{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:30:50Z","timestamp":1775010650790,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PAPIIT-UNAM, Programa Institucional de Salud y Ambiente of the Instituto de Investigaciones Biom\u00e9dicas","award":["IN216121"],"award-info":[{"award-number":["IN216121"]}]},{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), M\u00e9xico"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Healthcare workers (HCWs) are at high risk of breakthrough SARS-CoV-2 infections despite complete vaccination schedules. There are gaps in our understanding of the specific antibody isotypes and cytokine profiles produced during an infection following vaccination. In this study, we evaluated SARS-CoV-2\u2212specific antibody isotypes and their association with cytokine production in HCWs with breakthrough infections. Methods: Serum samples from 114 HCWs were analyzed for antibody isotypes against the nucleoprotein (NCP) and the receptor binding domain (RBD) of the spike protein, as well as for a panel of 13 cytokines. Results: Vaccinated SARS-CoV-2+ HCWs showed a higher prevalence of anti-SARS-CoV-2 antibodies against NCP (IgM = 93.8%, IgG = 93.8%, IgA = 28.1%) and RBD (IgM = 46.9%, IgG = 100%, IgA = 90.6%). A specific IgM response to NCP was more frequent in vaccinated SARS-CoV-2+ individuals, whereas IgA responses were predominantly specific for RBD. Both pro- and anti-inflammatory cytokines were elevated in vaccinated HCWs with breakthrough infections compared with unvaccinated and uninfected individuals. Interestingly, infected IgG+ HCWs with IgM specific for both NCP and RBD exhibited significantly higher IL-8, IL-6, TNF-\u03b1, IFN-\u03b3, IL-2, IL-10, and TGF-\u03b2 concentrations. Conclusion. Our data show that breakthrough infections in vaccinated HCWs induce a robust pro-and anti-inflammatory cytokine profile, which is associated with a broader IgM response directed against both NCP and RBD.<\/jats:p>","DOI":"10.3390\/v17111517","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:17:27Z","timestamp":1763551047000},"page":"1517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokine and Antibody Isotype Responses in Vaccinated Healthcare Workers with SARS-CoV-2 Breakthrough Infections"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1417-5309","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Fern\u00e1ndez-Rojas","sequence":"first","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-8651","authenticated-orcid":false,"given":"Tanya","family":"Plett-Torres","sequence":"additional","affiliation":[{"name":"Plan de Estudios Combinados en Medicina, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermina","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-8357","authenticated-orcid":false,"given":"Mirza","family":"Romero-Valdovinos","sequence":"additional","affiliation":[{"name":"Hospital General \u201cDr. Manuel Gea Gonz\u00e1lez\u201d, SSA. Calzada de Tlalpan 4800, Col. Seccion XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mar\u00eda","family":"Salazar","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monserrat","family":"Sordo","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Ch\u00e1vez-Vargas","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar Josu\u00e9","family":"Coeto \u00c1ngeles","sequence":"additional","affiliation":[{"name":"Hospital General \u201cDr. Manuel Gea Gonz\u00e1lez\u201d, SSA. Calzada de Tlalpan 4800, Col. Seccion XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayra","family":"Cruz-Rivera","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-7318","authenticated-orcid":false,"given":"Carlos","family":"Santiago-Olivares","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-613X","authenticated-orcid":false,"given":"Juan Pablo Ram\u00edrez","family":"Hinojosa","sequence":"additional","affiliation":[{"name":"Hospital General \u201cDr. Manuel Gea Gonz\u00e1lez\u201d, SSA. Calzada de Tlalpan 4800, Col. Seccion XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-9447","authenticated-orcid":false,"given":"Pablo","family":"Maravilla","sequence":"additional","affiliation":[{"name":"Hospital General \u201cDr. Manuel Gea Gonz\u00e1lez\u201d, SSA. Calzada de Tlalpan 4800, Col. Seccion XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8564-3472","authenticated-orcid":false,"given":"Patricia","family":"Ostrosky-Wegman","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fela","family":"Mendlovic","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"},{"name":"Facultad de Ciencias de la Salud, Universidad An\u00e1huac M\u00e9xico Norte, Huixquilucan 52786, State of Mexico, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Flisser","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda y Parasitolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grupo T\u00e9cnico Asesor de Vacunaci\u00f3n COVID-19 (2020). 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