{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:26:18Z","timestamp":1784042778316,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationUE as part of PNRR MUR\u2014M4C2\u2014Investimento 1.3\u2014Public Call \u201cPartenariatiEstesi\u201d","award":["341\/2022"],"award-info":[{"award-number":["341\/2022"]}]},{"name":"European Union\u2014NextGenerationUE as part of PNRR MUR\u2014M4C2\u2014Investimento 1.3\u2014Public Call \u201cPartenariatiEstesi\u201d","award":["PE_00000019-CUP D73C22001230006"],"award-info":[{"award-number":["PE_00000019-CUP D73C22001230006"]}]},{"name":"Progetto HEAL ITALIA \u201cHealth Extended Alliance for Innovative Therapies, Advanced Lab-research","award":["341\/2022"],"award-info":[{"award-number":["341\/2022"]}]},{"name":"Progetto HEAL ITALIA \u201cHealth Extended Alliance for Innovative Therapies, Advanced Lab-research","award":["PE_00000019-CUP D73C22001230006"],"award-info":[{"award-number":["PE_00000019-CUP D73C22001230006"]}]},{"name":"Integrated Approaches of Precision Medicine\u201d-acronimo HEAL ITALIA","award":["341\/2022"],"award-info":[{"award-number":["341\/2022"]}]},{"name":"Integrated Approaches of Precision Medicine\u201d-acronimo HEAL ITALIA","award":["PE_00000019-CUP D73C22001230006"],"award-info":[{"award-number":["PE_00000019-CUP D73C22001230006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization. Dimeric IgA has been reported to be 10 to 15 times more potent than its equivalent IgG, suggesting that this isotype may be particularly interesting in developing new monoclonal antibodies and\/or new vaccines efficiently neutralizing the virus at the mucosal sites. It is still unclear whether IgA antibodies in BAL might play a role in the disease course and if their presence may have a prognostic significance. However, a harmful effect on diseases with high IgA titers has been reported. This study evaluated mucosal-specific IgA and IgG profiles in BAL of patients with COVID-19 acute respiratory failure admitted to the ICU. We included 57 patients (41 males and 16 females), admitted to the ICU of the University of Foggia. We used a commercially available ELISA assay to evaluate the presence of SARS-CoV-2 IgG and IgA antibodies in plasma and BAL of the 57 hospitalized patients with severe COVID-19 respiratory failure. However, 40\/57 BAL and plasma from infected patients were available for the ELISA test; the remaining specimens were unsuitable. IgG and IgA antibodies against SARS-CoV-2 were detectable in 37 (92.5%) and 40 (100%) plasma specimens, respectively. IgG antibodies were found in a single sample, while IgAs were detected in 19 of 40 BAL samples analyzed. Correlations between these parameters and patient outcomes reveal a signature associated with survival. Interestingly, a statistically significant inverse correlation was found between the mortality rate and the presence of IgA to SARS-CoV-2 in BAL specimens. None of the 19 patients with a positive IgA died, compared to 7 out of 12 patients with a negative IgA-BAL (p: &lt;0.0004). Despite being limited in size, this study suggests a significant protective effect of mucosal immunity in COVID-19 patients, even in advanced disease stages, and a role of IgA in the defense against the virus, as well as the possible use of effective vaccines and therapeutic strategies based on IgA antibodies.<\/jats:p>","DOI":"10.3390\/v16121851","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T10:19:42Z","timestamp":1732789182000},"page":"1851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Possible Protective Effect of IgA Against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in Bronchoalveolar Lavage in COVID-19 Patients Admitted to Intensive Care Unit"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-0953","authenticated-orcid":false,"given":"Mariantonietta","family":"Di Stefano","sequence":"first","affiliation":[{"name":"Department of Surgical and Medical Science, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Mirabella","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cotoia","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-3890","authenticated-orcid":false,"given":"Giuseppina","family":"Faleo","sequence":"additional","affiliation":[{"name":"Department of Surgical and Medical Science, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-7454","authenticated-orcid":false,"given":"Michela","family":"Rauseo","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e8 Ramon","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Surgical and Medical Science, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-2893","authenticated-orcid":false,"given":"Gilda","family":"Cinnella","sequence":"additional","affiliation":[{"name":"Anesthesia and Intensive Care Unit, Department of Surgical and Medical Science, Policlinico Riuniti di Foggia, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6424-7841","authenticated-orcid":false,"given":"Gaetano","family":"Serviddio","sequence":"additional","affiliation":[{"name":"C.U.R.E. (University Center for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Montague, B.T., Wipperman, M.F., Chio, E., Crow, R., Hooper, A.T., O\u2019Brien, M.P., and Sim\u00f5es, E.A.F. (2022). Elevated serum IgA following vaccination against SARS-CoV-2 in a cohort of high-risk first responders. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-19095-7"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gupta, S.L., Tyagi, R., Dhar, A., Oswal, N., Khandelwal, A., and Jaiswal, R.K. (2023). Children\u2019s SARS-CoV-2 Infection and Their Vaccination. Vaccines, 11.","DOI":"10.3390\/vaccines11020418"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bohl\u00e4nder, F. (2023). A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1127339"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41573-022-00495-3","article-title":"Antibodies to combat viral infections: Development strategies and progress","volume":"21","author":"Pantaleo","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabd2223","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":"ref_6","doi-asserted-by":"crossref","first-page":"e24031","DOI":"10.1016\/j.heliyon.2024.e24031","article-title":"Immunoglobulin A response to SARS-CoV-2 infection and immunity","volume":"10","author":"Esmat","year":"2024","journal-title":"Heliyon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S2213-2600(21)00557-9","article-title":"Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged \u226565 years: A phase 2, randomized, open-label study","volume":"10","author":"Izikson","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, M.H., Kim, H.J., and Chang, J. (2019). Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus. PLoS ONE., 14.","DOI":"10.1371\/journal.pone.0220196"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Norton, N.J., Ings, D.P., Fifield, K.E., Barnes, D.A., Barnable, K.A., Harnum, D.O.A., Holder, K.A., Russell, R.S., and Grant, M.D. (2023). Characteristics of Vaccine- and Infection-Induced Systemic IgA Anti-SARS-CoV-2 Spike Responses. Vaccines, 11.","DOI":"10.3390\/vaccines11091462"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1016\/j.jaip.2023.02.016","article-title":"Selective IgA deficiency and COVID-19","volume":"11","author":"Magen","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"228","DOI":"10.7883\/yoken.JJID.2021.281","article-title":"Relationship between Selective IgA Deficiency and COVID-19 Prognosis","volume":"75","author":"Kandemir","year":"2022","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ruiz, M.J., Siracusano, G., Cottignies-Calamarte, A., Tudor, D., Real, F., Zhu, A., Pastori, C., Capron, C., Rosenberg, A.R., and Temperton, N. (2022). Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1\u03b2 associate with COVID-19 fatal outcome: A cross-sectional analysis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.842468"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108790","DOI":"10.1016\/j.celrep.2021.108790","article-title":"Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2","volume":"34","author":"Gasser","year":"2021","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1111\/trf.16435","article-title":"Are We Forgetting About IgA? A Re-examination of Coronavirus Disease 2019 Convalescent Plasma","volume":"61","author":"Verkerke","year":"2021","journal-title":"Transfusion"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction\/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1097\/00003246-198510000-00009","article-title":"APACHE II: A severity of disease classification system","volume":"13","author":"Knaus","year":"1985","journal-title":"Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1164\/ajrccm.156.4.9701065","article-title":"Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: Incidence and diagnosis","volume":"156","author":"Delclaux","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gededzha, M.P., Mampeule, N., Jugwanth, S., Zwane, N., David, A., Burgers, W.A., Blackburn, J.M., Grove, J.S., George, J.A., and Sanne, I. (2021). Performance of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies in South Africa. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252317"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tyagi, R., Basu, S., Dhar, A., Gupta, S., Gupta, S.L., and Jaiswal, R.K. (2023). Role of Immunoglobulin A in COVID-19 and Influenza Infections. Vaccines, 11.","DOI":"10.3390\/vaccines11111647"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eabf1555","DOI":"10.1126\/scitranslmed.abf1555","article-title":"Enhanced SARS-CoV-2 neutralization by dimeric IgA","volume":"13","author":"Wang","year":"2021","journal-title":"Sci Transl Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/imr.13014","article-title":"Know your enemy or find your friend?\u2014Induction of IgA at mucosal surfaces","volume":"303","author":"Bemark","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"de Sousa-Pereira, P., and Woof, J.M. (2019). IgA: Structure, Function, and Developability. Antibodies, 8.","DOI":"10.3390\/antib8040057"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.4161\/mabs.3.4.16092","article-title":"Immunoglobulin A: A next generation of therapeutic antibodies?","volume":"3","author":"Bakema","year":"2011","journal-title":"MAbs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/mi.2011.39","article-title":"Structure and function relationships in IgA","volume":"4","author":"Woof","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.cca.2020.04.026","article-title":"IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study","volume":"507","author":"Padoan","year":"2020","journal-title":"Clin. Chim. Acta."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fimmu.2013.00222","article-title":"Secretory IgA: Designed for Anti-Microbial Defense","volume":"4","author":"Brandtzaeg","year":"2013","journal-title":"Immunol. Front."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.immuni.2011.01.015","article-title":"Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges","volume":"34","author":"Bomsel","year":"2011","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Khamassi, M., Xu, L., Rey, J., Duchemin, M., Bouceba, T., Tuffery, P., Tudor, D., and Bomsel, M. (2020). The CH1\u03b1 domain of mucosal gp41 IgA contributes to antibody specificity and antiviral functions in HIV-1 highly exposed Sero-Negative individuals. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009103"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Butler, S.E., Crowley, A.R., Natarajan, H., Xu, S., Weiner, J.A., Bobak, C.A., Mattox, D.E., Lee, J., Wieland-Alter, W., and Connor, R.I. (2021). Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.618685"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2001526","DOI":"10.1183\/13993003.01526-2020","article-title":"Distinct features of SARS-CoV-2-specific IgA response in COVID-19 patients","volume":"56","author":"Yu","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1002\/jmv.27058","article-title":"SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection","volume":"93","author":"Zervou","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1038\/s41467-020-18058-8","article-title":"A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction","volume":"11","author":"Ejemel","year":"2020","journal-title":"Nat Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ymthe.2024.01.025","article-title":"Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2","volume":"32","author":"Groppelli","year":"2024","journal-title":"Mol. Ther."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:41:55Z","timestamp":1760114515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,28]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["v16121851"],"URL":"https:\/\/doi.org\/10.3390\/v16121851","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,28]]}}}