{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:11:10Z","timestamp":1792757470561,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Impaired spermatogenesis has been reported in coronavirus disease 2019 (COVID-19) patients. However, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility remains unclear. The purpose of this multicenter study was to investigate the possible impact of SARS-CoV-2 infection on male fertility and determine the potential reasons leading to impaired male reproductive functions. <jats:italic>In silico<\/jats:italic> approach identified ~60 amino acid sequences containing at least five continuous residues shared by SARS-CoV-2 Spike glycoprotein and spermatogenesis-linked proteins. Four synthetic peptides were tested with sera from independent cohorts of patients with acute and long COVID-19 syndrome (LCS), and na\u00efve vaccinated subjects. Immunogenicity and pathogenicity studies were performed by immunizing mice with two selected peptides and testing the antigenicity of induced antibodies. While none of four peptides were recognized by antibodies from vaccinated people, infected patients exhibited high reactivity to peptide 4, and LCS patients, especially women, showed elevated antibody levels against peptide 2. Women with LCS and chronic fatigue syndrome had higher levels of peptide 2\u2013reacting antibodies than those with idiopathic chronic fatigue syndrome. Noteworthy, peptide 2 antibodies showed, in <jats:italic>in vitro<\/jats:italic> experiment, a specific interaction with mouse testicular tissue antigens. These findings raise the possibility that cross-reactive epitopes between SARS-CoV-2 Spike protein and spermatogenesis-related antigens may affect infected patients\u2019 fertility, suggesting a potential for autoimmune responses with human consequences.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1540341","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:24:22Z","timestamp":1748323462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Long COVID-19 autoantibodies and their potential effect on fertility"],"prefix":"10.3389","volume":"16","author":[{"given":"Laura","family":"Talamini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennyson Leandro M.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darja","family":"Kanduc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Chaloin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Verdot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Galmiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arad","family":"Dotan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Salerno","family":"Filgueiras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Orietta","family":"Borghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Meroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Y.","family":"Gavrilova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varvara A.","family":"Ryabkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid P.","family":"Churilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Halpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lensch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Thurner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew-Wai","family":"Fong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.P.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"R\u00e9nia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnaby E.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Chien","family":"Lye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ot\u00e1vio","family":"Cabral-Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehuda","family":"Shoenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylviane","family":"Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/JLB.5COVA0620-370RR","article-title":"B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19","volume":"109","author":"Wildner","year":"2021","journal-title":"J Leukoc Biol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101783","article-title":"Risk of autoimmune diseases in patients with COVID-19: a retrospective cohort study","volume":"56","author":"Chang","year":"2023","journal-title":"eClinicalMedicine"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102792","article-title":"The SARS-CoV-2 as an instrumental trigger of autoimmunity","volume":"20","author":"Dotan","year":"2021","journal-title":"Autoimmun Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI154886","article-title":"The intersection of COVID-19 and autoimmunity","volume":"131","author":"Knight","year":"2021","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03631-y","article-title":"Diverse functional autoantibodies in patients with COVID-19","volume":"595","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5417","DOI":"10.1038\/s41467-021-25509-3","article-title":"New-onset IgG autoantibodies in hospitalized patients with COVID-19","volume":"12","author":"Chang","year":"2021","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1038\/s41467-022-28905-5","article-title":"Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity","volume":"13","author":"Cabral-Marques","year":"2022","journal-title":"Nat Commun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-325353","article-title":"Diet quality and risk and severity of COVID-19: a prospective cohort study","volume":"70","author":"Merino","year":"2021","journal-title":"Gut"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001115R","article-title":"Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes","volume":"34","author":"Debnath","year":"2020","journal-title":"FASEB J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/art.41619","article-title":"COVID-19 outcomes in patients with systemic autoimmune rheumatic diseases compared to the general population: A US multicenter, comparative cohort study","volume":"73","author":"D\u2019Silva","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218946","article-title":"Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis","volume":"80","author":"Akiyama","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.103012","article-title":"Autoantibodies and SARS-CoV2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies","volume":"21","author":"Damoiseaux","year":"2022","journal-title":"Autoimmun Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201129","article-title":"SARS-CoV-2\u2013triggered neutrophil extracellular traps mediate COVID-19 pathology","volume":"217","author":"Veras","year":"2020","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.10.012","article-title":"Molecular mimicry and autoimmunity","volume":"95","author":"Rojas","year":"2018","journal-title":"J Autoimmun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.617089","article-title":"Reaction of human monoclonal antibodies to SARS-coV-2 proteins with tissue antigens: implications for autoimmune diseases","volume":"11","author":"Vojdani","year":"2021","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4081\/aiua.2021.1.115","article-title":"COVID-19 and male fertility: Taking stock of one year after the outbreak began","volume":"93","author":"Delle Fave","year":"2021","journal-title":"Arch Ital Urol E Androl"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26259","article-title":"Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients","volume":"93","author":"Ma","year":"2021","journal-title":"J Med Virol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.05.028","article-title":"Assessment of SARS-CoV-2 in human semen\u2014a cohort study","volume":"114","author":"Holtmann","year":"2020","journal-title":"Fertil Steril"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20340","article-title":"Persistent oligonecrozoospermia after asymptomatic SARS-CoV-2 infection. A case report and literature review","volume":"9","author":"Paira","year":"2023","journal-title":"Heliyon"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab026","article-title":"Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19","volume":"36","author":"Gacci","year":"2021","journal-title":"Hum Reprod"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/frph.2024.1403143","article-title":"COVID-19 and male fertility: short- and long-term impacts of asymptomatic vs. symptomatic infection on male reproductive potential","volume":"6","author":"Majzoub","year":"2024","journal-title":"Front Reprod Health"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/pathophysiology28040030","article-title":"Pathogenesis of autoimmune male infertility: juxtacrine, paracrine, and endocrine dysregulation","volume":"28","author":"Chereshnev","year":"2021","journal-title":"Pathophysiology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.729539","article-title":"Varicocele-mediated male infertility: from the perspective of testicular immunity and inflammation","volume":"12","author":"Fang","year":"2021","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"Bateman","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks419","article-title":"PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides","volume":"40","author":"Thevenet","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1021\/ct500592m","article-title":"Improved PEP-FOLD approach for peptide and miniprotein structure prediction","volume":"10","author":"Shen","year":"2014","journal-title":"J Chem Theory Comput"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2009.04.010","article-title":"Visualisation of cyclic and multi-branched molecules with VMD","volume":"28","author":"Cross","year":"2009","journal-title":"J Mol Graph Model"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.930074","article-title":"Anti-phospholipid antibodies and coronavirus disease 2019: vaccination does not trigger early autoantibody production in healthcare workers","volume":"13","author":"Borghi","year":"2022","journal-title":"Front Immunol"},{"key":"B30","article-title":"Development of a fully automated multichannel peptide synthesizer with integrated TFA cleavage capability","volume":"6","author":"Neimark","year":"1993","journal-title":"Pept Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13494","article-title":"Molecular mimicry between SARS-CoV-2 and the female reproductive system","volume":"86","author":"Dotan","year":"2021","journal-title":"Am J Reprod Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2174\/1871530314666140715115257","article-title":"Describing the potential crossreactome between mumps virus and spermatogenesis-associated proteins","volume":"14","author":"Kanduc","year":"2014","journal-title":"Endocrine, Metab Immune Disord-Drug Targets"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/psc.2419","article-title":"Homology, similarity, and identity in peptide epitope immunodefinition","volume":"18","author":"Kanduc","year":"2012","journal-title":"J Pept Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2174\/1389203711314020003","article-title":"Pentapeptides as minimal functional units in cell biology and immunology","volume":"14","author":"Kanduc","year":"2013","journal-title":"Curr Protein Pept Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.400978","article-title":"Heat shock protein 90 functions to stabilize and activate the testis-specific serine\/threonine kinases, a family of kinases essential for male fertility","volume":"288","author":"Jha","year":"2013","journal-title":"J Biol Chem"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23539","article-title":"TSSK3, a novel target for male contraception, is required for spermiogenesis","volume":"88","author":"Nayyab","year":"2021","journal-title":"Mol Reprod Dev"},{"key":"B37","doi-asserted-by":"publisher","first-page":"186999","DOI":"10.1242\/dev.186999","article-title":"MLL4 is required after implantation whereas MLL3 becomes essential during late gestation","volume":"147","author":"Ashokkumar","year":"2020","journal-title":"Development"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1485022","article-title":"The impact of COVID-19 on women\u2019s reproductive system","volume":"11","author":"Dong","year":"2024","journal-title":"Front Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102703","article-title":"Durable antibody response one year after hospitalization for COVID-19: A longitudinal cohort study","volume":"123","author":"Masi\u00e1","year":"2021","journal-title":"J Autoimmun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines7030116","article-title":"Role of antisperm antibodies in infertility, pregnancy, and potential forContraceptive and antifertility vaccine designs: research progress and pioneering vision","volume":"7","author":"Vickram","year":"2019","journal-title":"Vaccines"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2024.02.028","article-title":"Antisperm antibody levels after vasectomy reversal are not associated with pregnancy rates or method of conception","volume":"186","author":"Nam","year":"2024","journal-title":"Urology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00603","article-title":"Mechanisms of autoantibody-induced pathology","volume":"8","author":"Ludwig","year":"2017","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1540341\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:24:25Z","timestamp":1748323465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1540341\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2025.1540341"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1540341","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,27]]},"article-number":"1540341"}}