{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:33:40Z","timestamp":1792427620612,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Long COVID and post-COVID syndromes represent a significant global health crisis and a substantial societal challenge. Although an altered immunological response has been suggested as a possible underlying mechanism, the antibody response to vaccination and infection of the patients remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied a post-COVID syndrome cohort compared to a COVID-recovered cohort. Initially, we established the risk factors and the evolution of symptoms. Then, we analyzed the antibody response, focusing on immunoglobulin subclasses. Apart from determining immunoglobulin G (IgG) against the Nucleocapsid, which is a marker of infection, we analyzed IgG and its subclasses against the full-length Spike, and against the receptor-binding domain (RBD). Additionally, we examined the switch to IgG4, which can be promoted by repeated antigen exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show the major risk factors for developing post-COVID syndrome, such as infection before vaccination and comorbidities. Furthermore, we describe the evolution of the post-COVID symptoms, which agrees with previous reports. Regarding the antibody response, we found that compared to COVID-recovered individuals, post-COVID patients present readily detectable anti-Nucleocapsid IgG but low quantities of anti-Spike antibodies. Nevertheless, the anti-RBD IgG1 levels are similar between post-COVID and COVID samples. Interestingly, post-COVID patients with three vaccine doses, who were infected before vaccination by the Wuhan strain and subsequently reinfected post-Omicron, show decreased Spike response but intensified anti-RBD IgG4\/IgG1 switch, compared to their non-reinfected post-COVID counterparts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our results support a differential antibody response in post-COVID versus COVID-recovered patients, which might be relevant for post-COVID syndrome treatment, including appropriate recall vaccination strategies for the still-circulating SARS-CoV-2.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1670324","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T05:31:25Z","timestamp":1759383085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Post-COVID syndrome patients show reduced anti-Spike antibodies compared to COVID-recovered controls, but enhanced IgG4\/IgG1 switch after the third vaccine dose"],"prefix":"10.3389","volume":"16","author":[{"given":"Nineth","family":"Rossi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Ben\u00edtez-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Mar\u00edn-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel G.","family":"Azc\u00e1rate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Gonz\u00e1lez-Escalada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar 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