:03:12Z","timestamp":1789966992581,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>SARS-CoV-2 infection after vaccination remains a clinical and public-health challenge because protection against infection may vary with time since vaccination, host factors, previous infection, and ongoing viral evolution. Although vaccination substantially reduces the risk of severe COVID-19, post-vaccination infections may still occur and may be mild, atypical, or asymptomatic. This narrative review examines the complementary roles of reverse-transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) in the diagnosis, genomic characterization, and surveillance of post-vaccination SARS-CoV-2 infection. RT-PCR remains the first-line method for confirming acute infection because it is rapid, widely available, and clinically actionable, although its clinical performance depends on appropriate specimen collection and timing. NGS complements RT-PCR by providing viral genomic characterization, including lineage assignment, mutation detection, investigation of suspected transmission clusters, and population-level surveillance. Sequencing may provide additional value in selected settings, particularly suspected reinfection, persistent infection in selected immunocompromised patients, outbreak investigations, and representative or event-triggered genomic surveillance. Its use should therefore be guided by a predefined clinical, epidemiological, or surveillance objective rather than applied routinely to all post-vaccination infections. An integrated strategy combining first-line RT-PCR with objective-driven sequencing can preserve diagnostic efficiency while providing genomic information when it is most likely to influence patient-level investigation, infection-control assessment, or public-health surveillance.<\/jats:p>","DOI":"10.3390\/vaccines14090812","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:23:53Z","timestamp":1789496633000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Complementary Roles of RT-PCR and Next-Generation Sequencing in Post-Vaccination SARS-CoV-2 Infection: Clinical Diagnosis, Genomic Characterization, and Surveillance"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-811X","authenticated-orcid":false,"given":"Vasiliki E.","family":"Georgakopoulou","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-8489","authenticated-orcid":false,"given":"Vassiliki C.","family":"Pitiriga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School of Athens, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months","volume":"385","author":"Thomas","year":"2021","journal-title":"N. 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