{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:04:20Z","timestamp":1786122260694,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background: Sex-related differences in SARS-CoV-2 viral susceptibility, severity, and recovery are prevalent. Factors such as age and biological variation provide some explanation for immune response, yet the use of biological sex as a variable may limit understanding of underlying individual mechanisms related to endocrine\u2013immune function involved in long-term immune memory. Endogenous sex hormone concentrations provide a means to assess the magnitude or durability of antibody persistence and disease recovery. Objective: This study examined salivary concentrations of 17\u03b2-estradiol and testosterone, as well as the number of weeks since prior SARS-CoV-2 viral infection. The study aimed to determine whether endogenous sex hormones contributed additional explanatory value to antibody persistence beyond biological sex. Methods: A cross-sectional study included 75 college students (63% female) who reported weeks since previous SARS-CoV-2 infection (M = 15.41, SD = 7.13), confirmed through a positive SARS-CoV-2 anti-N rapid antibody test. Participants provided saliva samples, which were tested for concentration of 17\u03b2-estradiol and testosterone. Hierarchical multiple regression analyses examined the effects of biological sex and endogenous sex hormones on the persistence of SARS-CoV-2 antibodies following natural infection. Results: 17\u03b2-estradiol was the strongest positive predictor of SARS-CoV-2 antibody persistence (\u03b2 = 0.63, p &lt; 0.001). Departing from previous findings, biological sex was not a significant predictor of antibodies targeting the SARS-CoV-2 N protein. Conclusions: Findings underscored the role of estradiol on immune recovery in a healthy young adult population. Individual hormone variation appears more informative than sex classification for understanding antibody persistence and immune response.<\/jats:p>","DOI":"10.3390\/antib15040072","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:14:28Z","timestamp":1786094068000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endogenous Sex Hormones Explain Variation in Long-Term SARS-CoV-2 Antibody Persistence Beyond Biological Sex"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2755-226X","authenticated-orcid":false,"given":"Nicole","family":"Ivaska","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Ursinus College, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rothschild","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Ursinus College, Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1002\/jmv.27098","article-title":"Quantitation of Antibodies against SARS-CoV-2 Spike Protein after Two Doses of CoronaVac in Healthcare Workers","volume":"93","author":"Bayram","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.molimm.2023.03.007","article-title":"Influence of Age, Gender, Previous SARS-CoV-2 Infection, and Pre-Existing Diseases in Antibody Response after COVID-19 Vaccination: A Review","volume":"156","author":"Fernandes","year":"2023","journal-title":"Mol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110859","DOI":"10.1016\/j.biopha.2020.110859","article-title":"Innate and Adaptive Immune Responses against Coronavirus","volume":"132","author":"Hosseini","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","first-page":"19102","article-title":"Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis","volume":"13","author":"Shenai","year":"2021","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Antia, A., Ahmed, H., Handel, A., Carlson, N.E., Amanna, I.J., Antia, R., and Slifka, M. (2018). Heterogeneity and Longevity of Antibody Memory to Viruses and Vaccines. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006601"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100902","DOI":"10.1016\/j.eclinm.2021.100902","article-title":"A Population-Based Analysis of the Longevity of SARS-CoV-2 Antibody Seropositivity in the United States","volume":"36","author":"Alfego","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Al-Shudifat, A.-E., Al-Tamimi, M., Dawoud, R., Alkhateeb, M., Mryyian, A., Alahmad, A., Abbas, M.M., and Qaqish, A. (2023). Anti-S and Anti-N Antibody Responses of COVID-19 Vaccine Recipients. Vaccines, 11.","DOI":"10.3390\/vaccines11091398"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lee, N., Jeong, S., Lee, S.K., Cho, E.-J., Hyun, J., Park, M.-J., Song, W., and Kim, H.S. (2022). Quantitative Analysis of Anti-N and Anti-S Antibody Titers of SARS-CoV-2 Infection after the Third Dose of COVID-19 Vaccination. Vaccines, 10.","DOI":"10.3390\/vaccines10071143"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.0022-202X.2005.23856.x","article-title":"Old Meets New: The Interaction Between Innate and Adaptive Immunity","volume":"125","author":"Clark","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1001\/jama.2020.16656","article-title":"COVID-19 and the Path to Immunity","volume":"324","author":"Stephens","year":"2020","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s11673-020-09996-5","article-title":"Antibodies as Currency: COVID-19\u2019s Golden Passport","volume":"17","author":"Bramstedt","year":"2020","journal-title":"Bioethical Inq."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2037384","DOI":"10.1080\/21645515.2022.2037384","article-title":"Longevity of Immunity Following COVID-19 Vaccination: A Comprehensive Review of the Currently Approved Vaccines","volume":"18","author":"Jamshidi","year":"2022","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1080\/22221751.2021.1969869","article-title":"High Estradiol and Low Testosterone Levels Are Associated with Critical Illness in Male but Not in Female COVID-19 Patients: A Retrospective Cohort Study","volume":"10","author":"Schroeder","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2217\/cer-2022-0027","article-title":"COVID-19 Complications in Males and Females: Recent Developments","volume":"11","author":"Chaturvedi","year":"2022","journal-title":"J. Comp. Eff. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13293-020-00330-7","article-title":"Sex Differences in Severity and Mortality from COVID-19: Are Males More Vulnerable?","volume":"11","author":"Pradhan","year":"2020","journal-title":"Biol. Sex Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1016\/j.immuni.2023.10.008","article-title":"Sex Hormone Signaling and Regulation of Immune Function","volume":"56","author":"Hoffmann","year":"2023","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s42000-021-00300-7","article-title":"The Role of Estradiol in the Immune Response against COVID-19","volume":"20","year":"2021","journal-title":"Hormones"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sciarra, F., Campolo, F., Franceschini, E., Carlomagno, F., and Venneri, M.A. (2023). Gender-Specific Impact of Sex Hormones on the Immune System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076302"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s11897-022-00555-0","article-title":"Evaluation of the Interaction of Sex Hormones and Cardiovascular Function and Health","volume":"19","author":"Willemars","year":"2022","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/1008-682X.122356","article-title":"Androgens and Estrogens in Skeletal Sexual Dimorphism","volume":"16","author":"Laurent","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1152\/advan.90111.2008","article-title":"Skeletal Muscle and Bone: Effect of Sex Steroids and Aging","volume":"32","author":"Brown","year":"2008","journal-title":"Adv. Physiol. Educ."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Harding, A.T., and Heaton, N.S. (2022). The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection. Cancers, 14.","DOI":"10.3390\/cancers14040909"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0010-7824(95)00102-G","article-title":"Effect of Levonorgestrel-Releasing Intrauterine Device on Hormonal Profile and Menstrual Pattern after Long-Term Use","volume":"51","author":"Xiao","year":"1995","journal-title":"Contraception"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/eje.0.1480227","article-title":"Diurnal Rhythm of Free Estradiol during the Menstrual Cycle","volume":"148","author":"Bao","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1515\/CCLM.1998.081","article-title":"Biological Day-to-Day Variation and Daytime Changes of Testosterone, Follitropin, Lutropin and Oestradiol-17beta in Healthy Men","volume":"36","author":"Ahokoski","year":"1998","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.4049\/jimmunol.2101156","article-title":"SARS-CoV-2 Antibody Response Is Associated with Age and Body Mass Index in Convalescent Outpatients","volume":"208","author":"Zhai","year":"2022","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00275-21","DOI":"10.1128\/mSphere.00275-21","article-title":"Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals","volume":"6","author":"Markmann","year":"2021","journal-title":"mSphere"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gubbels Bupp, M.R., Potluri, T., Fink, A.L., and Klein, S.L. (2018). The Confluence of Sex Hormones and Aging on Immunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01269"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1046\/j.1365-2265.2003.01669.x","article-title":"The Importance of Oestrogens in Males","volume":"58","author":"Pols","year":"2003","journal-title":"Clin. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1210\/jcem-71-6-1442","article-title":"Androgens, Estrogens, and Sex Hormone-Binding Globulin in Middle-Aged Men","volume":"71","author":"Longcope","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1093\/humrep\/den213","article-title":"Body Fat, Energy Balance and Estradiol Levels: A Study Based on Hormonal Profiles from Complete Menstrual Cycles","volume":"23","author":"Ziomkiewicz","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1002\/ijc.33010","article-title":"Body Size and Composition, Physical Activity and Sedentary Time in Relation to Endogenous Hormones in Premenopausal and Postmenopausal Women: Findings from the UK Biobank","volume":"147","author":"Reeves","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.mehy.2007.05.020","article-title":"Obesity in Men: The Hypogonadal\u2013Estrogen Receptor Relationship and Its Effect on Glucose Homeostasis","volume":"70","author":"Cohen","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/0026-0495(79)90163-X","article-title":"The Effect of Alcohol Ingestion on Hepatic Aromatase Activity and Plasma Steroid Hormones in the Rat","volume":"28","author":"Gordon","year":"1979","journal-title":"Metab. Clin. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70221","DOI":"10.1111\/acer.70221","article-title":"Alcohol and the Endocrine System: A Critical Review of Disruptions, Potential Mechanisms, and Health Implications","volume":"50","author":"Molina","year":"2026","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_36","first-page":"195","article-title":"Alcohol\u2019s Effects on Male Reproduction","volume":"22","author":"Emanuele","year":"1998","journal-title":"Alcohol Health Res. World"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.clinbiochem.2016.09.016","article-title":"Salivary Estradiol as a Surrogate Marker for Serum Estradiol in Assisted Reproduction Treatment","volume":"50","author":"Fiers","year":"2017","journal-title":"Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jsxm.2021.03.004","article-title":"Testosterone\u2019s Role in COVID-19","volume":"18","author":"Auerbach","year":"2021","journal-title":"J. Sex Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2111398","DOI":"10.1001\/jamanetworkopen.2021.11398","article-title":"Association of Circulating Sex Hormones with Inflammation and Disease Severity in Patients with COVID-19","volume":"4","author":"Dhindsa","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/andr.13097","article-title":"Testosterone in Males with COVID-19: A 7-month Cohort Study","volume":"10","author":"Salonia","year":"2022","journal-title":"Andrology"},{"key":"ref_41","first-page":"150","article-title":"Estradiol and COVID-19: Does 17-Estradiol Have an Immune-Protective Function in Women Against Coronavirus?","volume":"15","author":"Zangeneh","year":"2021","journal-title":"J. Fam. Reprod. Health"},{"key":"ref_42","first-page":"38","article-title":"Possible Protective Role of 17\u03b2-Estradiol against COVID-19","volume":"1","author":"Khan","year":"2020","journal-title":"J. Allergy Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1128\/JVI.02081-13","article-title":"17\u03b2-Estradiol Protects Females against Influenza by Recruiting Neutrophils and Increasing Virus-Specific CD8 T Cell Responses in the Lungs","volume":"88","author":"Robinson","year":"2014","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12695","DOI":"10.1111\/aji.12695","article-title":"Estradiol and Progesterone Influence on Influenza Infection and Immune Response in a Mouse Model","volume":"78","author":"Davis","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0091-6749(99)70503-8","article-title":"Estrogen Enhances Immunoglobulin Production by Human PBMCs","volume":"103","author":"Kanda","year":"1999","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/JVI.74.11.4999-5005.2000","article-title":"Induction of CD4(+) T-Cell-Independent Immunoglobulin Responses by Inactivated Influenza Virus","volume":"74","author":"Sha","year":"2000","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41577-020-00436-4","article-title":"Not Just Antibodies: B Cells and T Cells Mediate Immunity to COVID-19","volume":"20","author":"Cox","year":"2020","journal-title":"Nat. Rev. Immunol."}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/72\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:24:03Z","timestamp":1786094643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/72"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antib15040072"],"URL":"https:\/\/doi.org\/10.3390\/antib15040072","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}