{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:09:38Z","timestamp":1792076978659,"version":"4.4.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Understanding the role of mucosal immune responses in preventing coronavirus replication is essential for the development of broad-spectrum therapeutics and vaccines capable of interrupting transmission. Investigating the relationship between mucosal antibodies and viral shedding may provide critical insights into protective mechanisms against SARS-CoV-2 and inform strategies for enhancing mucosal immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a subset of the larger CoVPN 5001 cohort, 143 participants from the US, Mexico, and South America were characterized as either short (&amp;lt;7 days), intermediate (7\u201321 days), or prolonged (&amp;gt;21 days) virus shedders based on RT-qPCR measurements over the first month of acute SARS-CoV-2 infection. We measured systemic circulating serum IgA and secretory IgA (SIgA) in serially collected nasal lavage fluids to 15 SARS-CoV-2 antigens, including spike variants, receptor binding domain (RBD), and N-terminal Domain (NTD) and evaluated the relationship between antibody titers and duration of viral shedding using multivariate and binary logistic regression modeling. We also assessed antibody responses to RBD proteins of endemic alpha and beta coronaviruses to compare variations in antibody kinetics throughout the course of infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that increased serum IgA and mucosal secretory IgA antibody titers during the earliest phase of acute infection were associated with decreased viral shedding duration, with nasal IgA responses to the spike NTD being the strongest factor associated with viral shedding (adjusted p&amp;lt;0.1). In contrast, antibody titers against endemic human coronaviruses remained stable throughout the course of infection, consistent with a specific role for newly elicited SARS-CoV-2 antibodies in virus control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that early rises in serum and mucosal IgA titers are associated with reduced duration of viral shedding. Notably, nasal secretory IgA responses targeting the spike N-terminal domain were most strongly associated with shorter shedding, suggesting a potentially protective role for SARS-CoV-2-specific nasal IgA during acute SARS-CoV-2 infection. These results highlight the importance of mucosal immunity for limiting viral transmission and shedding, offering future insights for pan-coronavirus therapeutics and vaccine development aimed for enhancing SARS-COV-2 mucosal antibody responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1722585","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:04:33Z","timestamp":1772003073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Early rise in nasal secretory IgA associated with shorter duration of SARS-CoV-2 virus shedding in an acute infection cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Caroline","family":"Brackett","sequence":"first","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bich T. N.","family":"Do","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saman","family":"Baral","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh H.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William O.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Carnacchi","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sir\u2019Tauria","family":"Hilliard","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying S.","family":"Li","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmanane","family":"Premkumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina","place":["Chapel Hill, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L.","family":"Greninger","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center","place":["Seattle, WA, United States"]},{"name":"Department of Laboratory Medicine and Pathology, University of Washington Medical Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ollivier","family":"Hyrien","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Seaton","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia D.","family":"Tomaras","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Integrative Immunobiology, Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","unstructured":"COVID-19 epidemiological update \u2013 15 July 2024\n          \n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127401","article-title":"Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines","volume":"14","author":"Liu","year":"2023","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00517-8","article-title":"Dealing with a mucosal viral pandemic: lessons from COVID-19 vaccines","volume":"15","author":"Mouro","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/v14092071","article-title":"Vaccination decreases the infectious viral load of delta variant SARS-coV-2 in asymptomatic patients","volume":"14","author":"Plante","year":"2022","journal-title":"Viruses"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9080881","article-title":"Single-dose intranasal administration of adCOVID elicits systemic and mucosal immunity against SARS-coV-2 and fully protects mice from lethal challenge","volume":"9","author":"King","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"103037","DOI":"10.1016\/j.isci.2021.103037","article-title":"Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2","volume":"24","author":"An","year":"2021","journal-title":"iScience"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e2202069119","DOI":"10.1073\/pnas.2202069119","article-title":"Intranasal inoculation of an MVA-based vaccine induces IgA and protects the respiratory tract of hACE2 mice from SARS-CoV-2 infection","volume":"119","author":"Americo","year":"2022","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B8","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41392-023-01423-6","article-title":"Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41541-024-00857-5","article-title":"An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza","volume":"9","author":"Xing","year":"2024","journal-title":"Nature.com"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.618685","article-title":"Distinct features and functions of systemic and mucosal humoral immunity among SARS-coV-2 convalescent individuals","volume":"11","author":"Butler","year":"2020","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jaci.2020.10.040","article-title":"Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19","volume":"147","author":"Cervia","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac934","article-title":"Comparison of levels of nasal, salivary, and plasma antibody to severe acute respiratory syndrome coronavirus 2 during natural infection and after vaccination","volume":"76","author":"Cohen","year":"2023","journal-title":"Clin Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd2223","article-title":"IgA dominates the early neutralizing antibody response to SARS-CoV-2","volume":"13","author":"Sterlin","year":"2021","journal-title":"Sci Transl Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.655896","article-title":"IgA antibodies and igA deficiency in SARS-coV-2 infection","volume":"11","author":"Quinti","year":"2021","journal-title":"Front Cell Infection Microbiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01091-0","article-title":"Innate immunity: the first line of defense against SARS-CoV-2","volume":"23","author":"Kanneganti","year":"2022","journal-title":"Nat Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2032057","DOI":"10.1155\/2020\/2032057","article-title":"The effects of secretory igA in the mucosal immune system","volume":"2020","author":"Li","year":"2020","journal-title":"BioMed Res Int"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00822-w","article-title":"SARS-CoV-2 viral load and shedding kinetics","volume":"21","author":"Puhach","year":"2022","journal-title":"Nat Rev Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.648660","article-title":"SARS-coV-2 viral shedding and transmission dynamics: implications of WHO COVID-19 discharge guidelines","volume":"8","author":"Badu","year":"2021","journal-title":"Front Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"104402","DOI":"10.1016\/j.ebiom.2022.104402","article-title":"SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination","volume":"87","author":"Liew","year":"2023","journal-title":"EBioMedicine"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf176","article-title":"Mucosal and systemic antibody responses after boosting with a bivalent messenger RNA severe acute respiratory syndrome coronavirus 2 vaccine","volume":"232","author":"Atmar","year":"2025","journal-title":"J Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn2364","article-title":"Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa","volume":"16","author":"Declercq","year":"2024","journal-title":"Sci Trans Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.05.011","article-title":"Advances in intranasal vaccine delivery: A promising non-invasive route of immunization","volume":"41","author":"Kehagia","year":"2023","journal-title":"Vaccine"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301456110","article-title":"Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG","volume":"110","author":"Tomaras","year":"2013","journal-title":"Proc Natl Acad Sci"},{"key":"B24","volume-title":"SARS-CoV-2 Viral Variant is Strongly Associated with Viral Load During Infection with Minimal Contribution from Host Effects","author":"Hahn","year":"2024"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1722585\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:04:36Z","timestamp":1772003076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1722585\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":24,"alternative-id":["10.3389\/fimmu.2026.1722585"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1722585","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"article-number":"1722585"}}