{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:01:19Z","timestamp":1760234479622,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The virological meaning of the different patterns of serology in COVID-19 has been little examined in clinical settings. Asymptomatic subjects with IgM-spike (S) and IgG-nucleocapsid (N) determinations by chemiluminescence were studied for SARS-CoV-2 shedding in respiratory secretions by transcription-mediated amplification (TMA). In subjects showing IgM-S positive and IgG-N negative, IgG-S was determined by lateral flow assay. A total of 712 individuals were tested: 30.0% presented IgM-S(+)\/IgG-N(\u2212), 25.8% had IgM-S(+)\/IgG-N(+) and 44.2% had IgM-S(\u2212)\/IgG-N(+); the proportion with TMA(+) were comparable in these three groups: 12.1, 8.7 and 10.5%, respectively. In individuals with IgM-S(+)\/IgG-N(\u2212), IgG-S(+) was detected in 66.5%. The frequency of IgM-S(+)\/IgG-S(\u2212) in the total population was 10.0%, of whom 24.1% had TMA(+); the chances for TMA(+) in subjects with an IgM-S(+) alone pattern were 2.4%. Targeting of the same SARS-CoV-2 antigen seems to be better for the characterization of IgM\/IgG patterns of response. IgM-S(+) alone reactivity is rare, and a small proportion is associated with viral shedding.<\/jats:p>","DOI":"10.3390\/v13050874","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T10:49:51Z","timestamp":1620643791000},"page":"874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Virological Correlates of IgM\u2013IgG Patterns of Response to SARS-CoV-2 Infection According to Targeted Antigens"],"prefix":"10.3390","volume":"13","author":[{"given":"Pablo","family":"Barreiro","sequence":"first","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"},{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Javier","family":"Candel","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"},{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1453-8536","authenticated-orcid":false,"given":"Juan Carlos","family":"Sanz","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"San Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"},{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"del Mar Carretero","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"},{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-9437","authenticated-orcid":false,"given":"Marta","family":"P\u00e9rez-Abeledo","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Ramos","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"Vi\u00f1uela-Prieto","sequence":"additional","affiliation":[{"name":"Public Health Regional Laboratory, Hospital Isabel Zendal, Av. Manuel Fraga Iribarne, 2, 28055 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5231-9721","authenticated-orcid":false,"given":"Jes\u00fas","family":"Canora","sequence":"additional","affiliation":[{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Javier","family":"Mart\u00ednez-Peromingo","sequence":"additional","affiliation":[{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1301-1289","authenticated-orcid":false,"given":"Antonio","family":"Zapatero","sequence":"additional","affiliation":[{"name":"Council of Public Health, Community of Madrid, Calle O\u2019Donnell, 50, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e120","DOI":"10.1056\/NEJMp2025631","article-title":"Rethinking Covid-19 Test Sensitivity\u2014A Strategy for Containment","volume":"383","author":"Mina","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.jinf.2020.06.055","article-title":"Outbreak of COVID-19 in a nursing home in Madrid","volume":"81","author":"Bouza","year":"2020","journal-title":"J. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(20)31483-5","article-title":"Prevalence of SARS-CoV-2 in Spain (ENE-COVID): A nationwide, population-based seroepidemiological study","volume":"396","author":"Oteo","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity","volume":"183","author":"Moderbacher","year":"2020","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","article-title":"A dynamic COVID-19 immune signature includes associations with poor prognosis","volume":"26","author":"Laing","year":"2020","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.abc6261","article-title":"Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans","volume":"369","author":"Arunachalam","year":"2020","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1128\/JCM.02107-20","article-title":"Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate","volume":"58","author":"Addetia","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_9","first-page":"30496","article-title":"SARS-CoV-2 mRNA vaccines foster potent anti-gen-specific germinal center responses associated with neutralizing antibody generation","volume":"7613","author":"Lederer","year":"2020","journal-title":"Immunity"},{"key":"ref_10","unstructured":"Centers for Disease Control and Prevention (2021, April 05). Interim Guidelines for COVID-19 Antibody Testing, Available online: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/lab\/resources\/antibody-tests-guidelines.html#print."},{"key":"ref_11","unstructured":"Hanson, K., Caliendo, A., Arias, C., Englund, J., Lee, M., Loeb, M., Patel, R., el Alayli, A., Kalot, M.A., and Falck-Ytter, Y. (2020). Infectious Diseases Society of America guidelines on the diagnosis of coronavirus disease 2019. Clin. Infect. Dis., in press."},{"key":"ref_12","first-page":"665","article-title":"Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in patients with pneu-monia due to the SARS coronavirus","volume":"11","author":"Woo","year":"2004","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1473-3099(20)30196-1","article-title":"Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study","volume":"20","author":"To","year":"2020","journal-title":"Lancet Infect Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104613","DOI":"10.1016\/j.jcv.2020.104613","article-title":"Comparison of eight commercial, high-throughput, automated or ELISA assays detecting SARS-CoV-2 IgG or total antibody","volume":"132","author":"Trabaud","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_15","first-page":"Doc22","article-title":"Evaluation of the SARS-CoV-2-IgG response in outpatients by five commercial immunoassays","volume":"8","author":"Wellinghausen","year":"2020","journal-title":"GMS Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e01742-20","DOI":"10.1128\/JCM.01742-20","article-title":"Detection of SARS-CoV-2 IgG targeting nucleocapsid or spike Protein by four high-throughput immunoassays authorized for emergency use","volume":"58","author":"Prince","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ripperger, T.J., Uhrlaub, J.L., Watanabe, M., Wong, R., Castaneda, Y., Pizzato, H.A., Thompson, M.R., Bradshaw, C., Weinkauf, C.C., and Bime, C. (2020). Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure. Immunity, in press.","DOI":"10.1101\/2020.08.14.20174490"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104663","DOI":"10.1016\/j.jcv.2020.104663","article-title":"Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect","volume":"133","author":"Maine","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"258","DOI":"10.37201\/req\/052.2020","article-title":"Utility of lateral flow tests in SARS-CoV-2 infection monitorization","volume":"33","author":"Candel","year":"2020","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1128\/JCM.01669-20","article-title":"Performance characteristics of a high-throughput automated transcription-mediated amplification test for SARS-CoV-2 detection","volume":"58","author":"Pham","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1097\/CM9.0000000000000820","article-title":"Detection of serum immunoglobulin M and immunoglobulin G antibodies in 2019 novel coronavirus infected patients from different stages","volume":"133","author":"Gao","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1515\/cclm-2020-0548","article-title":"Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays","volume":"58","author":"Qian","year":"2020","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rikhtegaran, Z., Saadat, S., Saleh, E., Ouyang, X., Constantine, N., DeVico, A.L., Harris, A.D., Lewis, G.K., Kottilil, S., and Sajadi, M.M. (2020). Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays. PLoS ONE, 15.","DOI":"10.1101\/2020.08.05.20168476"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41591-020-0897-1","article-title":"Antibody responses to SARS-CoV-2 in patients with COVID-19","volume":"26","author":"Long","year":"2020","journal-title":"Nat. Med."},{"key":"ref_25","first-page":"9878453","article-title":"Temporal course of SARS-CoV-2 antibody positivity in patients with COVID-19 following the first clinical presentation","volume":"16","author":"Risch","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Grandjean, L., Saso, A., Ortiz, A., Lam, T., Hatcher, J., Thistlethwaite, R., Harris, M., Best, T., Johnson, M., and Wagstaffe, H. (2020). Humoral response dynamics following infection with SARS-CoV-2. medRxiv.","DOI":"10.1101\/2020.07.16.20155663"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/s41591-020-0965-6","article-title":"Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections","volume":"26","author":"Long","year":"2020","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nri2508","article-title":"B-cell responses to vaccination at the extremes of age","volume":"9","author":"Siegrist","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.imlet.2014.06.006","article-title":"Immunosenescence and vaccine failure in the elderly: Strategies for improving response","volume":"162","author":"Boraschi","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1056\/NEJMc2025179","article-title":"Rapid decay of anti-SARS-CoV-2 an-tibodies in persons with mild Covid-19","volume":"383","author":"Ibarrondo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Dan, J., Mateus, J., Kato, Y., Hastie, K.M., Faliti, C.E., Ramirez, S.I., Frazier, A., Yu, E.D., Grifoni, A., and Rawlings, S.A. (2020). Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv.","DOI":"10.1101\/2020.11.15.383323"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gaebler, C., Wang, Z., Lorenzi, J., Muecksch, F., Finkin, S., Tokuyama, M., Ladinsky, M., Cho, A., Jankovic, M., and Schaefer-Babajew, D. (2020). Evolution of antibody immunity to SARS-CoV-2. BioRxiv.","DOI":"10.1101\/2020.11.03.367391"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Demonbreun, A.R., McDade, T.W., Pesce, L., Vaught, L.A., Reiser, N.L., Bogdanovic, E., Velez, M.E., Hsieh, R.R., Klaisner, C., and Simons, L.M. (2020). Patterns and persistence of SARS-CoV-2 IgG antibodies in a US metropolitan site. medRxiv.","DOI":"10.1101\/2020.11.17.20233452"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.abc6952","article-title":"A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2","volume":"369","author":"Chi","year":"2020","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112937","DOI":"10.1016\/j.jim.2020.112937","article-title":"Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples","volume":"489","author":"Mazzini","year":"2021","journal-title":"J. Immunol. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"198141","DOI":"10.1016\/j.virusres.2020.198141","article-title":"Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic de-velopment","volume":"288","author":"Samrat","year":"2020","journal-title":"Virus Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e02005-20","DOI":"10.1128\/JCM.02005-20","article-title":"Serological assays estimate highly variable SARS-CoV-2 neutralizing antibody activity in recovered COVID-19 patients","volume":"58","author":"Luchsinger","year":"2020","journal-title":"J. Clin. Microbiol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/5\/874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:58:48Z","timestamp":1760162328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/5\/874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,10]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["v13050874"],"URL":"https:\/\/doi.org\/10.3390\/v13050874","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,5,10]]}}}